Therapeutic classes

- Thiazide diuretics

- Renin system blocker angiotensin aldosterone

(ACE inhibitor and ARA II angiotensin receptor antagonist 2)

- Calcium channel blockers

- Beta blockers

- 2nd line anti-hypertensive drugs

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1/ THIAZIDE DIURETICS

Thiazide diuretic = inhibitor of the renal distal convoluted tube Na/Cl

Natriuretic effect (moderate: 90% reabsorption at the proximal convoluted tubule) decrease in extracellular volumes and stimulation of the renin-angiotensin system

Lowering of peripheral resistances (poorly determined mechanism)

Molecules

Hydrochlorothiazide (Esidrex®)

Indapamide (Fludex®)

Cicletanin (Tenstaten®)

 

Undesirable effects

• Hypokalemia and metabolic alkalosis: common (less than loop diuretics)

• Hyponatremia: especially in the elderly with a low-sodium diet and abundant drinking without salt intake

• Volume depletion

• Hypercalcemia: increased reabsorption of renal calcium

• Hyperuricemia: frequent, usually asymptomatic

• Glucose intolerance, hypercholesterolemia and hypertriglyceridemia: frequent, moderate, often transient

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2/ RENIN-ANGIOTENSIN SYSTEM BLOCKER = ACE/ARA2

- ACE inhibitor: competitive inhibition of converting enzyme decreasing the conversion of angiotensin 1 to angiotensin 2 and increasing bradykinin concentrations

- Angiotensin 2 receptor antagonist (ARA2): competitive inhibition of angiotensin 2 AT1 receptors

- Antihypertensive effect by decreasing peripheral arterial resistance and sodium retention (decrease in aldosterone), without increase in heart rate or sympathetic tone

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Molecules

IEC

- Pril

- Enalapril (Renitec®) - Benazepril - Fosinopril - Moexipril - Zofenopril

- Perindopril (Coversyl®) - Captopril - Imidapril - Quinapril - Trandolapril

- Ramipril (Triatec®) - Cilazapril - Lisinopril

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ARA2

- sartan

- Candesartan (Atacand®, Kenzen®) - Olmesartan (Alteis®, Olmetec®) - Losartan (Cozaar®) - Telmisartan

- Irbesartan (Aprovel®) - Valsartan (Tareg®, Nisis®) - Eprosartan

 

​Undesirable effects:

• Orthostatic hypotension

• Possible sudden drop in BP after the 1st dose if prior stimulation of the RAS (heart failure, etc.)

• Cough to ACE inhibitors = related to accumulation of bradykinin and substance P (common = 5 to 20%): dry irritative cough, not positional, occurring within 1 to 6 weeks, regressive 4 days after discontinuation

• Hyperkalemia: mainly in cases of renal insufficiency, concomitant use of K+ or potassium sparer

• Decreased kidney function: transient serum creatinine < 10-15%

• Acute functional renal failure

• Angioneurotic edema: only with ACE inhibitors

• 2nd and 3rd trimester foetopathy: oligoamnios, pulmonary hypoplasia, IUGR, renal dysgenesis, anuria

• Captopril: taste modification, skin rash, neutropenia, agranulocytosis

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3/ CALCIUM INHIBITOR

- Calcium channel blocker = voltage-gated L-type calcium channel blocker and calcium flux reduction: results in a peripheral vasodilator effect

- Selective vascular duct effect: dihydropyridine

- Mixed vascular and cardiac effect: verapamil and diltiazem !!! Verapamil also has a class IV anti-arrhythmic effect: slowing of sinus activity and conduction Atrioventricular

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Molecules

Dihydropyridine

(-dipine)

- Amlodipine (Amlor®)

- Lercanidipine (Lercan®)

- Nicardipine (Loxen®) IV

- Nifedipine (Chronadalate®)

- Others: felodipine, isradipine, lacidipine, manidipine, nitrendipine

Benzothiazine - Diltiazem (Monotildiem®)

Phenylalkylamine - Verapamil (Isoptine®)

 

Undesirable effects: 

• By vasodilation: headache, dizziness, vasomotor flush

• Edema of the lower limbs

• Verapamil: constipation

• Diltiazem/verapamil: bradycardia, conduction disorder (BSA, BAV, intraventricular block), heart failure

• 1st generation dihydropyridine (nifedipine, nicardipine): sinus tachycardia

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4/ BETA BLOCKERS

β-blocker = competitive β-adrenergic antagonist of catecholamines:

- Cardiac effects: . Bradycardia = negative chronotropic .Decreases Cardiac contractility = negative inotropic

- Cardiac conduction = negative dromotropic . Decreases Cardiac excitability = negative bathmotropic

Other effects:

- Bronchial β2 blockade: bronchoconstriction

- Vascular β2 blockade: releases the tone α vasoconstrictor

- Stimulation of digestive peristalsis

- Inhibits renin and aldosterone secretion = IEC-like effect

- Interferes with lipid and glycemic metabolism

 

Molecules

​β1-selectivity = cardio-selectivity: preferential stimulation β1 > β2

- Intrinsic sympathomimetic activity (acebutolol, pindolol): partial agonist reduces the resting effect

- Peripheral vasodilator effect:

- Associated α1-adrenergic receptor blockade: labetalol

- Other vasodilator mechanisms: celibrolol, cartéolol, nebivolol

-Physicochemical:

- Lipophilicity: hepatic elimination, short half-life, brain passage (nightmares)

- Hydrophilicity: renal elimination, long half-life, little brain passage

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β1-selective

- Acebutolol (Sectral®) - Metoprolol (Lopressor®)

- Oral atenolol (Ternomine®) or IV - Nebivolol (Temerit®) vasodilator

- Bisoprolol (Bisoce®, Detensiel®) - Celiprolol (Celectol®) vasodilator

Non-selective - Propranolol (Avlocardyl®) - Labetalol (Trandate®) IV route α-blocker

- Timolol (Timacor®) - Cartéolol (Mikelan®) vasodilator

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Effects:

Side effects, in general:

• Diarrhea, nausea

• Insomnia, nightmares

• Impotence, libido disorder

•Psoriasis

Side effects, at the cardiac level:

​• Sinus bradycardia, asthenia

• Conduction disorder: BSA, BAV, intraventricular block

•Heart failure

 

Bronchial - Worsening of asthma or COPD

!!! In COPD patients with cardiovascular disease, the benefit/risk ratio appears to be positive

Vascular - Cooling of the extremities, Raynaud's phenomenon, coronary spasm

- Worsening of PAD> benefit/risk ratio favourable to β1-selective

Metabolic - Change in lipid profile: HDL, LDL, triglycerides (minor atherogenic risk)

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5/ 2ND LINE ANTIHYPERTENSIVE DRUGS

- α-blocker = competitive antagonist of α1-adrenergic receptors of catecholamines: vascular resistance

- Central antihypertensive = decrease in sympathetic discharge from the vasopressor centers of the brainstem: central α2-adrenergic receptor agonist (clonidine, methyldopa) or imidazoline receptor agonist (moxonidine, rilmenidine)

- Renin inhibitor: 2nd line renin-angiotensin system blocker

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a/ α-blocker

- Doxazosin

- Prazosin (Alpress®, Minipress®)

- Uradipil (Eupressyl®, Mediatensyl®) oral or IV

 

Undesirable effects

- Orthostatic hypotension

- Significant response to the 1st dose

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b/ Central antihypertensive

- Clonidine (Catapressan®) IV

- Methyldopa (Aldomet®)

- Monoxidine (Physiotens®)

- Rilmenidine (Hyperium®)

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Unwanted Effest

• Dry mouth

• Drowsiness, impaired alertness

• Orthostatic hypotension

•Impotence

• Depressive syndrome

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c/ Renin inhibitor

-kiren

- Aliskirène (Rasilez®) - ISIS of the SRA blockers

-Diarrhea

 

d/ Diuretic - Piretanide (Eurelix®)

 

e/ Potassium-sparing diuretic

- Spironolactone (Aldactone®)

- Amiloride (Modamide®)

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f/ K-ATP channel opener - Minoxidil (Lonoten®)

Side effects that may be aggravated with LONOTEN:

Peripheral edema associated or not with weight gain.

Acceleration of the heart rate.

Hypertrichosis.

Temporary decrease in haemoglobin and haematocrit.

Temporary elevation of serum creatinine and azotemia.