ANTI HYPERTENSION DRUGS

1. ANTI-HYPERTENSION

2. Introduction:
• Hypertension Or High Blood Pressure is defined as a reading of 140/90 on three
consecutive measurements at least 6 hours apart.
• Consistently high BP causes the heart to work harder than it should and can damage
the coronary arteries, the brain, the kidneys and the eyes.
• Hypertension is major cause of STROKE.
Blood pressure = CO X SVR (CO= cardiac output, SVR= systemic vascular resistance)

3. • Normal - <120/80
• Pre-hypertension – 120-139/80-89
• Hypertension –
• Stage 1 – 140-159/ 90-99
• Stage 2 - ≥ 160/ ≥ 100

4. TYPES:
Primary/Essential
hypertension Secondary hypertension
• Specific cause unknown.
• 90% of the cases.
• Also known as essential or idiopathic
hypertension
• May due to stress, obesity, smoking,
more Na+ intake, insomnia and life style.
• Cause is known (Renal artery disease,
pregnancy etc)
• 10% of the cases.

5. ANTI- HYPERTENSIVES
• These are the drugs which are used in the treatment of hypertension.
• Following categories can be given as single or in combinations based
on patient condition.

6. Classification Of Anti-hypertensives
1. ACE Inhibitors* Captopril, Enalapril, Lisinopril, Ramipril, etc.
2. Angiotensin receptor
Antagonist*
Losartan, Candesartan, Irbesartan, Valsartan,Telmisartan
3. Calcium channel
blockers*
Verapamil, Diltiazem, Nifedipine, Felodipine,Amlodipine
4. Diuretics Hydrochlorothiazide, Indapamide Furosemide, Amiloride
5. α Adrenergic blockers Prazosin, Terazosin, Doxazosin, Phentolamine, Phenoxybenzamine
6. β Adrenergic blockers Propranolol, Metoprolol, Atenolol, etc.
7. Central sympatholytics Clonidine, Methyldopa
8. Vasodilators Arteriolar: Hydralazine, Minoxidil, Diazoxide
Arteriolar + venous: Sodium nitroprusside
CHECK DIGESTER(4) PAGE
NO.60

7. 1. ACE Inhibitors
• Captopril, Enalapril, Lisinopril, Ramipril, Etc.
• These are the first choice of drugs in the treatment of hypertension
renal artery stenosis & Renal disease where excessive levels of renin
are released, causing high levels of angiotensin ( a potent
vasoconstrictor ) and aldosterone.
• ACE inhibitors lower circulating angiotensin II and increase Bradykinin,
a potent vasodilator.

8. Mechanism Of Action
Angiotensinogen
RENIN
renal arterial pressure
renal sympathetic
nerve activity
Vasoconstrictor
Na+ in renal tubular
fluid
Angiotensin-I
Angiotensin-II
X ACE
Na+ & H20 retention
B P Blood volume

9. Pharmacokinetics:
• Well oral absorption
• half life is 11-12 hours.
• Primary eliminated by kidney than bile and faces
• Care should be taken if given to patient with liver and kidney failure
• Adverse effects:
• Dry cough (dur to bradykinins)
• Hyperkalemia
• Angioedema
• Loss of taste sensation
• Tachycardia, pulpitation

10. 2. Angiotensin Receptor Antagonist
• Losartan -- it’s a competitive antagonist of Angiotensin II.
• It blocks all the action of Angiotensin II like vasoconstriction etc
• MOA:
Angiotensine-II
Effects
3. Release of
adrenaline
4. Central and peripheral
stimulation
1. Vasoconstriction
2. Release of
Aldosterone

11. Pharmacokinetics:
• Well oral absorption
• Losartan –Dose – 50 mg /day
• Metabolized in liver and excreted out by kidney
• Additionally 12.5 mg/day hydrochlorthiazide can be given to enhance the
overall action.
• comparatively safe – do not cause increase in bradykinin levels
• Adverse effects:
• No side effects
• Rarely - Angioedema
• Loss of taste sensation and urticaria

12. 3. Calcium channel blockers:
• Verapamil, Diltiazem, Nifedipine, Felodipine, Amlodipine.
• (A) Phenyl Alkylamine:verapamil
• (B) Benzothiazepine: Diltiazem
• (C) Dihydropyridines: Nifedipine, Felodipine, Amlodipine

13. MOA
• Causes smooth muscles relaxation by blocking the binding of Ca+ to its
receptor – preventing muscle contraction
• This causes decreased in peripheral smooth muscles tone and
decreased systemic vascular resistance
Decreased blood pressure

14. Pharmacokinetics:
• 90–100% absorbed orally, peak occurring at 1–3 hr (except amlodipine 6–9 hr).
• The oral bioavailability of ca2+ channel blockers is incomplete with marked
inter- and intraindividual variations due to high first pass metabolism
• All are highly plasma protein bound (min.: Diltiazem 80%, max.: Felodipine
99%).
• High clearance drugs with extensive tissue distribution.
• > 90% metabolized in liver and excreted in urine.
• The elimination t½ are in the range of 2–6 hr.
• Adverse effects:
• Headache, constipation, rash, nausea, flushing, edema (fluid accumulation in tissues), drowsiness.

15. Uses/indications:
1) Hypertension
2) Angina Pactoris
3) Cardiac Arrhythmias
4) Congestive Heart Failure
5) Myocardial Infraction
6) Alopecia
7) Bronchial Asthma
8) Urinary Urge Incontinence
9) Other Uses- Nifedipine Is An Alternative Drug For Premature
Labour, Erectile Dysfunction

16. Side Effects
Calcium Channel Blockers
• Cardiovascular
– hypotension, palpitations, tachycardia
• Gastrointestinal
– constipation, nausea
• Other
– rash, flushing, peripheral edema, dermatitis

17. 4. Diuretics
• Hydrochlorothiazide, Indapamide Furosemide, Amiloride
• Diuretics Have Been The Standard Antihypertensive Drugs Over The
Past 4 Decades, Though They Directly Don’t Decrease BP.

18. • Decrease the plasma and extracellular fluid volumes/ Blood volume
• Results: decreased preload
decreased cardiac output
decreased total peripheral resistance
• Overall effect: decreased workload of the heart,
and decreased blood pressure
MOA:

19. SIDE EFFECTS
• Low sodium in your blood (hyponatremia)
• Dizziness.
• Headaches.
• Dehydration.
• Muscle cramps.
• Joint disorders (gout)
• Impotence

20. 5. ALFA- Adrenergic Blockers
• Prazosin, Terazosin, Doxazosin, Phentolamine, Phenoxybenzamine
• They Are Mild Anti Hypertensives. Used for stage 1 otherwise given as a combination with
other drugs.
• Prazosin :This Prototype Selective Α1 Antagonist Dilates Both Resistance Vessels. There Is
Little Reflex Cardiac Stimulation And Renin Release During Long-term Therapy
• Postural Hypotension And Fainting May Occur In The Beginning—called ‘First Dose Effect’,
And With Dose Increments. This Disappears With Continued Therapy, But May Persist In
The Elderly. For This Reason, Prazosin Is Always Started At Low Dose (0.5 Mg) Given At
Bedtime And Gradually Increased With Twice Daily Administration Till An Adequate
Response Is Produced (Max. Dose 10 Mg BD).

21. Side effects:
• Prazosin Is Generally Well Tolerated At Low Doses. But Some Time
• Postural Hypotension
• Headache,
• Drowsiness, Dry Mouth,
• Weakness, Palpitation,
• Nasal Blockade, Blurred Vision And Rash.
• Ejaculation May Be Impaired In Males: Especially With Higher Doses.
• USES:
• PRazosin is a moderately potent antihypertensive with many desirable
features, but is noT Used as a first line drug because fluid retention and
tolerance gradually develops with monotherapy

22. 6. BETA ADRENERGIC BLOCKER
• They are mild antihypertensives; do not significantly lower BP in
normotensives. Used alone they suffice in 30–40% patients—mostly mild to
moderate cases. In the large majority of the rest, they can be usefully
combined with other drugs.
• The hypotensive response to β blockers develops over 1–3 weeks and is well
sustained.
• Despite short and differing plasma half lives, the antihypertensive action of
most β blockers is maintain
• Because of absence of postural hypotension, bowel alteration, salt and water
retention; a low incidence of side effects, low cost; once a day regimen and
cardioprotective potential,

23. 7. CENTRAL SYMPATHOLYTICS
• Clonidine, Methyldopa
• MoA: stimulate alfa 2 receptor of vasomotor center
• Central outflow increases
• Sympathetic outflow increases
• Increase in BP
THESE DRUGS INHIBIT GIVEN
PATHWAY

24. CLONIDINE
• It is an imidazoline derivative having complex actions. Clonidine is a partial agonist
with high affinity and high intrinsic activity at α2 receptors, especially α2a subtype
in brainstem. The major haemodynamic effects result
• From stimulation of α2a receptors present mainly postjunctionally in medulla
(vasomotor centre)→ decrease sympathetic out flow → fall in BP and bradycardia
(also due to enhanced vagal tone). Plasma NA declines
• MOA: SAME
• Pharmacokinetics: Clonidine is well absorbed orally; peak occurs in 2–4 hours;
• 1/2 to 2/3 of an oral dose is excreted unchanged in urine, the rest as metabolites.
• Plasma t½ is 8–12 hours.
• Effect of a single dose lasts for 6–24 hours.

25. Adverse effects
• Sedation, mental depression, disturbed sleep; dryness of mouth, nose and
eyes (secretion is decreased by central action),
• Constipation (antisecretory effect on the intestines).
• Impotence, salt and water retention, bradycardia (due to reduced
sympathetic tone).
• Postural hypotension occurs, but is mostly asymptomatic.
• Alarming rise in bp, in excess of pretreatment level,
• With tachycardia, restlessness, anxiety, sweating
• Drug interactions: tricyclic antidepressants and chlorpromazine abolish the
antihypertensive action of clonidine, probably by blocking α receptors on
which clonidine acts.

26. 8. VASODILATORS
• Arteriolar: Hydralazine, Minoxidil, Diazoxide
• Arteriolar + Venous: Sodium Nitroprusside
• MOA:
• Directly Relaxes Arteriolar Smooth Muscle
• Results:
• Decreased Systemic Vascular Response,
• Decreased Afterload, And
• PERIPHERAL VASODILATION

27. Hydralazine
• It is a directly acting arteriolar vasodilator
• MOA: The mechanism of vascular smooth muscle relaxant action of hydralazine is
not clearly known. It is partly endothelium dependent: may involve generation of
NO (nitric oxide) and stimulation of cgmp. Direct effects on membrane potential
and on ca2+ fluxes have also been proposed.
• Pharmacokinetics: Hydralazine is well absorbed orally, and is subjected to first pass
metabolism in liver. The chief metabolic pathway is acetylation. there are slow and
fast acetylators. Bioavailability is higher in slow acetylators,
• Hydralazine is completely metabolized both in liver and plasma; the metabolites
are excreted in urine,
• t½ 1–2 hours. However, hypotensive effect lasts longer (12 hours), probably
because of its persistence in the vessel wall

28. Adverse effects
• Are frequent and mainly due to vasodilatation.
1. Facial flushing, conjunctival injection, throbbing, headache, dizziness, palpitation,
nasal stuffiness, fluid, retention, edema.
2. Angina and MI may be precipitated in patients with coronary artery disease.
3. Postural hypotension is not prominent because of little action on veins: venous
return and C.O. Are not reduced.
4. Paresthesias, tremor, muscle cramps.
USES:
• Used in moderate-to-severe hypertension. It is not Used alone.
• Hydralazine can be used in patients with renal involvement, but is contraindicated
in older patients and in those with ischaemic heart disease.
• It is one of the preferred antihypertensives during pregnancy because of decades
of experience and record of safety.

29. • Minoxidil : it is a powerful vasodilator, the pattern of action resembling hydralazine,
i.E. Direct relaxation of arteriolar smooth muscle
• Minoxidil is a prodrug—converted to an active metabolite (by sulfate conjugation)
which is an opener of ATP operated K+ channels; acts by hyperpolarizing smooth
Muscle.
• Minoxidil is indicated only rarely in severe or life-threatening hypertension.
• Use in alopecia: minoxidil increases growth of body hair. Applied topically (2% twice
daily) it promotes hair growth in male pattern baldness and alopecia areata.
• The response is slow (takes 2– 6 months) and incomplete, but upto 60% subjects
derive some benefit. Baldness recurs when therapy is discontinued. The mechanism
of increased hair growth is notKnown; may involve:
• (A) enhanced microcirculation around hair follicles.
• (B) direct stimulation of resting hair follicles.
• (C) alteration of androgen effect on genetically programmed hair follicles.