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Diabetes Insipidus
What is the difference between diabetes insipidus and diabetes mellitus ?
DI should not be confused with diabetes mellitus (DM), DI and DM are unrelated, although they can have similar signs and symptoms, like excessive thirst and excessive urination.
, .

Diabetes Mellitus (blood sugar)

results from insulin deficiency or resistance leading to high blood glucose More common &receives more news coverage has two main forms, type 1 diabetes and type 2 diabetes. lower urine volume & high concentrated

Diabetes Insipidus
Other causes as below Less common ,receives less news coverage a different form of illness altogether. Higher urine volume & less concentrated.

How is fluid in the body normally regulated?

1- For balanced volume and composition of body fluids. The kidneys remove extra body fluids from the bloodstream. 2-These fluids are stored in the bladder as urine. Normally , the kidneys make less urine to conserve fluid when water intake is decreased or water is lost, for ex:( sweating or diarrhea). The kidneys also make less urine at night when the body's metabolic processes are slower. 3-The rate of fluid intake is governed by thirst, and the rate of excretion is governed by the production of antidiuretic hormone (ADH), also called vasopressin. 4-This hormone is made in the hypothalamus , a small gland located in the brain. ADH is stored in the nearby pituitary gland and released into the bloodstream when necessary. When ADH reaches the kidneys, it directs them to concentrate the urine by reabsorbing some of the filtered water to the bloodstream and therefore make less urine.

*this material is free to be used in any educational procedure, downloaded , copied or shared once used without any content modification .* 5- DI occurs when this precise system for regulating the kidneys' handling of fluids is disrupted.

Symptoms:
1- frequent urination even at night, which can disrupt sleep and, on occasion, cause bedwetting . 2-The large volume of urine is diluted, mostly water . 3-To make up for lost water, patient may feel thirst . 4-dehydration if they do not drink enough water. 5- Children with DI may be irritable or listless and may have fever, vomiting, or diarrhea.

Types of Diabetes Insipidus D.I.: (4types) Central DI (Neurogenic) Nephrogenic DI Dipsogenic DI

by a defect in or damage to the thirst mechanism, which is located in the hypothalamus. This defect results in an abnormal increase in thirst and fluid intake that suppresses ADH secretion and increases urine output.

Gestation al DI
occurs only during pregnancy and results when an enzyme made by the placenta destroys ADH in the mother. The placenta is the system of blood vessels and other tissue that develops with the fetus. The placenta allows exchange of nutrients and waste products

Causes

The most common form of serious DI.

It results from damage to the pituitary gland or hypothalamus, which disrupts the normal storage and release of ADH that caused by different diseases as well as by ( head injuries, neurosurgery, or genetic disorders).

results when the kidneys are unable to respond to ADH. The kidneys' ability to respond to ADH , can be impaired : -by drugs-like lithium , for example. - by chronic disorders including polycystic kidney disease, sickle cell disease, kidney failure, partial blockage of the ureters, chronic renal insufficiency , and inherited genetic disorders. -Sometimes the cause of nephrogenic DI is never discovered.

*this material is free to be used in any educational procedure, downloaded , copied or shared once used without any content modification .* between mother and fetus.

Diagno ses

Because DM is more common and because DM and DI have similar symptoms, a health care provider may suspect that a patient with DI has DM. But testing should make the diagnosis clear. A doctor must determine which type of DI is involved before proper treatment can begin. Diagnosis is based on a series of tests, including urinalysis and a fluid deprivation test. 1-Urinalysis: is the physical and chemical examination of urine. -The urine of a person with DI will be less concentrated( the salt and waste concentrations are low and the amount of water excreted is high). - A physician evaluates the concentration of urine by measuring how many particles are in a kilogram of water or by comparing the weight of the urine with an equal volume of distilled water. 2-A fluid deprivation test helps determine whether DI is caused by one of the following: excessive intake of fluid a defect in ADH production a defect in the kidneys' response to ADH This test measures changes in body weight, urine output, and urine composition when fluids are withheld. Sometimes measuring blood levels of ADH during this test is also necessary. In some patients, a magnetic resonance imaging (MRI) of the brain may be necessary as well.

Note:
1 000,52 , , , : Familial diabetes insipidus autosomal dominant disorder.

Treatment:
NB:Milder forms of DI can be managed by drinking enough water, usually between 2 and 2.5 liters a day. DI
severe enough to endanger a person's health is rare.

Central D.I.
Desmopressin
synthetic hormone) : (a

Nephrogenic D.I.
Desmopressin will not work for this form of DI.

Hydrochlorothiazide (HCTZ):

Indomethacin

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Overview:
can be taken by (an injection, a nasal spray, or a pill),It is a synthetic replacement for vasopressin. While taking desmopressin, a person should drink fluids only when thirsty and not at other times. The drug prevents water excretion, and water can build up now that the kidneys are making less urine and are less responsive to changes in body fluids.

(Microzide)
Overview:
It is a first-line diuretic drug of the

Overview:
is a non-steroidal antiinflammatory drug commonly used to reduce fever,pain, stiffness, and swelling. It works by inhibiting the production of prostaglandins, molecules known to cause these symptoms.

thiazide class that acts by inhibiting the kidneys' ability to retain water, this reduces the blood volume, decreasing blood return to the heart and thus cardiac output and, by other mechanisms, is believed to lower peripheral vascular resistance. It is a calcium-sparing diuretic,

Mechamism of action:
Indomethacin is a nonselective inhibitor of cyclooxygenase (COX) 1 and 2, enzymes that participate in prostaglandin synthesis from arachidonic acid. Prostaglandins are hormone-like molecules normally found in the body, where they have a wide variety of effects, some of which lead to pain, fever, and inflammation. Prostaglandins also cause uterine contractions in pregnant women. Indomethacin is an effective tocolytic agent, able to delay premature labor by reducing uterine contractions through inhibition of PG synthesis in the uterus and possibly through calcium channel blockade. Indomethacin has two additional modes of actions with clinical importance: It inhibits motility of polymorphonuclear leukocytes, similar to colchicine. It uncouples oxidative phosphorylation in cartilaginous (and hepatic) mitochondria, like salicylates.

Mechanism of action:
It works by limiting the amount of water that is eliminated in the urine. Desmopressin binds to V2 receptors in renal collecting ducts, increasing water reabsorption. It also stimulates release of von Willebrand factor from endothelial cells due to stimulation of the V1a receptor. Desmopressin is degraded more slowly than recombinant vasopressin, and requires less frequent administration. In addition, it has little effect on blood pressure, while vasopressin may cause arterial hypertension.

Mechanism of action:
acting on the kidneys to reduce sodium (Na) reabsorption in the distal convoluted tubule. The major site of action in the nephron appears on an electroneutral Na+-Cl- co-transporter by competing for the chloride site on the transporter. By impairing Na transport in the distal convoluted tubule, hydrochlorothiazide induces a natriuresis and concomitant water loss. Thiazides increase the reabsorption of calcium in this segment in a manner unrelated to sodium transport.

Side effects:
-Emergency Cases: Allergic reaction to hydrochlorothiazide: shivers; difficulty breathing; swelling of face, lips, tongue, or throat. -Serious side effects that need immediate stop of drug: eye pain, vision problems; dry mouth, thirst, nausea, vomiting;

Side effects:
headaches facial flushing nausea hyponatremia seizures

*this material is free to be used in any educational procedure, downloaded , copied or shared once used without any content modification .* feeling weak, drowsy, These additional effects account restless, or light-headed; as well for the analgesic and the fast or uneven anti-inflammatory properties. heartbeat; Indomethacin readily crosses the muscle pain or placenta and can reduce fetal weakness; urine production to treat numbness or tingly polyhydramnios. It does so by feeling; reducing renal blood flow and a red, blistering, increasing renal vascular peeling skin rash; or resistance, possibly by enhancing nausea, stomach the effects of vasopressin on the pain, low fever, loss of fetal kidneys. appetite, dark urine, claySide effects: colored stools, jaundice -Emergency Cases: (yellowing of the skin or eyes). hives; difficulty breathing; swelling -Less serious hydrochlorothiazide of your face, lips, tongue, or side effects may include: throat. diarrhea; -Serious side effects that need mild stomach pain; immediate stop of drug: constipation; or chest pain, weakness, blurred vision. shortness of breath, slurred speech, problems with vision or balance; black, bloody, or tarry stools; coughing up blood or vomit that looks like coffee grounds; swelling

Minirin 10mcg/dose Nasal solution

Hydretic 12.5 mg/Tab

Indomethacin 25&50mg caps

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Liometacen

Hydrozide 25 mg/Tab Minirin 100 mcg tablets

Moduretic (Amiloride 5mg + Hydrochlorothiazide 50mg )tab

NB: with this combination of drugs, one should drink fluids only when thirsty and not at other times

Dipsogenic DI

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Desmopressin or other drugs should not be used to treat dipsogenic DI because they may decrease urine output but not thirst and fluid intake. This fluid overload can lead to water intoxication, a condition that lowers the concentration of sodium in the blood and can seriously damage the brain. Scientists have not yet found an effective treatment for dipsogenic DI.

Gestational DI
Most cases of gestational DI can be treated with desmopressin. In rare cases, however, an abnormality in the thirst mechanism causes gestational DI, and desmopressin should not be used.

References:
http://kidney.niddk.nih.gov/kudiseases/pubs/insipidus/ http://en.wikipedia.org/wiki/Desmopressin http://www.usermeds.com/medications/ddavp http://en.wikipedia.org/wiki/Hydrochlorothiazide http://en.wikipedia.org/wiki/Indometacin http://www.rxlist.com/indocin-drug.htm http://www.arabrxlist.com/en/drug-index/list-alpha/i/6 http://psc1948.yoo7.com/t751-topic