INTRODUCTION:

Vasopressin is a antidiuretic hormone (ADH) that is synthesized in hypothalamic supraoptic and paraventricular nuclei and released by posterior pituitary along with oxytocin. Vasopressin is a nonapeptide and between cysteine residues it has a disulfide bridge. Antidiuretic and vasopressor actions like glycogenolysis have carried by this bridge. Conservation of body water and reduce the loss of water through urine is the main physiological action of antidiuretic hormone. Furthermore, the osmolarity of urine is maintained by ADH. There are some receptors which are present in hypothalamus, regulate the amount of ADH which has to be released and these receptors are known as osmoreceptors. If the changes are occur in the osmotic pressure of plasma, osmoreceptor’s cells sense them and produce response. The low pressure and the arterial receptor and the high pressure and arterial baroreceptor are also believed to participate in reflex control of arginine vasopressin (AVP) and also in renin secretion. A negative feedback loop control the amount of ADH which has to be released. ADH act in the kidney and regulate the volume and osmolarity of urine after releasing from posterior pituitary. DCT (distal convoluted tubule) and CT (collecting duct) are the two sites that are present in kidneys on which the ADH shows its action. [1-5]

ADH RECEPTORS:

ADH receptors have two sub types which are G protein couple receptors are as follows:

· V1 receptor: - function exert mainly via phospholipase C-IP3/DAG Pathway.

V1a:-It is present in vascular smooth muscles and cortical cells of kidney.

V1b:- Localized in:- interior pituitary, certain area in brain and pancreas.

· V2 receptor :-present on the principle cells of collecting duct (CDs),

Endothelium of blood vessels,

TAL (thin ascending limb). [6]

ROLE OF VASOPRESSIN AND ITS ANALOUGE IN DIABETES INSIPIDUS(DI):

when our body is not able to balance the body’s fluid level properly then there is an uncommon disorder occur in our body which is called as diabetes insipidus.[7] Diabetes insipidus is defined as the passage of large volume (3L/24hrs) of dilute urine (<300mOsm/kg). A hormone which is known as antidiuretic hormone or vasopressin, helps to control the amount of fluid to be secreted. How fast or slow fluid are excreted from the body is regulated by this hormone. If we have diabetes insipidus our body can’t balance body fluid level properly. The cause of DI various depending upon the type of diabetes insipidus we have:

(a) Central DI: It occurs when pituitary or/and hypothalamus are damages due to surgery, a tumor, a head injury or an illness. It cause central DI by affecting the usual production, storage and release of ADH.

(b) Nephrogenic DI: It occurs due to the defect in the kidney tubule. our kidneys unable to response properly to ADH due to this effect.

(c) Gestational DI:It is rare and occur only during pregnancy. In this an enzyme which is made by the placenta destroyed ADH in the mother.[7]

So in central DI there is a lack of vasopressin because a part of hypothalamus or pituitary is distructed. The nephrogenic DI there is a resistance of the kidney to vasopressin’s action. Due to which clinically, the vast quantity of dilute urine is produced by the patient.So vasopressin word via V1 receptor and reduced portal blood flow, total systemic collateral blood flow, and variceal blood pressure. Terlipressin which is a prodrug of vasopressin is commonly used.[8]

HISTORYOF DI:

In the early 20^th century it was recognized that posterior pituitary had two great hormones that are vasopressin and oxytocin from which vasopressin is responsible for maintaining body fluid osmolarity. Deficiency of this hormone lead to a disease called diabetes insipidus.[9]

In 1913, Farini and Van den Velden were the first who was first used vasopressin to treat central DI, by using pituitary extracts which contain oxytocin and vasopressin.[10] it was the first succesfull for a peptide hormone deficiency. Their patients responded with decrease urine output, increase urine osmolality, and reduced thirst[9]. Pitressin(vasopressin tannate in oil) become available for clinical use in 1930s. The year 2013 marked the 100^th anniversary of vasopressin treatment for DI. It was the principle drug almost until the 1970s when desmopressin was introduced for the treatment of DI. There are various synthetic vasopressin analogs at present. After the development of vasopressin analogs which have longer half life and have great receptor specificity enhance the practical application of vasopressin therapy. At present the only clinically used vasopressin analogs are Terlipressin (TB) and desmopressin (DDAVP) [10].

DIABETES INSIPIDUS Vs DIABETES MELLITUS:

Diabetes and diabetes mellitus share the same symptoms like excessive urination and extreme thirst, tiredness, weakness but these symptoms have different causes. For example, when we have diabetes insipidus we may feel extremely tired due to dehydration [1] but in diabetes mellitus we feel tired due to very low or high blood glucose level.[11]

Diabetes insipidus is caused by problem with hormones known as vasopressin which is responsible for maintaining the fluid volume in body. It is characterized by the inability of kidney to conserve water. It can be generally treated by desmopressin and vasopressin pills and low salt intake in diet should be advised.[1] Diabetes insipidus is a rare disease and the incidence is only about 3 in 100,000.[12] Diabetes mellitus is a very common disease caused by a problem with another hormone known as Insulin and it is characterized by high blood sugar level.[11] It is common and its incidence is 770 in 100,000.[12]

PATHOPHYSIOLOGY OF DI:

Fig:-1.1 (Path Physiology of DI) [13]

NEPHROGENIC DI:

· lack of aquaporin channel in the distal duct

· Inability of nephron to respond to ADH.

· As a result kidney in insensitive to vasopressin.

· Kidney tubules fails to reabsorb water

· Large amount of dilute urine excreted

· Diabetes insipidus occur[14]

CENTRAL DI :

· Loss of vasopressin producing cells

· Causing deficiency of ADH synthesis or release

· Deficiency in ADH resulting in an ability to conserve water

· Leading to extreme polyurea and polydipsia[15]

SIGN AND SYMPTOMS OF DI:

The symptoms of diabetes insipidus include:

· Extreme thirst (polydipsia)

· Excessive amount of urine (polyuria)

· Colourless urine

· Dry skin

· Weak muscles

· Fatigue

· Tiredness [16]

MECHANISM OF ACTION

Fig: - 1.2 (Mechanism of ADH) [17]

Vasopressin is instrumental in rapid adjustments of water excretion according to the state of body hydration, as well as in dealing with conditions prevailing over long term. The v2 subtype of ADH receptors are present in the basolateral membrane of principle cell in collecting duct (CDs).activation of these receptors increase cAMP formation intracellularà activation of cAMP dependent protein kinase Aàphosphorylation of relevant proteins which promoted exocytosis of aquaporin-2 water channel containing vesicles (WCVs) through the apical membrane àmore aqueous channel gets inserted into the apicle membrane.

The rate of endocytosis and degradation of WCVs is concurrently reduced. The water permeability of CD cell is increased in proportion to the population of aquaporin-2cahnnel in the apical membrane at any given time. Continued V2 receptor stimulation in addition upregulated aquaporin-2 synthesis through cAMP respond element of the gene encoding aquaporin-2.[1]

MEDICATION:

The following list of medications that are used in the treatment of this condition.

· Hydrochlorothiazide [18]

· Desmopressin(2gm i.m).[19] it is a synthetic analogue of AVP with a potent antidiuretic activity

· Microzide [20]

· Minirin

· Vasopressin(5-10 uniti.m/sc)[19]

· DDAVP nasal[21]

· Carbamazepine

· 4- antilipidemic agents

· Chlorpropamide.

· Chlorthalidone [22]

· DDAVP rhinal tube[19]

Hormone deficiency is the primary cause of central DI so we can replace it with desmopressin. If response is not complete then nonhormonal drug are usually effective.

DIAGNOSIS TESTFORDI.:

· Water deprivation test

· Magnetic resonance imaging(MRI)

· Genetic screening[22]

ADVERSE/SIDE EFFECT OF VASOPRESSIN AND DESMOPRESIN:

Desmopressin produced fewer adverse effect than vasopressin. However transient flushing and headache are minor adverse effect of desmopressin.[24]

Local side effects are:

· Nasal irritation

· Congestion

· Rhinitis

· Anaphylaxis

· Erythema

Systemic side effects are:

· Tremors

· Vertigo

· Nausea

· Abdominal cramps

· Pallor

· Backache in female

· fluid retention and hyponatremia may develop[22]

CONTRAINDICATIONS:-

· Desmopressin: contraindicated in hypersensitivity.

· Vasopressin: contraindicated in hypersensitivity, hypertension, angina, coronary artery disease.

· Chlorpropamide: contraindicated during severe renal or hepatic impairment, type-1 diabetes, thyroid dysfunction.

· Carbamazepine: contraindicated in history of bone marrow suppression.[23]

CONCLUSION:

Diabetes insipidus may result from impaired synthesis and release of vasopressin from the hypothalamic-pituitary unit (neurogenic DI) or renal insensitivity to circulating vasopressin (nephrogenic DI)[24]. Here we review the role of desmopressin and vasopressin in DI.

Vasopressin is a homeostatic neuroendocrine hormone whose major role is to maintain plasma osmolality [25]. It helps to control how fast or slow fluid are excreted [7].

The management of central diabetes insipidus has been greatly simplified when desmopressin(DDAVP) was introduced. Desmopressin proves to be the preparation of choice for all V2 receptor related indication. It is easy to administration and it has a great safety and tolerability which make DDAVP the first line agent for treatment of central diabetes insipidus. Sodesmopressin continues to be valuable drug after many years since the introduction and provides an effective therapeutic option for diabetes insipidus.[26]

ACKNOWLEDGEMENT:

I would like to express my special thanks of gratitude to my guide “Miss Neha Kumari” for their able guidance and support in completing my article. I would like to extend my gratitude to the Principal of “Sri Sai college of Pharmacy” for providing me with all the facility that was required.

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Received on 05.05.2020 Accepted on 09.06.2020

Int. J. Tech. 2020; 10(1):7-12.

DOI: 10.5958/2231-3915.2020.00002.4