Table 1. Summary of Some Important Pharmacological Characteristics of Thiazide and Thiazide-Like Diuretics (TD), Calcium Channel Blockers (CCBs), Angiotensin-Converting Enzyme Inhibitors (ACE-I), and Angiotensin Receptor Blockers (ARBs).

drug class	pharmacodynamics and therapeutic considerations	pharmacokinetics
		absorption	distribution	metabolism	excretion
TD	Blocking NaCl symporter in the distal tubules causing diuresis and lowering of blood pressure	Most compounds are well absorbed after oral administration; neither the rate nor extent is affected by food.15	Repeated daily doses of bendroflumethiazide do not accumulate in patients. It follows linear elimination kinetics with doses between 2.5 and 10 mg.15	Bendroflumethiazide is mainly metabolized hepatically.15 Hyponatremia and hypokalemia are potential side effects in the elderly and patients with liver dysfunctions.15	Most compounds are secreted directly in the proximal tubules, except bendroflumethiazide.15 Organic anion transporters 1 and 3 (OAT1, OAT3) and multidrug-resistance-associated-protein-2 (MRP2) have a key role in tubular secretion.12
	Indirectly activates the renin–angiotensin aldosterone system (RAAS)
	Causes vasodilatation, which has a minor role.12
	Disruptions in the electrolyte balance can provoke encephalopathy.12−14
CCBs	Dihydropyridines (e.g., amlodipine and nifedipine) are used in the treatment of hypertension.	Are well absorbed from the GI tract.16,17	The plasma concentrations of nifedipine correlate with the blood pressure, heart rate, negative ionotropic effects, and lower esophageal sphincter pressure.16	Nifedipine has a high first-pass effect and is metabolized mainly by cytochrome P4503A4 (CYP3A4).16,17 Amlodipine has a longer elimination half-life than nifedipine.16 In elderly and liver dysfunction patients, the elimination half-life of nifedipine is doubled due to reduced hepatic blood flow and reduced first-pass metabolism.16	Metabolites of nifedipine and amlodipine are excreted by the kidneys.16,17
	Inhibiting allosterically the α1 subunit (dihydropyridine binding site) of the L-type calcium channels, causing vasodilatation of the smooth muscles in arteries and arterioles.12
ACE-I	Inhibits the conversion of angiotensin I to the potent vasoconstrictor angiotensin II by blocking ACE resulting in the reduction of arterial pressure and reducing cardiac load.12	Food has no effect on the absorption phase of enalapril, in contrast to captopril food that decreases the absorption of captopril by 50%.18	In hypertensive patients, the plasma concentration of enalaprilic acid correlates with the blood pressure-lowering effect.18 Enalapril and enalaprilic acid bound approximately 50% to plasma proteins.17 Steady state is reached after the 4th day of dosing, and no accumulation has been seen after repeated dosages. Enalaprilic acid distributes to most of the tissues, especially to the kidneys and vascular tissues.17	Some ACE-I act directly (e.g., lisinopril), whereas others are prodrugs (enalapril). The metabolite enalaprilic acid is more potent than enalapril.18	Enalapril is excreted mainly by the kidneys; patients with a renal clearance <30 mL/min accumulation of enalaprilat can take place.17
	Toxicity is mainly related to the presence of the sulfhydryl group and not to the mechanism of action.18 Potential side effects of ACE inhibitors are dry cough, angioedema, orthostatic hypotension, especially in heart failure patients using loop diuretics, renal failure in patients with renal artery stenosis, and hyperkalemia.12
ARBs	Blocking angiotensin II receptor type 1 (AT1).12,19 Also, ARBs can cause hyperkalemia, renal impairment, and hypotension.12,19	The absorption of losartan is fast, and after oral administration losartan is metabolized by hepatic CYP enzymes. Food decreases the absorption and lowers the Cmax, but the AUC is not affected by food. However, food decreases the AUC of valsartan by 40% and Cmax by 50%.19	Both losartan and valsartan are highly bound to plasma proteins, especially albumin. The plasma binding to albumin for losartan and valsartan is, respectively, 98.7% and 94%. After repeated administration, no accumulation occurs.19 Bioavailability of losartan is around 33%. The Cmax and AUC increase linearly with increasing dose. In elderly patients, the AUC of valsartan and half-life is higher, 70% and prolonged with 35%, respectively.19	Losartan is metabolized by CYP2C9. The metabolite EXP3174 is 10–40 times more potent than losartan. Liver dysfunction and grapefruit juice affect the AUC and clearance of losartan.19	In the elderly, the AUC is increased by 70% and the clearance is prolonged by 13%. In patients with liver dysfunctions, the AUC is doubled, and the clearance is 50% lower.19 Valsartan is not metabolized by CYP enzymes; it is converted to inactive metabolites.