Reserpine

(BAN, rINN)
Reserpine Chemical formula
Synonyms: Reserpiini; Reserpin; Reserpina; Réserpine; Reserpinum; Reszerpin; Rezerpin; Rezerpina; Rezerpinas. Methyl 11,17 oxy-18 carboxylate; Methyl O-(3,4,5-trimethoxybenzoyl)reserpate.
Cyrillic synonym: Резерпин.

💊 Chemical information

Chemical formula: C33H40N2O9 = 608.7.
CAS — 50-55-5.
ATC — C02AA02.
ATC Vet — QC02AA02.

Pharmacopoeias.

In Chin., Eur., Int., Jpn, US, and Viet.

Ph. Eur. 6.2

(Reserpine). It occurs as small, white to slightly yellow crystals or a crystalline powder. It darkens slowly on exposure to light. Practically insoluble in water; very slightly soluble in alcohol. Protect from light.

USP 31

(Reserpine). A white or pale buff to slightly yellowish, odourless, crystalline powder. It darkens slowly on exposure to light, but more rapidly when in solution. Insoluble in water; soluble 1 in 1800 of alcohol and 1 in 6 of chloroform; freely soluble in acetic acid; very slightly soluble in ether; slightly soluble in benzene. Store in airtight containers at a temperature of 25°, excursions permitted between 15° and 30°. Protect from light.

Stability.

Reserpine is unstable in the presence of alkalis, particularly when the drug is in solution.

💊 Adverse Effects

Adverse effects commonly include nasal congestion, headache and CNS symptoms including depression, drowsiness, dizziness, lethargy, nightmares, and symptoms of increased gastrointestinal tract motility including diarrhoea, abdominal cramps, and, at higher doses, increased gastric acid secretion. Respiratory distress, cyanosis, anorexia, and lethargy may occur in infants whose mothers have taken reserpine before delivery. Higher doses may cause flushing, bradycardia, severe depression which may lead to suicide, and extrapyramidal effects. Hypotension, coma, convulsions, respiratory depression, and hypothermia also occur in overdosage. Hypotension is also more common in patients after a cerebrovascular accident. Breast engorgement and galactorrhoea, gynaecomastia, increased prolactin concentrations, decreased libido, impotence, sodium retention, oedema, decreased or increased appetite, weight gain, miosis, dry mouth, sialorrhoea, dysuria, rashes, pruritus, and thrombocytopenic purpura have also been reported. Large doses of reserpine have been shown to be tumorigenic in rodents. Several reports have suggested an association between reserpine and the development of neoplasms of the breast (see below) but other surveys have failed to confirm this.

Neoplasms of the breast.

Although early studies suggested that the incidence of breast cancer was up to 3 to 4 times greater in hypertensive women treated with rauwolfia preparations than in control groups, analysis1 of both prospective trials and casecontrol studies found only a low-grade association between use of rauwolfia preparations and risk of malignancy.
1. Grossman E, et al. Antihypertensive therapy and the risk of malignancies. Eur Heart J 2001; 22: 1343–52.

💊 Treatment of Adverse Effects

Withdrawal of reserpine or reduction of the dosage causes the reversal of many adverse effects although mental disorders may persist for months and hypotensive effects may persist for weeks after the cessation of treatment. If overdosage occurs activated charcoal may be considered within 1 hour of ingestion. Treatment is generally supportive and symptomatic. Severe hypotension may respond to placing the patient in the supine position with the feet raised. Direct-acting sympathomimetics may be effective for treatment of severe hypotension, but should be given with caution. The patient must be observed for at least 72 hours.

💊 Precautions

Reserpine should not be used in patients with depression or a history of depression, with active peptic ulcer disease or ulcerative colitis, or in patients with Parkinson’s disease. It should also be avoided in phaeochromocytoma. It should be used with caution in debilitated or elderly patients, and in the presence of cardiac arrhythmias, myocardial infarction, renal insufficiency, gallstones, epilepsy, or allergic conditions such as bronchial asthma. Reserpine is contra-indicated in patients having ECT and an interval of at least 7 to 14 days should be allowed between the last dose of reserpine and the start of any ECT. It is probably not necessary to stop reserpine during anaesthesia, although the effects of CNS depressants may be enhanced by reserpine.

💊 Interactions

Patients taking reserpine may be hypersensitive to adrenaline and other direct-acting sympathomimetics, which should not be given except to antagonise reserpine. The effects of indirect-acting sympathomimetics such as ephedrine may be decreased by reserpine. The hypotensive effects of reserpine are enhanced by thiazide diuretics and other antihypertensives. Reserpine may cause excitation and hypertension in patients receiving MAOIs. Use of digitalis or quinidine with reserpine may cause cardiac arrhythmias. Reserpine may enhance the effects of CNS depressants.

Antiparkinsonian drugs.

For the inhibitory effect of reserpine on the antiparkinsonian actions of levodopa, see Antihypertensives.

💊 Pharmacokinetics

Reserpine is absorbed from the gastrointestinal tract with a bioavailability of 50%. It is extensively metabolised and is excreted slowly in the urine and faeces. In the first 4 days, about 8% is excreted in the urine, mainly as metabolites, and about 60% in the faeces, mainly unchanged. Reserpine crosses the placenta and the blood-brain barrier and also appears in breast milk.

💊 Uses and Administration

Reserpine is an alkaloid obtained from the roots of certain species of Rauwolfia (Apocynaceae), mainly Rauwolfia serpentina and R. vomitoria, or by synthesis. The material obtained from natural sources may contain closely related alkaloids. Reserpine is an antihypertensive drug that causes depletion of noradrenaline stores in peripheral sympathetic nerve terminals and depletion of catecholamine and serotonin stores in the brain, heart, and many other organs resulting in a reduction in blood pressure, bradycardia, and CNS depression. The hypotensive effect is mainly due to a reduction in cardiac output and a reduction in peripheral resistance. Cardiovascular reflexes are partially inhibited, but orthostatic hypotension is rarely a problem at the doses used in hypertension. When given orally the full effect is only reached after several weeks of treatment and persists for up to 6 weeks after treatment is stopped. Reserpine has been used in the management of hypertension and in chronic psychoses such as schizophrenia. It has also been used in the treatment of Raynaud’s syndrome. In hypertension, reserpine may be given orally in an initial dose of up to 500 micrograms daily for about 2 weeks, subsequently reduced to the lowest dose necessary to maintain the response; some sources recommend an initial dose of 50 to 100 micrograms. A maintenance dose of about 100 to 250 micrograms daily may be adequate and 500 micrograms should not normally be exceeded. To reduce adverse effects and tolerance smaller doses of reserpine may be used with a thiazide diuretic. Reserpine has been used in chronic psychoses in daily doses of up to 1 mg.

💊 Preparations

USP 31: Reserpine and Chlorothiazide Tablets; Reserpine and Hydrochlorothiazide Tablets; Reserpine Elixir; Reserpine Injection; Reserpine Tablets; Reserpine, Hydralazine Hydrochloride, and Hydrochlorothiazide Tablets.

Proprietary Preparations

Braz.: Ortoserpina†; Indon.: Resapin; Serpasil; Port.: Serfinato†. Multi-ingredient: Arg.: Hygroton-Reserpina†; Normatensil†; Austria: Brinerdin; Darebon; Braz.: Adelfan-Esidrex†; Higroton Reserpina; Id Sedin†; Vagoplex†; Cz.: Crystepin; Neocrystepin; Fr.: Tensionorme; Ger.: Adelphan-Esidrix†; Barotonal†; Bendigon N†; Briserin N; Darebon†; Disalpin†; Durotan†; Modenol†; Tri-Thiazid Reserpin†; Triniton; Gr.: Hygroton-Reserpine; Neourizine; Hong Kong: Adelphane-Esidrex; India: Adelphane; Adelphane-Esidrex; Indon.: Dellasidrex; Ser-Ap-Es; Ital.: Brinerdina; Igroton-Reserpina; Mex.: Higroton-Res; Pol.: Normatens; Port.: Brinerdine†; Rus.: Adelphane-Esidrex (Адельфан-эзидрекс); Crystepin (Кристепин); Triresid K (Трирезид К); S.Afr.: Brinerdin; Hygroton-Reserpine†; Protensin-M; Spain: Adelfan-Esidrex†; Brinerdina†; Higrotona Reserpina†; Tensiocomplet; Switz.: Adelphan-Esidrex; Brinerdine; HygrotonReserpine; Thai.: Bedin; Brinerdin; Hydrares; Hyperdine†; Hypery†; IsoTriraupin†; Mano-Ap-Es; Medeserpine Co†; Reser; Ser-Ap-Es; Turk.: Adelphan; Adelphan-Esidrex; Regroton; USA: Demi-Regroton; Diupres; Diutensen-R†; Hydrap-ES†; Hydro-Serp†; Hydropres; Hydroserpine†; Marpres; Metatensin†; Regroton; Renese R†; Salutensin†; Ser-Ap-Es†; TriHydroserpine†.
Published May 08, 2019.