Antihypertensive drugs interactions

Table 24.3 Antihypertensive drug interactions involving drugs with...

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

If 50% of Europeans with essential hypertension are affected by this disease because of an elevated secretion of endogenous ouabain, then there might be a chance to block its interaction at the cardiac glycoside binding site of Na+/K+-ATPase and thus lower blood pressure. This therapeutic approach seems to be successfiil. Recent studies provide evidence that the cardenolide analogue Rostafuroxin (PST 2238 Fig. 4) at very low concentrations can overcome the ouabain-induced tise of hypertension in experimental animals [6]. This compound has recently entered the phase I of clinical trials and is certainly a prototype of a new class of antihypertensive drugs. 

VMATs are irreversibly inhibited by the potent antihypertensive drug reserpine. The depressive effects of reserpine helped to formulate the original monoamine hypothesis of affective disorders. Reseipine also appears to interact with the transporters near the site of substrate recognition. Tetrabenazine, which is used in treatment of movement disorders, inhibits VMAT2 much more potently than VMAT1, consistent with the less hypotensive action of this agent. 

Discuss the general drug actions, uses, adverse reactions, contraindications, precautions, and interactions of the antihypertensive drugs. 

The hypotensive effects of most antihypertensive dru are increased when administered with diuretics and other antihypertensives. Many dnigp can interact with the antihypertensive drugs and decrease their effectiveness (eg, antidepressants, monoamine oxidase inhibitors, antihistamines, and sympathomimetic bronchodilators). When the ACE inhibitors are administered with the NSAIDs, their antihypertensive effect may be decreased. Absorption of the ACE inhibitors may be decreased when administered with the antacids. Administration of potassium-sparing diuretics or potassium supplements concurrently with the ACE inhibitors may cause hyperkalemia. When the angiotensin II receptor agonists are administered with... 

The most potentially serious drug interactions include the concomitant use of NSAIDs with lithium, warfarin, oral hypoglycemics, high-dose methotrexate, antihypertensives, angiotensin-converting enzyme inhibitors, fi-blockers, and diuretics. 

Schelleman, H., Strieker, B. H., Verschuren, W. M., et al. (2006) Interactions between five candidate genes and antihypertensive drug therapy on blood pressure. Pharmacogenomics. J. 6, 22-26. 

Lithium intoxication can be precipitated by the use of diuretics, particularly thiazides and metola-zone, and ACE inhibitors. NSAIDs can also precipitate lithium toxicity, mainly due to NSAID inhibition of prostaglandin-dependent renal excretion mechanisms. NSAIDs also impair renal function and cause sodium and water retention, effects which can predispose to interactions. Many case reports describe the antagonistic effects of NSAIDs on diuretics and antihypertensive drugs. The combination of triamterene and indomethacin appears particularly hazardous as it may result in acute renal failure. NSAIDs may also interfere with the beneficial effects of diuretics and ACE inhibitors in heart failure. It is not unusual to see patients whose heart failure has deteriorated in spite of increased doses of frusemide who are also concurrently taking an NSAID. 

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). 

Drug interactions Proleukin may affect central nervous system function. Therefore interactions could occur following concomitant administration of psychotropic drugs. Concurrent administration of drugs possessing nephrotoxic, myelotoxic, cardiotoxic, or hepatotoxic effects with Proleukin may increase toxicity in these organ systems. Reduced kidney and liver function secondary to Proleukin treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs. Beta-blockers and other antihypertensives may potentiate the hypotension seen with Proleukin. 

Elevations of TCA levels may occur when combined with CYP2D6 inhibitors or from constitutional factors. About 7% of the Caucasian population in the USA has a CYP2D6 polymorphism that is associated with slow metabolism of TCAs and other 2D6 substrates. Combination of a known CYP2D6 inhibitor and a TCA in a patient who is a slow metabolizer may result in additive effects. Such an interaction has been implicated, though rarely, in cases of TCA toxicity. There may also be additive TCA effects such as anticholinergic or antihistamine effects when combined with other agents that share these properties such as benztropine or diphenhydramine. Similarly, antihypertensive drugs may exacerbate the orthostatic hypotension induced by TCAs. 

Drug Interactions Other antihypertensive agents Carbamazepine (vasodilators, ACE inhibitors, Rifampin diuretics, and beta-blockers) Phenobarbital Digoxin Cyclosporine Disopyramide Theophylline Flecainide Inhalation anesthetics Quinidine Neuromuscular blocking agents Cimetidine Lithium ... 

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. 

Corticosteroids interact with barbiturates, carbamazepine, phenytoin, primidone, frusemide, thiazide, NSAIDs, antidiabetics, and antihypertensive drugs. Benzquinamide hydrochloride is incompatible with chlordiazepoxide, diazepam, and some barbiturates. Care should be exercised when handling bisacodyl to avoid contact with skin and mucosal membranes. 

Q8 A pregnancy test is necessary because hypertension is a feature of preeclampsia, a serious condition which can occur in pregnancy and which threatens the life of both mother and foetus. Also, many antihypertensive drugs are contraindicated in pregnancy. It is necessary to know whether the patient is taking prescribed medicines or is self-medicating, as some drugs, such as monoamine oxidase inhibitors (MAOIs), can interact with dietary components to cause a very rapid rise in BP. 

Markowitz JS, Wells BG, Carson WH. Interactions between antipsychotic and antihypertensive drugs. Ann Pharmacother 1995 29(6) 603-9. 

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