Академический Документы
Профессиональный Документы
Культура Документы
Cyclosporine
Presented by:
Hatem Al-Nasser
Medical Student
July 2008
Mechanism of action
The NF-ATcNF-ATn
complex binds to the
promoter of the interleukin 2
(IL-2) gene and initiates IL-2
production. Consequently, T
cells do not produce IL-2,
which is necessary for full Tcell activation. Therefore It
inhibits T cell activation
:Pharmacokinetics
Cyclosporine absorption is incomplete and some what erratic,
although a new microemulsion formulation improves its
. consistency and provides 20-30% bioavailability
.More recently, the salt mycophenolate sodium has also been introduced
:Mechanism of action
MMF is converted to mycophenolic acid, the active form of the drug. The
active product inhibits cytosine monophosphate dehydrogenase and,
secondarily, inhibits T cell lymphocyte proliferation; downstream it interferes
with leukocyte adhesion to endothelial cells through inhibition of E-selectin, P.selectin, and intercellular adhesion molecule 1
:Pharmacokinetics
Mycophenolate is derived from the fungus Penicillum stoloniferum.
Mycophenolate mofetil is metabolized in the liver to its active moiety
mycophenolic acid. It inhibits inosine monophosphate dehydrogenase, the
enzyme that controls the rate of synthesis of guanine monophosphate in the
denovo pathway of purine synthesis used in the proliferation of B and T
.lymphocytes
. transplantation in adults
Mycophenolate sodium has also been used for the prevention of rejection in
liver, heart, and/or lung transplant. It is also utilized as a steroid sparing
treatment in immune-mediated disorders including immunoglobulin A
.nephropathy, small vessel vasculitides, and psoriases
Its increasing application in treating lupus nephritis has demonstrated more
frequent complete response and less frequent complications compared to
cyclophosphamide bolus therapy, a regimen with risk of bone marrow
. suppression, infertility, and malignancy
:Side effects
The most common side effects with mycophenolate include upset stomach,
nausea, vomiting or diarrhea. Other possible side effects include headache,
dizziness, difficulty sleeping, tremor and, occasionally, rash. These side effects
.usually go away with time, but tell a doctor if they persist
Less common but more serious side effects include a reduction of white blood
cells (increasing the chances of infections), red blood cells that ferry oxygen to
tissues (which may lead to anemia), and platelets that aid clotting (which can lead
to gastrointestinal bleeding). Periodic blood tests can detect reduced blood counts
.early on to avoid these problems
Patients older than 65 may be at increased risk for some side effects, especially
infections and gastrointestinal bleeding. People who have had ulcers or other
serious gastrointestinal conditions should talk with their doctors before taking this
.medication
Prednisone
:Mechanism of action
Glucocorticoids are naturally occurring hormones that prevent or suppress
inflammation and immune responses when administered at pharmacological
doses. At a molecular level, unbound glucocorticoids readily cross cell
membranes and bind with high affinity to specific cytoplasmic receptors. This
binding induces a response by modifying transcription and, ultimately protein
.synthesis to achieve the steroid's intended action
Such actions may include: inhibition of leukocyte infiltration at the site of
inflammation, interference in the function of mediators of inflammatory
response, and suppression of humeral immune responses. Some of the net
effects include reduction in edema or scar tissue, as well as a general
suppression in immune response. The degree of clinical effect is normally
. related to the dose administered
The anti-inflammatory actions of corticosteroids are thought to involve
phospholipase A2 inhibitory proteins, collectively called lipocortins.
Lipocortins, in turn, control the biosynthesis of potent mediators of
inflammation such as prostaglandins and leukotrienes by inhibiting the release
of the precursor molecule arachidonic acid. Likewise, the numerous adverse
effectsrelated to corticosteroid use are usually related to the dose
. administered and the duration of therapy
:Pharmacokinetics
Prednisone is rapidly absorbed across the GI membrane following oral
administration. Peak effects can be observed after 12 hours. The
circulating drug binds extensively to the plasma proteins albumin and
. transcortin, with only the unbound portion of a dose active
Systemic prednisone is quickly distributed into the kidneys, intestines,
skin, liver and muscle. Corticosteroids distribute into the breast milk
and cross the placenta. Prednisone is metabolized by the liver to the
active metabolite prednisolone, which is then further metabolized to
. inactive compounds
These inactive metabolites, as well as a small portion of unchanged
drug, are excreted in the urine. The plasma elimination half-life is 1
hour whereas the biological half-life of prednisone is 1836 hours
:Indications
Endocrine disorders: primary or secondary adrenocortical
insufficiency (hydrocortisone or cortisone is the first choice; synthetic
analogs may be used in conjunction with mineralocorticoids where
applicable; in infancy mineralo-corticoid supplementation is of
particular importance); congenital adrenal hyperplasia; hypercalcemia
. associated with cancer; non-suppurative thyroiditis
:Contraindications/precautions
abrupt discontinuation
breast-feeding
cataracts
children
coagulopathy
Cushing's syndrome
diabetes mellitus
diverticulitis
fungal infection
GI disease
glaucoma
heart failure
hepatic disease
herpes infection
hypertension
hypothyroidism
infection
inflammatory bowel disease
measles
myasthenia gravis
myocardial infarction
osteoporosis
peptic ulcer disease
psychosis
renal disease
seizure disorder
surgery
thromboembolic disease
tuberculosis
ulcerative colitis
vaccination
varicella
viral infection
visual disturbance
Absolute contraindications are in italics
:Side effects
abdominal pain
acne vulgaris
adrenocortical insufficiency
amenorrhea
angioedema
anorexia
anxiety
appetite stimulation
arthralgia
avascular necrosis
bone fractures
cataracts
constipation
Cushing's syndrome
depression
diabetes mellitus
diaphoresis
diarrhea
dysmenorrhea
ecchymosis
edema
EEG changes
emotional lability
erythema
esophageal ulceration
euphoria
exfoliative dermatitis
exophthalmos
fever
fluid retention
gastritis
growth inhibition
headache
heart failure
hirsutism
hypercholesterolemia
hyperglycemia
hypernatremia
hypertension
hypocalcemia
hypokalemia
hypotension
(HPA) suppression
immunosuppression
impaired wound healing
increased intracranial pressure
infection
insomnia
lethargy
menstrual irregularity
metabolic alkalosis
mood lability
myalgia
myopathy
nausea/vomiting
ocular hypertension
optic neuritis
osteoporosis
palpitations
pancreatitis
papilledema
peptic ulcer
peripheral neuropathy
petechiae
phlebitis
physiological dependence
pseudotumor cerebri
psychosis
restlessness
retinopathy
seizures
sinus tachycardia
skin atrophy
sodium retention
striae
thrombocytopenia
thromboembolism
thrombosis
urinary incontinence
urinary urgency
urticaria
vertigo
visual impairment
weakness
weight gain
weight loss
withdrawal
Thank you
Done by: Hatem AL-Nasser