Antihypertensive Agents

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Antihypertensive Agents

• Dr S. O. Olayemi

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HYPERTENSION

• Chronically persistent elevated blood
  pressuregt/140 mm Hg systolic blood pressure and
  or diastolic gt/ 90 mmHg in individual above 18
  years of age
• Controlled BP SBP lt140mmHg and DBPlt90mmHG

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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

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TREATMENT GOAL

• Prevent morbidity and mortality associated with
  high blood pressure.
• Achieving control through least intrusive means
  possible
• Control other modifiable cardiovascular risk
  factors.

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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

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• 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

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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.

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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

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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

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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

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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.
•  

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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

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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

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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.

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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 lt30ml/min
• Side effects Hypokalaemia, Hyponatreamia,
  Hypercalcemia, Hyperglyceamia, Hyperlipidaemia,
  Hyperuricaemia (Problematic in gout),

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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

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

• ActionThey 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

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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).

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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.

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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

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CONTD

• MI Beta Blockers without intrinsic
  sympathomimetic activity, ACEI
• Osteoporosis Thiazide diuretics
• BPH Alpha antagonists
• Pregnancy Methyldopa, Beta blockers, Labetalol,
  Hydralazine /-calcium antagonists
•  

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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

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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 gt160/gt100 Two drug combination (usually
  a thiazide diuretican ACEI, an ARB, a B
  blocker, or calcium blocker

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THE END

• THANK YOU.