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Antihypertensive drugs
Hypertension
• Most common CVS condition
• Persistant and sustained increased BP has
damaging effect on heart, brain, kidney, eye
• Types
– Primary /essential
• No specific cause 95% cases
– Secondary hypertension
• Due to specific disease or drug 5% cases
Physiology of Hypertension
Angiotensin I
Angiotensin II
Aldosterone
Na+ retention
Volume ↑ Arteriolar wall
↑Blood pressure
Renin
Central Mechanisms
Hypothalamus
Sympathetic Ganglia
Post ganglionic adrenergic
nerve endings
Baroreceptors
Classification Of Antihypertensives
1. Angiotensin Converting Enzyme inhibitors
– Captopril, Enalapril, Lisinopril, Ramipril
2. Angiotensin II receptor Antagonists
– Losartan
3. Calcium channel blockers
– Verapamil, Nifedipine, Amlodipine
4. Diuretics
5. Sympatholytics
6. Vasodilators
Classification of antihypertensives
• Diuretics
– Thiazides: Hydrochlorthiazide, chlorthalidone
– Loop diuretics: furosemide
– K sparing diuretics: Spironolactone, Amiloride,
Triamterine
• Sympatholytics
– Centrally acting: clonidine, Methyl dopa
– Adrenergic receptor blocker:
• Alpha blocker: Prazozin
• Beta Blockers: propranolol, atenolol
• Combined ALPHA + BETA blocker: Labetolol
• Vasodilators:
– Arterial dilators: Hydralazine, minoxidil, diazoxide
– Arteriovenous dilators: sodium nitroprusside
Classification of antihypertensives
Angiotensin converting enzyme
inhibitors (MOA)
• Inhibit generation of Angiotensin II
• Inhibit degradation of bradykinin which is
potent vasodilator
• Dilates both arteries & vein
• Blood flow to vital organs increases
• Decrease aldosterone production indirectly
Pharmacokinetics
• All are prodrugs except captopril & lisinopril
• All are well absorbed orally
• Food reduces absorption of captopril
• DOA of captopril is 8-12 hrs rest others > 24
hrs
• All are excreted through the kidneys
Adverse effects
• Cough
• Angioedema (0.1%)
• Proteinuria
• Taste alterations
• Teratogenic
• Severe hypOtension : first dose phenomenon
• Neutropenia
• Rashes
• Itching
• Loss of appetite, nausea, vomiting, diarrhoea
• Hyperkalemia: in renal insufficiency and with K+
sparing diuretics
Advantages of ACE inhibitors
• Lack of postural hypotension
• Safe in asthmatics, diabetes
• ↓ incidence of Type 2 DM in high risk cases
• Prevent potassium loss due to diuretics
• Reverse Left ventricular hypertrophy
• No hyperuricemia or derangement of lipids
• No rebound hypertension
• No effect on sexual functions
Uses of ACE inhibitors
• Hypertension: first line drug for all grades of
hypertension but specially indicated in
– Hypertension with diabetes
– Left ventricular hypertrophy
• Congestive cardiac failure
• Myocardial Infarction
• Diabetic Nephropathy
• Scleroderma renal crisis
Angiotensin receptor blockers(ARBs)
(Losartan)
• AT1:
– Vasoconstriction, aldosterone secretion, release NA
• AT2 receptor:
– Function is not known
• ARBs: competitively inhibit binding of angiotensin
II to AT1 receptor
• Has similar effects like ACE inhibitors
• Uses are similar to ACE inhibitors
• Mainly used in patients who cough with ACE
inhibitors
Advantage of Losartan over ACE
inhibitors
•There is no increase in
bradykinin levels
•So less adverse effects like
dry cough & angioedema
Adverse effects
• Headache
• Hypotension
• Hyperkalemia
• Weakness, rashes
• Vomiting
• Teratogenic
Calcium channel blockers
• Nifedipine & Amlodipine preferred
• MOA: decrease PVR without compromising
cardiac output (Vasodilation)
• Adverse effects:
– Headache, flushing, tachycardia, Palpitation
• Sustained release preparations have less side
effects
• Beta blockers counteract reflex tachycardia
• Useful in pt with angina, Ashtma, PVD,
Migraine, hyperlipidemia, diabetes
Diuretics
Inhibit Na+-Cl- Symport in early DCT
Promote Na & water excretion
↓COP & BP ↓Na+ conc in vascular smooth muscles
↓PVR
↓BP
Adverse effects of Thiazide diuretics
• Hypokalemia
• Hyperglycemia
• Hyperuricemia
• Hypercalcemia
• Impotence & decreased libido
• Low doses 12.5 mg of hydrochlorthiazide
preferred
Sympatholytics
Beta Blockers
• MOA
– ↓ sympathetic outflow
– ↓ HR, ↓ Force of contraction and ↓COP
– ↓ renin release
• Beta blockers mainly useful in
– Young hypertensives with ↑ renin
– Associated angina, post MI, Migraine
– Patients receiving vasodilators to counteract reflex
tachycardia
Alpha adrenergic blockers
• Non selective
– Phenoxybenzamine, phentolamine
• Selective alpha1
– Prazosin, terazosin
Centrally acting sympatholytics
• Clonidine
– Highly lipid soluble, crosses blood brain barrier
– Stimulates 2a receptors in vasomotor centre
– ↓ sympathetic outflow from VMC leading to ↓HR , ↓
COP & ↓PVR thus ↓ ↓ BP.
– Adverse effects
• Dryness of mouth eyes
• Sedation, bradycardia, impotence
• Sudden withdrawal = withdrawal symptoms
• Uses:
– opioid withdrawl, diabetic neuropathy, with
anaesthetics
Vasodilators
• Hydralazine
– Direct arterial dilator
– Can be given orally
– Can cause reflex tachycardia, palpitations , Na &
water retention
– Can be countered by giving with diuretic or beta
blocker
– Other S/E: Hypotension, flushing, angina, MI,
coronary steal phenomenon, lupus erythematosus
Minoxidil
• K channel opener
• Causes hyperpolarization of vascular smooth
muscles , vasodilation and decrease BP
• Used to promote hair growth
Diazoxide
• Treatment of hypertensive emergencies
Antihypertensives to be avoided in
pregnancy
• Diuretics
– Risk of placental wastage, still births
• ACE inhibitors
– Risk of fetal damage, growth retardation
• Beta blocker
– LBW, neonatal bradycardia, hypoglycemia
Safe drugs in pregnancy
• Hydralazine
• Alpha methyl dopa
• CCBs
• Prazosin
• Clonidine
• Cardioselective beta blockers
NICE Guidelines for management of
Hypertension
*NICE: National Institute of health and Care Excellence
A= ACE INHIBITORS
C= CALCIUM CHANNEL BLOCKERS
D= DIURETICS
Younger (<55
years) and
non-Black
older (>= 55
years) or black
Step 1 A C
Step 2 A plus C C plus A
Step 3 A + C + D A + C +D
Step 4:
Resistant
Hypertension
A + C + D + consider further diuretic
(or alpha- or beta-blocker )
Consider seeking specialist advice
Drugs to be avoided in specific
conditions
• Asthma
• Peripheral vascular disease
• Diabetes
• Hyperlipidemia: Thiazides, -Blockers
• Gout: thiazides
• Sexually active males: 1-blockers, diuretics
-Blockers
Hypertensive crisis
• Hypertensive urgencies
– DBP>120 mm Hg or higher with impending
complications
– DBP needs to be reduced to 100 mm Hg in 24-48 hrs
– Severe epistaxis
– Unstable angina
• Hypertensive emergencies
– Evidence of target organ damage
– AMI, LVF, Encephalopathy
– Rapid lowering of BP within 1 hr to 150/100 mm hg
Drugs used in hypertensive crisis
• Sodium nitroprusside
• Nitroglycerine
• Labetolol
• Nifedipine
• Captopril
IV
Sublingual

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Antihypertensive drugs naser

  • 2. Hypertension • Most common CVS condition • Persistant and sustained increased BP has damaging effect on heart, brain, kidney, eye • Types – Primary /essential • No specific cause 95% cases – Secondary hypertension • Due to specific disease or drug 5% cases
  • 3. Physiology of Hypertension Angiotensin I Angiotensin II Aldosterone Na+ retention Volume ↑ Arteriolar wall ↑Blood pressure Renin Central Mechanisms Hypothalamus Sympathetic Ganglia Post ganglionic adrenergic nerve endings Baroreceptors
  • 4. Classification Of Antihypertensives 1. Angiotensin Converting Enzyme inhibitors – Captopril, Enalapril, Lisinopril, Ramipril 2. Angiotensin II receptor Antagonists – Losartan 3. Calcium channel blockers – Verapamil, Nifedipine, Amlodipine 4. Diuretics 5. Sympatholytics 6. Vasodilators
  • 5. Classification of antihypertensives • Diuretics – Thiazides: Hydrochlorthiazide, chlorthalidone – Loop diuretics: furosemide – K sparing diuretics: Spironolactone, Amiloride, Triamterine • Sympatholytics – Centrally acting: clonidine, Methyl dopa – Adrenergic receptor blocker: • Alpha blocker: Prazozin • Beta Blockers: propranolol, atenolol • Combined ALPHA + BETA blocker: Labetolol
  • 6. • Vasodilators: – Arterial dilators: Hydralazine, minoxidil, diazoxide – Arteriovenous dilators: sodium nitroprusside Classification of antihypertensives
  • 7. Angiotensin converting enzyme inhibitors (MOA) • Inhibit generation of Angiotensin II • Inhibit degradation of bradykinin which is potent vasodilator • Dilates both arteries & vein • Blood flow to vital organs increases • Decrease aldosterone production indirectly
  • 8. Pharmacokinetics • All are prodrugs except captopril & lisinopril • All are well absorbed orally • Food reduces absorption of captopril • DOA of captopril is 8-12 hrs rest others > 24 hrs • All are excreted through the kidneys
  • 9. Adverse effects • Cough • Angioedema (0.1%) • Proteinuria • Taste alterations • Teratogenic • Severe hypOtension : first dose phenomenon • Neutropenia • Rashes • Itching • Loss of appetite, nausea, vomiting, diarrhoea • Hyperkalemia: in renal insufficiency and with K+ sparing diuretics
  • 10. Advantages of ACE inhibitors • Lack of postural hypotension • Safe in asthmatics, diabetes • ↓ incidence of Type 2 DM in high risk cases • Prevent potassium loss due to diuretics • Reverse Left ventricular hypertrophy • No hyperuricemia or derangement of lipids • No rebound hypertension • No effect on sexual functions
  • 11. Uses of ACE inhibitors • Hypertension: first line drug for all grades of hypertension but specially indicated in – Hypertension with diabetes – Left ventricular hypertrophy • Congestive cardiac failure • Myocardial Infarction • Diabetic Nephropathy • Scleroderma renal crisis
  • 12. Angiotensin receptor blockers(ARBs) (Losartan) • AT1: – Vasoconstriction, aldosterone secretion, release NA • AT2 receptor: – Function is not known • ARBs: competitively inhibit binding of angiotensin II to AT1 receptor • Has similar effects like ACE inhibitors • Uses are similar to ACE inhibitors • Mainly used in patients who cough with ACE inhibitors
  • 13. Advantage of Losartan over ACE inhibitors •There is no increase in bradykinin levels •So less adverse effects like dry cough & angioedema
  • 14. Adverse effects • Headache • Hypotension • Hyperkalemia • Weakness, rashes • Vomiting • Teratogenic
  • 15. Calcium channel blockers • Nifedipine & Amlodipine preferred • MOA: decrease PVR without compromising cardiac output (Vasodilation) • Adverse effects: – Headache, flushing, tachycardia, Palpitation • Sustained release preparations have less side effects • Beta blockers counteract reflex tachycardia • Useful in pt with angina, Ashtma, PVD, Migraine, hyperlipidemia, diabetes
  • 16. Diuretics Inhibit Na+-Cl- Symport in early DCT Promote Na & water excretion ↓COP & BP ↓Na+ conc in vascular smooth muscles ↓PVR ↓BP
  • 17. Adverse effects of Thiazide diuretics • Hypokalemia • Hyperglycemia • Hyperuricemia • Hypercalcemia • Impotence & decreased libido • Low doses 12.5 mg of hydrochlorthiazide preferred
  • 18. Sympatholytics Beta Blockers • MOA – ↓ sympathetic outflow – ↓ HR, ↓ Force of contraction and ↓COP – ↓ renin release • Beta blockers mainly useful in – Young hypertensives with ↑ renin – Associated angina, post MI, Migraine – Patients receiving vasodilators to counteract reflex tachycardia
  • 19. Alpha adrenergic blockers • Non selective – Phenoxybenzamine, phentolamine • Selective alpha1 – Prazosin, terazosin
  • 20. Centrally acting sympatholytics • Clonidine – Highly lipid soluble, crosses blood brain barrier – Stimulates 2a receptors in vasomotor centre – ↓ sympathetic outflow from VMC leading to ↓HR , ↓ COP & ↓PVR thus ↓ ↓ BP. – Adverse effects • Dryness of mouth eyes • Sedation, bradycardia, impotence • Sudden withdrawal = withdrawal symptoms • Uses: – opioid withdrawl, diabetic neuropathy, with anaesthetics
  • 21. Vasodilators • Hydralazine – Direct arterial dilator – Can be given orally – Can cause reflex tachycardia, palpitations , Na & water retention – Can be countered by giving with diuretic or beta blocker – Other S/E: Hypotension, flushing, angina, MI, coronary steal phenomenon, lupus erythematosus
  • 22. Minoxidil • K channel opener • Causes hyperpolarization of vascular smooth muscles , vasodilation and decrease BP • Used to promote hair growth Diazoxide • Treatment of hypertensive emergencies
  • 23. Antihypertensives to be avoided in pregnancy • Diuretics – Risk of placental wastage, still births • ACE inhibitors – Risk of fetal damage, growth retardation • Beta blocker – LBW, neonatal bradycardia, hypoglycemia
  • 24. Safe drugs in pregnancy • Hydralazine • Alpha methyl dopa • CCBs • Prazosin • Clonidine • Cardioselective beta blockers
  • 25. NICE Guidelines for management of Hypertension *NICE: National Institute of health and Care Excellence A= ACE INHIBITORS C= CALCIUM CHANNEL BLOCKERS D= DIURETICS Younger (<55 years) and non-Black older (>= 55 years) or black Step 1 A C Step 2 A plus C C plus A Step 3 A + C + D A + C +D Step 4: Resistant Hypertension A + C + D + consider further diuretic (or alpha- or beta-blocker ) Consider seeking specialist advice
  • 26. Drugs to be avoided in specific conditions • Asthma • Peripheral vascular disease • Diabetes • Hyperlipidemia: Thiazides, -Blockers • Gout: thiazides • Sexually active males: 1-blockers, diuretics -Blockers
  • 27. Hypertensive crisis • Hypertensive urgencies – DBP>120 mm Hg or higher with impending complications – DBP needs to be reduced to 100 mm Hg in 24-48 hrs – Severe epistaxis – Unstable angina • Hypertensive emergencies – Evidence of target organ damage – AMI, LVF, Encephalopathy – Rapid lowering of BP within 1 hr to 150/100 mm hg
  • 28. Drugs used in hypertensive crisis • Sodium nitroprusside • Nitroglycerine • Labetolol • Nifedipine • Captopril IV Sublingual

Editor's Notes

  1. BP = COP X TPR
  2. Ganglion blocker: trimethaphan Adrenergic neurone blocker: Guanethidine, reserpine
  3. Preferred in younger age group Scleroderma renal crisis
  4. Two types of receptors AT1 receptors present in Vascular and myocardial tissue, brain , kidney and adrenal glomerular cells
  5. Losartan is a competitive antagonist and inverse agonist at AT1 receptors it is 10,000 more selective , 33 % bioavailable, 98% plasma protein bound , doesnot cross the BBB Dose= 50 mg OD
  6. Verapamil & diltiazem – no reflex tachycardia, due to their greater cardiac depressant effect. Advantages:No sedation, CNS side effects, do not impair renal perfusion, do not effect male sexual dysfunction. No teratogenicity.
  7. Caution: PPT CHF, bronchial asthma, diabetics, should not be withdrawn abruptly
  8. Alpha 1 inhibition: vasodilation, decreased bp, alpha 2 inhibition-increases the NA release and increases the heart rate Selective alpha 1 blockers cause no increase in HR. Non selective drugs preferred for hypertenive treatment of pheochromocytoma, clonidine withdrawl and cheese reaction Side effect: postural hypotension.
  9. Uses: hypertension, treatment of opioid and alcohol addict, preanaesthetic medication, antidiarrhoeal in diabetic neuropathy , glaucoma, migraine, hot flushes
  10. Metabolized by acetylation