Anti Hypertensive Drugs
Anti Hypertensive Drugs
Anti Hypertensive Drugs
DRUGS
Types of
Hypertension
Essential Secondary
• BP = CO × PVR
Introduction
Outcomes of Hypertension :-
Atherosclerosis
Ischemic heart disease & cerebrovascular
accidents (CVA)
Nephropathy
Congestive heart failure
1. Diuretics:
Thiazides: Hydrochlorothiazide, Chlorthalidone,
Indapamide
High ceiling: Furosemide
K+ sparing: Spironolactone, Triamterene, Amiloride
10. Vasodilators:
Pnemonic : ABCD
A (ACEI, ARBs, alpha blockers) B(beta blockers)C (CCB,
centrally acting) D (Diuretics, direct renin inhibitors,
dilators)
Each group of drugs will be discussed
under the following headings
Loop diuretics
Cause more fluid & electrolyte imbalance. They are
indicated in HTN only if it is complicated by:-
- Chronic renal failure
- Refractory CHF
- Resistance to thiazides
- Marked fluid retention.
K+ sparing diuretics
Used only in conjunction with Thiazides to prevent K+
loss & to supplement their antihypertensive action.
Angiotensin Converting Enzyme (ACE)
Inhibitors
Examples :-
Captopril, Lisinopril., Enalapril, Ramipril , Fosinopril
WHAT IS RAAS???
Next slide
RAAS
Renin is produced by JG cells of kidney in response to
Fall in BP or blood volume
Decrease Na+ in macula densa
Renin acts on a plasma protein Angiotensinogen to convert it
to Angiotensin-I
Angiotensin-I is rapidly converted to Angiotensin-II by ACE
(present in luminal surface of vascular endothelium)
Angiotensin-II is degraded by peptidases to produce
Angiotensin-III
Increased
Blood Vol.
Rise in BP
Vasoconstriction
Kidney
(Adrenal cortex)
ACE inhibitors
No postural hypotension
Not much electrolyte imbalance
Renal perfusion well maintained
Reverses the ventricular hypertrophy
No hyperuricemia
No deleterious effect on plasma lipid profile
No rebound hypertension
Only minimal worsening of quality of life like general
wellbeing, sleep and work performance.
ACE inhibitors
Drawbacks/ adverse effects
Cough – persistent brassy cough due to inhibition of bradykinin
breakdown in lungs
Hyperkalemia (in renal failure patients, those with K+ sparing
diuretics, NSAID and beta blockers (routine check of K+ level))
First dose Hypotension – sharp fall may occur
Angioedema: swelling of lips, mouth, nose etc.
Rashes, urticaria
Dysgeusia: loss or alteration of taste
Foetopathic: hypoplasia of organs, growth retardation etc
Neutropenia
Proteinuria
Acute renal failure ( occurs in patients with bilateral renal artery
stenosis)
ACE inhibitors
Current status
1st line antihypertensive Drug
Used in relatively young patients
Most appropriate antihypertensives in patients with:-
Diabetes,
Chronic kidney disease,
CHF
Left ventricular hypertrophy,
Angina, post MI, stroke
Dyslipidemia,
Gout
Avoid in : Pregnancy, bilateral renal artery stenosis,
hypersensitivity , hyperkalaemia , Preexisting dry
cough
ACE inhibitors (2 important ones)
Captopril
Sulfhydryl containing dipeptide.
Not a prodrug. Has drawbacks mentioned earlier
Half life: 2 Hrs, multiple doses
Enalapril
Prodrug – converted to enalaprilate
Advantages over captopril:
More potent
Longer duration of action-once daily dose
Absorption not affected by food
Rash and loss of taste are less frequent
Slower onset of action, hence first dose hypotension
ACE inhibitors – other uses
(to be discussed under ACE inhibitors chapter)
Desirable properties
Do not compromise haemodynamics – no
impairment of work capacity
No deleterious effect on lipid profile, uric acid or
electrolyte balance.
Can be given to asthma, angina and PVD patients
No renal and male sexual function impairment
No adverse fetal effects and can be given in
pregnancy
Minimal effect on quality of life
Calcium Channel Blockers
Drawbacks
- Worsen GERD
- Negative chronotropic effect can worsen Conduction
defects
- Worsen BHP & bladder voiding difficulty in males
Calcium Channel Blockers
Current status
Hydralazine
Directly acting vasodilator
MOA: hydralazine causes NO release – relaxation of
vascular smooth muscle – fall in BP.
Uses: 1) Moderate hypertension when 1st line fails
2) Hypertension in Pregnancy
Minoxidil
Relaxes smooth muscle & relaxes arterioles.
Used only in life threatening HTN & topically in alopecia
Sodium Nitroprusside