Anti-hypertensive drugs

Question 1

What are the factors determining blood pressure?

Answer 1

Cardiac output (stroke volume x heart rate)
○ Heart rate
○ Contractility
○ Filling pressure
 Circulating blood volume
 Venous tone 

Peripheral resistance
arterial blood pressure = cardiac output x peripheral resistance

Question 2

What are the mechanisms involved in regulating blood pressure?

Answer 2

Neuronal:
 Sympatho-adrenal
system (S)
 Central regulation of S

Humoral:
 RAAS
 Others: NO

Local:
 Intracellular calcium

Question 3

How are antihypertensive drugs classified?

Answer 3

 Diuretics

 Drugs acting on RAAS:
 АСЕ-inhibitors
 АТ1 receptor blockers (ARBs)
 Direct renin inhibitors
 Aldosterone antagonists

 Adrenergic agents:
 Beta adrenergic blockers (BABs)
 1-selective blockers
 Centrally acting sympatholytic drugs

 Calcium channel blockers
 Vasodilators

Question 4

How are diuretics classified?

Answer 4

 Thiazides and analogs:

• Hydrochlorothiazide
• Chlorthalidone
• Indapamide

 Loop diuretics:

• Furosemide
• Torаsemide

 Potassium-sparing
diuretics:
 Aldosterone antagonists
○ Spironolactone
○ Eplerenone
 Blockers of amilorid-sensitive
sodium channels
○ Triamterene

Question 5

What is the mechanism of action, clinical use, ADR of thiazides, and analogs?

Answer 5

Thiazides and analogs: (Hydrochlorothiazide, Chlorthalidone)

 Mechanism:
○ Direct vasodilating effect (lower doses) – opening of K+ channels
○ Diuretic effect (higher doses)

 Clinical use:
○ Evidence-based efficacy in hypertension – recognized as first-line therapy
○ Preferred in patients with isolated systolic hypertension and concomitant chronic
heart failure
○ Cheap drugs

 ADR:
○ Potassium loss
○ Hyperuricemia (contraindicated in gout)
○ Hyperglycemia (not preferred in patients with diabetics and reduced glucose
tolerance)
○ Hyperlipidemia (↑ cholesterol and LDL)
○ Allergic reactions (cross-hypersensitivity to sulfonamides)

Question 6

What is the clinical use of loop diuretics?

Answer 6

Loop diuretics: (Furosemide, Torаsemide)
 Clinical use:
○ In emergency: hypertensive crisis

Question 7

What are the clinical uses of potassium-sparing diuretics?

Answer 7

Potassium-sparing diuretics (Spironolactone, Eplerenone, Triamterene)
 Clinical use:
○ In combination with potassium-losing diuretic to prevent potassium loss

Question 8

What is the mechanism, PD, ADR, and clinical uses of indapamide?

Answer 8

 Mechanism:
○ Vasodilation
 Block of Ca2+ channels
  PGE and PGI2
○ Weak diuretic effect

 PD
○  moderately the systolic and diastolic blood pressure
○ Neutral to carbohydrate and lipid metabolism

 ADR
 Mild hypokalemia
 Mild hyperuricemia

 Clinical use
○ Only as an antihypertensive drug
○ It is preferred in patients with concomitant diabetes

Question 9

Which adrenergic drugs are used as anti-hypertensives?

Answer 9

 Non-selective (beta1
, beta2)
-Propranolol

 Selective (beta1)

• Metoprolol
• Atenolol
• Bisoprolol

 Vasodilating

• Carvedilol
• Nebivolol

Question 10

What is the mechanism of the antihypertensive effect of BAB?

Answer 10

Mechanisms of the antihypertensive effect:
 decreased cardiac output (beta1)
○ ↓ stroke volume
○ ↓ heart rate
 decreased release of renin (beta1)
 Pre-synaptic beta-blockade (beta2)
 Central effect (lipophilic BABs)

Question 11

What is the mechanism counteracting the antihypertensive effect of BAB?

Answer 11

Mechanisms counteracting the antihypertensive effect:

 Increase in the peripheral resistance (beta2) – nonselective BABs

Question 12

What is the clinical use of BABs as antihypertensive drugs?

Answer 12

 For monotherapy and combination therapy in hypertension
 In patients with hypertension + angina
pectoris
 In patients with hypertension +
supraventricular tachyarrhythmias
 In pregnancy

Question 13

Which alpha-adrenergic blockers are used as antihypertensive drugs? what is their mechanism of actuon? what are the other effects and clinical uses?

Answer 13

 Drugs
 Prazosin, doxazosin

Mechanism of action
 α1-block -> decrease peripheral resistance &
decrease hypertrophy of LV and vascular wall

Other effects
 In prostate hypertrophy
 increased HDL

 Clinical use
 Not recommended as first-line therapy
 In combination regimens
 Useful for patients with prostate hypertrophy and with diabetes

Question 14

Which are the centrally acting sympatholytic drugs? what are their clinical uses?

Answer 14

Drugs
 α2-agonists: Clonidine, Methyldopa –
presynaptic effect:  release of NE

 I1
(imidazolyl) agonists: Moxonidine,
Rilmenidine – in depressor regions in the
medulla

Clinical use
 In combination with other antihypertensive
drugs
 In an emergency (hypertensive crises)
(Сlonidine)
 In pregnancy (Methyldopa)

Question 15

What is the pathogenic role of RAAS in hypertension?

Answer 15

Long-term activation
of RAAS leads to:

 Elevation of blood
pressure
-Vasoconstriction
-Na+
re-absorption
and water retention
 LV hypertrophy
 Glomerulosclerosis
with proteinuria

Question 16

What are the effects of ACEis in hypertension?

Answer 16

Effects in hypertension
 decreased peripheral resistance
 Reversal of cardiovascular remodeling
○ decreased LV hypertrophy
○ decreased M/L ratio in vascular wall
 Reversal of endothelial dysfunction
 Anti-inflammatory potential (decreased C-reactive protein)

Clinical use
 First-line drugs in hypertension, especially in patients with diabetic
nephropathy
 Mandatory in patients with chronic heart failure (if not
contraindicated)

Question 17

What are the uses of ARBs in antihypertensive drugs?

Answer 17

Angiotensin receptor blockers (ARBs): Losartan,
Valsartan, etc.
 Clinical use
 As ACEI alternatives in intolerant patients

Question 18

What is the use of direct renin inhibitors - aliskiren as anti-hypertensives?

Answer 18

Direct renin inhibitors: Aliskiren
 Clinical use
- Arterial hypertension; especially in patients with
diabetes (renal protection)

Question 19

What is the use of aldosterone antagonists as antihypertensive drugs?

Answer 19

Effects
 decreased cardiac and vascular remodeling
 Renoprotective action (in diabetic/hypertensive
patients)
 Diuretic effect

Clinical use
 In combination with thiazides and related drugs

Question 20

What is the mechanism of CCBs as antihypertensive agents?

Answer 20

Mechanism of antihypertensive action :
 DHP: decreased peripheral resistance (tendency to cause
reflex tachycardia)
 Non-DHP: decreased cardiac output

Clinical use
 Drugs for monotherapy, particularly in patients
with:
○ asthma
○ diabetes
○ peripheral vascular disease
 In combination with other antihypertensive drugs

Question 21

What is the use of nitroprusside (vasodilator) as an antihypertensive drug?

Answer 21

Nitroprusside:
 IV administration (continuous infusion
because of the short t1/2 due to rapid
metabolism); sensitive to light
 Prompt vasodilation (arteriolar and
venous) and rapid reduction of blood
pressure
○ Mechanism: stimulation of GC (↑ cGMP) directly or
release of NO

 Clinical use
○ In hypertensive emergencies
○ In acute heart failure