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Rauwolfia serpentina

Rauwolfia serpentina                               Common name: Indian Snakeroot            

Family: Apocynaceae

Part used: Root

Constituents: Indole Alkaloids (mainly reserpine)

Actions: Hypotensive

Medical uses: 

  • Behavioural and Psychological Conditions: Has been used in the symptomatic treatment of agitated psychotic states such as schizophrenic disorders. Although other antipsychotic agents have generally replaced the alkaloids, Rauwolfia alkaloids may be beneficial in some patients who cannot tolerate other antipsychotic agents or who also require antihypertensive therapy.
  • Cardiovascular Conditions: The main indication for Rauwolfia is in the management of mild to moderate hypertension as the alkaloids create a gentle hypotensive effect. Blood pressure will take 2-3 weeks to respond, but may return to pre-treatment levels several weeks after discontinuation. In the stepped-care approach to antihypertensive drug therapy, adrenergic inhibitors including Rauwolfia alkaloids generally are considered step 2 drugs and generally are reserved for patients who fail to respond to nondrug therapies and who fail to respond to therapy with a step 1 drug (e.g., diuretics, beta-adrenergic blocking agents, angiotensin-converting enzyme [ACE] inhibitors, alpha1-adrenergic blocking agents). Are generally most effective when used with a diuretic.
  • May be useful in the management of thyrotoxicosis

Pharmacology:

  • The precise mechanism of the hypotensive action  has not been established.
  • Alkaloids deplete catecholamine and serotonin stores in many organs, including the brain and adrenal medulla, and reduce uptake of catecholamines by adrenergic neurons. An increased sensitivity of the effector cells to catecholamines reportedly may result. 
  • With repeated doses, depletion of catecholamine stores occurs very slowly, resulting in a very gradual decrease in peripheral vascular resistance and blood pressure which is frequently associated with bradycardia. With prolonged therapy, venous dilation and peripheral pooling of blood reduce venous return to the heart and cause decreased cardiac output; a slight decrease in renal blood flow and glomerular filtration rate may result.
  • Alkaloids also produce a tranquilizing effect, apparently due to depletion of serotonin and catecholamines in the brain.
  • The onset and duration of pharmacologic effects do not appear to be related to alkaloid concentrations in the blood or brain.

Pharmacy:

  • Begin with small doses and increase gradually until there is a drop in blood pressure or side-effects develop (nasal congestion, diarrhea, depression).
  • A whole extract used in the powdered form is most desirable:  50-300 mg daily
  • The pure alkaloid reserpine is initially dosed at 0.5 mg daily for 1-2 weeks, which is then lowered to a maintenance dose of 0.1-0.25 mg daily.
  • The full effects of fixed oral doses of the drugs are usually delayed for at least 2—3 weeks; CNS and cardiovascular effects may persist several days to several weeks after chronic oral therapy is discontinued.
  • Best used in combination with other anti-hypertensives in order to avoid large doses.
  • By using moderate therapeutic doses, the maximum therapeutic effect of Rauwolfia may not be evident for 6-12 months after beginning continuous treatment with it (however, larger doses may cause nasal congestion, diarrhea, and depression).

Contraindications: Pregnancy (teratogen and abortifacaent), depression, peptic ulcers, hyperprolactinemia

Toxicity:

  • Signs of toxicity include: sedation, depression, nightmares, abdominal cramps, diarrhea, gastrointestinal ulceration and hemorrhage, water retention, nasal congestion, flushing of the skin, pinpoint pupils, hypotension, bradycardia, vertigo, stupor, tremors, coma.
  • Convulsions and extrapyramidal reactions have occurred following large doses.
  • Small doses may stimulate respiration, large doses produce respiratory depression.
  • Increased parasympathomimetic activity resulting from adrenergic inhibition produces increased GI motility, bradycardia, increased gastric acid secretion, decreased body temperature, and miosis.
  • During prolonged therapy, atrioventricular (AV) conduction time may increase, apparently due to an increase in the refractory period of the AV conduction system following depletion of myocardial catecholamine stores as well as adrenergic blockade.
  • Sodium and water retention may occur, especially if a diuretic is not administered concurrently, and may result in tolerance to the hypotensive effect of the drugs.
  • May increase prolactin secretion (dopamine is PRL inhibiting factor).

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