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ANTI ANGINA THERAPY Angina Pectoris : Mismatch between myocardial oxygen supply and demand.

Symptom: Retrosternal discomfort, pressure like, occurs with exertion, relieved by rest, may radiate down arm or into neck. Drug Organic nitrates: 1)nitorglycerin 2)isosorbide dinitrate 3)isosorbide-5mononitrate Mech of action/ indication decompose to NO activate guanylate cyclase, so cGMP, cGMP activate protein kinase, lead to intracellular Ca. in smooth muscle, reduced phosphorylation of myosin light chain, reduced calcium, and relaxation. At concentration, nitrates decrease preload, so reduce workload on heart. At concentration, nitrate cause vasodilaton of coronary A and blood supply to myometrium I angina, MI, heart failure Metabolism/ drug interaction A)Tolerance =continue exposure to nitrates leads to decrease magnitude of pharmacological effect. =due to decrease in free SH group require nitrate free 24-h B) Interaction with Phosphodiesterase 5 inhibitors: - sildenafil (viagra) -taldalafil (cialis) -vardenafil (levitra) combination of nitrates with this drug causes extreme hypotension Side effect/ contraindication Clinical use

-Headache, = stable angina - hypotension, = unstable angina -transiet of hypotension worsen = MI with alcohol = HF = hypertensive

Method of administration : a)sublingual= nitoglycerin b)oral = isosorbide dinitrate c)cutaneous = transdermal patch d)IV -blocker:

- block action of NA n Adrenaline at beta adrenergic receptor

-bronchoconstriction (block = angina stable beta 2 mediated smooth muscle = MI relaxation) = HF

Non selective: 1) propanolol, 2) timolol Cardioselective: 1)Metaprolol 2)Atenolol

-reduce mortaliti and infarction -reduce myocardial O2 demand by: a) HR b) BP (afterload) c) contarctility

-mask symptom of hypoglycemia -HF -bradycardia -somnolence(induce sleep) -depression -impotence

= arrythmias

Alpha 1 antagonist xtvt: 1)carvedilol Result = 1-heart ratecontractility 2- contract SM (blood vessel and bronchi) 1- smooth muscle relaxation - Block L-type calcium Ca channel blocker channels, so Ca entry, so Dihydropyridine: intracellular Ca 1)nifedipine 2)amlodipine - In SMOOTH muscle = =affect vasculature vascular smooth muscle (decrease BP) relaxation - in HEART = contractility Non Dihydropyridine; 1)verapramil -can alter ratio of O2 2)diltiazem supply/demand in CHRONIC =affect heart (decrease STABLE ANGINA: HR) a) arteriolar Pressure b) myocardial contractility c) HR Gene therapy new vessel formation (eg:VGEF)

Headache, dizziness Flushing Oedema Tachycardia Constipation Hypotension

=arrythmias = hypertension = chronic stable angina, not used in unstable angina

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