Antihypertensive Agents Antihypertensive Agents

Dr S. O. OlayemiDr S. O. Olayemi

HYPERTENSIONHYPERTENSIONChronically persistent elevated blood Chronically persistent elevated blood

pressure>/=140 mm Hg systolic blood pressure>/=140 mm Hg systolic blood pressure and or diastolic >/= 90 pressure and or diastolic >/= 90

mmHg in individual above 18 years of mmHg in individual above 18 years of ageage

Controlled BP SBP <140mmHg and Controlled BP SBP <140mmHg and DBP<90mmHGDBP<90mmHG

Expert Committee on non Expert Committee on non Communicable diseasesCommunicable diseases

• One third of Nigerian adults above 15 One third of Nigerian adults above 15 years of age are hypertensives, from years of age are hypertensives, from this one third are aware of the this one third are aware of the hypertensive status, and one third hypertensive status, and one third are on treatment.are on treatment.

• Control definition?Complex?Control definition?Complex?compliance/cost etccompliance/cost etc

TREATMENT GOALTREATMENT GOALPrevent morbidity and mortality Prevent morbidity and mortality

associated with high blood associated with high blood pressure.pressure.

Achieving control through least Achieving control through least intrusive means possibleintrusive means possible

Control other modifiable Control other modifiable cardiovascular risk factors.cardiovascular risk factors.

Ace Inhibitors:Ace Inhibitors:

• Captopril (Capoten) 12.5 – 150mg Captopril (Capoten) 12.5 – 150mg dailydaily

• Enalapril (Vasotec) 5 – 40 mg dailyEnalapril (Vasotec) 5 – 40 mg daily

• Lisinopril (Zestril) 5 – 40mg dailyLisinopril (Zestril) 5 – 40mg daily

• Ramipril (Tritace) 2.5 – 10mg dailyRamipril (Tritace) 2.5 – 10mg daily

• Perindopril (Aceon) 4 – 16 mg dailyPerindopril (Aceon) 4 – 16 mg daily

• Fosinopril (Monopril) 5 – 40mg Fosinopril (Monopril) 5 – 40mg dailydaily

• ActionAction: ACEI block conversion of : ACEI block conversion of Angiotensin 1 to Angiotensin 11 Angiotensin 1 to Angiotensin 11 thereby blocking stimulation of thereby blocking stimulation of aldosterone.aldosterone.

• Major site of Angiotensin II production – Major site of Angiotensin II production – Vessels and not the kidneys.Vessels and not the kidneys.

• reduce peripheral resistance and salt reduce peripheral resistance and salt and water retention.and water retention.

• Side EffectSide Effect: Cough, Rashes, : Cough, Rashes, Leukopenia, Hyperkalaemia, Angio-Leukopenia, Hyperkalaemia, Angio-Odema Odema

ACE inhibitorsACE inhibitors

• Reduce dose in volume depleted Reduce dose in volume depleted pt, elderly(hypotension)pt, elderly(hypotension)

• May be combined with diureticsMay be combined with diuretics

• Hyperkalaemia – CKD pts, Hyperkalaemia – CKD pts, potassium sparing diuretics and potassium sparing diuretics and angiotensin receptor blockers.angiotensin receptor blockers.

• ARF- renal artery stenosisARF- renal artery stenosis

• Contraindicated in pregnancy and Contraindicated in pregnancy and pt with hx of angioodema.pt with hx of angioodema.

ANGIOTENSIN II RECEPTOR ANTAGONISTSANGIOTENSIN II RECEPTOR ANTAGONISTS

• Losartan (Cozaar) 50 – 100 mg dailyLosartan (Cozaar) 50 – 100 mg daily

• Valsartan (Diovan) 80 – 320 mg dailyValsartan (Diovan) 80 – 320 mg daily

• Temilsartan (Micardis) 20 – 80 mg dailyTemilsartan (Micardis) 20 – 80 mg daily

• Irbesartan (Avapro) 150 –300mg dailyIrbesartan (Avapro) 150 –300mg daily

• Olmesartan (Benicar) 20 – 40 mg dailyOlmesartan (Benicar) 20 – 40 mg daily

• Candesartan (Atacand) 8 – 32 mg dailyCandesartan (Atacand) 8 – 32 mg daily

ANGIOTENSIN II RECEPTOR ANGIOTENSIN II RECEPTOR ANTAGONISTS: ARBsANTAGONISTS: ARBs

• ActionAction: They directly block the angiotensin II : They directly block the angiotensin II type 1 (AT1) receptors – vasoconstriction, type 1 (AT1) receptors – vasoconstriction, aldosterone release, sympathetic activation, aldosterone release, sympathetic activation, ADH release, constriction of efferent renal ADH release, constriction of efferent renal arteriolesarterioles

• Beneficial AT2-vasodilation,tissue repair and Beneficial AT2-vasodilation,tissue repair and inhibition of cellular growth in blood vesselsinhibition of cellular growth in blood vessels

(reduce peripheral resistance and salt/water (reduce peripheral resistance and salt/water retention)retention)

• Side Effects: Rashes, Side Effects: Rashes, Leukopenia,Hyperkalaemia but no coughLeukopenia,Hyperkalaemia but no cough

ARBsARBs

• Reduce dose in volume depleted Reduce dose in volume depleted pt, elderly(hypotension)pt, elderly(hypotension)

• May be combined with diureticsMay be combined with diuretics• Hyperkalaemia – CKD pts, Hyperkalaemia – CKD pts,

potassium sparing diuretics and potassium sparing diuretics and angiotensin receptor blockers.angiotensin receptor blockers.

• ARF- renal artery stenosisARF- renal artery stenosis• Contraindicated in pregnancy Contraindicated in pregnancy • Do not induce cough as in ACEIsDo not induce cough as in ACEIs

VASODILATORS ; VASODILATORS ; Hydralazine (Apresoline Hydralazine (Apresoline 20 – 100 mg daily, Minoxidil (Loniten) 10 – 20 – 100 mg daily, Minoxidil (Loniten) 10 – 40mg daily, 40mg daily,

• ActionAction: They decrease peripheral : They decrease peripheral resistance by dilating arteries/arterioles.resistance by dilating arteries/arterioles.

• Combined with diuretic/B blockers –diminish Combined with diuretic/B blockers –diminish fluid retention/reflex tarchycardia.fluid retention/reflex tarchycardia.

• Side EffectSide Effect: Hydralazine (Headache, lupus-: Hydralazine (Headache, lupus-like syndrome), like syndrome),

• Minoxidil (Orthostasis, facial hirsutism),Minoxidil (Orthostasis, facial hirsutism),• Diazoxide (Hyperglycaemia.Diazoxide (Hyperglycaemia.•   

CALCIUM CHANNEL BLOCKERSCALCIUM CHANNEL BLOCKERS

• DihydropyridinesDihydropyridines : :• Nifedipine (Adalat/ProcardiA) 20 – 90 mg dly, I, Nifedipine (Adalat/ProcardiA) 20 – 90 mg dly, I,

Felodipine (Plendil) 5 – 20 mg dly, Felodipine (Plendil) 5 – 20 mg dly, • Amlodipine (Norvasc) 2.5 – 10 mg dlyAmlodipine (Norvasc) 2.5 – 10 mg dly• Nicardipine (Cardene) 60 – 120 mg dlyNicardipine (Cardene) 60 – 120 mg dly•   PhenylakylaminePhenylakylamine: Verapamil 100 – 400 mg : Verapamil 100 – 400 mg

dlydly• BenzothiazepineBenzothiazepine: Diltiazem 120 – 480 mg dly.: Diltiazem 120 – 480 mg dly.• ActionAction: Reduce smooth muscle tone and cause : Reduce smooth muscle tone and cause

vasodilation: may reduce cardiac output.vasodilation: may reduce cardiac output.• Verapamil/diltiazem: decrease HR/delay A-V Verapamil/diltiazem: decrease HR/delay A-V

nodal conduction – Supra ventricular nodal conduction – Supra ventricular tachycardiatachycardia

Calcium channel blockersCalcium channel blockers

• Avoid immediate release nifedipines etcAvoid immediate release nifedipines etc

• Dihydropyridines are more potent Dihydropyridines are more potent peripheral vasodilators compared to peripheral vasodilators compared to non-dihydropyridines.non-dihydropyridines.

• Side effectSide effect: Dihydropyridines – reflex : Dihydropyridines – reflex sympathetic discharge (tarchycardia) sympathetic discharge (tarchycardia) Headache, flushing, peripheral oedema.Headache, flushing, peripheral oedema.

• Non dihyropyridines – variable heart Non dihyropyridines – variable heart blockblock

DIURETICSDIURETICS • Loop diureticsLoop diuretics – Frusemide (Lasix) – Frusemide (Lasix)

20mg – 1 g, Bumetanide (Bumex) 0.5-20mg – 1 g, Bumetanide (Bumex) 0.5-4mg Torsemide (Demadex) – 5mg dly.4mg Torsemide (Demadex) – 5mg dly.

• Site of ActionSite of Action: Loop of Henle, Reduce : Loop of Henle, Reduce Na+/K+/Cl- cotransporter: reduce Na+/K+/Cl- cotransporter: reduce urine concentration; Increase calcium urine concentration; Increase calcium excretion.excretion.

• Preferrably morning/afternoon (avoid Preferrably morning/afternoon (avoid nocturnal diuresis)nocturnal diuresis)

• Higher doses in patients with CKD.Higher doses in patients with CKD.• Side effectSide effect: Ototoxicity, : Ototoxicity,

Hypokalaemia, Hypotension, Gout.Hypokalaemia, Hypotension, Gout.

DIURETICSDIURETICS::

• ThiazidesThiazides: Chlorthalidone (Hygroton) 6.25 – : Chlorthalidone (Hygroton) 6.25 – 25mg dly, Hydrochlorothiazides (Esidrix) 12.5 – 25mg dly, Hydrochlorothiazides (Esidrix) 12.5 – 50mg dly Bendrofluazide 2.5 – 5mg dly50mg dly Bendrofluazide 2.5 – 5mg dly

• Site of Action: Site of Action: Early distal tubule, they reduce Early distal tubule, they reduce NaCl reabsorption thereby reducing the diluting NaCl reabsorption thereby reducing the diluting capacity of nephron. Decrease Calcium capacity of nephron. Decrease Calcium excretion.excretion.

• Dose in Morning (avoid noctunal diuresis)Dose in Morning (avoid noctunal diuresis)

• More effective antihypertensives than loops More effective antihypertensives than loops except in CKD (GFR <30ml/minexcept in CKD (GFR <30ml/min

• Side effectsSide effects: Hypokalaemia, Hyponatreamia, : Hypokalaemia, Hyponatreamia, Hypercalcemia, Hyperglyceamia, Hypercalcemia, Hyperglyceamia, Hyperlipidaemia, Hyperuricaemia (Problematic in Hyperlipidaemia, Hyperuricaemia (Problematic in gout),gout),

Potassium sparing Potassium sparing diureticsdiuretics• Aldosterone antagonistAldosterone antagonist: Spironolactone : Spironolactone

(Aldactone) 25 –50 mg dly, Epleronone (Inspra) (Aldactone) 25 –50 mg dly, Epleronone (Inspra) 50 – 100 mg dly50 – 100 mg dly

• Site of Action: Site of Action: Cortical collecting tubule, Cortical collecting tubule, They block Na+ channelsThey block Na+ channels

• Side effectsSide effects: Hyperkalemia, Sexual : Hyperkalemia, Sexual dysfunctiondysfunction

• Potassium Sparing:Potassium Sparing: Amiloride/hydrothiaz- Amiloride/hydrothiaz-Moduretic 5 – 10/50 –100 mg dly, Moduretic 5 – 10/50 –100 mg dly,

• Triamterene/hydrothiaz 37.5 – 75/25 50 mg dlyTriamterene/hydrothiaz 37.5 – 75/25 50 mg dly• Aldosterone antagonist : Gynaecomastia.Aldosterone antagonist : Gynaecomastia.• ActionAction: Reduce extracellular fluid volume and : Reduce extracellular fluid volume and

thereby reduce vascular resistancethereby reduce vascular resistance

CENTRALLY ACTING DRUGSCENTRALLY ACTING DRUGS: Methyl dopa : Methyl dopa (Aldomet) 250mg – 1g dly, Clonidine (Aldomet) 250mg – 1g dly, Clonidine (Catapres) 0.1-0.8mg dly, (Catapres) 0.1-0.8mg dly,

• ActionAction:They inhibit Sympathetic Nervous :They inhibit Sympathetic Nervous System via Central Alpha 2 Adrenergic System via Central Alpha 2 Adrenergic Receptors.Receptors.

• Clonidine withdrawal –Rebound BP elevationClonidine withdrawal –Rebound BP elevation

• Side EffectsSide Effects : Somnolence, Orthostasis, : Somnolence, Orthostasis, Impotence, Rebound Hypertension Impotence, Rebound Hypertension

• RESERPINE (0.05-0.25mg) dly- RESERPINE (0.05-0.25mg) dly-

• Combined with diuretics-reduce fluid Combined with diuretics-reduce fluid retentionretention

BETA BLOCKERSBETA BLOCKERS • Selective CardioselectiveSelective Cardioselective: Atenolol : Atenolol

(Tenormin) 25 – 100 mg dly, Metropolol (Tenormin) 25 – 100 mg dly, Metropolol (Lopressor) 50 – 200mg dly, Bisprolol (Zebetal) (Lopressor) 50 – 200mg dly, Bisprolol (Zebetal) 2.5-10mg dly Bexalolol (Kerlone) 5-20 mg dly.2.5-10mg dly Bexalolol (Kerlone) 5-20 mg dly.

• Non Selective: Non Selective: Propranolol (Inderal) 40-Propranolol (Inderal) 40-320mg dly, Nadolol(Corgard) 40 – 120mg dly, 320mg dly, Nadolol(Corgard) 40 – 120mg dly, Timolol Blocaden) 10 – 40 mg dly.Timolol Blocaden) 10 – 40 mg dly.

• Intrinsic Sympathomimetic activity: Intrinsic Sympathomimetic activity: Pindolol (Visken) 10 – 60mg dly, Pindolol (Visken) 10 – 60mg dly, Penbutolol(Levatol) 10 – 40mg dly, Acebutolol Penbutolol(Levatol) 10 – 40mg dly, Acebutolol (Sectral) 200 – 800 mg dly.(Sectral) 200 – 800 mg dly.

• Alpha and Beta Blockers: Alpha and Beta Blockers: Labetalol Labetalol (Trandate (Trandate

• 200-800 mg dly, Carvedilol (Coreg) 12.5 –200-800 mg dly, Carvedilol (Coreg) 12.5 –50mg dly).50mg dly).

Beta BlockersBeta Blockers• ActionsActions: They reduce cardiac : They reduce cardiac

contractility and Rennin release.contractility and Rennin release.• Additional benefit-Additional benefit-

Tarchyarrythmias,essential tremor, Tarchyarrythmias,essential tremor, migraine headache and thyrotoxicosismigraine headache and thyrotoxicosis

• Side EffectSide Effect: Bronchospasm ( in : Bronchospasm ( in severe asthma), bradycardia (A-V severe asthma), bradycardia (A-V Block), Congestive Heart Failure Block), Congestive Heart Failure exacerbation, impotence, fatigue, exacerbation, impotence, fatigue, depression.depression.

• Abrupt withdrawal-rebound Abrupt withdrawal-rebound hypertension.hypertension.

Antihypertensive Medications indicated in specific Antihypertensive Medications indicated in specific

Patient PopulationPatient Population • Diabetes with proteinuriaDiabetes with proteinuria

• Ace Ace Inhibitors (ACEI)Inhibitors (ACEI)

• Congestive Heart FailureCongestive Heart FailureACEI, Diuretics +/-Beta ACEI, Diuretics +/-Beta

BlockersBlockers

• Isolated systolic HypertensionIsolated systolic Hypertension

• Diuretics preferred: long acting Diuretics preferred: long acting dihyropyridine calcium channel dihyropyridine calcium channel blockersblockers

CONTDCONTD

• MIMI Beta Blockers without intrinsic Beta Blockers without intrinsic sympathomimetic activity, ACEIsympathomimetic activity, ACEI

• OsteoporosisOsteoporosis Thiazide diureticsThiazide diuretics• BPHBPH Alpha antagonistsAlpha antagonists• PregnancyPregnancy Methyldopa, Beta blockers, Methyldopa, Beta blockers,

Labetalol, Hydralazine +/-calcium Labetalol, Hydralazine +/-calcium antagonistsantagonists

  

Antihypertensives in Antihypertensives in pregnancypregnancy• Methyldopa-preferred based on safety dataMethyldopa-preferred based on safety data

• B Blockers- Safe, but IUGR reportedB Blockers- Safe, but IUGR reported

• Labetalol-preffered over methyldopa Labetalol-preffered over methyldopa because of fewer side effectsbecause of fewer side effects

• Clonidine- Limited data availableClonidine- Limited data available

• CCBs-Limited data available, no CCBs-Limited data available, no teratogenicity with exposureteratogenicity with exposure

• Diuretics-not first line agents but probably Diuretics-not first line agents but probably safe in low dosessafe in low doses

• ACEIs/ARBs- major teratogenicity on ACEIs/ARBs- major teratogenicity on exposureexposure

JNC 7 MANAGEMENT OF HYPERTENSIONJNC 7 MANAGEMENT OF HYPERTENSION

• Prehypertension 120-139/80-89- Prehypertension 120-139/80-89- Life style modification.Life style modification.

• Stage 1 140-159/90-99-Thiazides, Stage 1 140-159/90-99-Thiazides, may consider ACEI,ARB, B Blockers may consider ACEI,ARB, B Blockers Calcium blockers or a combinationCalcium blockers or a combination

• Stage 2 >160/>100 – Two drug Stage 2 >160/>100 – Two drug combination (usually a thiazide combination (usually a thiazide diuretic+an ACEI, an ARB, a B diuretic+an ACEI, an ARB, a B blocker, or calcium blockerblocker, or calcium blocker

THE ENDTHE END

• THANK YOU.THANK YOU.