Reserpine side effects

Reserpine inhibits the synaptic vesicular storage of the monoamines dopamine, serotonin and noradrenaline. As a result they leak out into the cytoplasm where they are inactivated by monoamine oxidase this causes their long-lasting depletion. The resulting low levels of dopamine underlie the antipsychotic actions of reserpine (Chapter 11), whereas the reduced noradrenaline levels underlie its antihypertensive actions. Finally, the resulting low levels of serotonin and noradrenaline mean that reserpine also induces depression. These severe side effects mean that reserpine is no longer used clinically as a treatment for schizophrenia (Chapter 11). 

Reserpine s strong inhibition of sympathetic activity allows increased parasympathetic activity to occur, which is responsible for side effects of nasal stuffiness, increased gastric acid secretion, diarrhea, and bradycardia. 

Because of the side effects (psychic depression, gastrointestinal disorders) of reserpine, extended research work has been carried out to find a proper analog or... 

The primary limiting effect of reserpine is depression. Depletion of central monoamines is believed to be the mechanism for this effect (Heninger et al. 1996 Charney 1998). The depression may occur in a gradual and insidious manner, and the causal association between the drug and depression may be missed (Oates 1996). Rauwolfia alkaloids are contraindicated in anyone with a history of depression, and careful vigilance is required to ensure that they do not induce depression in otherwise normal individuals. Additional side effects are sedation and difficulty with concentration and performing complex mental tasks. 

Reserpine is used for treating hypertension however, it is not the drug of choice because of a number of side effects. A number of drugs combined with other hypertensive agents— diuretics in particular—are based on reserpine. Reserpine is prescribed under a number of names, including serpasil, brinerdin, diupres, and others. 

Since the main clinical use for antisympathotonics is in the treatment of essential hypertension, such drugs will be discussed in Chapter 20 in more detail. The alkaloid reserpine from Rauwolfia serpentina was the first drug used clinically to reduce sympathetic tone. Reserpine reduce the ability of storage and release of various transmitters (adrenaline, noradrenaline, serotonine and dopamine) by an irreversible destruction of the axonal vesicle membranes. The duration of the reserpine effect is actually determined by the de novo synthesis of these structure. Beside various central side effects like sedation, depression, lassitude and nightmares the pattern of unwanted effects of reserpine is determined by the shift of the autonomic balance towards the parasympathetic branch myosis, congested nostrils, an altered saliva production, increased gastric acid production, bardycardia and diarrhea. As a consequence of the inhibition of central dopamine release, reserpine infrequently shows Parkinson-like disturbances of the extrapyramidal system. 

Like reserpine guanethidine interferes with the ability of vesicular transmitter storage. In contrast to reserpine, guanethidine is unable to enter the central nervous system and is therefore void of any centrally mediated side effects. 

In comparison with more modem antihypertensives reserpine causes unpleasant side-effects, such as sedation, depression and various effects reflecting a dominant parasympathetic system (nasal congestion, diarrhea and exacerbation of peptic ulcers). Reserpine should be considered as an antihypertensive of second choice, although in certain countries it is still used because of its low price. 

Reserpine also interferes with the neuronal storage of a variety of central transmitter amines such that significant depletion of norepinephrine, dopamine, and 5-hydroxytryptamine (serotonin) occurs. This central transmitter depletion is responsible for the sedation and other CNS side effects associated with reserpine therapy. The depletion of brain amines also may contribute to the antihypertensive effects of reserpine. 

Peripheral nervous system side effects are the result of a reserpine-induced reduction of sympathetic function and unopposed parasympathetic activity symptoms include nasal congestion, postural hypotension, diarrhea, bradycardia, increased gastric secretion, and occasionally impotence. Because of the increased gastric secretion, reserpine is contraindicated for patients... 

Conversely, certain drugs modify the effectiveness or side effects of aspirin. Phenobarbital, occasionally used for seizures, induces liver enzymes that increase the metabolism and excretion of aspirin, (3-adrenoceptorblocking drugs, such as propranolol, and decrease the antiinflammatory effects of aspirin, whereas reserpine decreases its analgesic effects. Antacids decrease the absorption of aspirin. Alcohol consumption in combination with aspirin increases the latter s ulcerogenic effects. 

About the same time as the reserpine finding, physicians noticed that some of the drugs used to treat other diseases appeared to have a beneficial side effect—raising the patient s mood. Upon further testing, a chemically modified version of one of these drugs effectively reduced the symptoms of depressed patients. This drug, iproniazid, inhibits MAO, the enzyme that destroys the monoamine neurotransmitters— dopamine, norepinephrine, and serotonin. As a result, more of these... 

Drug treatment with certain agents such as specific types of neuroleptics and reserpine produce PD as a side effect. 

Reserpine (Serpasil) depletes the store of catecholamine peripherally and centrally and attenuates, but does not abolish, sympathetic reflexes. Reserpine is useful in the management of mild to moderate hypertension. Its onset of action is very slow (2 to 3 weeks) when given orally. The side effects of reserpine are manifested by cholinergic hyperactivity such as diarrhea, bradycardia, and nasal stuffiness. Reserpine can activate a peptic ulcer (cholinergic dominance) and cause depression (depletes norepinephrine stores). Reserpine and propranolol have potential cardiac depressant activity and should not be used together. 

Reserpine, a drug used for the treatment of high blood pressure, was known to have the side effect of depression. Upon studying this effect, scientists observed that this drug caused a depletion of the amine neurotransmitters serotonin and norepinephrine. Neurotransmitters transmit information from one nerve to another across a synapse. The neurotransmitters are than reabsorbed by the first nerve in the process called reuptake. 

The depletion of the neurotransmitters—as observed with reserpine—came under study as the possible cause of depression and became known as the amine hypothesis of depression. The drug iproniazid reversed some of these negative side effects, confirming the usefulness of drugs in the treatment of depression. 

MAO inhibitors will act peripherally and may act centrally, again depending on their pharmacokinetic properties. They have, like reserpine, been used for both antihypertensive and antipsychotic treatment but now been superseded by more selectively acting drugs. However, there recently has been renewed interest in the development of MAO B-selec-tive inhibitors, since that enzyme subtype acts preferentially on serotonin and in the central nervous system some of the side effects could thus be avoided or ameliorated. MAO B inhibitors have also been reported to increase the lifetime of dopamine and therefore to be beneficial in Parkinson s disease similarly, inhibitors of COMT have more recently been introduced as a supplement to therapy in this disease. 

Reserpine is an alkaloid from plants of the genus Rauwolfia, used in medicine since ancient times in southern Asia, particularly for insanity more recently, reserpine was extensively used in psychiatry but is now obsolete. Reserpine depletes adrenergic nerves of noradrenaline primarily by blocking amine storage within vesicles present in the nerve ending, so reducing stores of releasable transmitter. Its antihypertensive action is due chiefly to peripheral action, but it enters the CNS and depletes catecholamine stores there too this explains the sedation, depression and parkinsonian (extrapyramidal) side effects that can accompany its use. The effects on catecholamine storage persist for days to weeks after it is withdrawn. 

Metirosine (a-methyl-p-t5n osine) is a competitive inhibitor of the eruyme tyrosine hydroxylase, which converts t5U-osine to dopa as dopa is further converted to noradrenaline and adrenaline they are similarly depleted by metirosine. It is used as an adjuvant (with phenoxybenzamine) to treat phaeo-chromocytomas that caimot be removed surgically. Catecholamine synthesis is reduced by up to 80% over 3 days. It also readily penetrates the CNS and depletes brain noradrenaline and dopamine causing reserpine-like side effects (see above). Hence, in patients whose life expectancy is threatened more by tumour invasion than by mild or moderate hypertension, the need for the drug should be weighed carefully. 

Purified reserpine was one of the first of the modem tranquillizers, acting by reducing 5-hydroxytryptamine concentrations, but it was associated with severe side-effects in humans. Low-dose oral reserpine (5 mg) has been used in the treatment of postpartum mares with agalactia caused by fescue toxicosis and resulted in semm reserpine concentrations that were below the... 

The side-effects of reserpine include hypotension, bradycardia and increased gastrointestinal motility and diarrhea (Lloyd et al 1985), all resulting from decreased sympathetic tone and increased parasympathetic tone. The hypotensive effects of reserpine may take days to several weeks to occur but may persist for 1 to 6 weeks after the withdrawal of the dmg. Administration of induction agents, such as xylazine and ketamine, that produce hypotension may be fatal in horses treated with reserpine. 

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