This document discusses various classes of antihypertensive drugs including diuretics, ACE inhibitors, angiotensin receptor blockers, and calcium channel blockers. It provides details on their mechanisms of action, pharmacokinetics, therapeutic uses, side effects, and contraindications. Diuretics are first-line treatment for mild to moderate hypertension and work by increasing sodium excretion. ACE inhibitors and ARBs block the renin-angiotensin-aldosterone system to lower blood pressure. Calcium channel blockers inhibit calcium channels to cause vasodilation and lower blood pressure.
2. TOPICS TO BE DISCUSSED
▪ Diuretics
▪ ACE inhibitors
▪ Angiotensin receptor blockers
▪ Calcium channel blockers
3. Diuretics
First line of drugs for mild to moderate Hypertension
Used in patients with adequate renal function.
They do not lower BP in normotensives.
4. Diuretics-Definition And Classification
Def : These are the drugs which cause a net loss of sodium and water
in urine.
Classification :
1) Thiazides : Hydrochlorothiazide, Chlorthalidone, Indapamide.
2) High ceiling : Furosemide.
3) Potassium sparing : Spironolactone , Amiloride.
6. ADVANTAGES OF USING THIAZIDES
▪ During long term treatment with thiazides – heart rate and
cardiac output remain unaffected.
▪ It has no effect on capacitance vessels .
▪ Sympathetic reflexes are not impaired.
▪ Postural hypotension is rare.
12. Loop Diuretics
▪ The loop diuretics act promptly, even in patients with poor renal
function or who have not responded to thiazides or other
diuretics.
▪ Loop diuretics cause decreased renal vascular resistance and
increased renal blood flow.
▪ Loop diuretics increase the Ca2+ content of urine, whereas
thiazide diuretics decrease it.
13. Loop diuretics-mechanism of action
inhibits apical Na-K-2Cl transporter in thick ascending loop of
henle
competes with Cl- binding site
enhances passive Mg2+ and Ca2+ excretion
increased K+ and H+ excretion in CCD
inhibits reabsorption of ~25% of glomerular filtrate
19. K+ sparing diuretics
▪ Spironolactone or Amiloride lower B.P slightly
▪ They are used only in conjugation with thiazide diuretics to
prevent K+ loss
augment anti-hypertensive action
used in HTN due to primary hyperaldosteronism
20. Mechanism of Action
K+ sparing diuretics function in CCD
decrease Na+ transport in collecting tubule
Triamterene/Amiloride
inhibit apical Na+ channel
Spironolactone
competitive antagonist for mineralocorticoid receptor
prevents aldosterone stimulated increases in Na+ transporter expression
25. RENIN ANGIOTENSIN-ALDOSTERONE
SYSTEM
▪ A system which works to increase Blood pressure when the pressure
within the kidney drops.
▪ As a result of low blood pressure and/or oxygenation in the nephron,
renin is released from Juxtaglomerular cells.
▪ Renin travels to the liver via the cardiovascular system and combines
with angiotensinogen to formAngiotensin 1.
▪ Angiotensin 1 travels through the cardiovascular system and arrives
at the lungs where it is changed into Angiotensin 2.
▪ The alveoli use Angiotensin Converting Enzyme also known as Kinase
2 to cause this conversion.
26. CONTD...
▪ Angiotensin 2 is a powerful vasoconstrictor which causes a rise in
peripheral resistance and increases pressure.
▪ Angiotensin 2 works to increase the release of Aldosterone from the
adrenal glands.
▪ Aldosterone causes renal retention of sodium and water, which
further increases blood pressure by increasing volume.
27. And 2 types of Drugs Act on
This Renin Angiotensin
Aldosterone system
1.ACE Inhibitors
2.ARBs
29. Introduction
These drugs block the ACE that cleaves Angiotensin-1 to form potent
vasoconstrictor Angiotensin-2.
These are first choice of drugs in All grades of essential as well as Reno-Vascular
Hypertension.
These drugs lower BP by reducing peripheral vascular resistance without reflexively
increasing Cardiac output rate or contractility.
They have Renal blood flow improving action and also have potential to retard
Diabetic Nephropathy
More effective in younger hypertensives than in elderly.
More effective when given in conjugation with Diuretics or Beta blockers.
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32. Pharmacokinetics
▪ All ACEs except Captopril and Lisinopril are connverted to active
metabolites.
▪ Enalapril : Converted to Enalaprilat, t ½ is 11 hours, renally
excreted , unchanged .
▪ Captopril Short t ½ of 3 hours.
▪ lisinopril : water soluble , not hepatically metabolised.
33. Clinical uses of ACEIs
▪ Treatment of hypertension .
▪ Treatment of heart failure .
▪ Secondary prevention after myocardial infarction .
▪ Diabetic nephropathy in insulin dependent diabetes .
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34. Side effects
▪ Cough that is nonproductive not dose related caused by
accumulation of kinins in the lung .
▪ Postural hypotension can occur , particularly after the first
dose .
▪ Rashes .
▪ Angioedema .
▪ Hyperkalemia.
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36. Interactions
▪ Drug-drug :
Digoxin: may increase digoxin level by 15% to 30%.
Iithium :increase lithium levels and symptoms of toxicity possible.
K sparing diuretics , K supplements may cause hyperkalemia.
▪ Drug-food:
salt substitutes containing K : increase K level .
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38. Introduction
▪ Angiotensin 2 is a very potent chemical that causes the muscles
surrounding the blood vessels to contract, thus narrowing of
vessels causing high Blood pressure.
▪ The angiotensin II receptor blockers (ARBs) are alternatives to the
ACE inhibitors.
▪ These drugs allow angiotensin1 to be converted to angiotensin2
but block the receptors that receive Angiotensin2
▪ block vasoconstriction and release of Aldosterone
▪ ARBs decrease the nephrotoxicity of diabetes, making them an
attractive therapy in hypertensive diabetics.
39. Angiotensin Receptor
▪ Distinct subtypes of Ang2 receptors are designated as AT1 and
AT2.
▪ The AT1 receptor subtype is located predominantly in vascular
and myocardial tissue and also in the brain, kidney, and adrenal
glomerulosa cells , which secretes Aldosterone.
42. Mechanism of Action
▪ Block AT1 receptors in
Vascular Smooth muscle Adrenal Cortex
Vaso dilatation Reduced Aldosterone Secretion
43. Contd...
▪ they do not inhibit AT2 receptors.
▪ Have no effect on bradykinin metabolism and are more selective
blockers of angiorensin effects than ACE inhibitors.
47. Advantages of ARBs over ACE inhibitors
Do not induce cough
Low incidence of Angioedema, rash , dysguesia.
They are as effective as ACE inhibitors in CHF, MI and Diabetic
Nephropathy.
49. Introduction
▪ Calcium-channel blockers are recommended when the preferred
first-line agents are contraindicated or ineffective.
▪ They are effective in treating hypertension in patients with angina
or diabetes.
▪ High doses of short-acting calcium channel blockers should be
avoided because of increased risk of myocardial infarction due to
excessive vasodilation and marked reflex cardiac stimulation.
51. CCBs – Mechanisms of Action
They act by inhibiting L type of voltage sensitive calcium channels
in smooth muscles and heart.
This causes decreased peripheral smooth muscle tone,
decreased systemic vascular resistance
Result : decreased blood pressure
52. Why Do CCBs Act Selectively
on Cardiac andVascular Muscle?
53. CCBs Act Selectively on CardiovascularTissues
Neurons rely on N-and P-type Ca2+ channels
Skeletal muscle relies primarily on [Ca]i
Cardiac muscle requires Ca2+ influx through
L-type Ca2+ channels
- contraction
- upstroke of AP
Vascular smooth muscle requires Ca2+ influx
through L-type Ca2+ channels for contraction
54. Pharmacokinetics
▪ Well absorbed through GIT.
▪ First pass metabolism.
▪ Highly bound to plasma proteins.
▪ Metabolism in liver.
▪ Excreted through urine.
55. USES OF CCBs..
1. angina pectoris - Due to decrease in myocardial oxygen consumption, and dilatation of
coronary arteries.
2. supraventicular arrhythmias - because of its depressant action on S-A and A-V nodes.
3. hypertension - they control blood pressure by their vasodilatory effect.
4. Migraine
5. raynaud’s phenomenon - due to their vasodilatory property.
56. Side Effects of calcium antagonists
1. Arterial dilation: headache, flush, dizziness,
ankle swelling
2. Bradycardia and AV block
3. cardiodepression.
4. Constipation
5. Haemorrhagic gingivitis
58. CONTRAINDICATIONS
o Heart failure
o Bradycardia
o Atrioventricular block.
o Dihydropyridine calcium-channel blockers should not be used in people
with uncontrolled heart failure.
