Antihypertensive Agents
Dr S. O. Olayemi
HYPERTENSION
Chronically persistent elevated blood
pressure>/=140 mm Hg systolic blood
pressure and or diastolic >/= 90 mmHg in
individual above 18 years of age
Controlled BP SBP <140mmHg and
DBP<90mmHG
Expert Committee on non
Communicable diseases
• One third of Nigerian adults above 15
years of age are hypertensives, from this
one third are aware of the hypertensive
status, and one third are on treatment.
• Control
definition?Complex?compliance/cost etc
TREATMENT GOAL
Prevent morbidity and mortality
associated with high blood pressure.
Achieving control through least
intrusive means possible
Control other modifiable
cardiovascular risk factors.
Ace Inhibitors:
• Captopril (Capoten) 12.5 – 150mg daily
• Enalapril (Vasotec) 5 – 40 mg daily
• Lisinopril (Zestril) 5 – 40mg daily
• Ramipril (Tritace) 2.5 – 10mg daily
• Perindopril (Aceon) 4 – 16 mg daily
• Fosinopril (Monopril) 5 – 40mg daily
• Action: ACEI block conversion of
Angiotensin 1 to Angiotensin 11 thereby
blocking stimulation of aldosterone.
• Major site of Angiotensin II production
– Vessels and not the kidneys.
• reduce peripheral resistance and salt
and water retention.
• Side Effect: Cough, Rashes,
Leukopenia, Hyperkalaemia, AngioOdema
ACE inhibitors
• Reduce dose in volume depleted pt,
elderly(hypotension)
• May be combined with diuretics
• Hyperkalaemia – CKD pts, potassium
sparing diuretics and angiotensin
receptor blockers.
• ARF- renal artery stenosis
• Contraindicated in pregnancy and pt
with hx of angioodema.
ANGIOTENSIN II RECEPTOR ANTAGONISTS
• Losartan (Cozaar) 50 – 100 mg daily
• Valsartan (Diovan) 80 – 320 mg daily
• Temilsartan (Micardis) 20 – 80 mg daily
• Irbesartan (Avapro) 150 –300mg daily
• Olmesartan (Benicar) 20 – 40 mg daily
• Candesartan (Atacand) 8 – 32 mg daily
ANGIOTENSIN II RECEPTOR ANTAGONISTS:
ARBs
• Action: They directly block the angiotensin II
type 1 (AT1) receptors – vasoconstriction,
aldosterone release, sympathetic activation,
ADH release, constriction of efferent renal
arterioles
• Beneficial AT2-vasodilation,tissue repair and
inhibition of cellular growth in blood vessels
(reduce peripheral resistance and salt/water
retention)
• Side Effects: Rashes,
Leukopenia,Hyperkalaemia but no cough
ARBs
• Reduce dose in volume depleted pt,
elderly(hypotension)
• May be combined with diuretics
• Hyperkalaemia – CKD pts, potassium
sparing diuretics and angiotensin
receptor blockers.
• ARF- renal artery stenosis
• Contraindicated in pregnancy
• Do not induce cough as in ACEIs
VASODILATORS ; Hydralazine (Apresoline 20 –
100 mg daily, Minoxidil (Loniten) 10 – 40mg daily,
• Action: They decrease peripheral resistance by
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dilating arteries/arterioles.
Combined with diuretic/B blockers –diminish
fluid retention/reflex tarchycardia.
Side Effect: Hydralazine (Headache, lupus-like
syndrome),
Minoxidil (Orthostasis, facial hirsutism),
Diazoxide (Hyperglycaemia.
CALCIUM CHANNEL BLOCKERS
• Dihydropyridines :
• Nifedipine (Adalat/ProcardiA) 20 – 90 mg dly,
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I, Felodipine (Plendil) 5 – 20 mg dly,
Amlodipine (Norvasc) 2.5 – 10 mg dly
Nicardipine (Cardene) 60 – 120 mg dly
Phenylakylamine: Verapamil 100 – 400 mg
dly
Benzothiazepine: Diltiazem 120 – 480 mg
dly.
Action: Reduce smooth muscle tone and
cause vasodilation: may reduce cardiac
output.
Verapamil/diltiazem: decrease HR/delay A-V
Calcium channel blockers
• Avoid immediate release nifedipines etc
• Dihydropyridines are more potent
peripheral vasodilators compared to
non-dihydropyridines.
• Side effect: Dihydropyridines – reflex
sympathetic discharge (tarchycardia)
Headache, flushing, peripheral oedema.
• Non dihyropyridines – variable heart
block
DIURETICS
• Loop diuretics – Frusemide (Lasix)
20mg – 1 g, Bumetanide (Bumex) 0.54mg Torsemide (Demadex) – 5mg dly.
• Site of Action: Loop of Henle, Reduce
Na+/K+/Cl- cotransporter: reduce urine
concentration; Increase calcium
excretion.
• Preferrably morning/afternoon (avoid
nocturnal diuresis)
• Higher doses in patients with CKD.
• Side effect: Ototoxicity, Hypokalaemia,
Hypotension, Gout.
DIURETICS:
• Thiazides: Chlorthalidone (Hygroton) 6.25 –
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25mg dly, Hydrochlorothiazides (Esidrix) 12.5 –
50mg dly Bendrofluazide 2.5 – 5mg dly
Site of Action: Early distal tubule, they reduce
NaCl reabsorption thereby reducing the diluting
capacity of nephron. Decrease Calcium excretion.
Dose in Morning (avoid noctunal diuresis)
More effective antihypertensives than loops
except in CKD (GFR <30ml/min
Side effects: Hypokalaemia, Hyponatreamia,
Hypercalcemia, Hyperglyceamia, Hyperlipidaemia,
Hyperuricaemia (Problematic in gout),
Potassium sparing diuretics
• Aldosterone antagonist: Spironolactone
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(Aldactone) 25 –50 mg dly, Epleronone
(Inspra) 50 – 100 mg dly
Site of Action: Cortical collecting tubule,
They block Na+ channels
Side effects: Hyperkalemia, Sexual
dysfunction
Potassium Sparing: Amiloride/hydrothiazModuretic 5 – 10/50 –100 mg dly,
Triamterene/hydrothiaz 37.5 – 75/25 50 mg
dly
Aldosterone antagonist : Gynaecomastia.
Action: Reduce extracellular fluid volume
CENTRALLY ACTING DRUGS: Methyl dopa
(Aldomet) 250mg – 1g dly, Clonidine (Catapres)
0.1-0.8mg dly,
• Action:They inhibit Sympathetic Nervous
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System via Central Alpha 2 Adrenergic
Receptors.
Clonidine withdrawal –Rebound BP elevation
Side Effects : Somnolence, Orthostasis,
Impotence, Rebound Hypertension
RESERPINE (0.05-0.25mg) dlyCombined with diuretics-reduce fluid retention
BETA BLOCKERS
• Selective Cardioselective: Atenolol
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(Tenormin) 25 – 100 mg dly, Metropolol
(Lopressor) 50 – 200mg dly, Bisprolol
(Zebetal) 2.5-10mg dly Bexalolol (Kerlone) 520 mg dly.
Non Selective: Propranolol (Inderal) 40320mg dly, Nadolol(Corgard) 40 – 120mg dly,
Timolol Blocaden) 10 – 40 mg dly.
Intrinsic Sympathomimetic activity:
Pindolol (Visken) 10 – 60mg dly,
Penbutolol(Levatol) 10 – 40mg dly, Acebutolol
(Sectral) 200 – 800 mg dly.
Alpha and Beta Blockers: Labetalol
(Trandate
Beta Blockers
• Actions: They reduce cardiac
contractility and Rennin release.
• Additional benefitTarchyarrythmias,essential tremor,
migraine headache and thyrotoxicosis
• Side Effect: Bronchospasm ( in severe
asthma), bradycardia (A-V Block),
Congestive Heart Failure exacerbation,
impotence, fatigue, depression.
• Abrupt withdrawal-rebound
hypertension.
Antihypertensive Medications indicated in specific Patient
Population
• Diabetes with proteinuria
• Ace
Inhibitors (ACEI)
• Congestive Heart Failure
ACEI, Diuretics +/-Beta
Blockers
• Isolated systolic Hypertension
• Diuretics preferred: long acting
dihyropyridine calcium channel
blockers
CONTD
• MI Beta Blockers without intrinsic
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sympathomimetic activity, ACEI
Osteoporosis Thiazide diuretics
BPH
Alpha antagonists
Pregnancy Methyldopa, Beta blockers,
Labetalol, Hydralazine +/-calcium
antagonists
Antihypertensives in
pregnancy
• Methyldopa-preferred based on safety data
• B Blockers- Safe, but IUGR reported
• Labetalol-preffered over methyldopa because
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of fewer side effects
Clonidine- Limited data available
CCBs-Limited data available, no teratogenicity
with exposure
Diuretics-not first line agents but probably
safe in low doses
ACEIs/ARBs- major teratogenicity on
exposure
JNC 7 MANAGEMENT OF HYPERTENSION
• Prehypertension 120-139/80-89- Life
style modification.
• Stage 1 140-159/90-99-Thiazides, may
consider ACEI,ARB, B Blockers Calcium
blockers or a combination
• Stage 2 >160/>100 – Two drug
combination (usually a thiazide
diuretic+an ACEI, an ARB, a B blocker,
or calcium blocker
THE END
• THANK YOU.