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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

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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


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, Angio-Odema


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 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, 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 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) 0.5-4mg 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.


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

  • 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,

  • 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

  • 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 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

  • Diabetes with proteinuria

  • Ace Inhibitors (ACEI)

  • Congestive Heart FailureACEI, Diuretics +/-Beta Blockers

  • Isolated systolic Hypertension

  • Diuretics preferred: long acting dihyropyridine calcium channel blockers


CONTD

  • MIBeta Blockers without intrinsic sympathomimetic activity, ACEI

  • OsteoporosisThiazide diuretics

  • BPHAlpha antagonists

  • PregnancyMethyldopa, 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 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.


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