Clonidine drug interactions

The most common side effects of clonidine are constipation, dizziness, drowsiness, dryness of mouth, and unusual tiredness or weakness. However, there are more severe side effects that clinicians and patients should be aware of, such as allergic reaction, decreased heart rate, or unusually elevated or decreased blood pressure, as well as contraindications and drug interactions that should be evaluated prior to prescription. 

Numerous drug-drug interactions have been reported with the antipsychotic agents. These may be mediated through pharmacodynamic effects. For example, antipsychotics that block aj-adrenergic receptors may potentiate the antihypertensive effects of prazosin, labetalol, and some other antihypertensive agents. Conversely, antipsychotics associated with a2-adrenergic receptor blockade may interfere with the antihypertensive effects of clonidine and methyldopa (Richelson, 1999). 

Yohimbine, an indole alkaloid, is an -selective antagonist. It has no established clinical role. Theoretically, it could be useful in autonomic insufficiency by promoting neurotransmitter release through blockade of presynaptic 02 receptors. It has been suggested that yohimbine improves male sexual function however, evidence for this effect in humans is limited. Yohimbine can abruptly reverse the antihypertensive effects of an 2-adrenoceptor agonist such as clonidine—a potentially serious adverse drug interaction. 

The drug should not be given to patients who are at risk for mental depression and should be withdrawn if depression occurs during therapy. Concomitant treatment with tricyclic antidepressants may block the anti hypertensive effect of clonidine. The interaction is believed to be due to cr-adrenoceptor-blocking actions of the tricyclics. 

The glucuronide metabolite of AZT was isolated from rat and human liver microsomal incubations (177), and the formation of a toxic metabolite of AZT was demonstrated in rat hepatocytes and liver microsomes (177). The metabolism of tamoxifen was examined in human liver homogenate and human Hep G2 cell line preparations by LC/API/MS (178). Several metabolites were detected in the human liver homogenate extracts, namely, N-didesmethyltamoxifen, a-hydroxy-tamoxifen, 4-hydroxytamoxifen, N-desmethyltamoxifen, and tamoxifen N-oxide. All of these metabolites, except the N-didesmethyltamoxifen, were observed in the samples after incubating tamoxifen with the human Hep G2 cell line. In-vitro studies have also used MS to examine potential drug-drug interactions. For example, (179) demonstrated that the a2-agonist, dexmedetomidine, inhibited metabolism of the anesthetic alfentanil, whereas clonidine had no effect. 

Adverse drug interactions with adrenergic agonists are rare. Diuretics predictably potentiate the hypotensive effect of these drugs. Tricyclic antidepressants may inhibit the antihypertensive effect of clonidine by unknown mechanisms. 

Tricyclic drug interactions (Table 30-3) include additive depression of the CNS with other central depressants, including ethanol, barbiturates, benzodiazepines, and opioids. Tricyclics may also cause reversal of the antih)pertensive action of guanethidine by blocking its transport into sympathetic nerve endings. Less commonly, tricyclics may interfere with the antihypertensive actions of methylnorepinephrine (the active metabolite of methyl-dopa) and clonidine. 

Tricyelic chugs block the uptake of guanethidine into sympathetic nerve endings, thus reversing its beneficial effects on blood pressure. While the precise mechanism is not defined, the tricyclics may also block the antihypertensive effects of clonidine and methyldopa. All of the other drug interactions have been reported. The answer is (D). 

Pettinger WA, Mitchell HC, Gullner H-G. Clonidine and the vasodilating beta blocker antihypertensive drug interaction. CUn Pharmacol Ther ( 977) 22,164-71. 

Drugs that may interact with clonidine include beta-adrenergic blocking agents and tricyclic antidepressants. 

Drugs that interact may include beta blockers, indomethacin, verapamil, and clonidine. 

Clonidine Inhibits adenylyl cyclase and interacts with other intracellular pathways Vasoconstriction is masked by central sympatholytic effect, which lowers BP Hypertension Oral transdermal peak effect 1-3 h half-life of oral drug 12 h produces dry mouth and sedation... 

Caution [C, ] CrCl <30 Contra Component sensitivity, asthma, severe COPD, sinus bradycardia Disp Soln SE Irritation, bitter taste, superficial keratitis, ocular allergic Rxn EMS Drug is absorbed systemically OD May cause electrolyte disturbances (K), acidosis and bradycardia monitor ECG Doxazosin (Cardura, Cardura XL) [Antihypertensive/Alpha Blocker] Uses HTN symptomatic BPH Action < [-Adrenergic blocker relaxes bladder neck smooth muscle Dose HTN Initial 1 mg/d PO may be T to 16 mg/d PO BPH Initial 1 mg/d PO, may T to 8 mg/d XR 2-8mg qAM Caution [B, ] Use w/ PDE5 inhibitor (eg, sildenafil) can cause 1 BP Contra Component sensitivity Disp Tabs SE Dizziness, HA, drowsiness, sexual dysfxn, doses >4 mg T postural BP risk Interactions T Effects W/ nitrates, antihypertensives, EtOH i effects W/ NSAEDs, butcher s broom -t effects OF clonidine EMS Concurrent EtOH use can T drowsiness syncope may occur w/in 90 min of initial dose OD May cause profound hypotension place pt in supine position, give IV fluids, use pressors if needed... 

A second hypothesis to explain the cardiovascular effects of clonidine involves an interaction with imidazoline-1 receptors (Bousquet and Feldman 1999). However, the available evidence at present does not prove conclusively the imidazoline hypothesis for the mechanism of action of clonidine and analog drugs, like rilmeni-dine and moxonidine (Szabo 2002). 

A cooperative interaction between imidazoline receptors and a 2-adrenoceptors seems to account for the marked and rapid hypotensive effect caused by hybrid drugs, such as clonidine. 

Phentolamine is useful in hypertensive conditions precipitated by excessive catecholamines in circulation. It is therefore still considered in the management of pheochro-mocytoma (preceding or during surgery on the tumor), accidental overdoses and hypertensive crises from drug or food interactions with MAO inhibitors, or the abrupt withdrawal of clonidine therapy. Both drugs, however, are rapidly becoming obsolete in view of new developments. 

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