Systemic hypertension is a chronic disease which results in complications
such as heart failure, renal failure or stroke. Polypharmacy is getting more important in
this population. There are many mechanisms by which drugs may interact, mostly
pharmacokinetic (absorption, distribution, metabolism, and elimination) or
pharmacodynamic, or additive toxicity. Absorption of drugs can be affected by foods,
antacids and antidiarrhoeals.
Distribution of the drugs can be changed by the volumetric status of the body and
binding of drugs to proteins such as p-glycoproteins.
The most important class of drug interactions involves the cytochrome P450 (CYP)
microsomal enzyme system, which metabolizes a variety of drugs and herbal products.
Cytochrome P450 enzymes metabolize approximately 60% of prescribed drugs, with
CYP3A4 responsible for about half of this metabolism.
Diuretics are renally eliminated and more vulnerable to drug interactions which take
place in the kidney. Probenecid, nonselective nonsteroidal antiinflammatory drugs
(NSAIDs), beta-lactam antibiotics, valproic acid, methotrexate, cimetidine and
antivirals decrease the tubular secretion of loop diuretics from the proximal tubulus.
Pharmacodynamic interactions between similarly acting drugs may lead to additive or
even over-additive effects (potentiation). A good example for antihypertensive drugs is
the combination of intravenous verapamil and a β-blocker, which may cause additive
impairment and increase the risk of A-V (atrio-ventricular) block.
The interaction of antihypertensives and NSAIDs is another important type of
interaction. In this chapter, we mentioned all the interactions of antihypertensive agents
through kinetic and dynamic ways.
Keywords: Systemic hypertension, Polypharmacy, Pharmacokinetic, Absorption,
Distribution, Elimination, Pharmacodynamic, Additive toxicity, Antidiarrhoeals,
Pharmacokinetic interactions, Cytochrome P450, Losartan, Kinins, Eplerenone,
Propranolol, Bioavailability, Antihypertensives, Diuretics, Digoxin, Renin
inhibitors.
