kindly chek it out

1. Dr Mohammad Adil
PG student
Deptt of pharmacology
GMC Sgr

2.  Hypertension is a hemodynamic disorder
 One of the leading causes of global burden
of disease.
 In US , approximately 30% of adults, or at
least 65 million individuals have
hypertension

3. Year 2000
 26.4% of world adult
population had
hypertension
 Total of 972 million adults
Kearney PM et al. Lancet. 2005;365:217-223
Year 2025
• 29.2% of world adult
population will have
hypertension
• Total of 1.56 billion adults
(60%  overall; 24%  in
developed nations, 80% 
in developing nations)

5. Hypertension is defined as any of the following
:
- Systolic BP ≥ 140mm Hg
- Diastolic BP ≥ 90mm Hg
- Intake of antihypertensive medications.

6.  Normal SBP < 120 and DBP< 80
 Pre hypertension SBP= 120-139 or DBP=80-89
 Stage 1 hypertension SBP= 140-159 or DBP=90-99
 Stage 2 hypertension SBP ≥ 160 or DBP ≥ 100
 Isolated systolic SBP ≥ 140 and DBP < 90
hypertension

7. A) Essential or Primary HTN
 95%
 No underlying cause
B) Secondary HTN
 Underlying cause

8.  Renal
 Reno vascular
 Adrenal
 Coarctation of aorta
 OSA
 Preeclampsia/ eclampsia
 Endocrine
 Medications
 Mendelian forms of HTN

9.  Decreased vascular compliance
(arteriosclerosis)
 Increased CO
- Aortic Regurgitation
- Thyrotoxicosis
- Fever
- AV fistula
- PDA

10. Medical history
Physical Examination
Laboratory investigation

11. SYSTEM TEST
Renal Microscopic urinalysis, albumin
excretion, serum BUN and/or
creatinine
Endocrine Serum sodium, potassium, calcium,
TSH
Metabolic Fasting blood glucose, total
cholesterol, HDL and LDL (often
computed) cholesterol,
triglycerides
Other Hematrocrit, electrocardiogram

12. Only 1/2 have been
diagnosed
Only 1/2 of those
diagnosed have been
treated
Only 1/2 of those
treated are adequately
controlled
Not
diagnosed
Not treated
Not
controlled
Controlled

14. • Reduce Cardiac and renal morbidity and mortality.
• Treat to BP <140/90 mmHg
or BP <130/80 mmHg (in patients with diabetes or
chronic kidney disease)―JNC 7

15. Class of Drugs Class of Drugs
Diuretics Β-blockers
ACE inhibitors α-blockers
ARBs Central Sympatholytics
Direct Renin inhibitor Vasodilators
Ca channel blockers

16.  Thiazides: hydrochlorothiazide,
chlorthalidone
 High ceiling: furosemide
 K sparing: spironolactone, amiloride

17. Example: Hydrochlorothiazide
MOA: Inhibits Na-Cl symport at the luminal
membrane ( early DT-site 3)
 Act by decreasing blood volume and cardiac
output as a result of diuresis
 Decrease peripheral resistance during
chronic therapy
 Fall in BP develops gradually in 2-4 weeks
 Mild effect, average fall in BP ~ 10mmHg
 Effective in ISH

18. Effective in low grade HTN but potentiate
other antihypertensive drugs (except DHPs)
Effect attenuated by NSAIDs and high salt
intake
Diuretic of choice in uncomplicated HTN
Drug of choice in elderly hypertensive patients
Once a day dosing

19. Side effects-
• Hypokalaemia
• Hyponatraemia
• Hyperuricaemia (hence contraindicated in
gout)
• Hyperglycaemia and Hyperlipidaemia
• Hypercalcemia
• Not safe in renal and hepatic insufficiency
• GIT Disturbances

20.  Example : Frusemide
 MOA: inhibits Na-K-2Cl cotransport in thick AscLH(site
2)
 Strong diuretic
 Indicated in HTN complicated by:
 CRF
 Coexisting refractory CHF
 Resistance to combination regimens
containing a thiazide, or marked fluid retention due to
use of potent vasodilators
 Hypertensive emergencies

21.  Hearing loss
 Hyperuricemia : less pronounced than thiazides
 Hypocalcemia

22. Spironolactone, eplerenone, triamterene and amiloride
MOA:
 Aldosterone antagonists (Spironolactone, eplerenone)
 Inh of Renal ep Na channel (triamterene and
amiloride)
 Used only in conjunction with a thiazide diuretic to
prevent K loss
 Spironolactone not favoured (due to ADRs)
 Hyperkalemia to be watched when used with
ACEI/ARBs

25. CCBs reduce vascular resistance through L channel
blockade, reduces intracellular Ca & blunts
vasoconstriction
CCBs inhibit Ca mediated slow channel component of
action potential in smooth/cardiac muscle cells,
leading to:
 SM esp. vascular relaxation( markedly relax
arterioles than veins)
 Negative chronotropic, inotropic and dromotropic
action on heart.

26. Example : Amlodipine
 cause arteriolar dilatation, TPR decreases and BP
falls.
 Cardiodepressant actions only at high doses/prior β
blockade.
 Reflex tachycardia.
 good oral bioavailability, long T½, once a day dosing.
 Neutral effect on glucose and lipid levels
 No effect on uric acid level and electrolyte imbalance

27.  Drugs of choice in elderly hypertensives and
those with co-existing asthma, angina and PVD
patients
 Preferred in elderly and prevents stroke
 No adverse fetal effects and can be given in
pregnancy
 CCBs are effective in low Renin hypertension
 Preparation and dosage:
◦ Amlodipine – 2.5, 5 and 10 mg tablets (5-10 mg
OD) – Stamlo, Amlopres, Amlopin etc.

28.  As per JNC 7 CCBs are not 1st line of
antihypertensive
 However its been used as 1st line by many
because of excellent tolerability and high
efficacy
Side effects
Flushing, headache, Pedal edema

29.  Dilates arterioles
 Little α adrenergic blocking activity
 ↓ TPR , BP modestly lowered
 HR generally decreases, AV conduction slowed, but
CO maintained
 C/I in 2nd and 3rd degree AV Block
 Cardiac arrest can occur on i.v inj. or in patients with
sick sinus
 Not given with β blockers, quinidine, disopyramide

30.  Less potent vasodilator than nifedipine and
verapamil
 Little change (decrease) in HR
 C/I in AV nodal and myocardial disease

31.  Non selective: Propranolol (others: nadolol,
timolol, pindolol, labetolol)
 Cardioselective: Metoprolol (others: atenolol,
esmolol, betaxolol)
 With additional α blocking property: labetalol,
carvedilol
 With ISA: pindolol

32.  All beta-blockers similar antihypertensive effects –
irrespective of additional properties
◦ Reduction in BP is due to reduction in CO
(reduction of HR and contractililty)
◦ Adaptation by resistance vessels to chronically
reduced CO – tpr decreases (↓both SPB & DBP)
◦ Decreased renin release (beta-1 mediated)
◦ Reduced NA release and ↓central sympathetic
outflow
◦ Non-selective ones ↓GFR but not with selective
ones
◦ Drugs with ISA cause less reduction in HR and CO

33.  Advantages:
◦ No postural hypotension
◦ No salt and water retention
◦ Low incidence of side effects
◦ Once a day regime
◦ Preferred in young non-obese patients
◦ prevention of sudden cardiac death in post infarction
patients and progression of CHF
 Drawbacks (side effects):
◦ Fatigue, lethargy (low CO?) – decreased work capacity
◦ Loss of libido – impotence
◦ Cognitive defects – forgetfulness
◦ Difficult to stop suddenly
◦ Therefore cardio-selective drugs are preferred now

34.  Advantages of cardio-selective over non-selective:
◦ In asthma
◦ In diabetes mellitus
◦ In peripheral vascular disease
 Current status:
◦ JNC 7 recommends - 1st line of antihypertensive along with
diuretics and ACEIs
◦ Preferred in young non-obese hypertensive
◦ Angina pectoris and post angina patients
◦ Post MI patients – useful in preventing mortality
◦ In old persons, carvedilol – vasodilatory action ,can be given

35.  Specific alpha-1 blockers like prazosin, terazosin and
doxazosine are used
 PRAZOSIN is the prototype of the alpha-blockers
 Blockade of vasoconstrictor α₁ receptors→ Reduction
in t.p.r →reduction in venomotor tone→pooling of
blood→reduction in CO→fall in BP
 Dilates arterioles more than veins
 It also inhibits PDE→ ↓cAMP in SM
 Also Used in Raynauds disease and BHP

36.  Phentolamine/Phenoxybenzamine→ great value in
controlling BP during:
 Clonidine withdrawal
 Cheese reaction in patients on MAO inh
 Phentolamine: used to diagnose Pheochromocytoma
 Phenoxybenzamine: definitive therapy for inoperable
pheochromocytoma
( prazosin is an alternative ).

37.  Adverse effects:
◦ Prazosin causes postural hypotension(FIRST DOSE
EFFECT) – start low dose (0.5 mg) at bed time
◦ Reflex tachcardia
◦ Nasal stuffiness and miosis
◦ Fluid retention in monotherapy
◦ failure of ejaculation in males, may manifest as
impotence

38.  Current status:
◦ Several advantages – improvement of carbohydrate
metabolism – diabetics, lowers LDL and increases
HDL, symptomatic improvement in BHP
◦ But not used as first line agent, used in addition
with other conventional drugs which are failing –
diuretic or beta blocker
 Doses: Available as 0.5 mg, 1 mg, 2.5 mg, 5 mg etc.
dose:1-4 mg thrice daily (Minipress/Prazopress)

39.  Alpha-Methyldopa: a prodrug
◦ Precursor of Dopamine and NA
◦ MOA: Converted to alpha methyl noradrenaline
which acts on alpha-2 receptors in brain and
causes inhibition of adrenergic discharge in
medulla – fall in PVR and fall in BP
◦ Various adverse effects – cognitive impairement,
postural hypotension, positive coomb`s test etc.
Not used therapeutically now except in
Hypertension during pregnancy

40.  Clonidine: Imidazoline derivative, partial agonist of
central alpha-2 receptor
 High intrinsic activity at α2A subtype in brainstem
 Stimulation of α2A subtype postjunctionally in
medulla
(vasomotor centre)→Decreased sympathetic
outflow→fall in BP and bradycardia
 Rapid iv inj raises BP transiently(α2B)
 Not frequently used now because of tolerance and
withdrawal hypertension

41.  Directly acting Arteriolar vasodilator
 MOA: interference with Ca release, opening of K
channels &/or NO release – relaxation of vascular
smooth muscle – fall in BP
 Subsequently fall in BP – stimulation of adrenergic
system leading to Cardiac stimulation producing
palpitation and rise in CO even in IHD and patients→
hyper dynamic state – angina attack
 Preferred drug in pregnancy esp. Preeclampsia
 Hypertensive emergency

42. ◦ Reflex Tachycardia
◦ No reduction in renal blood flow
◦ Increased Renin secretion – Na+ and water
retention
◦ Tolerance countered by administration of beta
blockers and/or diuretics
◦ Antioxidant property
◦ Induces a lupus like condition
◦ Angina and MI may occur esp in CAD patients

43.  Powerful vasodilator, mainly 2 major uses – antihypertensive
and alopecia
 Prodrug and converted to an active metabolite( by sulfate
conj.) which acts by hyperpolarization of smooth muscles and
thereby relaxation of SM – leading to hydralazine like effects
 Rarely indicated in hypertension especially in life threatening
ones
 More often in alopecia to promote hair growth
 Used in patients with renal insufficiency who are refractory to
all other drugs

44.  Compensatory reflexes: ↑renin release→Na & water
retention→edema & CHF may occur
 These effects can be countered with a loop diuretic & a β
blocker
 Orally not used any more
 Topically as 2-5% lotion/gel and takes months to get effects
 MOA of hair growth:
◦ Enhanced microcirculation around hair follicles and also by
direct stimulation of follicles
◦ Alteration of androgen effect of hair follicles

45.  Rapidly and consistently acting vasodilator
 Relaxes both resistance and capacitance vessels and
reduces t.p.r and CO (decrease in venous return)
 Unlike hydralazine it produces decrease in cardiac
work and no reflex tachycardia.
 Improves ventricular function in heart failure by
reducing preload
 MOA: Endothelial cells & RBCs convert nitroprusside
to NO – relaxation also by non-enzymatically to NO
by glutathione

46.  Uses: Hypertensive Emergencies, 50 mg is added to
500 ml of saline/glucose and infused slowly with
0.02 mg/min initially and later on titrated with
response (wrap with black paper)
 Adverse effects:) –palpitation, pain abdomen,
disorientation.
 Psychosis, weakness and lactic acidosis→ Due to
release of cyanide

47. Hypertensive encephalopathy Nitroprusside, nicardipine, labetalol
Malignant hypertension (when IV
therapy is indicated)
Labetalol, nicardipine, nitroprusside,
enalaprilat
Stroke Nitroglycerin, nicardipine, labetalol,
esmolol
Acute left ventricular failure Nitroglycerin, enalaprilat,loop
diuretics
Aortic dissection Nitroprusside, esmolol, labetalol
Adrenergic crisis Phentolamine, nitroprusside
Postoperative hypertension Nitroglycerin, nitroprusside, labetalol,
nicardipine
Preeclampsia/ eclampsia of
pregnancy
Hydralazine, labetalol, nicardipine

48. WEIGHT REDUCTION ATTAIN AND MAINTAIN BMI < 25
Kg/m^2
Dietary salt reduction < 6 g NaCl/d
Adapt DASH-type dietary plan Diet rich in fruits, vegetables, and
low-fat dairy products with reduced
content of saturated and total far
Moderation of alcohol consumption For those who drink alcohol,
consume <2 drinks/day in men and
< 1 drink/day in women
Physical activity Regular aerobic activity, e.g, brisk
walking for 30 min/d

49. ◦ Heart failure
◦ Coronary artery disease
◦ H/o MI
◦ H/o stroke
◦ Diabetes
◦ Chronic Renal failure

51. JNC 8
Guidelines

52.  General population aged 60 years or older
SBP ≥150 mmHg
Or
DBP ≥ 90mmHg
Goal of Treatment
:
SBP <150 mmHg
OR
DBP of < 90mmHg.
Initiate Treatment at :

53.  General population < 60 years
SBP ≥ 140 mmHg
DBP ≥ 90mmHg
Goal of Treatment
:
SBP < 140 mmHg
DBP < 90 mm Hg
Initiate Treatment at :

54.  Population aged 18 years or older with CKD
or Diabetes
Initiate Treatment
at:
SBP ≥ 140 mmHg
Or
DBP ≥ 90 mmHg
Goal of Treatment
:
SBP < 140 mmHg
Or
DBP < 90 mmHg

55.  In General nonblack population, including
those with diabetes
 Initial antihypertensive treatment should
include any of the following:
 A thiazide-type diuretic
 Calcium channel blocker (CCB)
 Angiotensin-converting enzyme inhibitor (ACEI)
or
 Angiotensin receptor blocker (ARB).

56.  In general black population, including those
with diabetes:
 Initial antihypertensive treatment should
include :
 Thiazide-type diuretic
 CCB.

57.  Population aged 18 years or older with CKD
and hypertension
 Initial (or add-on) antihypertensive treatment
should include an ACEI or ARB to improve
kidney outcomes.
 This applies to all CKD patients with
hypertension regardless of race or diabetes
status.

58.  If goal BP cannot be reached with 2 drugs:
◦ Add and titrate a third drug from the list provided.
 Do not use an ACEI and an ARB together in
the same patient.
 If goal BP cannot be reached using the drugs
in recommendation 4 because of a
contraindication or the need to use more than
3 drugs to reach goal BP: antihypertensive
drugs from other classes can be used.