ADD-ONS / MEDICATION
Antihypertensive drugs
Updated on 11/07/2024, published on 09/07/2024
- antihypertensive drugs are used to manage hypertension and include ACE inhibitors, ARBs, beta-blockers, calcium channel blockers, diuretics, and alpha-blockers
- standard doses of oral medication for outpatients are summarised in this text
- intravenous antihypertensive drugs are discussed in the chapter on hypertensive crisis
- ACE inhibitors block the ACE (Angiotensin Converting Enzyme), preventing the formation of angiotensin II (AT II).
- they effectively reduce BP even in patients with carotid atherosclerotic disease without adversely affecting cerebral blood flow.
- other positive effects of ACE inhibitors:
- vaso- and cardioprotective effect (improvement of coronary perfusion, reduction of LV hypertrophy)
- nephroprotective effect (beneficial for diabetics)
- beneficial effect on glucose metabolism
- decrease of fibrinogen level, decrease of PAI1, and increase of tPA level
- sympathetic inhibition
- always monitor renal function and potassium levels during treatment; if creatinine increases by ≥ 30%, ACE inhibitors should be discontinued
Adverse effects
- dry irritating cough, sometimes very bothersome and leading to discontinuation of ACE inhibitors (due to slowed breakdown of bradykinin and subsequent pulmonary congestion) ⇒ switch to sartan if intolerable
- postural hypotension
- hyponatremia
- allergic reactions
- interaction with NSAIDs (reduced effect of ACE inhibitors)
Contraindications
- bilateral renal artery stenosis
- pregnancy and lactation
- relative CI in fertile women
- hypersensitivity to ACE inhibitors
- hyperkalemia
- porphyria
- history of angioneurotic edema
Long half-life | Initial dose | Maintenance dose |
perindopril (PRESTARIUM, PRENESSA)
|
4-5 mg once daily | 4-16 mg once daily |
ramipril (TRITACE, RAMIL, ALTACE)
|
2.5 mg once daily | 2.5-10 mg once daily (or in divided doses) |
fosinopril (MONOPRIL) | 10 mg once daily | 10-40 mg once daily |
Medium half-life | ||
enalapril (ENAP, VASOTEC)
|
2.5-5 mg once or twice daily | 10-40 mg once or twice daily |
Short-acting ACE-I | ||
captopril (TENSIOMIN, CAPOTEN)
|
6.25-12.5 mg three times daily |
- Angiotensin II Receptor Blockers (ARBs) or sartans are antihypertensive agents that can be used as initial treatment of hypertension (the same indications as ACE inhibitors)
- they do not cause cough and generally have a low risk of side effects
- renal function must be monitored during therapy; in combination with potassium supplements or potassium-sparing diuretics may cause hyperkalemia
Renin-Angiotensin-Aldosterone System (RAAS)
- the renin-angiotensin-aldosterone system (RAAS) is a significant homeostasis system that protects circulation during changes in salt and water concentration
- the key agent is renin, which cleaves angiotensinogen (produced in the liver) to angiotensin I
- angiotensin I is activated by ACE to angiotensin II, which causes arteriolar vasoconstriction in the kidney and systemic circulation, sodium reabsorption in the proximal nephron segment, and stimulates aldosterone secretion in the adrenal cortex leading to sodium retention
- RAAS thus not only maintains salt and water homeostasis but can also contribute to the development of hypertension
Side effects
- tachycardia, bradycardia
- hypotension
- edema (arms, legs, lips, tongue, or throat)
Contraindications
- pregnancy
- hyperkalemia
- renal artery stenosis (may cause kidney failure)
Sartan | Initial dose in hypertension treatment | Maintenance dose |
losartan (COZAAR, LOZAP) |
50 mg daily | 25-100 mg once daily or divided into two doses |
valsartan (VALZAP, DIOVAN) |
80-160 mg daily | 80-320 mg daily |
irbesartan (AVAPRO, IRBEC) |
150 mg daily | 150-300 mg daily |
candesartan (ATACAND, CARZAP) |
8 mg daily | 8-32 mg daily |
olmesartan (BENICAR) |
20 mg daily | 20-40 mg daily |
telmisartan (MICARDIS, TEZEO) |
40 mg daily | 20-80 mg daily |
eprosartan (TEVETEN) |
600 mg daily | 400-800 mg daily |
- beta-blockers (BB) slow down heart rate, reduce myocardial strain, and decrease myocardial oxygen consumption
- the main use of BB is in combination therapy, especially for hypertension associated with manifest CAD and/or chronic heart failure or significant left ventricular dysfunction
- BBs are divided into cardioselective and non-selective
- cardioselective BBs mainly affect receptors in the heart
- non-selective BBs have more pronounced effects on other organs
Adverse effects
- bradycardia or AV block due to their negative chronotropic effect
- bronchospasms (especially with non-selective BBs)
- negative impact on lipid and carbohydrate metabolism
- induce peripheral vasoconstriction
Contraindications
- bronchial asthma
- 2nd and 3rd degree AV block
- other bradyarrhythmias
- relative contraindication is peripheral arterial disease (⇒ vasoconstriction)
Betaxolol (LOKREN) | Initial dose | Maintenance dose |
|
10 mg once daily | 10-20 mg once daily |
Bisoprolol (CONCOR, CONCOR COR, MONOCOR, EMCOR) | ||
|
2.5-5 mg once daily | 10-20 mg once daily |
Metoprolol (VASOCARDIN, BETALOC ZOK, LOPRESSOR, CORVITOL) | ||
|
25-100 mg once daily (extended-release form) |
100-200 mg once daily |
Carvedilol (CORYOL, ATRAM, COREG, DILATRENT, CARVIL, etc.) | ||
|
12.5 mg once daily 6.25 mg twice daily |
25-50mg per day (divided into two doses) |
- do not adversely affect lipid and glucose metabolism
- do not cause bronchoconstriction and positively influence renal blood flow and peripheral circulation
- suitable for treating hypertension in the elderly and isolated systolic hypertension
- verapamil and diltiazem are not suitable for treating hypertension accompanied by heart failure or atrioventricular conduction disorders due to their negative inotropic and chronotropic effects
- most common side effects: flushing, peripheral edema
- relative contraindications:
- tachyarrhythmias
- heart failure
Initial Dose |
Maintenance dose |
|
amlodipine AGEN, APO-AMLO, ZOREM, NORVASC |
||
|
2.5-5 mg once daily | 5-10 mg once daily |
lercanidipine KAPIDIN, ZANIDIP |
||
|
10 mg once daily | 10-20 mg once daily |
nitrendipine LUSOPRESS |
||
|
10 mg once daily | 10-20 mg once daily |
felodipine PRESID, PLENDIL |
2.5-5 mg once daily | 5-10 mg once daily (max 20 mg) |
Loop diuretics (furosemide) | |
|
|
Distal diuretics (hydrochlorothiazide, indapamide)
|
|
|
|
Potassium-sparing diuretics (amiloride, spironolactone) | |
|
Loop diuretics | ||
furosemide (FUROSEMID)
|
20-40 mg twice daily | 20-80 mg twice daily |
Thiazide (distal) diuretics | ||
hydrochlorothiazide (HYDROCHLOROTHIAZIDE)
|
12.5 mg daily | 12.5-50 mg daily |
indapamide (INDAPAMID) | 1.25 – 2.5 mg once daily | 2.5-5 mg daily |
Potassium-sparing diuretics | ||
amiloride is commonly used in combination with HCT – 5/50 mg (MODURETIC, LORADUR, RHEFLUIN)
|
5/50 mg daily | 5/50 mg daily |
spironolactone (SPIRONOLACTONE, VEROSPIRON, ALDACTONE)
|
25 mg daily | 25-50 mg daily (hypertension) |
eplerenone (SELETRA, EPLERON, INSPRA)
|
25-50 mg daily | 25-50 mg daily |
- alpha-1 blockers, also known as alpha-1 adrenergic antagonists, are a class of antihypertensive agents that work by blocking alpha-1 receptors on blood vessels. This results in vasodilation and a subsequent decrease in blood pressure
- used primarily for the treatment of high blood pressure and benign prostatic hyperplasia
Adverse effects
- orthostatic hypotension
- reflex tachycardia
- nasal congestion
- headaches
- fatigue
Contraindications
- known hypersensitivity or allergic reactions to alpha-1 blockers or any components of the formulation
- severe hepatic impairment – use with caution
- history of orthostatic hypotension
- severe heart failure or other significant cardiac conditions – use with caution
- concurrent use with phosphodiesterase-5 (PDE-5) inhibitors
Initial dose | Maintenance dose | |
doxazosin (CARDURA, ZOXON, DOXAZOSIN)
|
1 mg once daily |
2-8 mg once daily (can be increased gradually based on patient response) |
terazosin (TERAZOSIN)
|
1 mg once daily |
1-5 mg once daily |
Centrally-acting antihypertensive drugs reduce blood pressure by acting on the CNS. They inhibit sympathetic outflow, leading to vasodilation and decreased cardiac output.
Medications with central and peripheral effects on alpha receptors | Initial dose | Maintenance dose |
urapidil (EBRANTIL) | 30 mg twice daily | 60-180 mg daily divided into two doses |
Alpha2 adrenergic agonist | ||
methyldopa (DOPEGYT)
|
250 mg once daily | 0,5 – 2 g daily divided into two to three doses |
clonidine (CATAPRES)
|
0.1 mg twice daily | 0.2-0.6 mg daily divided into two doses |
Imidazoline receptor agonists | ||
rilmenidine (TENAXUM, RILMENIDIN TEVA)
|
1 mg once daily (morning) | 1-2 mg daily (single 2mg dose, or 1 mg twice daily) |
moxonidine (CYNT, MOXOGAMMA)
|
0.2 mg once daily | 0.2-0.4 mg daily as a single dose or divided into two doses |
- combination therapy for hypertension is favored because of its higher efficacy and better tolerability and compliance
- with monotherapy, only 20-30% of patients achieve target levels
- initial dual therapy is recommended for patients with SBP > 160 mm Hg / DBP > 100 mm Hg and individuals at high cardiovascular risk
- adequate blood pressure control can be achieved in most hypertensive patients with a combination of 2-3 antihypertensive drugs
- combining drug classes provides more effective blood pressure control than doubling the dose of a single agent (which often leads to adverse effects)
- many patients require at least a triple combination
- prerequisites for effective combination therapy: drugs with similar duration of antihypertensive effect and, ideally, different mechanisms of action with additive impact on blood pressure reduction without increasing the incidence of adverse effects
- the most common dual combination is ACE-I/sartan + CCB/diuretics
- a fixed combination of ACE-I + CCB is the first choice in patients with hypertension and metabolic disorders (dyslipidemia, metabolic syndrome, impaired glucose tolerance, or diabetes), in patients with organ complications or associated cardiovascular and renal diseases
- improved patient compliance with treatment, better tolerability, and efficacy, lower cost
- both components have a vasodilator effect, which is beneficial in elderly hypertensive patients with increased peripheral resistance, endothelial dysfunction, atherosclerotic lesions, and reduced vascular compliance
- more effective than its individual components in monotherapy (e.g., TEAMSTA-5 study)
- more effective than ACEI + thiazide diuretic combination in preventing cardiovascular events (ACCOMPLISH trial)
- if ACE-I is not tolerated, an ARB can be used instead
- a diuretic should be part of the triple combination
- the optimal combination is ACEI/ARB + CCB + thiazide diuretic
- the fourth drug should be a BB, alpha-blocker, or spironolactone
- in multiple combinations, centrally acting drugs can be added: rilmenidine, moxonidine, urapidil
- not recommended combinations:
- BB + diuretic (accumulation of adverse metabolic effects)
- ACE-I + ARB (hyperkalemia, renal insufficiency)