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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.

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antihypertensive agents

Antihypertensive Agents

Dr S. O. Olayemi

hypertension

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
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

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
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
slide6
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, Angio-Odema
ace inhibitors7
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
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
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
slide10
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
VASODILATORS ; Hydralazine (Apresoline 20 – 100 mg daily, Minoxidil (Loniten) 10 – 40mg daily,
  • Action: They decrease peripheral resistance by 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
CALCIUM CHANNEL BLOCKERS
  • Dihydropyridines :
  • Nifedipine (Adalat/ProcardiA) 20 – 90 mg dly, 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 nodal conduction – Supra ventricular tachycardia
calcium channel blockers13
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
DIURETICS
  • Loop diuretics – Frusemide (Lasix) 20mg – 1 g, Bumetanide (Bumex) 0.5-4mg 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.
diuretics15
DIURETICS:
  • Thiazides: Chlorthalidone (Hygroton) 6.25 – 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
Potassium sparing diuretics
  • Aldosterone antagonist: Spironolactone (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/hydrothiaz-Moduretic 5 – 10/50 –100 mg dly,
  • Triamterene/hydrothiaz 37.5 – 75/25 50 mg dly
  • Aldosterone antagonist : Gynaecomastia.
  • Action: Reduce extracellular fluid volume and thereby reduce vascular resistance
centrally acting drugs methyl dopa aldomet 250mg 1g dly clonidine catapres 0 1 0 8mg dly
CENTRALLY ACTING DRUGS: Methyl dopa (Aldomet) 250mg – 1g dly, Clonidine (Catapres) 0.1-0.8mg dly,
  • Action:They inhibit Sympathetic Nervous System via Central Alpha 2 Adrenergic Receptors.
  • Clonidine withdrawal –Rebound BP elevation
  • Side Effects : Somnolence, Orthostasis, Impotence, Rebound Hypertension
  • RESERPINE (0.05-0.25mg) dly-
  • Combined with diuretics-reduce fluid retention
beta blockers
BETA BLOCKERS
  • Selective Cardioselective: Atenolol (Tenormin) 25 – 100 mg dly, Metropolol (Lopressor) 50 – 200mg dly, Bisprolol (Zebetal) 2.5-10mg dly Bexalolol (Kerlone) 5-20 mg dly.
  • Non Selective: Propranolol (Inderal) 40-320mg 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
  • 200-800 mg dly, Carvedilol (Coreg) 12.5 –50mg dly).
beta blockers19
Beta Blockers
  • Actions: They reduce cardiac contractility and Rennin release.
  • Additional benefit-Tarchyarrythmias,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
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
CONTD
  • MI Beta Blockers without intrinsic sympathomimetic activity, ACEI
  • Osteoporosis Thiazide diuretics
  • BPH Alpha antagonists
  • Pregnancy Methyldopa, Beta blockers, Labetalol, Hydralazine +/-calcium antagonists
antihypertensives in pregnancy
Antihypertensives in pregnancy
  • Methyldopa-preferred based on safety data
  • B Blockers- Safe, but IUGR reported
  • Labetalol-preffered over methyldopa because 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
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
THE END
  • THANK YOU.
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