Page 696 - Basic _ Clinical Pharmacology ( PDFDrive )

682 SECTION VII Endocrine Drugs

15 minutes, with renal and hepatic metabolism via reduction of bleeding. High-dose vasopressin as a 40-unit intravenous bolus
the disulfide bond and peptide cleavage. injection may be given to replace epinephrine in the Advanced
Desmopressin can be administered intravenously, subcutane- Cardiovascular Life Support (ACLS) resuscitation protocol for
ously, intranasally, or orally. The half-life of circulating desmo- pulseless arrest.
pressin is 1.5–2.5 hours. Nasal desmopressin is available as a unit Desmopressin is also used for the treatment of coagulopathy in
dose spray that delivers 10 mcg per spray; it is also available with hemophilia A and von Willebrand disease (see Chapter 34).
a calibrated nasal tube that can be used to deliver a more precise
dose. Nasal bioavailability of desmopressin is 3–4%, whereas oral Toxicity & Contraindications
bioavailability is less than 1%.
Headache, nausea, abdominal cramps, agitation, and allergic reac-
Pharmacodynamics tions occur rarely. Overdosage can result in hyponatremia and
seizures.
Vasopressin activates two subtypes of G protein–coupled recep- Vasopressin (but not desmopressin) can cause vasoconstriction
tors (see Chapter 17). V receptors are found on vascular smooth and should be used cautiously in patients with coronary artery
1
muscle cells and mediate vasoconstriction via the coupling protein disease. Nasal insufflation of desmopressin may be less effective
G and phospholipase C. V receptors are found on renal tubule when nasal congestion is present.
2
q
cells and reduce diuresis through increased water permeability
and water resorption in the collecting tubules via G and adenylyl
s
cyclase. Extrarenal V -like receptors regulate the release of coagu- VASOPRESSIN ANTAGONISTS
2
lation factor VIII and von Willebrand factor, which increases
platelet aggregation. A group of nonpeptide antagonists of vasopressin receptors has
been investigated for use in patients with hyponatremia or acute
Clinical Pharmacology heart failure, which is often associated with elevated concentrations
of vasopressin. Conivaptan has high affinity for both V and V
1a
2
Vasopressin and desmopressin are treatments of choice for receptors. Tolvaptan has a 30-fold higher affinity for V than for
2
pituitary diabetes insipidus. The dosage of desmopressin is V receptors. In several clinical trials, both agents promoted the
1
10–40 mcg (0.1–0.4 mL) in two to three divided doses as a excretion of free water, relieved symptoms, and reduced objective
nasal spray or, as an oral tablet, 0.1–0.2 mg two to three times signs of hyponatremia and heart failure. Conivaptan, administered
daily. The dosage by injection is 1–4 mcg (0.25–1 mL) every intravenously, and tolvaptan, given orally, are approved by the
12–24 hours as needed for polyuria, polydipsia, or hypernatre- FDA for treatment of hyponatremia. Tolvaptan treatment dura-
mia. Bedtime desmopressin therapy, by intranasal or oral admin- tion is limited to 30 days due to risk of hepatotoxicity, including
istration, ameliorates nocturnal enuresis by decreasing nocturnal life-threatening liver failure. Several other nonselective nonpeptide
urine production. Vasopressin infusion is effective in some vasopressin receptor antagonists are being investigated for these
cases of esophageal variceal bleeding and colonic diverticular conditions (see Chapter 15).

SUMMARY Hypothalamic & Pituitary Hormones 1

Mechanism of Pharmacokinetics,
Subclass, Drug Action Effects Clinical Applications Toxicities, Interactions

GROWTH HORMONE (GH)
• Somatropin Recombinant form of Restores normal growth and Replacement in GH deficiency SC injection • Toxicity: Pseudotumor
human GH • acts metabolic GH effects in • increased final adult height in cerebri, slipped capital femoral
through GH receptors GH-deficient individuals children with certain conditions epiphysis, edema, hyperglycemia,
to increase production • increases final adult height associated with short stature (see progression of scoliosis, risk of
of IGF-I in some children with short Table 37–4) • wasting in HIV asphyxia in severely obese patients
stature not due to GH infection • short bowel syndrome with Prader-Willi syndrome and upper
deficiency airway obstruction or sleep apnea
IGF-I AGONIST
• Mecasermin Recombinant form of Improves growth and Replacement in IGF-I deficiency that SC injection • Toxicity: Hypoglycemia,
IGF-I that stimulates metabolic IGF-I effects in is not responsive to exogenous GH intracranial hypertension, increased
IGF-I receptors individuals with IGF-I liver enzymes
deficiency due to severe GH
resistance
(continued)