This document provides information on anti-hypertensive drugs. It defines classifications of blood pressure and hypertension. It discusses the epidemiology of hypertension in India. It lists risk factors and causes of primary and secondary hypertension. It describes non-pharmacological and pharmacological management of hypertension including classifications of anti-hypertensive drugs like diuretics, ACE inhibitors, ARBs, calcium channel blockers, beta blockers, and alpha blockers. It discusses the pathophysiology of hypertension including the renin-angiotensin-aldosterone system. It provides details on mechanisms of action, uses, adverse effects and contraindications of different anti-hypertensive drug classes.

1. Anti-Hypertensive Drugs

2. • Elevated blood pressure
BP Category Systolic BP (mmHg) Diastolic BP (mmHg)
Normal < 120 < 80
Elevated 120-139 80-89
Hypertension
Stage 1 140-159 90-99
Stage 2 ≥ 160 ≥ 100
White Coat
Hypertension
Office/Clinic/ Healthcare Setting Hypertension
> 130 /80 mmHg but less than < 160/100 mmHg
Masked Hypertension Home/Nonhealthcare Hypertension
Hypertension

3. • 1 in 4 adults in India has
hypertension
• Out of them, 12% under control
• Target to decrease the prevalence
of hypertension by 25% by 2025
• 24% in men and 21% in women
Epidemiology
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4. Risk Factors Present in Patients with Hypertension
• Smoking
• Diabetes mellitus
• Dyslipidemia
• Hypercholesterolemia
• Overweight / Obesity
• Physical inactivity
• Unhealthy diet
Modifiable Non-Modifiable
• CKD
• Family history
• Increased age
• Low socioeconomic
• Educational status
• Male sex
• Obstructive sleep apnea
• Psychosocial stress

5. Secondary Hypertension
1. Renovascular diseases
2. Primary aldosteronism
3. Obstructive sleep Apnea
4. Drug / Alcohol
5. Pheochromocytoma
6. Cushing’s syndrome
7. Hypo/Hyperthyroidism
8. Aortic coarctation
Primary Hypertension
Idiopathic / Unknown
Genetic
Environmental:
Overweight and Obesity
Sodium Intake
Physical inactivity
Alcohol Consumption
Causes of Hypertension

6. Weight Loss Potassium supplementation
Dietary changes – DASH Diet Consume
a diet rich in fruits, vegetables, whole grains,
and low-fat dairy products, with reduced
content of saturated and total fat.
Increased physical activity 90–
150 min/week
Salt restriction - < 1500 mg/d Quit alcohol, smoking
Nonpharmacological Management

7. Pathophysiology of Hypertension
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↑ ↑ ↑ ↑

8. Pathophysiology of Hypertension
1. Decreased renal sodium reabsorption /
Sodium retention
2. Increased activity of renin angiotensin
aldosterone system
3. Activation of sympathetic nervous system /
Autonomic imbalance
4. Decreased diameter of small arteries and
arterioles and Remodeling

9. Pathophysiology of Hypertension
Prorenin
Renin
Angiotensinogen Angiotensin I
Angiotensin II Receptors
AT1 AT2
Angiotensin II
ACE
ACE = Angiotensin Converting Enzyme
Bradykinin Inactive peptides
Aldosterone
Sodium and
Water Retention
Low macula densa Na and Cl
Low glomerular afferent pressure
Enhanced sympathetic activIty

10. ↑ SNS
Activity
Pathophysiology of Hypertension
Systemic Inflammation
Stress
Increased Salt
Obesity
Baroreceptor Dysfunction
RAAS Activation
Vasoconstricti
on
Salt retention
Endothelial
Dysfunction

11. To decrease blood pressure to threshold level
Primary prevention of CVD in adults with no history of CVD
Secondary prevention of recurrent CVD events in
patients with clinical CVD
Goals of Anti-hypertensive Therapy
Why to treat hypertension……
To prevent end organ damage – Cerebrovascular disease, stroke,
TIA, Encephalopathy, glomerulopathy, renal failure

12. Classification of Anti-hypertensive Therapy

13. Classification of Anti-hypertensive Therapy

14. Diuretics - An agent that increases urine volume & sodium excretion.
High Ceiling
Diuretics
Furosemide,
Bumetanide,
Torasemide
Medium Ceiling
Diuretics
• Thiazide:
Hydrochlorothizide,
Benzthiazide
• Thiazide Like
Chlorthalidone,
Indapamide,
Metolazone,
Xipamide
Weak Diuretics
•Carbonic Anhydrase Inhibiotrs:
Acetazolamide
•Osmotic Diuretics: Mannitol,
Glycerol
•Potassium Sparing Diuretics
a. Aldosterone Antagonist:
Spironolactone, Eplerenone
b. Renal Epithelial Na+ Channel
Inhibitors: Amiloride, Triamterene

15. Thiazide Diuretics - Inhibitors of Na+-Cl- symport

16. Thiazide Diuretics - Inhibitors of Na+-Cl- symport
• Site of Action: Early DCT or Cortical Diluting segment
• Mechanism: inhibit Na+-Cl- symport at the luminal membrane
• Weak carbonic anhydrase activity
• ↓ GFR; not effective in low GFR

17. Thiazide Diuretics - Inhibitors of Na+-Cl- symport
• S/E:
1. Hypotension
2. Metabolic and electrolyte abnormalities
• Hypokalemia, Hyponatremia, Hypochloremia , Metabolic alkalosis,
Hypomagnesemia, Hypercalcemia
• Hyperuricemia, Hyperglycemia, Dyslipidemia
3. Hypersensitivity reactions – Sulfa group
4. Erectile Dysfunction
5. Drug Interactiosn:
1. ↓ effects of uricosuric agents used to treat gout, sulfonylureas, and insulin
2. Effect of thiazides decreased by NSAIDs
3. QTc prolongation if given with drugs that prolong the QT interval

18. Thiazide Diuretics - Inhibitors of Na+-Cl- symport
• Uses:
1. Hypertension – 12.5-25 mg/d
2. Edema – CCF, Cirrhosis, Nephrotic syndrome
3. Diabetes insipidus
4. Calcium stone prevention

19. Loop Diuretics – Na+-K+-2Cl− Symport Inhibitors

20. • Site of Action: ascending limb of loop of Henle (TAL)
• Mechanism: inhibit Na+-K+-2Cl− Symport Inhibitors
• Weak carbonic anhydrase activity
Loop Diuretics – Na+-K+-2Cl− Symport Inhibitors

21. • Adverse Effects:
1. Hypotension
2. Hyponatremia
3. Circulatory prolapse
4. Metabolic and electrolyte abnormalities
• Hypokalemia (arrhythmia), hypomagnesemia (cardiac arrhythmias),
hypocalcemia (tetany), Hypochloremic alkalosis
• Hyperuricemia (gout), hyperglycemia (precipitating diabetes mellitus), ↑
LDL and triglycerides while ↓ HDL cholesterol.
5. Ototoxicity - tinnitus, hearing impairment, deafness, vertigo, and
sense of fullness in the ears
Loop Diuretics – Na+-K+-2Cl− Symport Inhibitors

22. • Contraindications and Precautions:
1. Postmenopausal women with low calcium level
2. Avoided with other ototoxic drugs
3. Drug Interactions
• Aminoglycosides, carboplatin, paclitaxel, and others (synergism of ototoxicity)
• Digitalis glycosides (increased digitalis-induced arrhythmias)
• Sulfonylureas (hyperglycemia)
• Cisplatin (increased risk of diuretic-induced ototoxicity)
• NSAIDs (blunted diuretic response and salicylate toxicity with high doses of salicylates)
• Probenecid (blunted diuretic response)
• Thiazide diuretics (synergism of diuretic activity of both drugs  profound diuresis)
• Amphotericin B (increased potential for nephrotoxicity and ↑ electrolyte imbalance)
Loop Diuretics – Na+-K+-2Cl− Symport Inhibitors

23. • Uses:
1. Edema – CCF, Liver cirrhosis, Nephrotic syndrome, acute
pulmonary edema, chronic kidney disease
2. Forced diuresis in drug overdose
3. Hypercalcemia - with isotonic saline
4. Life threatening hyponatremia – with hypertonic saline
5. Hypertension – used in patients low GFR
Loop Diuretics – Na+-K+-2Cl− Symport Inhibitors

24. K+-Sparing Diuretics: Aldosterone Antagonists

25. K+-Sparing Diuretics: Inhibitors of Renal
Epithelial Na+ Channels
Late DCT and CT luminal membrane Renal Epithelial Na+ Channels (ENaC)
Na+ entry into cells
depolarizes the luminal membrane producing transepithelial voltage
secretion of K+ into the lumen via K+ channels
Amiloride Inhibits

26. • Spironolactone:
• Steroid
Aldosterone
late DT and CD cells
Bind intracellular mineralocorticoid receptor (MR)
Induces the formation of aldosterone-induced proteins(AIPs)
promote Na' reabsorption and K+ excretion
K+-Sparing Diuretics: Aldosterone Antagonists
Spironolactone binds

27. • Spironolactone:
• No effect on Na+ and K+ transport in the absence of aldosterone
• Affinity to progesterone and androgen receptors: gynecomastia, impotence,
and menstrual irregularities
• Uses:
1. Co-administered with thiazide or loop diuretics in the treatment of edema
and hypertension
2. Resistant hypertension due to primary hyperaldosteronism
3. Diuretics of choice in patients with hepatic cirrhosis
4. Added to other diuretics in heart failure with reduced ejection fraction
5. To decrease proteinuria in CKD patients
6. Hirsutism and acne
K+-Sparing Diuretics: Aldosterone Antagonists

28. • S/E, precautions, Drug interactions
1. Hyperkalemia – Avoided with K+ supplements, ACE inhibitors/ARBs.
2. Gynecomastia, impotence, decreased libido, and menstrual irregularities
3. Skin rashes, diarrhea and epigastric distress
4. Metabolic acidosis
5. Contraindicated in Peptic ulcer
6. Salicylates decrease diuretic efficacy of spironolactone
K+-Sparing Diuretics: Aldosterone Antagonists

29. Pathophysiology of Hypertension

30. Pathophysiology of Hypertension
Ang II

31. Pathophysiology of Hypertension
Angiotensin II Receptors
AT1 AT2
Vasodilation
Anti-hypertrophy
Anti-fibrosis
Natriuresis
Anti-apoptotic
Anti-Growth
↓ Remodeling
Vasoconstriction
Hypertrophy
Proliferation
Angiogenesis
Fibrosis
Inflammation
Nephropathy

32. Drugs affecting Renin Angiotensin Aldosterone
System
1. Angiotensin converting Enzyme Inhibitors –
Captopril, Enalapril, Lisinopril, Benazepril, Ramipri, Fosinopril,
Quinapri, Trandolapril, Perindopril
2. Angiotensin receptor blockers –
Losartan, Candesartan, Valsartan, Telmisartan, Olmesartan and
Irbesartan.
3. Direct Renin Inhibitors
Aliskiren`

33. Angiotensin Receptor Blockers
Prorenin
Renin
Angiotensinogen Angiotensin I Angiotensin II
ACE
ACE = Angiotensin Converting Enzyme
inhibitors
Bradykinin Inactive peptides
Aldosterone
Sodium and
Water Retention
Vasodilatation

34. Angiotensin Converting Enzyme Inhibitors
• Adverse Effects:
1. Hypotension
2. Dry Cough
3. Hyperkalemia
4. Rash, urticaria, angioedema
5. Dysgeusia
6. Fetopathic
7. Headache, dizziness, nausea and
bowel upset
8. Granulocytopenia and proteinuria
9. Acute Renal Failure
• Contraindications:
1. Pregnancy
2. K+ supplements/ K+ sparing
diuretics
3. Bilateral Renal Artery stenosis
4. Along with NSAIDs – reduce
antihypertensive effect
5. With digoxin/ lithium –
increase plasma level and
toxicity

35. Angiotensin Converting Enzyme Inhibitors
• Uses:
1. Hypertension
2. Congestive Cardiac Failure
3. Myocardial infarction
4. Prophylaxis in high CV subjects
5. Diabetic Nephropathy
6. Scleroderma Crisis
7. Captopril test – diagnosis of renovascular hypertension

36. Angiotensin Receptor Blockers
Prorenin
Renin
Angiotensinogen Angiotensin I
Angiotensin II Receptors
AT1 AT2
Angiotensin II
ACE
ACE = Angiotensin Receptor Blockers
Bradykinin Inactive peptides
Aldosterone
Sodium and
Water Retention

37. • Advantages over ACE inhibitors
1. Do not interfere with degradation of bradykinin and other ACE
substrates: cough is rare.
2. More complete inhibition of AT1 receptor activation
3. Indirect AT2 receptor activation.
4. ARBs cause little increase in the level of Ang( 1-7) which is raised by
ACE inhibitors
Angiotensin Receptor Blockers

38. • Uses:
1. Hypertension
2. Congestive Cardiac Failure
3. Myocardial infarction
4. Diabetic Nephropathy
Angiotensin Receptor Blockers

39. Calcium Channel Blockers
• Types of calcium Channels

40. Calcium Channel Blockers
• Classification

41. Calcium Channel Blockers
• Mechanism

42. Calcium Channel Blockers
• Mechanism

43. Calcium Channel Blockers
• Adverse Effects and drug interaction:
1. Hypotension
2. Verapamil
• Constipation, bradycardia, nausea
• Cardiac arrest in preexisting heart patients
• Contraindicated in AV / heart block, along with beta blockers, left
ventricular dysfunction
• ↑ digoxin toxicity
• Avoided with other cardiac depressants
3. DHPs
• Ankle edema,
• Reflex tachycardia, flushing, headache
• Worsening of GERD
• Avoided in left ventricular dysfunction Amlo/Felodipine

44. Calcium Channel Blockers
• Uses:
1. Hypertension
2. Angina pectoris
3. Cardiac arrhythmia – Supraventricular tachycardia
4. Hypertrophic Cardiomyopathy verapamil
5. Premature labour
6. Raynaud’s syndrome – nifedipine, amlodipine, felodipine
7. Migraine prophylaxis – verapamil

45. Calcium Channel Blockers
• Advantages of CCBs in hypertension
1. Improve arterial compliance
2. Do not compromise hemodynamics
3. No sedation
4. No contraindication in asthma, COPD, angina, PVD
5. Effective in elderly, black patients and low renin hypertensives
6. No effect on lipid, blood sugar, uric acid and electrolytes
7. No adverse foetal effects

46. Sympatholytic Agents β Blockers
• ↓ BP in only in hypertensive patients
• ↓ HR, Contractility
• Long term use ↓ CO → ↓ SVR → ↓ BP
• First line in stable angina
• Avoided in
• asthma and COPD patients
• SA or AV node dysfunction
• Along with verapamil and diltiazem
• Caution in diabetes mellitus
• Avoid abrupt discontinuation – rebound hypertension

47. Sympatholytic Agents β Blockers
• S/E:
• Bronchoconstriction – Avoided in bronchial asthma
• Bradycardia – SA or atrioventricular (AV) nodal dysfunction (Avoided along
with verapamil)
• Risk of hypoglycemic reactions may be increased in diabetics taking insulin or
sulfonamides
• Dyslipidemia
• Rebound hypertension

48. Sympatholytic Agents α1 Blockers
• Prazosin, terazosin, and doxazosin
• α1 Blockers → reduce arteriolar resistance and increase venous
capacitance →
• S/E
• First-dose phenomenon
• Reflex tachycardia and ↑ renin activity
• Postural hypotension

49. Sympatholytic Agents α+β Blockers
• Labetalol – eclampsia, preeclampsia, hypertension, and hypertensive
emergencies.
• Carvedilol – hypertension and symptomatic heart failure

50. Centrally Acting Sympatholytic Agents: Methyldopa
• Mechanism:
• Use:
1. Hypertension in pregnancy 250 mg
BD
• S/E:
1. Sedation
2. Dry mouth
3. diminished libido, hyperprolactinemia
4. Hepatotoxicity
5. Hemolytic anemia

51. Centrally Acting Sympatholytic Agents: Clonidine
Clonidine
activation of α2 receptors in the lower brainstem region
↓ sympathetic outflow from the CNS
↓ NE
↓ SVR
↓ HR and Contractility
↓ Renin release
↑ Sodium excretion
↓ BP

52. Centrally Acting Sympatholytic Agents: Clonidine
• Use:
1. Hypertension
2. Off label uses:
• Diarrhea in diabetic autonomic neuropathy
• Withdrawal from narcotics, alcohol, and tobacco
• Menopausal hot flashes
• Differential diagnosis of patients with hypertension and suspected
pheochromocytoma
• Atrial fibrillation
• Attention-deficit/hyperactivity disorder (ADHD)

53. Centrally Acting Sympatholytic Agents: Clonidine
• S/E:
1. Dry mouth (xerostomia) and Sedation
2. Postural hypotension
3. Sexual dysfunction
4. Contact dermatitis (transdermal)
5. Withdrawal reactions – headache, apprehensiontremors, abdominal pain, sweating,
and tachycardia.
6. Sleep disturbances nightmares,
7. Depression
8. Bradycardia

54. Vasodilators –
Hydralazine, Minoxidil, Sodium nitroprusside
• Hydralazine + ACEi + Diuretics + Beta blockers
• Mechanism of Action: ↓ SVR - ↓ CO - ↓ BP
Arteriolar smooth muscles
Hydralazine Vasodilatation
Cerebral,
Coronary
Renal
Due to inhibition of Ca2+ release
NO generation
Opening of K+ Channels
Reflex Tachycardia
↑ renin activity
Fluid retention

55. Vasodilators – Hydralazine
• Use: 25-100 mg twice daily
1. Severe hypertension
2. Hypertensive emergencies
3. Hypertension in pregnancy

56. Vasodilators – Hydralazine
• S/E:
1. Extension of pharmacological
actions: Headache, nausea,
flushing, hypotension,
palpitations, tachycardia,
dizziness, angina
2. Myocardial ischemia in CAD and
older patients
3. Drug induced lupus syndrome –
after 6 months of treatment; if
occur discontinue
4. Polyneuropathy

57. Vasodilators – Minoxidil
Arteriolar smooth muscles
Minoxidil (Inactive)
Activation of KATP channel
Hyperpolarization
Minoxidil sulfate Vasodilatation
Skin,
skeletal muscle,
GI tract, Renal,
Heart
Reflex ↑ in
contractility; CO
Due to ↑ SVR

58. Vasodilators – Minoxidil
• S/E:
1. Fluid and salt retention
2. Hypertrichosis / excess hair growth:
3. CV effects:
Myocardial ischemia in CAD patients
Cardiac failure
Pericardial effusion
• Use: 25-100 mg twice daily
1. Severe hypertension in renal insufficiency not responding to other treatment
2. Male pattern baldness and alopecia areata: Topical minoxidil

59. Vasodilators – Sodium Nitroprusside
• Arteriolar + Venous Dilator
• Rapid onset (within seconds); brief duration 2-5 minutes
• IV infusion
• No reflex tachycardia
• Mechanism:

60. Vasodilators – Sodium Nitroprusside
• Use:
1. Hypertensive emergencies (second line) – 50 mg in 500 mL of NS/D5% @
0.02 mg/min
Infusion bottle covered with paper
2. Controlled hypotension
3. Refractory CHF
4. Acute mitral regurgitation
• S/E:
• Hypotension,
• Palpitation, nervousness, perspiration
• Vomiting, abdominal pain, disorientation
• Cyanide toxicity – Lactic acidosis, (if infused @ 5 µg/kg/min for > 24-48 h);
Administer thiosulfate; Psychosis and raised ICP
• Worsen arterial hypoxemia in COPD

61. Adrenergic Neurone Blocker – Reserpine
• Alkaloid from roots of Rauwolfia serpentine
• Inhibit VMAT2 irreversibly → Deplete NA and 5-HT
• S/E:
1. Sedation
2. Mental Depression
3. Mild EPS

62. Pharmacotherapy of Hypertension

63. Pharmacotherapy of Hypertension
• Choice of Antihypertensive drugs
1. Angina pectoris – Beta Blockers , CCB
2. Previous myocardial infarction – ACE inhibitors, ARB, Beta Blockers
3. Heart failure – ACE inhibitors, ARB, Beta Blockers, diuretics, MRA
4. End-stage renal disease, proteinuria – ACE inhibitors
5. Diabetes mellitus – ACE inhibitors, ARB, CCB, diuretics
6. Pregnancy – Labetalol, Nifedipine, α-methyldopa
7. Asthma – ACE inhibitors, ARB, CCB
8. Left ventricular hypertrophy – ACE inhibitors, ARB, CCB
9. Peripheral artery disease – ACE inhibitors, CCB

64. Hypertensive emergencies
Systolic BP > 220 or diastolic BP > 120 mm Hg with evidence of active
target organ damage (TOD)
Hypertensive Urgency
Systolic BP > 220 or diastolic BP > 120 mm Hg with symptoms, but no
signs of acute TOD
Hypertensive emergencies and urgencies

65. Hypertensive emergencies and urgencies
• BP reduction – 25%
• Time – Over 1-2 h
• Not lower than 160/100 mmHg
• If reduce rapidly perfusion of vital organs may suffer leading to impairment of kidney
function, myocardial ischaemia, cerebral infarction, blindness etc.
• Drugs used: (IV/ IV infusion)
1. Sodium nitroprusside
2. Glyceryl trinitrate
3. Labetalol
4. Nicardipine
5. Hydralazine
6. Furosemide
7. Clevidipine
8. Fenoldopam

66. Hypertension in pregnancy