indication

Oral formulations may be used to manage primary nocturnal enuresis in adults and vasopressin sensitive diabetes insipidus, and for control of temporary polyuria and polydipsia following head trauma or surgery in the pituitary region. Intranasal and parenteral formulations may be used to manage spontaneous or trauma-induced bleeds (e.g. hemarthrosis, intramuscular hematoma, mucosal bleeding) in patients with hemophilia A or von Willebrand's disease Type I. May also be used parenterally to prevent or treat bleeding in patients with uremia.

pharmacology

Desmopressin is a synthetic analogue of the natural antidiuretic hormone (ADH or vasopressin) that is produced by the hypothalamus and stored in the posterior pituitary gland. The main function of ADH is to regulate extracellular fluid volume in the body. ADH secretion is stimulated by angiotensin II, linking it to the renin-angiotensin-aldosterone system (RAAS). ADH stimulates water reabsorption in the kidneys by causing the insertion of aquaporin-2 channels on the apical surface of cells of the DCT and collecting tubules. It also causes vasoconstriction through its action on vascular smooth muscle cells of the collecting tubules. The efficacy of desmopressin for managing bleeds in patients with hemophilia A or von Willebrand’s disease Type I arises from its ability to elicit dose-dependent increases in plasma factor VIII (antihemophilic factor), plasminogen activator, and to a lesser extent, factor VIII-related antigen and ristocetin cofactor activities; these changes improve blood clotting.

mechanism of action

Desmopressin emulates the actions of endogenous human ADH (refer to Pharmacology section above). Desmpressin is a structural analogue of ADH modified by deamination of 1-cysteine and substitution of 8-L-arginine by 8-D-arginine. Compared to natural ADH, desmopressin elicits a great antidiuretic response on weight basis.

toxicity

Overdose may lead to increased duration of action and lead to symptoms such as fluid retention, headaches, abdominal cramps, nausea, and facial flushing. Adverse effects include headache, nausea, abdominal pain, facial flushing, dizziness, dry mouth, and hyponatremia. Nasal congestion and rhinitis have been reported with nasal spray formulations.

biotransformation

Metabolic fate unknown. Is not affected by liver microsomal cytochrome P450 enzymes.

absorption

Minimally absorbed from the GI tract (average absolute bioavailability = 0.08-0.16%). 10-20% absorbed from nasal mucosa.

half life

Oral t_1/2=1.5-2.5 hours. Intranasal t_1/2=3.3-3.5 hours. IV t_1/2 is biphasic: initial t_1/2=7.8 minutes, terminal t_1/2=0.4-4 hours.