Use of Drugs OFF LABEL PDF

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Unusual uses of common drugs by Ahmed Yossef

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Unusual uses of common drugs
By
PHARMACIST
Ahmed Mohammed Yossef
ahmed.yossef@hotmail.com
https://www.facebook.com/unusualusesofcommondrugs
http://unusualusesofcommondrugs.blogspot.com/
Copyright © 2015 unusual uses of common drugs™, All Rights Reserved.

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Acetyl salicylic acid …………………………..........…..6
Amitriptyline…………………………………….…………20
Betamethasone ………………………………...……….23
Bromocriptine………………………………..….………..28
Bupropion…………………………………………..……...32
Calcium…………………………………………...………...35
Cabergoline ……………………………………………….38
Combined oral contraceptive……………………..…40
Dexamethasone and betamethasone……………..68
Diltiazem…………………………………………………...17
Domperidone………………………………………………74
Erythromycin………………………………………………82
Finasteride……………………………………….………...85
Folic acid…………………………………………..……...700
Gonadotropins…………………………………………..170
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Insulin……………………………………………….........118
Liraglutide………………………………………............127
MegestrolAcetate………………………….........…….724
Metformin……………………………………..........……721
Metronidazole………………………………..........……135
Nifedipine……………………………………..........……138
Prednisolone….......................................................755
Propranolol.............................................................159
Sildenafil.................................................................712
Sodium bicarbonate..............................................787
Spironolactone.......................................................784
Sulfasalazine..........................................................200
Tadalafi....................................................................203
Topiramate..............................................................201
Trimethoprim-Sulfamethoxazole……......……….277
Vitamin D.................................................................274

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 Unusual uses of common drugs is a new vision to

experience the hidden side in medications effect.
 It is the indications that health care provider not used
to deal with it. Some indications may be approved by
FDA other indications may be not yet approved.
 Unusual uses of common drugs differ from off-label uses

that some indications approved by FDA. health care
provider awareness of these unusual indications leading
to the best counselling to the patient and let him use
these medications in best way, also give health care
provider many choices in some critical cases.
 Unusual uses of common drugs open the health care

provider’s mind towards a new ways to the effect of
medications.

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 A salicylate drug, often used as an analgesic to

relieve minor aches and pains, as an antipyretic to
reduce fever, and as an anti-
inflammatory medication.
 Aspirin also has an antiplatelet effect by inhibiting

the production of thromboxane, which under
normal circumstances binds platelet molecules
together to create a patch over damaged walls of
blood vessels. Because the platelet patch can
become too large and also block blood flow, locally
and downstream.

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1-Aspirin used in reducing risk of preeclampsia
 Pregnant women at high risk for

preeclampsia should take low-dose aspirin (75mg-
81mg) every day after their first trimester .
 Preeclampsia is a complex condition that occurs in

pregnant women and involves an increase in blood
pressure and excess protein in the urine after 20
weeks of pregnancy.

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 Daily low-dose aspirin in middle and late

pregnancy can significantly reduce the occurrence
of preeclampsia among these women and it can
lower the risk of preterm birth or low birth weight
resulting from the pregnancy-related condition
because aspirin helps blood flow between the
placenta and the fetus.
Mechanism
 High or normal doses (>325 mg) block production
of prostacyclin and thromboxane, and low-dose
aspirin (60–83 mg) results in selective block of
thromboxane production, and favors the
prostacyclin (vasodilation) pathway.
 This provides the basis for the use of low-dose

aspirin to forestall or prevent pregnancy-induced
hypertension. Importantly, low-dose aspirin does

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not completely inhibit thromboxane and does not

completely ‘spare’ prostacyclin. One group of
investigators found that 81 mg of aspirin inhibited
thromboxane by 75 percent, but also inhibited
prostacyclin by approximately 20 %.
References
 Drugs and Pregnancy: A Handbook By Bertis Little.
 Pregnancy Induced Hypertension edited by H. Seneviratn
 Aspirin and Related Drugs edited by Kim D. Rainsford
 National Institute for Health and Clinical Excellence:Hypertension in pregnancy clinical
guidelines CG107 full guideline August2010 .
 National Institute for Health and Clinical Excellence:Hypertension in pregnancy clinical
guidelines CG107 understanding NICE guidance written information for parents and
carers August2010.
 Roberge S, Nicolaides K, Demers S, Villa P, Bujold E. Prevention of perinatal death and adverse
perinatal outcome using low-dose aspirin: a meta-analysis. Ultrasound Obstet Gynecol. 2013 January
29. [Epub ahead of print]
 Askie LM, Duley L, Henderson-Smart DJ, Stewart LA; PARIS Collaborative Group. Antiplatelet agents
for prevention of pre-eclampsia: a meta-analysis of individual patient data. Lancet. 2007;369:1791-
1798.
 Duley L, Henderson-Smart DJ, Meher S, King JF. Antiplatelet agents for preventing pre-eclampsia and
its complications. Cochrane Database Syst Rev. 2007;CD004659.
 Bujold E, Morency AM, Roberge S, Lacasse Y, Forest JC, Giguère Y. Acetylsalicylic acid for the
prevention of preeclampsia and intra-uterine growth restriction in women with abnormal uterine artery
Doppler: a systematic review and meta-analysis. J Obstet Gynaecol Can. 2009;31:818-826.
 Bujold E, Roberge S, Lacasse Y, et al. Prevention of preeclampsia and intrauterine growth restriction
with aspirin started in early pregnancy: a meta-analysis. Obstet Gynecol. 2010;116(2 Pt 1):402-414.

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 Bakhti A, Vaiman D. Prevention of gravidic endothelial hypertension by aspirin treatment administered

from the 8th week of gestation. Hypertens Res. 2011;34:1116-1120.
 Mesdaghinia E, Talari H, Abedzadeh-Kalahroudi M. Effect of aspirin for prevention of preeclampsia in

women with abnormal ultrasonic findings in uterine artery. Feyz: Journal of Kashan University of
Medical Sciences. 2011;15:98-104.
 Ayala DE, Ucieda R, Hermida RC. Chronotherapy with low-dose aspirin for prevention of complications
in pregnancy. Chronobiol Int. 2013;30:260-279.
 la PM, Kajantie E, Räikkönen K, et al; PREDO Study group. Aspirin in the prevention of pre-eclampsia
in high-risk women: a randomised placebo-controlled PREDO Trial and a meta-analysis of randomised
trials. BJOG. 2013;120:64-74.
Links
 http://guidance.nice.org.uk/nicemedia/live/13098/50416/50416.pdf
 NHS Brand Guidelines :patient information ,written information, general guidelines Available
at: http// www.nhsidentity.nhs.uk/tools-and-resources/patient-information
 OUH Maternity information leaflet available at:
 http://www.ouh.nhs.uk/forpatients/patientinfoleaflets/maternityleaflets.aspx
 http://www.medicinenet.com/script/main/art.asp?articlekey=109584
 http://www.drugs.com/pregnancy/aspirin.html
 http://www.webmd.com/baby/news/20140407/aspirin-advised-for-women-at-high-risk-for-
pregnancy-complication
 http://www.ouh.nhs.uk/patient-guide/leaflets/files%5C5052Ppreeclampsia.pdf

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2-Topical Aspirin for Relief of Pain due to

Herpes Zoster and Postherpeic Neuralgia
 Topical aspirin dissolved in chloroform is an

effective means of reducing pain due to herpes
zoster and post herpetic neuralgia in most patients.
The locus of pain origin and analgesia induced by
topical aspirin is most likely at cutaneous free-
nerve ending pain receptors. The mechanism
responsible for the analgesic properties of aspirin is
probably not the same as that responsible for its
anti-inflammatory properties.
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References:
Pain management The Importance of Individualized Therapy Promed pharmacy
Aspirin and Related Drugs edited by Kim D. Rainsfor
Clinical Management of Herpes Viruses edited by Stephen L. Sack
Links
http://www.ncbi.nlm.nih.gov/pubmed/8215962

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3-Aspirin and Alzheimer's
 The Baltimore Longitudinal Study that appearing

in the journal Neurology reported that the
incidence of Alzheimer's was 45% lower for people
who took aspirin for more than two years, than
those who didn't.

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 This is not the first study to suggest that aspirin

may be effective in combating the onset of
Alzheimer's.
Mechanism
 There are numerous theories about why it appears
to work. For example, one theory is that
Alzheimer's is caused by an inflammatory process
in the brain. Taking an anti-inflammatory
medication might then reduce the risk. Another
theory is that with Alzheimer's, enzymes in the
brain cause a breakdown of proteins. When this
occurs, amyloid plaque is formed and disrupts
brain activity. Perhaps aspirin and other anti-
inflammatory medications prevent this from
occurring.

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Reference
Alzheimer Disease: New Insights for the Healthcare Professional: 2013 Edition
New Research on Aspirin and Health edited by Charles L. Millwood
Preventing Alzheimer's: Ways to Help Prevent, Delay, Detect, and Even Halt ... By William Rodman
Shankle, Daniel G. Amen
Links
http://www.webmd.com/alzheimers/news/20110718/baby-aspirin-may-help-memory-
thinking-skills
http://www.medscape.com/viewarticle/768489_2
http://www.nemahealth.org/programs/nac/alzheimers_n_aspirin.htm
http://www.pharmacytimes.com/publications/otc/2009/OTC-0609/OTC-Aspirin-0609
http://www.nia.nih.gov/alzheimers/publication/preventing-alzheimers-disease/search-
alzheimers-prevention-strategies

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4-Aspirin for the prevention of colorectal cancer
 Aspirin has been studied as adjuvant therapy for

colorectal cancer, with promising results. Earlier
prevention studies demonstrated the efficacy of
aspirin against the development of colorectal
tumors prompting investigation into its potential
treatment efficacy.
Mechanism
 The proposed mechanism draws on the fact that
certain colorectal tumors overexpress
prostaglandin-endoperoxide synthase 2 -- better
known as cyclooxygenase-2 (COX-2). Mutations of
the sort seen in colorectal cancer are known to
sustain tumor cell growth by preventing
apoptosis. By blocking COX-2, aspirin therapy is
hypothesized to suppress tumor growth.
 Taking aspirin in doses as low as 325 mg per day
reduces CRC risk also there is also strong evidence
from secondary analyses of cardiovascular trials
that daily doses as low as 75 mg per day may be
effective.
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References
Early Detection and Prevention of Colorectal Cancer edited by Karen E. Kim
Colon Cancer Prevention: Dietary Modulation of Cellular and ..., Volume 470 edited
by American Institute for Cancer Research
Cancer Prevention II By Hans-Jörg Senn, Ursula Kapp, Florian Otto
Colorectal Cancer: New Insights for the Healthcare Professional: 2013 Edition
National Comprehensive Cancer Network. NCCN Guidelines® for Colon Cancer.
V.3.2013.http://www.nccn.org/professionals/physician_gls/PDF/colon.pdf Accessed June 6, 2013.
20;376(9754):1741–50.
Links
http://www.pharmacytimes.com/news/Low-Dose-Aspirin-May-Reduce-Colon-
Cancer-Risk
http://www.mayoclinic.org/diseases-conditions/colon-cancer/basics/prevention/con-
20031877
http://www.health.harvard.edu/blog/taking-aspirin-linked-to-lower-risk-of-colorectal-
cancer-201307166473
http://www.medscape.com/viewarticle/767084
http://www.aspirin-foundation.com/news/conferences/prevention/familial.html
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3354696/

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5-Aspirin help in sore or ulcerated mouth
 Aspirin can be used as a gargle or mouthwash 300

mg of aspirin dissolved in half glass of water rinse
around mouth and spit out. Use up to 8 times in 24
hours half an hour before meals.
Reference
Patient information leaflets Oxford university hospitals
http://www.ouh.nhs.uk/patient-guide/leaflets/files/101028soremouth.pdf

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 This medication is used to treat mental/mood

problems such as depression. It may help improve
mood and feelings of well-being, relieve anxiety and
tension, help you sleep better, and increase your
energy level. This medication belongs to a class of
medications called tricyclic antidepressants. It
works by affecting the balance of certain natural
chemicals (neurotransmitters such as serotonin) in
the brain.
 Dose
10-25 mg orally at bed time

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Algorithm for pharmacologic migraine prophylaxis.
 References
http://reference.medscape.com/drug/levate-amitriptyline-342936
http://www.webmd.com/drugs/2/drug-8611/amitriptyline-oral/details#
http://www.aafp.org/afp/2006/0101/p72.html

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 Betamethasone topical is used to help relieve

redness, itching, swelling, or other discomfort
caused by skin conditions. Betamethasone foam is
used for scalp problems.
Betamethasone scalp application used as ear drop
 It is giving to try to manage excessive amount of

skin that building up in ear canals as a result of
eczema type conditions.

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Patient counselling
First 2 weeks of treatment:
• Warm the drops to body temperature before

you use them.
• You may find that the first time you use the
drops you experience a slight hot or burning
type sensation - this is normal.
• Put 2 drops in the affected ear / ears, every

night for 2 weeks then STOP.
-After the first 2 weeks of treatment you should

then use as follows:
• 2 drops of solution only in whichever ear
itches, whenever it itches.
If you have been advised to continue using the

drops in the long term
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it is better to dilute them. This will not affect its

ability to work:
• Dilute the Betnovate with equal parts of

sterile / cooled boiled water
(50:50). Store the made up solution in your
refrigerator for up to one month. Discard the
made up solution after a month.
• Do not use the drops more than twice a day.
.How to instil your ear drops
1- Lie on a bed with the ear to be treated

uppermost.
2. Take a firm hold of the ear; pull it gently

backwards, then up and
away from the head. This will make the ear
canal straighter, so
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that the drops go in more easily. Put the

prescribed amount of ear drops into the ear
canal.
3. Lie on your side for at least 5 minutes - time

it by the clock. This
gives the drops time to soak in.
4. Place a piece of cotton wool in the outer

canal, just to prevent
any of the drops running out. Remove the
cotton wool after 20 minutes.
5. Sit up slowly.
6. If both ears need drops, wait for 10 minutes

before treating the
second ear.
Reference
-
Oxford University Hospitals NHShttp://www.ouh.nhs.uk/
http://www.nlm.nih.gov/medlineplus/druginfo/meds/a682799.html

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 Bromocriptine is a dopamine agonist, it is

indicated for Amenorrhea,
female infertility, galactorrhea, hypogonadism,
and acromegaly may all be caused by pituitary
problems, such as hyperprolactinaemia, and
therefore, these problems may be treated with this
drug.
1-Bromocriptine in type 2 diabetes (FDA APPROVED USE)
 In 2009, bromocriptine mesylate was approved by

the FDA for treatment of type 2 diabetes as an
adjunct to diet and exercise to improve glycemic
control in adults.
 Note:- it is not used to treat type 1 diabetes

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Mechanism
It's not clear how bromocriptine improves

glycemic control in humans. But studies in
diabetic animals show that boosting
dopamine activity at a particular time of day
can "reset" the biological clock to improve
metabolism problems related to diabetes,
according to VeroScience, the company that
developed the first brand of bromocriptine
for type 2 diabetes mellitus.
Dose
The recommended dose is 1.6 mg to 4.8 mg

administered once daily within two hours
after waking in the morning and should be
taken with food
Reference
http://www.rxlist.com/cycloset-drug/indications-dosage.htm
http://www.drugs.com/cycloset.html
http://www.webmd.com/diabetes/news/20090507/new-diabetes-drug-cycloset-approved

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2- Bromocriptine in improvement of erectile

dysfunction
 Bromocriptine can be used to treat men who have

high prolactin levels, which can reduce the amount
of testosterone produced by the body and may lead
to problems such as infertility or erection
problems.
 Erectile function improved significantly. Sexual

desire, orgasmic function, and the patient's and his
partner's sexual satisfaction were also enhanced.
Bromocriptine may be an effective and safe
alternative agent for men with psychogenic ED.
Dose
 2.5–5 mg daily
Reference
http://ndt.oxfordjournals.org/content/15/10/1525.full
http://www.webmd.com/erectile-dysfunction/hormonal-therapy-for-erection-problems
http://press.endocrine.org/doi/full/10.1210/jc.2003-030852

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 Bupropion is antidepressants drug used to treat

seasonal affective disorder (SAD; episodes of
depression that occur in the fall and winter each
year.
Bupropion used in Smoking Cessation
Bupropion reduce the craving for tobacco.

The way it does this is not entirely known.
Bupropion does not contain nicotine and does
not help you quit smoking in the same way that
nicotine replacement therapy does. But like

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other medicines, it decreases cravings

and withdrawal symptoms.
Dose:
Bupropion: 150 mg orally every Day for 3

days, THEN Increase to 150 mg every 12hr;
should continue treatment for 7-12 weeks; if
patient successfully quits after 7-12 weeks,
consider ongoing maintenance therapy based
on individual patient risk/benefit
Dosing considerations
Begin therapy 1 week before target quit date

(usually second week of treatment)
May be used in combination with nicotine
patch
Reference
http://www.webmd.com/smoking-cessation/bupropion-hydrochloride-zyban-for-quitting-
smoking
http://reference.medscape.com/drug/wellbutrin-zyban-bupropion-342954
http://www.medicinenet.com/smoking_and_quitting_smoking/article.htm#smoking_and_
quitting_smoking_facts

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Calcium is a chemical element is essential for

living organisms, in particular in cell physiology,
where movement of the calcium ion into and out of
the cytoplasm functions as a signal for many cellular
processes. As a major material used in mineralization
of bone and teeth.
Calcium in hyperkalemia

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 Calcium polystyrene sulphonate is a calcium salt

polystyrene sulphonate is polymer and also
available as sodium salt.
It binds with potassium in the gut, forming a

complex that cannot be absorbed into the blood,
thus decreasing potassium level in blood.
Note:-it is used orally or rectally as an enema.

references
http://www.netdoctor.co.uk/…/medicines/calcium-resonium.html
http://www.drugs.com/…/calcium-polystyrene-sulphonate-powde…
http://reference.medscape.com/…/sps-kayexalate-sodium-polys…
http://www.mayoclinic.org/…/sodium…/description/drg-20073487
.

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Cabergoline in improvement of erectile

dysfunction
cabergoline can be used to treat men who have
high prolactin levels, which can reduce the amount
of testosterone produced by the body and may lead
to problems such as infertility or erection
problems.
Erectile function improved significantly. Sexual
desire, orgasmic function, and the patient's and his
partner's sexual satisfaction were also enhanced.
cabergoline may be an effective and safe alternative
agent for men with psychogenic ED.
Dose
0.5-1 mg weekly for 6 months

Reference
http://ndt.oxfordjournals.org/content/15/10/1525.full
http://www.webmd.com/erectile-dysfunction/hormonal-therapy-for-erection-problems
http://press.endocrine.org/doi/full/10.1210/jc.2003-030852
http://www.health.harvard.edu/blog/a-new-option-for-orgasm-problems-in-men-201205294804
http://www.rxlist.com/dostinex-drug.htm

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 The combined oral contraceptive pill (COCP), often

referred to as the birth-control pill .it includes a
combination of an estrogen (estradiol) and
a progesterone (progestin). When taken by mouth
every day, these pills inhibit female fertility.
 Estrogen and progesterone combined in OCs act in

a synergistic manner in the gonadotropin axis. They
decrease the secretion of hypophysial-luteinizing
hormone and follicle-stimulating hormone by
negative feedback, thereby inhibiting ovulation.

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1-Combined oral contraceptive in treatment of

acne for women. (FDA APPROVED USE)
 Acne is triggered by an excess production of sebum.

Sebum is an oil made by glands in your skin. Along
with skin cells, sebum can clog pores and promote
the growth of bacteria that contribute to acne.
Androgens, a group of hormones that includes
testosterone, stimulate your skin to produce sebum.
 A woman's ovaries and adrenal glands normally
produce a low level of androgens. Higher levels of
androgens can lead to excess sebum.

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Mechanism
 Estrogen and progesterone decrease the secretion of
luteinizing hormone and follicle-stimulating
hormone by negative feedback.
 Gonadotropin inhibition by oral contraceptive
reduce androgen production of ovarian theca cells
and adrenal gland.
 An additional anti androgenic effect of estrogens
comes from their stimulation of liver production of
sex hormone binding globulin (SHBG), a globulin
that binds free-circulating androgens and reduces
free available testosterone to peripheral tissues.
Note:-
 Only three types of birth control pills have been
approved by the FDA for treating acne.
 ethinyl estradiol+ norgestimate,ethinyl estradiol+
drospirenone and ethinyl estradiol+ norethindrone
 These three oral contraceptives have been approved
for treating moderate acne in women who:

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 Are at least 14 or 15 years old, Have already started

menstruating and Need contraception
 Combination oral contraceptives may be used as

second-line therapy in pubertal females with
moderate-to-severe acne
 Birth control pills work on only one acne-related

factor -- excess sebum. Doctors often prescribe
other forms of acne treatment -- topical medications
or antibiotics -- to be used alongside them for best
results in clearing the skin.
 Spironolactone may be used in combination with

OCPs in women who have limited response to OCPs
alone.

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References
1. Chang, MD, Louise. "Birth Control of Acne". WebMD, LLC. Retrieved 1 February 2013.
2. Arowojolu AO, Gallo MF, Grimes DA, Garner SE. Combined oral contraceptive pills for treatment
of acne. Cochrane Database Syst Rev. 2004;(3):CD004425.
3. James WD. Clinical practice. Acne. N Engl J Med. 2005;352:1463-1472. Abstract
4. Harper JC. Antiandrogen therapy for skin disease and hair disease. Dermatol Clin. 2006;24:137-
143. Abstract
5. Lynde CW. Hormonal approach to the treatment of acne: a Canadian perspective. J Cutan Med
Surg. 2004;8(Suppl 4):1-2. Abstract
Links
http://www.webmd.com/skin-problems-and-treatments/acne/birth-control-for-acne-treatment
http://www.medscape.org/viewarticle/578285
http://www.medicinenet.com/oral_contraceptives/article.htm
http://www.ecardiologynews.com/fileadmin/qhi_archive/ArticlePDF/CT/090020083.pdf
http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0053061/
http://www.webmd.com/sex/birth-control/combination-hormonal-birth-control-methods-pills-patch-or-
ring

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2-Oral contraceptive in treatment of hirsutism

for women.
 Hirsutism is a common, often distressing condition

in which a person develops excessive growth of hair

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Causes of hirsutism
 In many cases, the exact cause of hirsutism is not
known. However, there are several conditions that
are known to cause hirsutism. These conditions
include:
 The natural production of male hormones
(androgens). Women naturally produce androgen,
however, if a woman's androgen levels are higher
than normal, or if her hair follicles are more
sensitive to androgens, she may develop hirsutism.
 Polycystic ovarian syndrome (PCOS) is a common
hormonal condition that causes a woman to produce
too many androgens. Women with PCOS may also
have acne, irregular or absent menstrual periods,
diabetes, weight gain, and/or problems with
fertility.
 The hormonal changes of menopause may lead to
increased facial hair (mustache and whiskers).
 Hirsutism that occurs suddenly along with other
male characteristics, such as a deeper voice, acne, or

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increased muscle mass, may be caused by a more

serious condition, such as disorders of the adrenal
glands or ovaries.
 The following medications can cause hirsutism:
Anabolic steroids,testosterone,glucocorticoids,
minoxidil ,danazol and phenytoin .
Mechanism
 Estrogen and progesterone decrease the secretion of
luteinizing hormone and follicle-stimulating
hormone by negative feedback.
 Gonadotropin inhibition by oral contraceptive
reduce androgen production of ovarian theca cells
and adrenal gland.
 An additional anti androgenic effect of estrogens
comes from their stimulation of liver production of
sex hormone binding globulin (SHBG), a globulin
that binds free-circulating androgens and reduces
free available testosterone to peripheral tissues.
 Oral contraceptive can be used in combination with
one of the antiandrogens or other forms of therapy.
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References
Griffing GT, Melby JC . Hirsutism causes and treatments. Hosp Pract (Off Ed). 1991;265A:43–58.
Links
http://www.nhs.uk/Conditions/hirsutism/Pages/treatment.aspx
http://my.clevelandclinic.org/disorders/hirsutism/hic_hirsutism.aspx
http://www.aafp.org/afp/2003/0615/p2565.html#afp20030615p2565-b9
http://emedicine.medscape.com/article/121038-treatment

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3-Combined oral contraceptive Treat polycystic

ovary syndrome (PCOS) problems
 Polycystic ovary syndrome (PCOS is one of the most

common endocrine disorders among females. PCOS
has a diverse range of causes that are not entirely
understood, but there is strong evidence that it is
largely a genetic disease
 The most common immediate symptoms
are anovulation, excess androgenic hormones,
and insulin resistance. Anovulation results in
irregular menstruation, amenorrhea, and ovulation-

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related infertility. Imbalance generally

causes acne and hirsutism. Insulin resistance is
associated with obesity, Type 2 diabetes, and high
cholesterol levels. The symptoms and severity of the
syndrome vary greatly among affected women.
Mechanism
 Oral contraceptive pills are typically the first line of
therapy for management of irregular bleeding in
women with PCOS who are not interested in
conception.
 Cyclic withdrawal of estrogen and progesterone
leads to complete endometrial shedding and
resolution of most abnormal bleeding.
 Exposure to the progestin in oral contraceptives
leads to reduction in the risk of endometrial cancer
and hyperplasia. In addition, the steroids cause a
decrease in LH levels and a subsequent decrease in
androgen production.

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 Finally, they also increase SHBG production, and

the resulting decreased free testosterone levels lead
to diminished hirsutism and acne
References
Ehrmann DA. Polycystic ovary syndrome. New England Journal of Medicine. 2005; 352: 1223-1236.
American College of Obstetricians and Gynecologists (ACOG). Polycystic ovary syndrome guidelines. ACOG
Practice Bulletin. 2002; 41: 1-14.
Links
http://humrep.oxfordjournals.org/content/22/2/317.full
http://humupd.oxfordjournals.org/content/11/3/277.full
http://www.webmd.boots.com/a-to-z-guides/polycystic-ovary-syndrome-contraceptive-pills
http://www.webmd.com/sex/birth-control/combination-hormonal-birth-control-methods-pills-patch-or-
ring
http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/womens-health/polycystic-
ovary-syndrome/
http://www.medicinenet.com/polycystic_ovary/page5.htm

53

Dysmenorrhea
 Dysmenorrhea is the medical term for pain with

menstruation. There are two types of
dysmenorrhea: "primary" and "secondary".
 Primary dysmenorrhea is common menstrual
cramps that are recurrent and are not due to other
diseases. Cramps usually begin one to two days
after a woman starts getting her period. Pain
usually begins 1 or 2 days before or when menstrual
bleeding starts and is felt in the lower abdomen,
back, or thighs and can range from mild to severe.
Pain can typically last 12 to 72 hours and can be
accompanied by nausea, vomiting, fatigue, and even
diarrhea. Common menstrual cramps usually
become less painful as a woman ages and may stop
entirely if the woman has a baby.

54
 Secondary dysmenorrhea is pain that is caused by a

disorder in the woman's reproductive organs, such
as endometriosis, adenomyosis, uterine fibroids, or
infection. Pain from secondary dysmenorrhea
usually begins earlier in the menstrual cycle and
lasts longer than common menstrual cramps. The
pain is not typically accompanied by nausea,
vomiting, fatigue, or diarrhea.
CAUSE OF DYSMENORRHEA
 Prostaglandins are chemicals that are formed in the
lining of the uterus during menstruation. These
prostaglandins cause muscle contractions in the
uterus, which cause pain and decrease blood flow
and oxygen to the uterus. Similar to labor pains,
these contractions can cause significant pain and
discomfort. Prostaglandins may also contribute to
the nausea and diarrhea that some women
experience.

55
DYSMENORRHEA SYMPTOMS
 The pain of dysmenorrhea is crampy and usually
located in lower abdomen above the pubic bone (the
suprapubic region); some women also have severe
pain in the back or thighs. The pain usually begins
just before or as menstrual bleeding begins, and
gradually diminishes over one to three days. Pain
usually occurs intermittently, ranging from mild to
disabling
Mechanism
 Combined oral contraceptive work by thinning the
lining of the uterus, where prostaglandins are
formed, thereby decreasing the uterine contractions
and menstrual bleeding that contribute to pain and
cramping. Women may choose to use NSAIDs and
hormonal contraceptives simultaneously to control
dysmenorrhea.
 Obviously, hormonal methods of birth control do
not make sense for women who are trying to
become pregnant. However, women who are not
56
actively trying to become pregnant usually have

significantly less dysmenorrhea after using a
hormonal birth control treatment for two to three
months, even if the woman does not need to prevent
pregnancy (eg, if the woman is not sexually active or
if she or her partner has had a sterilization
procedure).

57
References
1. Wong CL, Farquhar C, Roberts H, Proctor M. Oral contraceptive pill as treatment for primary
dysmenorrhoea. Cochrane Database Syst Rev. Apr 15 2009;CD002120.
2. Sillem M, Schneidereit R, Heithecker R, Mueck AO. Use of an oral contraceptive containing

drospirenone in an extended regimen. Eur J Contracept Reprod Health Care. Sep 2003;8(3):162-
9.
3. Vercellini P, Frontino G, De Giorgi O, Pietropaolo G, Pasin R, Crosignani PG. Continuous use of

an oral contraceptive for endometriosis-associated recurrent dysmenorrhea that does not
respond to a cyclic pill regimen. Fertil Steril. Sep 2003;80(3):560-3.
4. Cheewadhanaraks S, Choksuchat C, Dhanaworavibul K, Liabsuetrakul T. Postoperative depot

medroxyprogesterone acetate versus continuous oral contraceptive pills in the treatment of
endometriosis-associated pain: a randomized comparative trial. Gynecol Obstet Invest.
2012;74(2):151-6.
5. Women's Health Across the Lifespan: A Pharmacotherapeutic Approach edited by Laura

Marie Borge
6. Clinical Reproductive Medicine and Surgery edited by Tommaso Falcone, William W. Hur
7. Urogenital Pain in Clinical Practice edited by Andrew P. Baranowski, Paul Abrams, Magnus Fall
8. In a Page: Signs & symptoms edited by Scott Kahan, Ellen G. Smith
9. Oski's Essential Pediatrics edited by Michael Crocetti, Michael A. Barone, Frank A. Osk
Links
http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/womens-health/female-
contraception/
http://www.mayoclinic.org/drugs-supplements/estrogen-and-progestin-oral-contraceptives-oral-
route/description/drg-20069422
http://my.clevelandclinic.org/disorders/dysmenorrhea/hic_dysmenorrhea.aspx
http://www.medicine.ox.ac.uk/bandolier/booth/painpag/dysmen/COCPdysmen.html
http://emedicine.medscape.com/article/253812-treatment#a1156
http://www.uptodate.com/contents/painful-menstrual-periods-dysmenorrhea-beyond-the-basics

58

female pattern hair loss (androgenetic alopecia)
 Life cycle of hair is divided into three phases

Anagen -- active hair growth that lasts between two to
six years
Catagen -- transitional hair growth that lasts two to
three weeks
Telogen -- resting phase that lasts about two to three
months; at the end of the resting phase the hair is

59
shed and a new hair replaces it and the growing cycle

starts again.
 As people age, their rate of hair growth slows
Almost every woman eventually develops some degree
of female pattern hair loss. It can start any time after
the onset of puberty, but women tend to first notice it
around menopause, when hair loss typically increases.
The risk rises with age, and it's higher for women
with a history of hair loss on either side of the family.
 As the name suggests, androgenetic alopecia
involves the action of the hormones called
androgens, which are essential for normal male
sexual development and have other important
functions in both sexes, including sex drive and
regulation of hair growth. The condition may be
inherited and involve several different genes. It can
also result from an underlying endocrine condition,
such as overproduction of androgen or an
androgen-secreting tumor on the ovary, pituitary,
or adrenal gland. In either case, the alopecia is

60
likely related to increased androgen activity. But

unlike androgenetic alopecia in men, in women the
precise role of androgens is harder to determine. On
the chance that an androgen-secreting tumor is
involved, it's important to measure androgen levels
in women with clear female pattern hair loss.
 In either sex, hair loss from androgenetic alopecia

occurs because of a genetically determined
shortening of anagen, a hair's growing phase, and a
lengthening of the time between the shedding of a
hair and the start of a new anagen phase. That
means it takes longer for hair to start growing back
after it is shed in the course of the normal growth
cycle. The hair follicle itself also changes, shrinking
and producing a shorter, thinner hair shaft — a
process called "follicular miniaturization." As a
result, thicker, pigmented, longer-lived "terminal"
hairs are replaced by shorter, thinner, non-
pigmented hairs called "vellus."

61
 FIRST-LINE THERAPY — for female pattern hair

loss (FPHL), topical minoxidil
Mechanism
 Estrogen and progesterone pills and creams are
probably the most common systemic form of
treatment for androgenetic alopecia for women in
menopause or whose estrogen and/or progesterone
are lacking for other reasons.
 Estrogens are indirect anti-androgens, and are

sometimes used for the treatment of androgenetic
alopecia in women in the form of a birth control
pill. When used systemically, estrogens increase
SHBG production, which binds to androgens,
including testosterone, reducing their
bioavailability. Topical estrogen compounds are
also commercially available in Europe.

62
 Hair follicles have estrogen receptors and it is

believed that topical compounds may act on the hair
follicles as direct hair growth promoters as well as
by antagonizing androgen activity. However, large
clinical studies demonstrating efficacy are lacking
and topical treatment is not generally available in
North America.
Notes
 Only low androgen index birth control pills should
be used to treat hair loss. High androgen index birth
control pills actually contribute to hair loss by
triggering it or enabling it once it's been triggered
by something else.
 Low-dose combined oral contraceptives with
minimal androgen effect. These contain
ethinylestrodiol and desorgestrel, gestodene or
norgestimate.

63
References
1. Blumeyer A, Tosti A, Messenger A, et al. Evidence-based (S3) guideline for the treatment of
androgenetic alopecia in women and in men. J Dtsch Dermatol Ges. 2011 Oct;9(Suppl 6):S1–57.
2.The New Harvard Guide to Women's Health By Karen J. Carlson, Stephanie A. Eisenstat, Terra
Diane Ziporyn
Links
http://www.drugs.com/hair-loss.html
http://www.health.harvard.edu/newsletters/Harvard_Womens_Health_Watch/2009/June/Treating-
female-pattern-hair-loss
http://www.americanhairloss.org/women_hair_loss/treatment.asp
http://www.drugs.com/female-pattern-baldness.html
http://www.webmd.com/skin-problems-and-treatments/guide/understanding-hair-loss-basics

64
6- Combined oral contraceptive in treatment of

osteoporosis in post-menopausal women (FDA APPROVED USE)
 Osteoporosis is a disease that weakens bones,

increasing the risk of sudden and unexpected
fractures. Literally meaning "porous bone," it
results in an increased loss of bone mass and
strength. The disease often progresses without any
symptoms or pain. Generally, osteoporosis is not
discovered until weakened bones cause painful
fractures (bone breakage) usually in the back
(causing chronic back pain) or hips.
 Unfortunately, once you have an osteoporotic

fracture, you are at high risk of having another.
These fractures can be debilitating. Fortunately,
there are steps you can take to prevent osteoporosis
from ever occurring. Treatments can also slow the
rate of bone loss if you have osteoporosis.

65
Mechanism
 Estrogen reduces the rate of bone resorption but
does not restore bone loss
 Estrogen cause Reduction in hip fractures by 25%;

reduction in vertebral fractures by 50%.
Dose:-
 For 17 beta-estradiol and norgestimate

 Adults—Oral, 1 mg estradiol for three days
followed by 1 mg of estradiol combined with 0.09
mg of norgestimate for three days. The regimen is
repeated continuously without interruption.
 For ethinyl estradiol and norethindrone
 Adults—Oral, 2.5 mcg (0.025 mg) ethinyl estradiol
and 0.5 mg norethindrone once daily.
 For estradiol and norethindrone
 Adults—Oral, 1 mg estradiol and 0.5 mg
norethindrone once daily.
66
 1. Raloxifene (Selective estrogen receptor

modulator)
Dose: 60 mg/day orally
 2. Conjugated estrogens and bazedoxifene (Duavee)
(Selective estrogen receptor modulator plus estrogen)
Dose: Conjugated estrogen 0.45 mg and bazedoxifene
20 mg/day orally

67
Links
http://www.drugs.com/cons/estrogen-and-progestin-combination-ovarian-hormone-therapy.html
http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm135339.htm
http://www.webmd.com/drugs/condition-2900-Post-
Menopausal+Osteoporosis+Prevention.aspx?diseaseid=2900&diseasename=Post-
Menopausal+Osteoporosis+Prevention&source=0
http://my.clevelandclinic.org/disorders/menopause/hic_menopause_and_osteoporosis.aspx
http://www.health.harvard.edu/newsweek/Update_on_osteoporosis_drugs.htm
http://www.medicinenet.com/script/main/art.asp?articlekey=6861&page=2
http://www.mayoclinic.org/diseases-conditions/menopause/in-depth/hormone-therapy/art-20046372

68

69
Dexamethasone and betamethasone in pregnancy
Dexamethasone and betamethasone used in

pregnancy to
1- speed up a preterm fetus's lung

development.
2- It helps prevent respiratory distress
syndrome (RDS) and related complications
following premature birth.
Mechanism
-Betamethasone and dexamethasone cause an

immature fetus's lungs to produce a compound
called surfactant. A full-term baby's lungs
naturally produce surfactant, which lubricates
70
the lining of the air sacs within the lungs.

-This allows the inner surfaces of the air sacs to
slide against one another without sticking
during breathing. Premature infants whose
lungs have begun producing surfactant are
more able to breathe on their own, or with less
respiratory treatment, after birth.
When it used?
Optimal gestational age for use of

dexamethasone therapy is 31 to 34 weeks of
gestation.
But Betamethasone or dexamethasone is most
effective if delivery occurs at least 24 hours
after the first dose of the medicine has been
given and less than 7 days after the last dose of
the medicine.
references
http://www.webmd.com/…/antenatal-corticosteroids-for-fetal-…
http://apps.who.int/…/…/cd004454_hofmeyrgj_com/en/index.html
http://humrep.oxfordjournals.org/content/14/2/303.long

71

72
Diltiazem is calcium channel blocker used in

hypertension, angina pectoris and some types
of arrhythmia.
Diltiazem in anal fissure
Mechanism
Diltiazem relaxes the smooth muscle around

the rectum and promotes blood flow to help
73
the growth of new skin over the tear in the

lining of the rectum. The ointment reduces
anal canal pressure, which diminishes pain
and spasm.
its pharmaceutical form in some countries

diltiazem 2% ointment it can be prepared by
mix 600 mg of Diltiazem in 30 gm of
petroleum jelly we may also add lidocaine
ointment to the preparation .
reference
http://www.guysandstthomas.nhs.uk/…/diltiazem-hydrochloride…
http://www.stmarksfoundation.org/…/pati…/PIL%20Diltiazem.pdf

74

75
Domperidone is a peripheral, specific blocker of

dopamine receptors. Domperidone is given in order to
relieve nausea and vomiting; to increase the transit of
food through the stomach as a prokinetic agent
Through increase in gastrointestinal peristalsis.
Domperidone Increase Breast Milk Production

Domperidone causes the increased production of the
hormone prolactin as a side effect to its normal uses.
Prolactin is the hormone which stimulates the cells in the
mother's breast to produce milk.

76
Mechanism
Domperidone increases prolactin secretion indirectly,

by interfering with the action of dopamine. One of the
actions of dopamine is to decrease the secretion of
prolactin by the pituitary gland.
Domperidone is generally used for disorders of the
gastrointestinal tract and is not licensed for use as a
stimulant for milk production, though this does not
mean that it cannot be prescribed for this reason.
Dose
Domperidone has no officially established dosage for

increasing milk supply. Most published studies have
used domperidone in a dosage of 10 mg 3 times daily
for 4 to 10 days. Two small studies found no
statistically significant additional increase in milk
output with a dosage of 20 mg 3 times daily compared
to a dosage of 10 mg 3 times daily and that
women who failed to respond to the low dosage did not
respond to the higher dosage.

77
Notes
Domperidone is not approved for marketing in

the United States by the US Food and Drug
Administration, but is available in Canada, Australia,
UK and other countries.
In some nations, including Australia, domperidone is
used off label, based on uncertain and anecdotal
evidence of its usefulness, as a therapy for mothers
who are having difficulty breastfeeding.
Effects in Breastfed Infants
One paper reported 2 studies. In one, 8 women

received domperidone 10 mg 3 times daily from day 2
to 5 postpartum. In the other, 9 women received
domperidone 10 mg 3 times daily for 10 days from
week 2 postpartum. No side effects were reported in
any of the breastfed (extent not stated) infants.
Eleven women took domperidone 10 mg 3 times daily
for 7 days to increase the supply of pumped milk for

78
their preterm neonates. No side effects were reported

in their infants.
Very small amount of Domperidone were detected in breast
milk samples.
References
 Newman, J. and T. Pitman. The Ultimate Breastfeeding Book of Answers. Roseville, CA:
Prima Publishing, 2000; 85, 86-89.
 Da Silva, O., Knoppert, D., Angelini, M., et al. Effect of domperidone on milk production in
mothers of premature newborns: a randomized, double-blind, placebo-controlled
trial. CMAJ2001; 164(1):17-21.
 Riordan, J. Breastfeeding and Human Lactation, 3rd edition. Sudbury, MA: Jones and
Bartlett Publishers, 2004.
 Hofmeyr, G., and B. van Iddeking. Domperidone and lactation. Lancet 1983; I: 647.
 Petraglia, F., De Leo, V., Sardelli, S., et al. Domperidone in defective and insufficient
lactation. Eur J Obstet Gynecol Reprod Biol May 1985; 19(5):281-87.
 Brown, T., Fernandes, P., Grant, L., et al. Effect of parity on pituitary prolactin response to
metoclopramide and domperidone: implications for the enhancement of lactation. J Soc
Gynecol Investig Jan-Feb 2000; 7(1):65-69.
 De Leo, V., Petraglia, F., Sardelli, S., et al. Use of domperidone in the induction and
maintenance of maternal breast feeding. Minerva Ginecol Apr 1986; 38(4): 311-15.
 Gabay, M. Galactogogues: medications that induce lactation. J Hum Lact 2002 Aug;
18(3):274-9.
 Newman, J. and T. Pitman. The Ultimate Breastfeeding Book of Answers. Roseville, CA:
Prima Publishing, 2000; 85-89.
 Hale, T. Medications and Mothers’ Milk, 11th edition. Amarillo, TX: Pharmasoft
Publishing, 2004; 259-60.
 ,Newman, J. Handout #19a, January 2005.
 Prakash, A. and A. Wagstaff. Domperidone. A review of its use in diabetic
gastropathy.Drugs. 1998 Sep;56(3):429-45.
 American Academy of Pediatrics, Work Group on Breastfeeding. Breastfeeding and the

use of human milk. Pediatrics 1997;100:1035-9.

79
 Canadian Paediatric Society clinical practice guideline: nutrition for healthy term
infants. Paediatr Child Health 1998;3:109-12.
 Schanler RJ, Hurst NM. Human milk for the hospitalized preterm infant.Semin
Perinatol 1994;18:476-86.
 Schanler RJ, Shulman RJ, Lau C. Feeding strategies for premature infants: beneficial
outcomes of feeding fortified human milk versus preterm
formula.Pediatrics 1999;103:1150-7.
 Nutrition Committee, Canadian Paediatric Society. Nutrient needs and feeding of

premature infants. CMAJ 1995;152(11):1765-84.
Available:www.cps.ca/english/statements/N/n95-01.htm
 Tudehope DI, Steer PA. Which milk for preterm infant? J Paediatr Child
Health 1996;32:275-7.
 Ogra PL, Rassin DK. Human breast milk. In: Remington JS, Klein JO, editors. Infectious
diseases of the fetus and newborn infant. 4th ed. Philadelphia: WB Saunders; 1995. p.
108-39.
 Delneri MT, Carbone SB, Silva ML, Palmeira P, Carneiro-Sampaio MM. Inhibition of
enteropathogenic Escherichia coli adhesion to HEp-2 cells by colostrum and milk from
mothers delivering low-birth-weight neonates. Eur J Pediatr 1997;156:493-8.
 Scariati PD, Grummer-Strawn LM, Fein SB. A longitudinal analysis of infant morbidity
and the extent of breastfeeding in the United States.Pediatrics 1997;99(6):E5.
 Hylander MA, Strobino DM, Dhanireddy R. Human milk feedings and infection among
very low birth weight infants. Pediatrics 1998;102(3):E38.
 Morley R. The influence of early diet on later development. J Biosoc Sci1996;28:481-7.
 Lucas A, Morley R, Cole TJ, et al. Early diet in preterm babies and development status at
18 months. Lancet 1990;335:1477-81.
 Feher SDK, Berger LR, Johnson JD, Wilde JB. Increasing breast milk production for
premature infants with a relaxation/imagery audiotape.Pediatrics 1989;83:57-60.

80
 Emery MM. Galactogogues: drugs to induce lactation. J Hum Lact1996;12:55-7.

 16.↵
 Hill PD, Aldag JC, Chatterton RT. The effect of sequential and simultaneous breast
pumping on milk volume and prolactin levels: a pilot study. J Hum Lact 1996;12:193-9.
 Lewis PJ, Devenish C, Kahn C. Controlled trial of metoclopramide in the initiation of

breast feeding. Br J Clin Pharmacol 1980;9:217-19.
 Ehrenkranz RA, Ackerman BA. Metoclopramide effect on faltering milk production by

mothers of premature infants. Pediatrics 1986;78:614-20.
 Kauppila A, Kivinen S, Ylikorkala O. A dose response relation between improved
lactation and metoclopramide. Lancet 1981;1:1175-7.
 Budd SC, Erdman SH, Long DM, Trombley SK, Udall JN. Improved lactation with
metoclopramide. Clin Pediatr 1993;35:53-7.
 Gupta AP, Gupta PK. Metoclopramide as a lactogogue. Clin Pediatr1985;24: 269-72.
 Kauppila A, Arvela P, Koivisto M, Kiniven S, Ylikorkala O, Pelkonen O. Metoclopramide
and breast feeding: transfer into milk and the newborn. Eur J Clin
Pharmacol 1983;25:819-23.
 Hofmeyr GJ, Van Iddekinge B. Domperidone and lactation. Lancet1983;1:647.
 Hofmeyr GJ, Van Iddekinge B, Blott JA. Domperidone: secretion in breast milk and effect
on puerperal prolactin levels. Br J Obstet Gynaecol1985;92:141-4.
 Engel JA, Lundborg P. Behavioral and biochemical effects in offspring of nursing rats
exposed to dopamine receptor antagonists. In vol 1 of 13th Congress of the Collegium
Internationale Neuro-Psychopharmacologicum; 1982 June 22; Jerusalem. Abstract 198.
 Brogden RN, Carmine AA, Heel RC, Speight TM, Avery GS. Domperidone: a review of its
pharmacological activity, pharmacokinetics and therapeutic efficacy in the symptomatic
treatment of chronic dyspepsia and as an antiemetic. Drugs 1982;24:360-400.
 Cann PA, Read NW, Holdsworth CD. Galactorrhoea as a side effect of domperidone
[letter]. BMJ 1983;286:1395-6.
 Brouwers JR, Assies J, Wiersinga WM, Huizing G, Tytgat GN. Plasma prolactin levels after
acute and subchronic oral administration of domperidone and metoclopramide: a cross-
over study in healthy volunteers. Clin Endocrinol (Oxf) 1980;12:435-40.
 Petraglia F, De leo V, Sardelli S, Pieroni ML, D'Antona N, Genazzani AR. Domperidone in
defective and insufficient lactation. Eur J Obstet Gynecol Reprod Biol 1985;19:281-7.
 Rolfini G, De Rosa D, Lupi AM, Petrelli V. [Hypogalactia: therapeutic possibilities]

[Italian]. Clin Ter 1989;129:185-91.

81
 Zavitsanos AP, MacDonald C, Bassoo E, Gopaul D. Determination of domperidone in

human serum and human milk by high-performance liquid chromatography-
electrospray mass spectrometry. J Chromatogr B1999;730:9-24.
 Heykants J, Hendriks R, Meuldermans W, Michiels M, Scheygrond H, Reyntjens H. On

the pharmacokinetics of domperidone in animals and man. IV: the pharmacokinetics of
intravenous domperidone and its bioavailability in man following intramuscular, oral
and rectal administration. Eur J Drug Metab Pharmacokinet 1981;6:61-70.
Links
http://www.drugs.com/breastfeeding/domperidone.html
http://www.bedfordhospital.nhs.uk/upload_folder/patient%20information/domperidone%20t
o%20increase%20breast%20milk%20production.pdf
http://www.crd.york.ac.uk/crdweb/ShowRecord.asp?LinkFrom=OAI&ID=12013006694#.U2_7g
_mSyPt
http://onlinelibrary.wiley.com/o/cochrane/clcentral/articles/698/CN-00881698/frame.html
http://onlinelibrary.wiley.com/o/cochrane/clcentral/articles/665/CN-00864665/frame.html
http://www.evidence.nhs.uk/search?q=DOMPERIDONE%20AND%20LACTATION
http://www.colchesterhospital.nhs.uk/patient_information/maternity/763n4%20Domperidone
.pdf
http://www.mayoclinic.org/drugs-supplements/domperidone-oral-route/side-effects/drg-
20063481
http://epe.lac-bac.gc.ca/100/201/300/cdn_medical_association/cmaj/vol-164/issue-
1/pdf/pg17.pdf
http://www.cmaj.ca/content/164/1/17.full?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=
&titleabstract=domperidone&searchid=1062535142179_2349&stored_search=&FIRSTINDEX=0
&journalcode=cmaj
http://www.lowmilksupply.org/domperidone.shtml
https://www.thewomens.org.au/health-information/fact-sheets/#b
http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm173886.htm

82

83
 Erythromycin belongs in macrolide antibiotics.

Macrolide antibiotics slow the growth of, or
sometimes kill, sensitive bacteria by reducing the
production of important proteins needed by the
bacteria to survive.
 Antibiotic macrolides are used to treat infections
caused by Gram-positive bacteria and
Haemophilus influenza infections such as
respiratory tract and soft-tissue infections.
 The antimicrobial spectrum of macrolides is
slightly wider than that of penicillin, and,
therefore, macrolides are a common substitute for
patients with a penicillin allergy. Beta-hemolytic
streptococci, pneumococci, staphylococci, and
enterococci are usually susceptible to macrolides.
Unlike penicillin, macrolides have been shown to
be effective against Legionella pneumophila,
mycoplasma, mycobacteria, some rickettsia, and
chlamydia.
84
Erythromycin as A prokinetic in the treatment

of gastro-paresis
 Gastro-paresis, also called delayed gastric

emptying, is a medical condition consisting of
a paresis (partial paralysis) of the stomach,
85
resulting in food remaining in the stomach for an

abnormally long time.
 Normally, the stomach contracts to move food
down into the small intestine for additional
digestion. The vagus nerve controls these
contractions. Gastro-paresis may occur when the
vagus nerve is damaged and the muscles of
the stomach and intestines do not properly
function. Food then moves slowly or stops moving
through the digestive tract.
Symptoms
 The most common symptoms of gastroparesis are

the following
 Chronic nausea (93%)
 Vomiting (especially of undigested food) (68-84%)
 Abdominal pain (46-90%)
 A feeling of fullness after eating just a few bites
(60-86%)
 Other symptoms include the following:
86
 Palpitations
 Heartburn
 Abdominal bloating
 Erratic blood glucose levels
 Lack of appetite
 Gastro esophageal reflux
 Spasms of the stomach wall
 Weight loss and malnutrition
 Morning nausea may also indicate gastroparesis.
Vomiting may not occur in all cases, as sufferers
may adjust their diets to include only small
amounts of food
Mechanism
 It enhances gastrointestinal motility by increasing

the frequency of contractions in the small
intestine or making them stronger, but without
disrupting their rhythm. They are used to relieve

87
gastrointestinal symptoms such as abdominal

discomfort, bloating, constipation, heart
burn, nausea, and vomiting.
 They are used to treat a number of gastrointestinal
disorders, including irritable bowel
syndrome, gastritis, acid reflux
disease, gastroparesis, and functional dyspepsia.
 Erythromycin is the most potent prokinetic drug
when given intravenously in the acute setting and
is therefore useful in the initial management
of hospitalized patients with severe gastroparesis.
Dose
 Erythromycin 200 mg was infused I.V. initially

followed by 250 mg orally 3 times/day 30 minutes
before meals. Lower dosages have been used in
some trials.
 Orally 250-500 mg PO three times daily before

meals.
88
References
 Current Therapy in Equine Medicine, 6edition By Norman Edward Robinson،Kim A. Sprayberr
 Pediatric Gastrointestinal Disease: Pathophysiology, Diagnosis. By W. Allan Walker.
 Diabetic Neuropathy By Friedrich A. Gries،Norman E. Camero
Links
http://www.drugs.com/erythromycin.html
http://www.globalrph.com/macrolides.htm
http://www.evidence.nhs.uk/document?ci=http%3A%2F%2Fwww.medicinesresources.nhs.uk%2Fupload%
2Fdocuments%2FEvidence%2FMedicines%20Q%20%26%20A%2FEA_QA198.3_erythromycinprokineticdose
.doc%3Ffromsource%3Dnelm&q=%22dose%20of%20erythromycin%20in%20adults%22&ReturnUrl=%2Fsea
rch%3Fq%3D%2522dose%2Bof%2Berythromycin%2Bin%2Badults%2522
http://www.medicine.virginia.edu/clinical/departments/pediatrics/education/pharm-news/2006-
2010/201004.pdf
http://jac.oxfordjournals.org/content/59/3/347.full
http://reference.medscape.com/drug/ery-tab-pce-dispertab-erythromycin-base-342526
http://www.medicine.virginia.edu/clinical/departments/medicine/divisions/digestive-health/nutrition-
support-team/nutrition-articles/ParrishGastroparesisArticle.pdf

89

90
 Finasteride is a synthetic drug for the treatment

of benign prostatic hyperplasia (BPH). It is a type
II 5α-reductase inhibitor. 5α-reductase is
an enzyme that converts testosterone to
dihydrotestosterone (DHT).
1-Finasteride is indicated for the treatment of

male pattern hair loss (FDA APPROVED USE)

91
Notes:-
 Safety and efficacy were demonstrated in men

between 18 to 41 years of age with mild to moderate
hair loss of the vertex and anterior mid-scalp area.
Life cycle of hair is divided into three phases
 Anagen -- active hair growth that lasts between two

to six years
 Catagen -- transitional hair growth that lasts two to
three weeks
 Telogen -- resting phase that lasts about two to
three months; at the end of the resting phase the
hair is shed and a new hair replaces it and the
growing cycle starts again.
As people age, their rate of hair growth slows
What is Androgenic alopecia??
 Androgenic alopecia (also known as male pattern

baldness) is hair loss that occurs due to an
underlying susceptibility of hair
92
follicles to androgenic miniaturization. It is the most

common cause of hair loss and will affect up to 70%
of men and 40% of women at some point in their
lifetime. Men typically present with hairline
recession at the temples and vertex balding while
women normally diffusely thin over the top of their
scalps. Both genetic and environmental factors play
a role, and many etiologies remain unknown.
 Classic androgenic hair loss in males begins above
the temples and vertex, or calvaria, of the scalp. As
it progresses, a rim of hair at the sides and rear of
the head remains and rarely progresses to complete
baldness.
Mechanism
 Finasteride is a competitive and specific inhibitor of

Type II 5α-reductase, anintracellular enzyme that
converts the androgen testosterone into DHT.
 Two distinct isozymes are found in humans: Type I
and II. Each of these isozymes is differentially
expressed in tissues and developmental stages. In
93
humans, Type I 5α-reductase is predominant in the

sebaceous glands of most regions of skin, including
scalp, and liver. Type I 5α-reductase is responsible
for approximately one-third of circulating DHT.
The Type II 5α-reductase isozyme is primarily
found in prostate, seminalvesicles, epididymides,
and hair follicles as well as liver, and is responsible
for two-thirds of circulating DHT.
 In humans, the mechanism of action of finasteride is
based on its preferential inhibition of the Type II
isozyme. Using native tissues (scalp and prostate), in
vitro binding studies examining the potential of
finasteride to inhibit either isozyme revealed a 100-
fold selectivity for the human Type II 5α-reductase
over Type I isozyme.
 For both isozymes, the inhibition by finasteride is
accompanied by reduction of the inhibitor to
dihydrofinasteride and adduct formation with
NADP+. The turnover for the enzyme complex is
slow (t½ approximately 30 days for the Type II
enzyme complex and 14 days for the Type I
94
complex). Inhibition of Type II 5α-reductase blocks

the peripheral conversion of testosterone to DHT,
resulting in significant decreases in serum and
tissue DHT concentrations.
 In men with male pattern hair loss
(androgenetic alopecia), the balding scalp contains
miniaturized hair follicles and increased amounts of
DHT compared with hairy scalp. Administration of
finasteride decreases scalp and serum DHT
concentrations in these men.
 The relative contributions of these reductions to the
treatment effect of finasteride have not been
defined. By this mechanism, finasteride appears to
interrupt a key factor in the development of
androgenetic alopecia in those patients genetically
Dose:-
 Finasteride may be administered with or without

meals.
 The recommended dose of PROPECIA is one tablet
(1 mg) taken once daily.
95
 In general, daily use for three months or more is

necessary before benefit is observed. Continued use
is recommended to sustain benefit, which should be
re-evaluated periodically. Withdrawal of treatment
leads to reversal of effect within 12 months.
References:-
1. ittmaster RS. Finasteride. N Engl J Med. Jan 13 1994;330(2):120-5.
2. Rossi A, Cantisani C, Scarnò M, Trucchia A, Fortuna MC, Calvieri S. Finasteride, 1 mg daily

administration on male androgenetic alopecia in different age groups: 10-year follow-up. Dermatol
Ther. Jul 2011;24(4):455-61.
Links
http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020788Orig1s022lbl.pdf
http://www.mayoclinic.org/drugs-supplements/finasteride-oral-route/description/drg-20063819
http://www.uptodate.com/contents/hair-loss-in-men-and-women-androgenetic-alopecia-beyond-the-
basics
http://www.rxlist.com/propecia-drug/clinical-pharmacology.htm
http://www.webmd.com/skin-problems-and-treatments/hair-loss/finasteride-for-male-hair-
loss#abh1918

96
2-Finasteride in hirsutism
Notes
 In women, Finasteride used in hirsutism (only

postmenopausal women with no chance of becoming
pregnant.)
 The main concern with finasteride, in women is the
risk of ambiguous genitalia in male fetuses exposed
to the enzyme inhibitor during the first trimester.

97
Introduction

Causes of hirsutism

include:
fertility.

98

glands or ovaries.
 Anabolic steroids,testosterone,glucocorticoids,
Notes
 None of the drugs used to treat hirsutism have US

Food and Drug Administration (FDA) approval for
such use
Mechanism
 Finasteride is a type of medication known as a 5-

alpha-reductase inhibitor. It works by preventing
testosterone (an androgen) from turning into a
stronger form of testosterone inside body’s cells.
99
Dose:-
 Finasteride dose (2.5 mg/day)

References
 Insulin Resistance and Polycystic Ovarian Syndrome: Pathogenesis, Evaluation... By
Evanthia Diamanti-Kandarakis, John E. Nestler, Dimitrios Panidis, Renato Pasqual
 Evidence-based Endocrinology edited by Pauline M. Camacho, Hossein Gharib, Glen W. Sizemore
 Polycystic Ovary Syndrome By R. Jeffrey Chang, Jerrold J. Heindel, Andrea Dunaif
Links
http://www.uptodate.com/contents/hirsutism-excess-hair-growth-in-women-beyond-the-basics

100

101
 Folic acid is a form of the water-soluble vitamin

B9. Folate is a naturally occurring form of the
vitamin, found in food, while folic acid is
synthetically produced, and used in fortified
foods and supplements.
 Folic acid is itself not biologically active, but its
biological importance is due totetrahydrofolate and
other derivatives after its conversion to dihydrofolic
acid in the liver.

102
 Vitamin B9 (folate converted from folic acid)

is essential for numerous bodily functions. Humans
cannot synthesize folate; therefore, folate has to be
supplied through the diet to meet their daily
requirements.
 The human body needs folate to synthesize DNA,
repair DNA, and methylate DNA as well as to act as
a cofactor in certain biological reactions.
 It is especially important in aiding rapid cell
division and growth, such as in infancy and
pregnancy. Children and adults both require folate
to produce healthy red blood cells and
prevent anemia.
 Folate occurs naturally in many foods, and among
plants are especially plentiful in dark green leafy
vegetables
 A lack of dietary folates can lead to folate
deficiency. A complete lack of dietary folate takes
months before deficiency develops as normal
individuals have about 500–20,000 µg of folate in
body stores.
103
 This deficiency can result in many health problems,

the most notable one being neural tube defects in
developing embryos.
 Common symptoms of folate deficiency
include diarrhea, macrocytic anemia with weakness
or shortness of breath, nerve damage with weakness
and limb numbness (peripheral
neuropathy), pregnancy complications, mental
confusion, forgetfulness or other cognitive deficits,
mental depression, sore or swollen tongue, peptic or
mouth ulcers, headaches, heart palpitations,
irritability, and behavioral disorders.
 Low levels of folate can also lead
to homocysteine accumulation. DNA synthesis and
repair are impaired, which could lead to cancer
development.

104
Folic acid in male infertility
 Folic acid with zinc role in sperm quality and in

sperm count
 New research also shows that men who have a folic
acid deficiency could notice a 90% reduction in
their sperm count. If men suffering with partial
infertility take folic acid it is proclaimed to increase
the quality and quantity of their sperm.
 Folate is necessary for fertility in both men and
women. It contributes to spermatogenesis.

105
Therefore, it is necessary to receive sufficient

amounts through the diet to avoid subfertility.
 Zinc and folic acid are elements essential to the
formation of DNA and creation of sperm. However,
the underlying mechanisms by which they affect
spermatogenesis are not known. Combination of
zinc and folic acid led to an increase in sperm
concentration, having an endocrine-independent
mechanism, as evidenced by an unchanged follicle-
stimulating hormone, testosterone, and inhibin.
 According to many studies, Total normal sperm
count found to be increases after combined zinc
sulfate and folic acid treatment in both sub fertile
and fertile men.
Dose
 Folic acid once daily dose of 5 mg

106
Some other interesting folic acid facts
Folic acid from supplements and fortified

products is absorbed easier by the body (100%
from supplements). Eating foods high in folic
acid is just as important as they also contain
other important essential nutrients (estimated
50% absorption rate). We recommend a
combination of both.
Stress and illness increase the body’s need of
folate.
Folate works very closely together with
vitamin B12 so a deficiency of one may result in
a deficiency of the other, resulting in anemia
(low levels of healthy red blood cells). If very
high doses of folic acid supplements are taken,
this can mask the symptoms of pernicious
anemia. Therefore it's usually recommended to
supplement both B9 and B12 together.
The daily upper limit from supplements
should not exceed 1,000 micrograms per day

107
(usually only taken if prescribed by a health

professional). This includes consuming large
amounts of fortified food. This is to avoid
risking neurological damage in case a B12
deficiency occurs.
As well as the folic acid co-dependency with
B12, the two vitamins also work along with
vitamin c for the breakdown, utilization and
formation of new proteins.
Because folic acid is absorbed through the
gastrointestinal tract, any conditions such as
celiac disease, colitis, diarrhea, vomiting or any
other disorder of the digestive system can result
in a deficiency.
This vitamin is primarily stored in the liver, so
alcohol interferes with folate absorption and
increases the excretion of the vitamin from the
body.
Folic acid can be destroyed by high
temperatures, light exposure or from being left
at room temperature for a long period of time.
108
Only lightly steam vegetables or eat them raw

whenever possible.
*Please note -The risk of folic acid toxicity is
extremely low as this is a water soluble vitamin
(although still possible). Caution is advised like
with all supplements. Do not exceed the
recommended dosage stated on the label.

109
References
1. Wong WY, Thomas CMG, Merkus JMWM, Zielhuis GA, Steegers-Theunissen RPM. Male factor
subfertility: possible causes and the impact of nutritional factors. Fertil Steril 2000;73(3):435–442
2. Ebisch IM, Pierik FH, DE Jong FH, Thomas CM, Steegers-Theunissen RP. Does folic acid and
zinc sulphate intervention affect endocrine parameters and sperm characteristics in men? Int J
Androl 2006;29(2):339–345
3. Gregory J, Foster K, Tyler H, Wiseman M. The dietary and nutritional survey of British adults. In:
Office of Population Censuses and Surveys. London: HMSO; 1990
4. de Bree A, van Dusseldorp M, Brouwer IA, van het Hof KH, Steegers-Theunissen RP. Folate
intake in Europe: recommended, actual and desired intake. Eur J Clin Nutr 1997;51(10):643–660
5. Spermatogenesis: New Insights for the Healthcare Professional: 2013 Edition ...
6. 6.Genes, Chromosomes, and Disease: From Simple Traits, to Complex raits, By Nicholas Wright
Gillham
7. Nutrition in Early Life jane B. Morgan،John W. T. dickerson
8. Surgical and Medical Management of Male Infertility Marc Goldstein،Peter N. Schlegel

9. Male Infertility: Contemporary Clinical Approaches, Andrology, ART ... By Sijo J. Parekattil،Ashok
Agarwal.
10. Textbook of Natural Medicine by Joseph E. Pizzorno،Michael T.Murra.
Links
http://www.nhs.uk/news/2007/January08/Pages/Folicacidboostssperm.aspx
http://humupd.oxfordjournals.org/content/13/3/225.full
http://www.webmd.com/infertility-and-reproduction/news/20020320/supplements-boost-sperm-count
http://www.clevelandclinic.org/reproductiveresearchcenter/docs/agradoc384.pdf
http://www.homehealth-uk.com/medical/folicacid.htm

110

111
 Gonadotropins (or glycoprotein hormones) are

protein hormones secreted by gonadotrope cells of
the anterior pituitary of vertebrates.
 This is a family of proteins, which include the
mammalian hormones follicle-stimulating hormone
(FSH), luteinizing hormone (LH), placental
chorionic gonadotropins hCG and eCG and
chorionic gonadotropin (CG), as well as at least two
forms of fish gonadotropins.
 These hormones are central to the complex
endocrine system that regulates normal growth,
sexual development, and reproductive function. The
hormones LH and FSH are secreted by the anterior
pituitary gland, while hCG and eCG are secreted by
the placenta.
In women.
 Luteinizing hormone (LH) and follicle-stimulating

hormone (FSH) are needed for egg production
(ovulation). Early in the menstrual cycle, a woman
112
with low hormone levels who is not ovulating can

have daily human menopausal gonadotropin (hMG)
or recombinant human FSH (rFSH) injections for
an average of 12 days. If this helps develop mature
follicles, the ovary is ready to ovulate. One dose of
human chorionic gonadotropin (hCG) is then used
to stimulate ovulation.
In women Gonadotropins may be used:
 To stimulate ovulation related to low natural

gonadotropin or estrogen levels. (This is most
commonly seen in women with excessive exercise or
eating disorders.)
 When clomiphene alone or clomiphene combined
with another medicine has been ineffective for
correcting irregular or no ovulation caused by
polycystic ovary syndrome (PCOS).
 For developing multiple egg follicles on the ovaries.
Multiple eggs are harvested and used in assisted
reproductive techniques such as in vitro fertilization
or gamete intrafallopian transfer.
113
 In combination with intrauterine insemination for

couples with unexplained infertility when
clomiphene has not worked.
1-Gonadotropins in men (FDA APPROVED USE)
 Gonadotropin therapy can treat low sperm counts

caused by low levels of natural gonadotropins.
Mechanism
 In men with low testosterone and FSH. LH
stimulates the production of testosterone, and FSH
promotes the formation of sperm. If a semen
analysis, LH testing, and FSH testing suggest that
abnormal hormone levels are preventing sperm
production, these gonadotropins may be prescribed
together to promote sperm formation.
114
Dose
 The man gets an HCG injection 3 times weekly until
blood testosterone level is within the normal range
(this may take 4 to 6 months). Treatment continues
with injections of HCG 2 times a week and hMG or
FSH 3 times a week until the sperm count rises to
normal levels.
 Male Patients with Hypo-gonadotropic
Hypogonadism
 Pretreat with HCG (1,000- 2,250 USP Units 2-3
x/week) until serum testosterone within normal
range (may require 3-6 months of treatment)
 Treatment- FSH used in conjunction with HCG,
FSH 150 international units SC 3 x/week
 HCG 1000 USP Units (or dose to maintain normal
serum testosterone levels) 3 x/week
 If azoospermia persists, may increase FSH to
maximum of 300 international units 3 x/week
 May need to administer for up to 18 months for
adequate response.

115
2-HCG in Prepubertal cryptorchidism Young boys

(FDA APPROVED USE)
 HCG is used in young boys when their testicles have

not dropped down into the scrotum normally. This
can be caused by a pituitary gland disorder.
Dose
 Therapy is usually instituted in children between
the ages of 4 and 9
 4,000 USP Units three times weekly for three weeks.
 5,000 USP Units every second day for four
injections.
116
 15 injections for 500 to 1,000 USP Units over a

period of six weeks.
 500 USP Units three times weekly for four to six
weeks. If this course of treatment is not successful,

another series is begun one month later, giving
1,000 USP Units per injection.

117
References
1. Andrology: Male Reproductive Health and Dysfunction By Eberhard Nieschlag،Hermann M.
Behre،Susan Nieschlag
2. Parhar, Ishwar S. (2002). Gonadotropin-releasing Hormone: Molecules and Receptors.
Amsterdam: Elsevier. ISBN 0-444-50979-8.
3. Pierce JG, Parsons TF (1981). "Glycoprotein hormones: structure and function". Annu. Rev.
Biochem. 50: 465–495. doi:10.1146/annurev.bi.50.070181.002341. PMID 6267989.
4. Stockell Hartree A, Renwick AG (1992). "Molecular structures of glycoprotein hormones and
functions of their carbohydrate components". Biochem. J. 287 (Pt 3): 665–679.
PMC 1133060. PMID 1445230.
5. Goodwin RG, Moncman CL, Rottman FM, Nilson JH (1983). "Characterization and nucleotide
sequence of the gene for the common alpha subunit of the bovine pituitary glycoprotein
hormones". Nucleic Acids Res. 11 (19): 6873–6882. doi:10.1093/nar/11.19.6873.
PMC 326420. PMID 6314263.
6. Godine JE, Chin WW, Habener JF (1982). "alpha Subunit of rat pituitary glycoprotein
hormones. Primary structure of the precursor determined from the nucleotide sequence of
cloned cDNAs". J. Biol. Chem. 257 (14): 8368–8371. PMID 6177696.
Links
http://www.drugs.com/cons/chorionic-gonadotropin-subcutaneous-intramuscular-injection.html
http://www.rxlist.com/pregnyl-drug/indications-dosage.htm
http://emedicine.medscape.com/article/2089158-overview
http://www.webmd.com/infertility-and-reproduction/gonadotropin-treatment-for-infertility
http://www.drugs.com/hcg.html
http://www.rxlist.com/pregnyl-drug/patient-images-side-effects.htm
http://www.drugs.com/mtm/human-chorionic-gonadotropin-hcg-injectable.html
http://www.drugs.com/pro/gonal-f.html
http://reference.medscape.com/drug/gonal-f-rff-follitropin-alfa-342804
http://www.webmd.com/drugs/2/drug-11192/hcg-intramuscular/details

118

119
Regular insulin in management of hyperkalemia.
Mechanism
Regular insulin stimulates cellular uptake of

potassium within 20-30 minutes and lasts for
4-6 hours. The serum potassium
concentration typically drops by 0.5-1.2
mEq/L.

120
Notes
1- Administer glucose along with insulin to

prevent hypoglycemia.
2- Monitor blood sugar levels frequently.
It is temporary effect; therefore, insulin
therapy should be followed by therapy that
actually enhances potassium clearance.
References
http://emedicine.medscape.com/article/240903-medication#4
http://www.nlm.nih.gov/medlineplus/ency/article/001179.htm
http://www.webmd.com/a-to-z-guides/hyperkalemia-causes-symptoms-treatments?page=2#3
http://www.medicinenet.com/hyperkalemia/page5.htm
.

121

122
Liraglutide is a long-acting glucagon-like

peptide-1 agonist (GLP-1 agonist) injection
for the treatment of type 2 diabetes.
Liraglutide for Obesity Treatment (FDA APPROVED USE)
Mechanism
liraglutide improves control of blood glucose.
It reduces meal-related hyperglycemia (for
24 hours after administration) by increasing
insulin secretion, delaying gastric emptying,
and suppressing prandial glucagon secretion.
123
references
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm427913.htm
http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/Endocrinologica
ndMetabolicDrugsAdvisoryCommittee/UCM413318.pdf
http://www.medicinenet.com/liraglutide/article.htm

124

125
Usually we deal with progesterone as an oral

contraceptive or Breast Cancer or Endometrial
Cancer but we will discuss unusual use of
progesterone 17α-acetoxy-6-dehydro-6-
methylprogesterone (MegestrolAcetate).
MegestrolAcetate as appetizer(FDA APPROVED USE)

MegestrolAcetate used as appetizer,
Management of anorexia, cachexia, or an
unexplained, substantial weight loss in HIV-
infected individuals.
Also has been used to stimulate appetite and

promote weight gain in a limited number of
patients with cachexia associated with
neoplastic disease.

126
Dose:-
Clinically effective dosages are expected to

range from 312.5–625 mg daily
References
http://www.rxlist.com/megace-drug/indications-dosage.htm
http://www.webmd.com/breast-cancer/megestrol-acetate

127

128
 Metformin is an oral ant diabetic in the biguanide

class. It is the first- line drug of choice for the
treatment of type 2 diabetes.
 Metformin decreases glucose production in the

liver, increases insulin sensitivity and enhances
peripheral glucose uptake. It doesn't stimulate
secretion of endogenous insulin.
 Metformin decreases hyperglycemia primarily by

suppressing glucose production by the liver (hepatic
gluconeogenesis).

129
1-Metformin for Polycystic Ovary Syndrome
 The condition, polycystic ovarian syndrome, known

as PCOS, is a common condition and is the
commonest cause of ovulation disorders in women
of reproductive age and usually present in late teens
or early twenties.
 (PCOS) characterized by the presence of many
minute cysts in the ovaries, excess production of
androgens and menstrual irregularities.

130
 Polycystic ovarian syndrome can be found in

apparently normal.
 Polycystic ovarian syndrome is frequently
associated with weight gain, excessive hair growth
in the face and body, irregular and infrequent
periods or absent periods, infrequent or absent
ovulation, miscarriage and infertility.
 Women with PCOS have both abnormally elevated
luteinizing hormone (LH) secretion and
hyperinsulinemia as a result of insulin resistance.
The combination of hyper-secretion of LH and
insulin causes ovarian androgen overproduction. In
turn, ovarian androgen overproduction causes
hirsutism and prevents normal ovarian follicle
growth, preventing regular ovulation.
 PCOS can be treated by lowering LH
hypersecretion (oral contraceptive pills or GnRH
agonist analogues) or by reversing the
hyperinsulinemia that is caused by insulin
resistance by Metformin or weight loss if she is
overweight.
131
Mechanism
 Many women with PCOS have decreased sensitivity
to insulin, and their bodies overcompensate by over-
producing insulin. Elevated levels of insulin are
common in women with PCOS, whether they are
obese or thin compared with weight matched
controls. Some experts believe that this excess
insulin is the underlying cause of PCOS because
insulin stimulates androgen production and effects
follicular development. As a consequence
 Metformin lowers insulin, androgen, and
cholesterol levels. It also improves metabolism in
women who are insulin-resistant, it increase
sensitivity of receptor to insulin and used in weight
loss.
 Metformin may help start ovulation in women with
PCOS who have not responded to treatment with
clomiphene. Some doctors may recommend taking
Metformin in addition to clomiphene to start
ovulation.

132
Dose
500-850 mg orally every 8hr
Links
http://www.drugs.com/sfx/metformin-side-effects.html
http://www.ivf-infertility.com/infertility/pcos.php
http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/womens -health/polycystic-
ovary-syndrome/
http://www.webmd.com/women/metformin-glucophage-for-polycystic-ovary-syndrome
http://www.nhs.uk/Conditions/Polycystic-ovarian-syndrome/Pages/ Treatment.aspx
http://reference.medscape.com/drug/glucophage-metformin-342717

133
2- Metformin in NIDDM patients with obesity.
Mechanism
 Metformin may be useful in aiding weight loss. In

diabetic patients, it suppresses endogenous glucose
production and may also act as an insulin sensitizer.
It also helps diabetic patients lose weight or at least
keep their weight stable.

134
 Metformin decreases calorie intake in a dose-

dependent manner and leads to a reduction in
bodyweight in NIDDM patients with obesity, in
addition to that one of the metformin side effect is
loss of appetite.
Dose
 According to several studies, Metformin dose made
little difference, with 1 g daily being only marginally
less effective than 2 g.
References
Wilson, D. Archives of Pediatric and Adolescent Medicine, February 2010; vol 164: pp 116-123. New s release,
American Medical Association.
Links
http://www.fda.gov/ohrms/dockets/dailys/02/May02/053102/800471e6.pdf
http://www.medscape.com/vie warticle/820763
http://www.medscape.com/vie warticle/514264_4
http://www.medicinenet.com/script/main/art.asp?articlekey=112905
http://www.webmd.com/children/ne ws/20100201/metformin-may-help-obese-teens-lose-weight
http://www.diabetes.co.uk/diabetes-medication/metformin-weight-loss.html
http://www.webmd.com/diabetes/news/20131216/diabetes-drug-metformin-tied-to-slight-weight-loss-
in-obese-kids
http://www.crd.york.ac.uk/crdweb/ShowRecord.asp?LinkFrom=OAI&ID=12013026896#.U27WD_m
SyPs

135

136
Metronidazole in treatment of acne rosacea
 Metronidazole is used to treat acne rosacea (adult

acne), a chronic condition in which the facial skin is
inflamed and sores develop. Metronidazole
decreases the redness and number of sores.
 Metronidazole comes as a cream, lotion, or gel to be
applied to skin, it usually used once or twice a day.

137
 Symptoms probably will improve within 3 weeks

and continue to improve over the following 6 weeks
or more.
 For acne, wash the affected skin area with mild soap
about 15-20 minutes before applying the
medication. Apply a thin layer of cream, lotion and
rub it gently into the affected area.
references
http://www.nlm.nih.gov/medlinepl…/druginfo/meds/a682244.html
http://www.medscape.org/viewarticle/441986_13
http://www.medicinenet.com/metronidazole_cream/article.htm
http://www.webmd.com/skin-problem…/rosacea-treatment-and-you
http://www.nhs.uk/Conditions/Rosacea/Pages/Treatment.aspx

138

139
 Nifedipine is a dihydropyridine calcium channel

blocker that primarily blocks L-type calcium
channels. Its main uses are as
an antianginal(especially in Prinzmetal's angina)
and antihypertensive.
 Nifedipine is on the World Health Organization's
List of Essential Medicines, a list of the most
important medication needed in a basic health
system.
1-Nifedipine as a Tocolytic in Preterm Labor.
 Preterm labor remains a difficult issue in current

obstetrics. Preterm birth still plays a major role in
perinatal mortality and morbidity in developed
countries, accounting for 60% to 80% of all
140
neonatal deaths among infants without congenital

anomalies.
 Tocolysis is the use of medication to prevent
preterm delivery. Preterm labor is defined as
regular uterine contractions causing cervical
dilation.
 According to WHO, dihydropiridine class of
calcium channel blockers (e.g. nifedipine and
nicardipine) are preferred to other agents for
stopping labor contractions.

141
Mechanism
 Smooth muscle tissue, like the uterus, needs calcium
to contract. Nifedipine blocks the passage of
calcium into certain tissues, relaxing the uterine
muscles and smooth muscles of blood vessels
throughout the body.
Dose
 -According to New South Wales (NSW) health
Australia (Quality & Patient Safety Committee)
 Initial dose 20 mg orally stat, If contractions persist
after 30 minutes further 20 mg orally may be given
at 30 min intervals for a further two doses.
 Maintenance 20-40 mg orally (four times daily) for
up to 48 hours.
MAXIMAL DOSE IS 160 mg per day.
 -According to several studies have ranged from 10

to 40 mg as an initial "one time" dose. Subsequent
dosages have ranged from 10 to 20 mg every 6 to 8
hours as needed and tolerated to delay delivery.

142
Notes
 Nifedipine tablets should be swallowed whole,
 Nifedipine is highly light sensitive.
References
 Peter S Bernstein, Mary King. Using Nifedipine as a Tocolytic in Preterm
Labor. Medscape. Aug 18, 2004.
 Haas DM (2011). Preterm birth, search date June 2010. BMJ Clinical Evidence. Available
online: http://www.clinicalevidence.com.
 High Risk Pregnancy: Management Options - Expert Consult By David K. James،Philip J.
Steer،Carl P.
 Pharmacology for Nursing Care By Richard A. Lehne
 Principles of Pharmacogenetics and Pharmacogenomics By Russ B. Altman،David
Flockhart،David B. Goldstein.
 Meyler's Side Effects of Cardiovascular Drugs By Jeffrey K. Aronson.
 Policy directive: Maternity - Tocolytic agents for threatened preterm labour before 34 weeks
gestation. PD2011-_025, 4/5/11. NSW Health.
Tocolysis for Women in Preterm Labour. RCOG Green TOP Guideline February 2011.
Links
http://apps.who.int/iris/bitstream/10665/93142/1/EML_18_eng.pdf?ua=1
http://www.webmd.com/baby/nifedipine-for-preterm-labor
http://faculty.washington.edu/jodavies/OB%20Anesthesia%20Articles/Tocolytics/MagvNifedTo
colysis.pdf
http://www.seslhd.health.nsw.gov.au/rhw/Manuals/documents/Preterm%20Labour/Nifedipin
e%20for%20Tocolysis%20Protocol%202012.pdf
http://apps.who.int/rhl/pregnancy_childbirth/complications/preterm_birth/socom/en/
http://www.drugs.com/dosage/nifedipine.html

143
2-Nifedipine in treatment of Raynaud's disease
 Raynaud's phenomenon is a blood vessel disorder.

When healthy people are in a cold environment, the
tiny blood vessels in their skin constrict, or narrow.
This is an effort by the body to conserve heat.
 In people with Raynaud's phenomenon, that natural
response to cold is exaggerated. The tiny blood
vessels go into spasm, narrowing and reducing the
blood flow to the affected areas. This response,
called vasospasm, is seen most often in the fingers
and toes. But it also can occur in the ears, cheeks
and nose.
 In some people, the constriction also can occur in
response to emotional stress or a rapid change of
temperature from warm to cool. Or, it may occur
for no apparent reason.
 The effect of this vasospasm can be dramatic and
frightening. But it is temporary and rarely
dangerous. Once the affected area is warmed, the
blood vessels relax and expand. This allows more
blood flow.
144
 People who do not have any other symptoms or

disease are said to have primary Raynaud's. People
who have Raynaud's as part of another disease are
said to have secondary Raynaud's.
 Secondary Raynaud's is commonly linked to
connective-tissue disorders, such as scleroderma
and lupus. It also can result from blood vessel
damage due to injury, frostbite or use of jarring
machinery, such as jackhammers or chainsaws.
Symptoms
 People with Raynaud's see and feel changes in their

fingers and toes when exposed to cold. The skin
blanches, or turns white, then blue. Fingers and toes
can tingle or feel numb.
 When rewarmed, the skin flushes pink or red. And
there can be throbbing or soreness as the blood
surges back into the tiny blood vessels.
 People with secondary Raynaud's often have
symptoms related to their underlying rheumatic

145
disease such as:Arthritis, Rash and thickening or

hardening of the skin
Mechanism
 Nifedipine makes blood vessels relax and widen.

This should help the blood flow to fingers and toes.
 A summary of lots of randomised controlled trials
has shown that nifedipine can help prevent
146
Raynaud's attacks or reduce the symptoms of an

attack.
Dose
 Nifedipine 10–30 mg 3 times daily orally

 Sustained-release nifedipine 30–120 mg/day orally

147
References
 Raynaud's Phenomenon By Jay Denton Coffman
 Questions and answers about Raynaud's phenomenon. National Institute of Arthritis and
Musculoskeletal and Skin Diseases.
http://www.niams.nih.gov/Health_Info/Raynauds_Phenomenon/default.asp. Accessed Aug.
2, 2011.
 Raynaud's disease. National Heart, Lung, and Blood Institute.
http://www.nhlbi.nih.gov/health/dci/Diseases/raynaud/ray_all.html. Accessed Aug. 2, 2011.
 Wigley FM. Nonpharmacologic therapy for the Raynaud phenomenon.
http://www.uptodate.com/home/index.html. Accessed Aug. 2, 2011.
 Wigley FM. Pharmacologic and surgical treatment of the Raynaud phenomenon.
http://www.uptodate.com/home/index.html. Accessed Aug. 2, 2011.
 Sayeed SM, et al. Raynaud's phenomenon. In: Ferri FF. Ferri's Clinical Advisor 2012.
Philadelphia, Pa.: Mosby Elsevier; 2011. http://www.mdconsult.com/books/page.do?eid=4-
u1.0-B978-0-323-05611-3..C2009-0-38601-8&isbn=978-0-323-05611-3&uniqId=270492172-
3#4-u1.0-B978-0-323-05611-3..C2009-0-38601-8--TOP. Accessed Aug. 2, 2011.
 Natural product effectiveness checker results: Raynaud's syndrome. Natural Medicines
Comprehensive Database. http://www.naturaldatabase.com. Accessed Aug. 9, 2011.
Links
http://www.mayoclinic.org/diseases-conditions/raynauds-disease/basics/definition/con-
20022916
http://www.nhs.uk/medicine-
guides/pages/medicineoverview.aspx?condition=raynaud%60s%20disease&medicine=nifedipin
e
http://www.columbia.edu/itc/hs/medical/pathophys/immunology/readings/Raynaud's_pheno
menon_review.pdf
http://www.webmd.boots.com/a-to-z-guides/raynauds-phenomenon-nifedipine
http://my.clevelandclinic.org/disorders/reynauds_phenomenon/rheumatology_overview.aspx

148
3- Nifedipine for anal fissure
 An anal fissure or rectal fissure is a break or tear in

the skin of the anal canal. Anal fissures may be
noticed by bright red anal bleeding on toilet paper,
sometimes in the toilet. If acute they may
cause pain after defecation but with chronic fissures
pain intensity is often less.
 Anal fissures usually extend from the anal opening
and are usually located posteriorly in the midline,
probably because of the relatively unsupported
nature and poor perfusion of the anal wall in that
location. Fissure depth may be superficial or
sometimes down to the underlying sphincter muscle.
 The goal of treatment for anal fissures is to break
the cycle of spasm of the anal sphincter and its
repeated tearing of the anoderm.

149
Mechanism
 Nifedipine relax the muscles of the internal

sphincter. They also expand the blood vessels of the
anoderm and increase the flow of blood. Although
healing of chronic fissures has been reported in up
to 67% of patients treated with nifedipine , they are
most effective with acute fissures.
Dose
 Nifedipine 0.2% ointment should be used twice a

day, once in the morning and once at night for 3-6
weeks.
 Oral nifedipine 20mg twice daily
150
References
1. PRODIGY (2011) Anal Fissure. http://prodigy.clarity.co.uk/anal_fissure (accessed 23/01/2013)
2. Nelson RL, Thomas K, Morgan J, Jones A. Non surgical therapy for anal fissure. Cochrane Database of
Systematic Reviews 2012, Issue 2. Art. No.: CD003431. DOI: 10.1002/14651858.CD003431.pub3. (accessed
23/01/2013)
3. Schouten WR, Briel JW, Auwerda JJ. Relationship between anal pressure and anodermal blood flow. The
vascular pathogenesis of anal fissure. Dis Colon Rectum 1994;37:664-669
4. Mayo Clinic staff, Anal fissure. August 8 2008. http://www.mayoclinic.com/health/anal-fissure/DS00762
(accessed 23/01/2013)
5. Cross KLR, Massey EJD, Fowler AL and Monson JRT. The management of anal fissure: ACPGBI Position
Statement, Colorectal Dis 2008;10:1-7
6. Lock MR, Thompson JPS. Fissure-in-ano: the initial management and prognosis. Br J Surg 1977;64:355-358
7. Martin JD. Postpartum anal fissure, Lancet 1953;1:271-273
8. Filingeri V, Giudiceandrea F, Vennarecci G et al. Anal fissure in children,
http://www.eurom.it/medicina/pr/pr10_1_05.html (accessed 8.6.09 and 31.1.09)
9. American Gastroenterological Association. Medical position statement: Diagnosis and care of patients with anal
fissure. Gastroenterology 2003;124;233-234
10. Madoff RD, FleshmanJW for the American Gastroenterological Association. AGA technical review on the
diagnosis and care of patients with anal fissure, Gastroenterology 2003;124:235-245
11. Perry WB, Dykes SL, Buie WD, et al. Practice Parameters for the Management of Anal Fissures (3rd Revision).
Dis Colon Rectum 2010; 53: 1110-5
12. Lund JN, Nystrom PO, Coremans G et al. An evidence-based treatment algorithm for anal fissure, Tech
Coloproctol 2006;10;177-180
13. Jones OM, Brading AF, Mortenson N. The physiology, pharmacology and therapeutic manipulation of the internal
anal sphincter. Can J Gastroenterol 2002;16:249-257
14. Knight JS, Birks K, Farouk R. Topical diltiazem ointment in the treatment of chronic anal fissure. Br J Surg 2001;
88: 553-6
15. Nash GF, Kapoor K, Saeb-Parsy K, et al. The long-term results of diltiazem treatment for anal fissure. Int J Clin
Pract 2006; 60: 1411-3
16. Jonas M, Speake W, Scholefield JH. Diltiazem heals glyceryl trinitrate-resistant chronic anal fissures: a
prospective study. Dis Colon Rectum 2002;45:1091-5
17. Sajid MS, Rimple J, Cheek E, Baig MK. The efficacy of diltiazem and glyceryl trinitrate for the medical
management of chronic anal fissure: a meta-analysis. Int J Colorectal Dis 2008; 23: 1-6
18. Sajid MS, Parampalli U, Baig MK. An updated meta-analysis on the topical application of diltiazem versus
glyceryltrinitrate for the pharmacological management of chronic anal fissure. Colorectal Dis 2011; 13(Suppl 6):
13
19. Shrivistava UK, Jain BK, Kumar P, Saifee Y. A comparison of the effects of diltiazem and glyceryl trinitrate
ointment in the treatment of chronic anal fissure: a randomised clinical trial. Surg Today 2007; 37: 483-5
20. Jawaid M, Masood Z, Salim M. Topical diltiazem hydrochloride and glyceryl trinitrate in the treatment of chronic
anal fissure. J Coll Phys Surg Pakistan 2009; 19: 614-7
21. Sanei B, Mahmoodieh M, Masoudpour H. Comparison of topical glyceryl trinitrate with diltiazem ointment for the
treatment of chronic anal fissure : A randomized clinical trial. Act Chir Belg 2009; 109: 727-30
22. Cevik M, Boleken ME, Koruk I, et al. A prospective, randomized, double-blind study comparing the efficacy of
diltiazem, glyceryl trinitrate, and lidocaine for the treatment of anal fissure in children. Pediatric Surg Int 2012; 28:
411-6
23. Arthur JD, Makin CA, El-Sayed TY, Walsh CJ. A pilot comparative study of fissurectomy/diltiazem and
fissurectomy/botulinum toxin in the treatment of chronic anal fissure. Tech Coloproctol 2008; 12: 331-6
24. Samim M, Twigt B, Stoker L, Pronk A. Topical diltiazem cream versus botulinum toxin a for the treatment of
chronic anal fissure: A double-blind randomized clinical trial. Ann Surg 2012; 255: 18-22
25. Leinonen PT, Riekki R, Oikarinen A. Contact allergy to diltiazem cream. Contact Dermatitis 2010; 63: 228-30
26. Cook TA, Smilgrin Humphreys MM, Mortensen NJl. Oral nifedipine reduces resting anal pressure and heals
chronic anal fissures. Br J Surg 1999; 86: 1269-73
27. Antropoli C, Perrotti P, Rubino M et al. Nifedipine for local use in conservative treatment of anal fissures:
preliminary results of a multicenter study. Dis Colon Rectum 1999; 42: 1011-5
28. Perrotti P, Bove A, Carmine A et al. Topical nifedipine with lidocaine ointment vs. active control for treatment of
chronic anal fissure: results of a prospective, randomized, double-blind study. Dis Colon Rect 2002; 45: 1468-75
29. Golfam F, Golfam P, Khalaj A, Mortaz SSS. The effect of topical nifedipine in treatment of chronic anal fissure.
Act Med Iranica 2010; 48: 295-9

151
30. Katsinelos P, Papaziogas B, Koutelidakis I, et al. Topical 0.5% nifedipine vs. lateral internal sphincterotomy for
the treatment of chronic anal fissure: long-term follow-up. Int J Colorectal Dis 2006; 21:179-83
31. Katsinelos P, Kountouras J, Paroutoglou G, et al. Aggressive treatment of acute anal fissure with 0.5% nifedipine
ointment prevents its evolution to chronicity. World J Gastroenterol 2006; 12: 6203-6
32. Lysy J, Israeli E, Levy S, et al. Long term results of "chemical sphincterectomy" for chronic anal fissure. Dis
Colon Rectum 2006; 49: 858-64
33-The Ascrs Textbook of Colon And Rectal Surgery By James W. Fleshman،Bruce G. Wolff،American Society of Colon
and Rectal Surgeons
Links
NHS Evidence website www.evidence.nhs.uk
http://www.medicinenet.com/anal_fissure/page3.htm
http://www.med.umich.edu/bowelcontrol/patient/teaching/NifedipineOintment.pdf
http://www.webmd.com/digestive-disorders/tc/anal-fissures-nifedipine-and-diltiazem-topic-
overview

152
4-Nifedipine (as secondary therapy) in expulsion

ureteral stones
 Nifedipine has been used for facilitating the

spontaneous expulsion of ureteral stones. It several
studies without significant biases showed higher
expulsion rates in comparison with control groups,
and events of renal colic were not reduced.
 The expulsion of the stones required an average
time of up to 12 days. It should be noted that the
majority of the studies include distal ureteral and
vesicoureteral stones.

153
References
Porpiglia F, Ghignone G, Fiori C, et al. Nifedipine versus tamsulosin for the management of lower ureteral stones. J
Urol 2004; 172:568.
Saita A, Bonaccorsi A, Marchese F, et al. Our experience with nifedipine and prednisolone as expulsive therapy for
ureteral stones. Urol Int 2004; 72 Suppl 1:43.
Dellabella M, Milanese G, Muzzonigro G. Randomized trial of the efficacy of tamsulosin, nifedipine and phloroglucinol
in medical expulsive therapy for distal ureteral calculi. J Urol 2005; 174:167.
Links
http://www.europeanurology.com/article/S1569-9056(11)00059-5/fulltext/medical-treatment-for-renal-
colic-and-stone-expulsion-img-src-manager-uploads-els-articles-s1569-9056-11-00059-5-assets-
eulogo1-jpg-alt-eulogo1
http://www.medicinenet.com/nifedipine/article.htm
http://emedicine.medscape.com/article/437096-overview

154
5- Nifedipine used in prevention of migraine

headaches in adults
 Migraine is a chronic neurological

disorder characterized by recurrent moderate to
severe headaches often in association with a number
of autonomic nervous system symptoms.
 Extended release tablets: 30 mg orally once a day

 Immediate release capsules: 10 mg orally 3 times a
day
References
 The Headaches By Jes Olese
 Drug Treatment of Migraine and Other Headaches by Hans-Christoph Diener
 Migraine : Manifestations, Pathogenesis, and Management: Manifestations ...
 By Physiology and Biophysics Robert A. Davidoff Professor of Neurology, and Molecular and Cellular
Pharmacology atUniversity of Miami School of Medicin
 Managing Your Migraine: A Migraine Sufferer's Practical Guide by susan L. Burks
 PROGRESS IN MEDICINAL CHEMISTRY, By Gwynn Pennant Ellis،GeoffreyBuck
Links
http://www.drugs.com/nifedipine.html
http://www.medicinenet.com/nifedipine/article.htm
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1071161/#!po=41.6667

155

156
Prednisolone in IVF AND pregnancy
Why Predisposition used in IVF AND pregnancy??
This is related to (Natural Killer Cell)

157
What (Natural Killer Cells) are??
It is immune cells in the uterus are important

in the early detection and elimination of
foreign cells, such as infections or cancer.
Natural Killer Cells bind themselves to the

diseased or infected target cells and release a
potent cytotoxic chemical called tumour
necrosis factor (TNF) that kills these cells.
Natural Killer Cells form a normal part of

our blood and play an important role in our
bodies’ defence mechanism.
Women who have fertility problems,

specifically miscarriage or unsuccessful IVF
are more likely to have higher levels of
activity of these Natural Killer cells than
other women. High natural killer cell activity
is a form of immunological infertility.

158
What is the role of Prednisolone in higher levels of

.
Natural Killer cells ??
Prednisolone used to suppress Natural Killer

cells and inflammation.
For many of patients, Prednisolone are

commenced on day 5-7 of your cycle or IVF
stimulation and continued until 12 weeks of
pregnancy.
references
http://www.fertility-academy.co.uk/recurrent-failure/immune-treatments/
http://www.infertility-guidance.co.uk/blog/2009/03/natural-killer-cells/
http://ebooks.cambridge.org/chapter.jsf?bid=CBO9780511777851&cid=CBO9780511777851A016&tabNa
me=Chapter
http://humrep.oxfordjournals.org/content/14/11/2727.full.pdf
https://books.google.com.sa/books?id=YP9XBvP0xwwC&pg=PA75&lpg=PA75&dq=uterine+natural+killer
+cells+and+pregnancy&source=bl&ots=Cc5yn-
E7DL&sig=VAIYpwOyoLuVuyJJDfzpG4ZqlR0&hl=ar&sa=X&ei=edqtVKPhFIq1Ufz6gMAE&ved=0CGkQ6
AEwCTgK#v=onepage&q=uterine%20natural%20killer%20cells%20and%20pregnancy&f=false
http://www.jci.org/articles/view/68991
https://books.google.com.sa/books?id=S-
iURx4w2r4C&pg=PA415&lpg=PA415&dq=natural+killer+cells+and+pregnancy&source=bl&ots=vWjgvNlQ
3P&sig=uEb6LdxQ5Z3Dvf1snAHfiu3QVXc&hl=ar&sa=X&ei=zNmtVMeCBcarUbKJg_AJ&ved=0CGcQ6A
EwCTge#v=onepage&q=corticosteroid&f=false
http://ivf.com.au/fertility-treatment/advanced-science/natural-killer-cell-testing#treatment-for-high-natural-
killer-cell-activity

159

160
Unusual uses of propranolol for migraine

prevention. (FDA APPROVED USE)
 Sufficient evidence and consensus exist to

recommend propranolol, timolol, amitriptyline,
divalproex, sodium valproate, and topiramate as
first-line agents for migraine prevention.
 The mechanism of the anti-migraine effect of
Propranolol has not been established. Beta-
adrenergic receptors have been demonstrated in the
pial vessels of the brain.
Prophylaxis dose
 80 mg/day orally divided every6-8hr initially; may

be increased by 20-40 mg/day every 3-4 weeks; not
to exceed 160-240 mg/day divided every6-8hr
 Withdraw therapy if satisfactory response not seen
after 6 weeks

161
Reference
http://www.drugs.com/inderal.html
http://reference.medscape.com/drug/inderal-inderal-la-propranolol-342364
http://www.nhs.uk/conditions/migraine/pages/MedicineOverview.aspx?condition=Migraine%20Headache&medi
cine=propranolol
http://www.rxlist.com/inderal-la-drug/indications-dosage.htm
http://www.americanheadachesociety.org/assets/1/7/Alan_Rapoport_-_Migraine_Prevention_Medications.pdf
http://brain.oxfordjournals.org/content/128/1/86
http://www.drugs.com/pro/propranolol.html

162

163
 A drug used to treat erectile dysfunction , It acts by

inhibiting cGMP-specific phosphodiesterase type
5 (PDE5), an enzyme that promotes degradation of
cGMP, which regulates blood flow in the penis.
1-Sildenafil help Women with Antidepressant-

Related Sexual Problems.
 Sexual dysfunction is a well-known side effect of

some antidepressants, with up to 70% of women on
antidepressants reporting sexual problems.

164
 According to study in the University of New Mexico

School of Medicine in Albuquerque. This study was
published in The Journal of the American Medical
Association.
 Before starting the study, the women reported a
variety of sexual problems, including lack of libido,
difficulty becoming aroused or becoming lubricated,
lack of orgasm, or delay in achieving orgasm
Dose
 Sildenafil doses started at 50 milligrams a day,

taken one or two hours before expected sexual
activity, and could be increased to 100 milligrams.
Mechanism
 Sildenafil found to increase the orgasm and the time

to orgasm. Sildenafil also improved the satisfaction
of the partner. But it didn't increase drive and
desire.

165
 The higher a woman's testosterone levels, the

researchers also found, the more likely a positive
treatment response occurred
 Sildenafil in women with normal testosterone levels
is engorge their clitoris with blood, which allows
them to have orgasm.
Notes
 Evaluating a woman's hormone levels before

prescribing Viagra for sexual problems is
important.
References
News release, The Journal of the American Medical Association.
Irwin Goldstein, MD, director, sexual medicine, Alvarado Hospital, San Diego; clinical professor of
surgery, University of California, San Diego; editor-in-chief, The Journal of Sexual
Medicine; director, San Diego Sexual Medicine.
Harry A. Croft, MD, medical director, San Antonio Psychiatric Research Center.
Nurnberg, H. The Journal of the American Medical Association; July 23, 2008; vol 300: pp 395-404.
Links
http://www.webmd.com/sexual-conditions/news/20080722/viagra-for-her

166
2- Sildenafil improve uterine artery blood flow

and endometrial development in patients
undergoing IVF.
 In order for successful implantation to occur, an

adequately prepared endometrium has to be built
up during the menstrual cycle. Endometrial
development is regulated by steroid hormones and
various growth factors and cytokines.

167
 Some of these factors are produced locally and act

via paracrine mechanisms; others have to be
transferred to the endometrium. Sufficient uterine
blood supply is required for these factors to reach
the endometrium, especially to its functional layer.
 Most studies agree that the endometrium has to
reach a certain thickness for successful pregnancy
to occur.
Mechanism
 Nitric oxide relaxes vascular smooth muscle, an

effect that is mediated by cyclic guanosine
monophosphate (cGMP). Guanylate cyclase and
cGMP have been detected in human myometrium
obtained from both non pregnant and pregnant
women.
 Sildenafil is a selective inhibitor of the type V
cGMP-specific phosphodiesterase. With the use of
sildenafil, cGMP levels remain elevated, which leads
to vascular relaxation and increased blood flow.

168
 Sildenafil increase the blood flow to the uterus and

to improve both the pattern and thickness of the
endometrium.
 Sildenafil improved pelvic blood flow can have a
beneficial effect on ovarian function. Sildenafil
suppositories rather than oral tablets were used in
order to reduce the side effects such as headaches
and low blood pressure because it deliver the drug
near the proximity of the uterus.

169
References
 Manuscript which appeared in Fertility & Sterility (The official journal of The American
Society of Reproductive Medicine) in October 2002.
 Kovacs P, Matyas S, Boda K, Kaali SG. The effect of endometrial thickness on IVF/ ICSI outcome. Hum
Reprod. 2003;18:2337-2341.
 Rubinstein M, Marazzi A, Polak de Fried E. Low-dose aspirin treatment improves ovarian
responsiveness, uterine and ovarian blood flow velocity, implantation and pregnancy rates in patients
undergoing in vitro fertilization: prospective, randomized, double-blind placebo-controlled assay.
Fertil Steril. 2000;73:1069-1071.
 Urman B, Mercan R; Alatas C, et al. Low-dose aspirin does not increase implantation rates in patients
undergoing intracytoplasmic sperm injection: a prospective randomized study. J Assist Reprod Genet.
2000;17:586-590.
 Weckstein LN, Jacobson A; Galen D; Hampton K; Hammel J. Low-dose aspirin for oocyte donation
recipients with a thin endometrium: prospective, randomized study. Fertil Steril. 1997;68:927-930.
 Sher G, Fisch JD. Vaginal sildenafil (Viagra): a preliminary report of a novel method to improve uterine
artery blood flow and endometrial development in patients undergoing IVF. Hum Reprod.
2000;15:806-809.
 Sher G, Fisch JD. Effects of vaginal sildenafil on the outcome of in vitro fertilization (IVF) after multiple
IVF failures attributed to poor endometrial development. Fertil Steril. 2002;78:1073-1076.
 Amit, A., Thaler, I., Paz, Y. and Itskovitz-Eldor, J. (1998) The effect of a nitric oxide donor on doppler
flow velocity waveforms in the uterine artery during the first trimester of pregnancy. Ultrasound
Obstet. Gynecol., 11, 94–98.
 Ballard, S.A., Gingell, C.J., Tang, K. et al. (1998) Effects of Sildenafil on the relaxation of human
corpus cavernosum tissue in vitro and on the activities of cyclic nucleotide phosphodiesterase
isoenzymes. J. Urol., 159, 2164–2171.
 Barroso, R.P., Osuampke, C., Nagamani, M. and Yallampalli, C. (1998) Nitric oxide inhibits
development of embryos and implantation in mice. Mol. Hum. Reprod., 4, 503–507.
 Boolell, M., Gepi-Attee, S., Gingell, J.C. and Allen, M.J. (1996) Sildenafil, a novel effective oral therapy
for male erectile dysfunction. Br. J. Urol., 78, 257–261.
 Cameron, I.T. and Cambell, S. (1998) Nitric oxide in the endometrium. Hum. Reprod. Update, 4, 565–
569.
 Fisch, J.D., Behr, B. and Conti, M. (1998) Enhancement of motility and acrosome reaction in human
spermatozoa: differential activation by type-specific phosphodiesterase inhibitors. Hum.
Reprod., 5, 1248–154.
 Gonen, Y. and Casper, R.F. (1990) Prediction of implantation by sonographic appearance during
controlled ovarian stimulation for in vitro fertilization (IVF). J. In Vitro Fertil. Embryo Transfer, 7, 146–152.

170
 Sher, G., Herbert, C., Jacobs, M. and Maassarani, G. (1991) Assessment of the late proliferative phase
endometrium by ultrasonography in patients undergoing in vitrofertilization and embryo transfer
(IVF-ET). Hum. Reprod., 6, 232–237.
 Sher, G., Dodge, S., Maassarani, G. et al. (1993) Management of suboptimal sonographic endometrial
patterns in patients undergoing in vitro fertilization and embryo transfer. Hum. Reprod., 8, 374–379.
 Smith, G.N. and Brien, J.F. (1998) Use of nitroglycerin for uterine relaxation. Obstet. Gynecol.
Surv., 53, 559–565.
 Telfer, J.F., Irvine, G.A., Kohnen, G. et al. (1997) Expression of endothelial and inducible nitric oxide
synthase in non-pregnant and decidualized human endometrium.Mol. Hum. Reprod., 3, 69–75.
 Weckstein, L.N., Jacobson, A., Galen, D. et al. (1997) Low-dose aspirin for oocyte donation recipients
with a thin endometrium: prospective, randomized study. Fertil. Steril., 68, 927–930.
Links
http://humrep.oxfordjournals.org/content/15/4/806.long#ref-list-1
http://www.ivf-infertility.com/help/news.php

171
3- Sildenafil in the treatment of pulmonary

arterial hypertension in infants and adults.
 Pulmonary arterial hypertension (PAH) is a

progressive, and often fatal, debilitating disorder.
 The increased pulmonary artery pressure found in
PAH is due to disturbances in key vascular
mediator pathways including relative deficiencies of
vasodilators such as nitric oxide (NO) and
172
prostacyclin, as well as exaggerated production of

vasoconstrictors such as endothelin and
thromboxanes.
Symptoms
 Progressive breathlessness, exertion limitation,

frequent decline and failure of the right ventricle.
Mechanism
 Sildenafil is a selective inhibitor of

phosphodiesterase type 5 (PDE5). Present
throughout the body, PDE5 is found in high
concentrations in the lungs. Inhibition of PDE5
enhances the vasodilatory effects of nitric oxide in
pulmonary hypertension by preventing the
degradation of cyclic guanosine monophosphate
(cGMP), which promotes relaxation of vascular
smooth muscle and increases blood flow.
 In animal models and human trials, sildenafil has
been found to produce a relatively selective
reduction in pulmonary artery pressure without

173
adverse systemic hemodynamic effects after 3

months of oral therapy.
 Inhibition of PDE5 by sildenafil may also enhance
the platelet antiaggregatory activity of nitric oxide
and inhibit thrombus formation.
Infant’s dose
 A single dose of sildenafil in infants prevented

rebound pulmonary hypertension and significantly
reduced the duration of mechanical ventilation in
intensive care unit (ICU) infants being withdrawn
from inhaled nitric oxide therapy.
Adult’s dose
 Oral: 5 mg or 20 mg three times a day taken at least

4 to 6 hours apart.
 Injection: 2.5 mg or 10 mg administered as an
intravenous bolus injection three times a day. The
injection dose does not need to be adjusted for body
weight.
174
At 2012 The U.S. Food and Drug Administration (FDA) is

recommending that not be prescribed to children
(ages 1 through 17) for pulmonary arterial hypertension. This
recommendation against use is based on a recent long-term
clinical pediatric trial showing that: (1) children taking a high
dose of had a higher risk of death than children
taking a low dose and (2) the low doses of are not
effective in improving exercise ability.
References
1) Clavecilla SQ. New insights into the treatment of pulmonary arterial hypertension. Formulary,
2003 Mar; 38(3): 150-4, 157-8, 160.
2) Mehta S. Sildenafil for pulmonary arterial hypertension: exciting, but protection required.
Chest. 2003 Apr; 123(4): 989-92.
3) Pfizer Inc. FDA Approves Pfizer’s Revatio as Treatment for Pulmonary Arterial
Hypertension.http://www.pfizer.com/pfizer/are/news_releases/2005pr/mn_2005_0606.jsp#additional. Accessed June
23, 2005.
4) Kataoka M, Satoh T, Manabe T, Anzai T, Yoshikawa T, Mitamura H, Ogawa S. Oral sildenafil

improves primary pulmonary hypertension refractory to epoprostenol. Circ J. 2005
Apr;69(4):461-5.
5) Kanthapillai P, Lasserson T, Walters E. Sildenafil for pulmonary hypertension. Cochrane

Database Syst Rev. 2004 Oct 18;(4):CD003562.
6) Karatza AA, Bush A, Magee AG. Safety and efficacy of Sildenafil therapy in children with
pulmonary hypertension. Int J Cardiol. 2005 Apr 20;100(2):267-73.
7) Leuchte HH, et al. Hemodynamic response to sildenafil, nitric oxide, and iloprost in primary
pulmonary hypertension. Chest. 2004 Feb; 125(2): 580-6.
8) Chockalingam A, Gnanavelu G, Venkatesan S, Elangovan S, Jagannathan V, Subramaniam T,

Alagesan R, Dorairajan S. Efficacy and optimal dose of sildenafil in primary pulmonary

175
hypertension. Int J Cardiol. 2005 Mar 10;99(1):91-5.
9) Lee AJ, Chiao TB, Tsang MP. Sildenafil for pulmonary hypertension. Ann Pharmacother. 2005
May;39(5):869-84.
10) Sastry BK. Clinical efficacy of sildenafil in primary pulmonary hypertension: a randomized,
placebo-controlled, double-blind, crossover study . J Am Coll Cardiol, 2004 Apr;43 (7), pp.
1149-53.
11) Ng J, Finney SJ, Shulman R, Bellingan GJ, Singer M, Glynne PA. Treatment of pulmonary
hypertension in the general adult intensive care unit: a role for oral sildenafil? Br J Anaesth.
2005 Jun;94(6):774-7.
12) American Heart Association rapid access journal report. Impotence drug may help children
with fatal lung disorder.
06/23/2005.http://www.americanheart.org/presenter.jhtml?identifier=3031499. Accessed: June
23, 2005.
National Heart, Lung, and Blood Institute: "What Is Pulmonary Arterial Hypertension?" National Heart, Lung,
and Blood Institute: "Living with Pulmonary Arterial Hypertension." WebMD Medical News: "Viagra Label May
Note Rare Vision Problems. “Viagra The Associated Press.
Links
http://www.sciencedaily.com/releases/2006/11/061101151450.htm
http://thoracic.org/career-development/residents/ats-reading-list/pulmonary-
hypertension.php
http://www.globalrph.com/sildenafil.htm

176
http://www.fda.gov/drugs/drugsafety/ucm317123.htm
http://www.sciencedirect.com/science/article/pii/S0735109704004759
http://www.webmd.com/lung/news/20050608/viagra-ingredient-okd-for-
lung-problem
http://eurheartj.oxfordjournals.org/content/25/5/431.full
http://www.nhs.uk/medicine-
guides/pages/medicineoverview.aspx?condition=Pulmonary%20hypertension&
medicine=sildenafil%20citrate
http://www.nejm.org/doi/full/10.1056/NEJMoa050010
http://www.nejm.org/doi/full/10.1056/NEJM200011023431814
http://www.drugs.com/dosage/sildenafil.html

177
4- Sildenafil for Raynaud’s syndrome
 Raynaud's phenomenon is a blood vessel disorder.

When healthy people are in a cold environment, the
tiny blood vessels in their skin constrict, or narrow.
This is an effort by the body to conserve heat.
178
 In people with Raynaud's phenomenon, that natural

response to cold is exaggerated. The tiny blood
vessels go into spasm, narrowing and reducing the
blood flow to the affected areas. This response,
called vasospasm, is seen most often in the fingers
and toes. But it also can occur in the ears, cheeks
and nose.
 In some people, the constriction also can occur in
response to emotional stress or a rapid change of
temperature from warm to cool. Or, it may occur
for no apparent reason.
 The effect of this vasospasm can be dramatic and
frightening. But it is temporary and rarely
dangerous. Once the affected area is warmed, the
blood vessels relax and expand. This allows more
blood flow.
 People who do not have any other symptoms or
disease are said to have primary Raynaud's. People
who have Raynaud's as part of another disease are
said to have secondary Raynaud's.

179
 Secondary Raynaud's is commonly linked to

connective-tissue disorders, such as scleroderma
and lupus. It also can result from blood vessel
damage due to injury, frostbite or use of jarring
machinery, such as jackhammers or chainsaws.
Symptoms
 People with Raynaud's see and feel changes in their

fingers and toes when exposed to cold. The skin
blanches, or turns white, then blue. Fingers and toes
can tingle or feel numb.
 When rewarmed, the skin flushes pink or red. And
there can be throbbing or soreness as the blood
surges back into the tiny blood vessels.
 People with secondary Raynaud's often have
symptoms related to their underlying rheumatic
disease such as:Arthritis, Rash and thickening or
hardening of the skin
 Patients taking sildenafil, Raynaud's attacks were
less frequent and shorter and the mean Raynaud's
Condition Score was significantly lower. In
180
addition, capillary blood flow velocity increased

more than quadrupled after treatment with
sildenafil.
References
Pulmonary Arterial Hypertension: Diagnosis and Evidence-Based Treatment book
Links
http://www.nhs.uk/Conditions/Raynauds-phenomenon/Pages/Treatment.aspx
http://www.drugs.com/health-guide/raynaud-s-phenomenon.html
http://www.emedicinehealth.com/raynaud_phenomenon/page9_em.htm
http://www.health.harvard.edu/press_releases/viagra-and-pulmonary-hypertension

181

182
Sodium bicarbonate As vaginal douche

Sodium bicarbonate used one hour before
intercourse to help in increase the vaginal
ph.
thus may affect the gender of the baby.

Ph of the vagina help in determine the type of
gender
Higher pH or alkaline media of vagina for a

Boy and lower pH or acidic media of vagina
for a girl.
How to prepare sodium chloride vaginal douche
Douche with baking soda one hour before
intercourse. Mix two tablespoons of baking
soda into one liter of warm tap water. Let
stand for 10 minutes. Stir again and make
sure the solution is fully dissolved. Insert into
the vagina with a douche or large syringe
while lying down.
183
References
http://www.webmd.com/baby/features/deciding-babys-sex
https://books.google.com.sa/books?id=hhBULeepguEC&pg=PA931&lpg=PA931&dq=Improvement+of+c
ervical+mucus+viscoelasticity+and+sperm+penetration+with+sodium+bicarbonate+douching&source=b
l&ots=j_JjBT1lTj&sig=bSLkqDDeP4ezXhW-
h1PCYMlJUJY&hl=en&sa=X&ei=IyAwVemiI46vaf3FgdAK&ved=0CEQQ6AEwBg#v=onepage&q=Improvem
ent%20of%20cervical%20mucus%20viscoelasticity%20and%20sperm%20penetration%20with%20sodiu
m%20bicarbonate%20douching&f=false
https://books.google.com.sa/books?id=ry_R-
PQBqD8C&pg=PA39&lpg=PA39&dq=sodium+bicarbonate+douching+before+interacourse&source=bl&ot
s=tTcPtWjEV-
&sig=wgZ_sOFBNdQrdeUOmW7qqIzz2fE&hl=en&sa=X&ei=CyEwVdQI0vFq8quBkAE&ved=0CEUQ6AEwC
DgU#v=onepage&q=sodium%20bicarbonate%20douching%20before%20interacourse&f=false
https://books.google.com.sa/books?id=wPuCv8pusN8C&pg=PA23&lpg=PA23&dq=sodium+bicarbonate+i
n+gender+selection&source=bl&ots=VraPuJ8qaG&sig=_TiwsZgwZ5K3GisJ1IGpDpYOk_4&hl=en&sa=X&e
i=hxwwVdTiG5G0adWKgfgP&ved=0CE4Q6AEwCDgK#v=onepage&q=sodium%20bicarbonate%20in%20
gender%20selection&f=false

184

185
 Spironolactone is used to treat high blood pressure.

Lowering high blood pressure helps prevent
strokes, heart attacks, and kidney problems.
 It is also used to treat swelling (edema) caused by
certain conditions (e.g., congestive heart failure) by
removing excess fluid and improving symptoms
such as breathing problems.
 This medication is also used to treat low
potassium levels and conditions in which the body is
making too much of a natural chemical
(aldosterone).Spironolactone is known as a "water
pill" (potassium-sparing diuretic)

186
1-Spironolactone in treatment of acne for

women.
 Acne is triggered by an excess production of sebum.

Sebum is an oil made by glands in your skin. Along
with skin cells, sebum can clog pores and promote
the growth of bacteria that contribute to acne.
Androgens, a group of hormones that includes
testosterone, stimulate your skin to produce sebum.

187
 A woman's ovaries and adrenal glands normally

produce a low level of androgens. Higher levels of
androgens can lead to excess sebum.
Mechanism
 Spironolactone is an aldosterone antagonist with
anti-androgenic properties.
 The mechanism of action includes competition for
the androgen receptor, suppression of cytochrome
P450, and inhibition of steroidogenesis, as well as
reduction in 5-α-reductase activity.
 Spironolactone also decreases sebum production

and improves acne.
Dose:
 The therapeutic dose for acne therapy is 50–100 mg
per day

188
Note
 Spironolactone may be used in combination with
combined oral contraceptive in women who have
limited response to OCPs alone.
References
1. Farquhar C, Lee O, Toomath R, et al. Spironolactone versus placebo or in combination with
steroids for hirsutism and/or acne. Cochrane Database Syst Rev (4):CD000194 (2003).
2. Speroff L, Glass RH, Kase NG. Hirsutism. In: Speroff L, Glass RH, Kase NG (eds). Clinical
gynecologic endocrinology and infertility. 6th ed. Baltimore: Williams and Wilkins, p523–56
(1999).
3. Armanini D, Karbowiak I, Goi A, et al. In-vivo metabolites of spironolactone and potassium

canrenoate: determination of potential anti-androgenic activity by a mouse kidney cytosol
receptor assay. Clin Endocrinol (Oxf) 23(4):341–7 (1985 Oct).
4. Berson DS, Chalker DK, Harper JC, et al. Current concepts in the treatment of acne: report from
a clinical roundtable. Cutis 72(1 Suppl):5–13 (2003 Jul).
5. Hughes BR, Cunliffe WJ (May 1988). "Tolerance of spironolactone". The British Journal of Dermatology118 (5): 687–
91. doi:10.1111/j.1365-2133.1988.tb02571.x. PMID 2969259.
Links
http://www.webmd.com/skin-problems-and-treatments/acne/features/adult-acne-is-treatable
http://www.medicinenet.com/spironolactone-oral/article.htm

189
2-Spironolactone in treatment of hirsutism for

women.

Causes of hirsutism
include:

190

fertility.
glands or ovaries.
Anabolic steroids,testosterone,glucocorticoids,

191
Mechanism
 Spironolactone blocks androgen receptors.
Spironolactone also decreases testosterone
production, making it additionally effective for
hirsutism.
Dose
 Spironolactone, in daily doses of 50-200 mg.
References
1. Moghetti P, Tosi F, Tosti A, Negri C, Misciali C, Perrone F, et al. Comparison of
spironolactone, flutamide, and finasteride efficacy in the treatment of hirsutism: a
randomized, double blind, placebo-controlled trial. J Clin Endocrinol Metab. 2000;85:89–94.
2. Wong IL, Morris RS, Chang L, Spahn MA, Stanczyk FZ, Lobo RA . A prospective
randomized trial comparing finasteride to spironolactone in the treatment of hirsute women. J
Clin Endocrinol Metab. 1995;80:233–8.
Links

192
3-Spironolactone Treat polycystic ovary

syndrome (PCOS) problems
 Polycystic ovary syndrome PCOS is one of the most

common endocrine disorders among females. PCOS
has a diverse range of causes that are not entirely
understood, but there is strong evidence that it is
largely a genetic disease
 The most common immediate symptoms
are anovulation, excess androgenic hormones,
and insulin resistance. Anovulation results in
irregular menstruation, amenorrhea, and ovulation-
related infertility. Imbalance generally
causes acne and hirsutism. Insulin resistance is
193
associated with obesity, Type 2 diabetes, and high

cholesterol levels. The symptoms and severity of the
syndrome vary greatly among affected women.
 Treatments for hirsutism in women with PCOS are

similar to those in women without PCOS, such as
patients with idiopathic hirsutism. Several
medications have been studied for the treatment of
hirsutism in women with PCOS. First-line agents
include spironolactone and metformin
Mechanism
 Spironolactone blocks androgen receptors.
Spironolactone also decreases testosterone
production, making it additionally effective for
hirsutism.

194
References
1. Ganie MA, Khurana ML, Eunice M, et al. Comparison of efficacy of spironolactone with metformin
in the management of polycystic ovary syndrome: an open-labeled study [published correction
appears in J Clin Endocrinol Metab. 2004;89(9):4655]. J Clin Endocrinol Metab.
2004;89(6):2756–2762.
2. . Moghetti P, Tosi F, Tosti A, et al. Comparison of spironolactone, flutamide, and finasteride
efficacy in the treatment of hirsutism: a randomized, double blind, placebo-controlled trial. J Clin
Endocrinol Metab. 2000;85(1):89–94.
3. Farquhar C, Lee O, Toomath R, Jepson R. Spironolactone versus placebo or in combination with
steroids for hirsutism and/or acne. Cochrane Database Syst Rev. 2003;(4);CD000194.
4. Inal MM, Yildirim Y, Taner CE. Comparison of the clinical efficacy of flutamide and spironolactone
plus Diane 35 in the treatment of idiopathic hirsutism: a randomized controlled study. Fertil Steril.
2005;84(6):1693–1697.
5. Spritzer PM, Lisboa KO, Mattiello S, Lhullier F. Spironolactone as a single agent for long-term
therapy of hirsute patients. Clin Endocrinol (Oxf). 2000;52(5):587–594.
Links
http://www.webmd.com/women/spironolactone-for-polycystic-ovary-syndrome-pcos
http://www.mayoclinic.org/diseases-conditions/pcos/basics/treatment/con-20028841
http://www.nhs.uk/Conditions/Polycystic-ovarian-syndrome/Pages/Treatment.aspx
http://clinicaltrials.gov/show/NCT01526616
http://www.medicinenet.com/spironolactone/article.htm

195
4-Spironolactone in treatment of female

pattern hair loss

196
 Life cycle of hair is divided into three phases

 Anagen -- active hair growth that lasts between two
to six years
 Catagen -- transitional hair growth that lasts two to
three weeks
 Telogen -- resting phase that lasts about two to
three months; at the end of the resting phase the
hair is shed and a new hair replaces it and the
growing cycle starts again.
 As people age, their rate of hair growth slows
 Almost every woman eventually develops some
degree of female pattern hair loss. It can start any
time after the onset of puberty, but women tend to
first notice it around menopause, when hair loss
typically increases. The risk rises with age, and it's
higher for women with a history of hair loss on
either side of the family.
 As the name suggests, androgenetic alopecia
involves the action of the hormones called
androgens, which are essential for normal male
sexual development and have other important
197
functions in both sexes, including sex drive and

regulation of hair growth.
 The condition may be inherited and involve several
different genes. It can also result from an
underlying endocrine condition, such as
overproduction of androgen or an androgen-
secreting tumor on the ovary, pituitary, or adrenal
gland. In either case, the alopecia is likely related to
increased androgen activity.
 But unlike androgenetic alopecia in men, in women
the precise role of androgens is harder to determine.
On the chance that an androgen-secreting tumor is
involved, it's important to measure androgen levels
in women with clear female pattern hair loss.
 In either sex, hair loss from androgenetic alopecia
occurs because of a genetically determined
shortening of anagen, a hair's growing phase, and a
lengthening of the time between the shedding of a
hair and the start of a new anagen phase. That
means it takes longer for hair to start growing back

198
after it is shed in the course of the normal growth

cycle.
 The hair follicle itself also changes, shrinking and
producing a shorter, thinner hair shaft — a process
called "follicular miniaturization." As a result,
thicker, pigmented, longer-lived "terminal" hairs
are replaced by shorter, thinner, non-pigmented
hairs called "vellus."
Mechanism
 Spironolactone is an antiandrogen that works in
two ways. Primarily it slows down the production of
androgens in the adrenal glands and ovaries.
Secondly it blocks the action of androgens in part
by preventing dihydrotestosterone from binding to
its androgenetic receptor.
Dose:
 100 to 200 milligrams daily

199
References
Sauer's Manual of Skin Diseases edited by Brian J. Hall, John C. Hall
Links
http://www.uptodate.com/contents/female-pattern-hair-loss-androgenetic-alopecia-in-women-
treatment-and-prognosis
http://www.drugs.com/female-pattern-baldness.html
http://www.health.harvard.edu/newsletters/Harvard_Womens_Health_Watch/2009/June/Treatin
g-female-pattern-hair-loss
http://www.drugs.com/hair-loss.html
http://www.webmd.com/skin-problems-and-treatments/guide/understanding-hair-loss-basics

200

201
Sulfasalazine for treating ulcerative colitis.
Unusual uses of sulfasalazine in treatment of

rheumatoid arthritis in adults and children
whose disease has not responded well to other
medications.

202
Mechanism:-
It is a prodrug, that is, it is not active in its

ingested form. It is broken down by bacteria
in the colon into 5-aminosalicylic acid (5-
ASA), and sulfapyridine.
5-aminosalicylic acid (5-ASA) may reduce
inflammation by blocking the activity of
cyclooxygenase thereby reducing the
production of prostaglandins and relief
rheumatoid arthritis pain.
references :-
http://www.medicinenet.com/sulfasalazine/article.htm
http://www.webmd.com/drugs/2/drug-6260/sulfasalazine-oral/details
http://www.mayoclinic.org/drugs-supplements/sulfasalazine-oral-route/description/drg-20066179

203

204
Tadalafil and BENIGN PROSTATIC

HYPERTROPHY (FDA APPROVED USE)
- Prostatic hypertrophy usually develops

after age 40.
- By age 60, half of all men have BPH; by age
85, 90% have BPH.
- Growth of the prostate gland leads to
narrowing of the urethra and obstruction of
urinary flow.

205
Mechanism:-
Tadalafil is Phosphodiesterase (PDE) type-5

inhibitors-induced smooth muscle relaxation
in the bladder urethra, and prostate.
Dose:-
5 mg once daily is approved for use in BPH.
links
http://www.mayoclinic.org/drugs-supplements/tadalafil-oral-route/description/drg-20067204
http://www.cialis.com/about-bph.aspx
http://www.drugs.com/comments/tadalafil/for-benign-prostatic-hyperplasia.html
http://www.rxlist.com/cialis-tadalafil/drug.htm
..

206

207
1-Unusual uses of Topiramate for Migraine

Prophylaxis in Adolescents (FDA APPROVED USE)
Sufficient evidence and consensus exist to

recommend propranolol, timolol,
amitriptyline, divalproex, sodium valproate,
and topiramate as first-line agents for
migraine prevention.

208
Dose
The recommended total daily dose of

Topiramate as treatment for adults and
adolescents 12 years of age and older for
prophylaxis of migraine headache is 100
mg/day administered in two divided doses
(Table 1). The recommended titration rate
for topiramate for migraine prophylaxis to
100 mg/day is:
References
http://www.americanheadachesociety.org/assets/1/7/Topiramate_for_Migraine_Preventio
n_May_2012.pdf
http://www.drugs.com/dosage/topamax.html
http://www.topamax.com/

209
2- Topiramate AND phentermine as an addition

to a reduced-calorie diet and exercise for chronic
weight management. (FDA APPROVED USE)
 Qsymia is a combination of two FDA-approved

drugs, phentermine and topiramate, in an extended-
release formulation.
MECHANISM
 Phentermine is a sympathomimetic agent that has

been used by itself for the treatment of obesity for
quite some time.
 Although the exact mechanism by which
phentermine works to promote weight loss is not
understood, it is thought to stimulate the release of
chemicals from the hypothalamus, the area of the
brain known to have a major role in regulating
hunger and food intake.
 Phentermine induced release of chemicals is
thought to reduce appetite and decrease food intake,
among other effects.
210
 Topiramate, the other medicine in Qsymia, is an

anti-seizure medication that has been observed to be
effective in causing weight loss. The precise
mechanism by which topiramate works to stimulate
weight loss is not yet understood. However, similar
to the actions of phentermine, topiramate is also
thought to suppress appetite and make a person feel
full even after eating less food than usual.
DOSE
The recommended daily dose of Qsymia contains 7.5 milligrams of phentermine and 46 mg of topiramate extended-
release. Qsymia is also available at a higher dose (15 mg phentermine and 92 mg of topiramate extended-release)
for select patients.
References
http://www.drugs.com/cdi/phentermine-topiramate-extended-release-capsules.html
http://www.rxlist.com/qsymia-drug/indications-dosage.htm
http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=40dd5602-53da-45ac-bb4b-15789aba40f9
http://www.medicinenet.com/phentermine_and_topiramate_extended-release/article.htm

211

212
Trimethoprim-Sulfamethoxazole in treatment of
acne vulgaris
Mechanism:
many bacteria are not capable of

incorporating exogenous folate, they are
dependent on their own ability to synthesize
folate that is needed for their own protein
and deoxyribonucleic acid (DNA) production.
TMP-SMZ inhibits folate production in
bacteria by blocking bacterial dihydrofolic
acid reductase, which causes reduced
production of purines and subsequently DNA.

213
Notes
1- this combination uses in Severe Acne.

2-it is less often used for acne BUT when
other antibiotics have failed, especially when
isotretinoin is not an option.
3-Some dermatologists claim that the
response to trimethoprim-sulfamethoxazole
is as impressive as the response to
isotretinoin. However, unlike isotretinoin, the
effect of trimethoprim-sulfamethoxazole is
not sustained after it is stopped.
Dose
1 DS tab or 1 regular-strength tab orally

every Day or every 12hr for up to 18 weeks.
.
.
references
http://reference.medscape.com/…/bactrim-trimethoprim-sulfam…
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3168244/…

214

215
VITAMIN-D in improvement of gestational

diabetes mellitus
Women with lower serum levels of vitamin D

during the first trimester of pregnancy are at
greater RISK for developing gestational
diabetes mellitus
216
Mechanism
The active metabolite, 1,25-dihydroxyvitamin

D, formed from 25-hydroxyvitamin D
(25OHD), is involved in calcium balance and
bone metabolism, acts as a transcription
factor, and functions in glucose metabolism
References
http://www.who.int/…/guidelin…/vit_d_supp_pregnant_women/en/
http://onlinelibrary.wiley.com/…/14651858.CD008873…/abstract

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Unusual uses of common drugs by Ahmed Yossef

Unusual uses of common drugs

Ahmed Mohammed Yossef

Copyright © 2015 unusual uses of common drugs™, All Rights Reserved.

Unusual uses of common drugs by Ahmed Yossef

Acetyl salicylic acid …………………………..........…..6

Combined oral contraceptive……………………..…40

Dexamethasone and betamethasone……………..68

Unusual uses of common drugs by Ahmed Yossef

 Unusual uses of common drugs is a new vision to

 Unusual uses of common drugs differ from off-label uses

 Unusual uses of common drugs open the health care

Unusual uses of common drugs by Ahmed Yossef

Unusual uses of common drugs by Ahmed Yossef

 A salicylate drug, often used as an analgesic to

 Aspirin also has an antiplatelet effect by inhibiting

Unusual uses of common drugs by Ahmed Yossef

1-Aspirin used in reducing risk of preeclampsia

 Pregnant women at high risk for

 Preeclampsia is a complex condition that occurs in

Unusual uses of common drugs by Ahmed Yossef

 Daily low-dose aspirin in middle and late

 This provides the basis for the use of low-dose

Unusual uses of common drugs by Ahmed Yossef

not completely inhibit thromboxane and does not

Unusual uses of common drugs by Ahmed Yossef

 Bakhti A, Vaiman D. Prevention of gravidic endothelial hypertension by aspirin treatment administered

 Mesdaghinia E, Talari H, Abedzadeh-Kalahroudi M. Effect of aspirin for prevention of preeclampsia in

Unusual uses of common drugs by Ahmed Yossef

2-Topical Aspirin for Relief of Pain due to

 Topical aspirin dissolved in chloroform is an

Aspirin and Related Drugs edited by Kim D. Rainsfor

Clinical Management of Herpes Viruses edited by Stephen L. Sack

Unusual uses of common drugs by Ahmed Yossef

3-Aspirin and Alzheimer's

 The Baltimore Longitudinal Study that appearing

Unusual uses of common drugs by Ahmed Yossef

 This is not the first study to suggest that aspirin

Unusual uses of common drugs by Ahmed Yossef

New Research on Aspirin and Health edited by Charles L. Millwood

Unusual uses of common drugs by Ahmed Yossef

4-Aspirin for the prevention of colorectal cancer

 Aspirin has been studied as adjuvant therapy for

Cancer Prevention II By Hans-Jörg Senn, Ursula Kapp, Florian Otto

National Comprehensive Cancer Network. NCCN Guidelines® for Colon Cancer.

V.3.2013.http://www.nccn.org/professionals/physician_gls/PDF/colon.pdf Accessed June 6, 2013.

Unusual uses of common drugs by Ahmed Yossef

5-Aspirin help in sore or ulcerated mouth

 Aspirin can be used as a gargle or mouthwash 300

Unusual uses of common drugs by Ahmed Yossef

Unusual uses of common drugs by Ahmed Yossef

 This medication is used to treat mental/mood

10-25 mg orally at bed time

Unusual uses of common drugs by Ahmed Yossef

Algorithm for pharmacologic migraine prophylaxis.

Unusual uses of common drugs by Ahmed Yossef

Unusual uses of common drugs by Ahmed Yossef

 Betamethasone topical is used to help relieve

Betamethasone scalp application used as ear drop

 It is giving to try to manage excessive amount of

Unusual uses of common drugs by Ahmed Yossef

• Warm the drops to body temperature before