Accounting Antecedents of Financial Crisis: Prudence vs. Liquidity

Antianginal Drugs Learning outcomes Recognize variables contributing to a balanced myocardial supply versusdemand Expand on the drugs used to alleviateacute anginal attacks versus those meant for prophylaxis & improvement ofsurvival Detail the pharmacology of nitrates, other vasodilators, and other drugs used as antianginal therapy

Calcium channel blockers Classification Selectivity Nifedipine Nifedipine , , Nicardipine, Vascular smooth Vascular smoothmuscle Nicardipine,Amlodepine muscle Amlodepine Dihydropyridines:- Nifedipine Nifedipine, , Cardi CardiV Vom omera eray yp po oa ac cm myt yti ie el ls s PV Vhee enra rayp plaa alm mkyi ill lamines:- Interm IntermDi Die elt ltd di ii ia aa az zt te ee em m BD Dei inlt ltzi ita ahz ziaem emzepines:-

Mechanism of Action Binding of calcium channel blockers [CCBs] to theL-type Ca channels their frequency ofopening in response todepolarization entryofCa No Stimulus-Contraction Coupling RELAXATION Carelease frominternalstores

Antianginal Action Cardiomyocyte Contraction their ve inotropic & chronotropic action (verapamil & diltiazem) myocardialoxygen demand cardiacworkthrough VSMC Contraction myocardial oxygen demand Afterload cardiacwork Coronary dilatation myocardial oxygensupply

Therapeutic Uses INShVoArRtIAaNctTinAgNGdIiNhAydropyridi Attacks prevented (> 60%)/ ne should be avoided?? Can be combined to -ARblockers??? IN UNSTABLEANGINA; Seldom added in refractorycases Can be combined withnitrates??? sometimes variablyaborted INDSihT A ydBrLoEpyArNidGeInNeAs;useful antRiaengguilnaarlpirfowpihthylCaxHiFs??

Beta Adrenoceptor Blockers Examples Atenolol, Bisoprolol, Metoprolol ( Selective) Antianginal Mechanism

Beta Adrenoceptor Blockers Indications in angina In stable angina Regular prophylaxis, selective are prefered? First choice for chronic use? Can be combined with nitrates? Can be combined with dihydropyridine CCB? Verapamil? In variant angina Contraindicated?

Beta Adrenoceptor Blockers Indications in angina In Unstable angina Halts progression to MI, improve survival In Myocardial infarction Reduce infarct size Reduce morbidity & mortality reduce O2 demand reduce arrhythmias

Beta Adrenoceptor Blockers - blockers should be withdrawngradually? Given to diabetics with ischemic heartdisease?

Minicase Which antianginal drug is the best choice for the case of Helmi? And Why?

Minicase If Helmi does not respond to monotherapy, what other drug should be added to his regimen?

Potassium channel openners Nicorandil Mechanism L It has dual mechanismof action; 1. Opens KATP channels(> arteriolardilator) 2. NO donner as it has a nitrate moiety (> venular dilator

Pharmacodynamic Effects As K channel openner OAnsvnaist rciucl aorxs mi doeo tdhomnuosrc l e s opening of Kchannels hyperpolarization vasodilatation NO cGMP/PKG vasoditation OncardiomyocytesopeningofK channels repolarization cardiacwork

Indications Prophylactic 2nd line therapy in stable angina &refractory variantangina ADRs Flushing,headache, Hypotension, palpitation,weakness Mouth & peri-anal ulcers, nausea andvomiting.

Think-pair-share A 5 5 - year - old woman complained to her physician of palpitations, flushing of the face, and vertigo. The woman, suffering from diabetes mellitus, was giving herself three daily doses of insulin. She had been recently diagnosed with exertional angina for which nitrate therapy was started with transdermal nitroglycerin and oral isosorbide mononitrate. After 3 weeks of therapy, her anginal attacks were less frequent but not completely prevented. Which would be an appropriate next therapeutic step for this patient?

ftetabolically ftetabolically Acting ActingAgents Agents e.g. e.g. Trimetazidine Trimetazidine O2 O2 requirement requirement of of glucose glucose pathway pathwayis is wer wer than than FFA lo lo FFApathway pathway ng ng ischemia, oxidized ischemia, oxidized FFA ting ting the the glucose glucosepathway blun blun FFAleve leve Duri Duri ls lsrise, rise, pathway Reduces Reduces O2 O2 demand demand without without altering alteringhemodynamics hemodynamics

T Tr ri im me et taz azi idine dine Indications Indications Used Used as as an add an add on ontherapy therapy ADRs ADRs GIT GIT disturbances disturbances Hypersensitivity Hypersensitivity reaction reaction Contrindications Contrindications Pregnancy Pregnancy & & lactation lactation

ftetabolically ftetabolically Acting ActingAgents Agents Ranolazine Ranolazine Inhibits Inhibits the during duringischemia the late sodium late sodium current ischemia current which whichincreases increases It prolongs Class Ia &I the QT interval so contraindicatedwit IIantiarrhthmics h; velops due to interaction with CYT 450 m, verapamil, ketoconazole, macrolide grapefruitjuice antibiotics, Toxicity de as; diltiaze inhibitors ADRs:- dizziness , constipation Used in chronic angina concommitanly with otherdrugs

Minicase Which antihyperlipidemic drug should be prescribed to Helmi?

Ivabradine Ivabradine Ivabradine Selectively blocksIf Ivabradine Ivabradine reduces slope of depolarization, slowing HR,reducing myocardila work & O2 demand UUsseeddiinntcr eoamt mb i neantti oonf cwhirtohnbi ce tsatabbl oleckae phaetai ernt tfsaiwluirteh wn oi trhmLaVlEsFi nluo ws er hrytthhamn w3 5 i- nbalodcekqeurastely controlled by beta bloc whose heart rate exceeds 70/min nrgsinain pineople with hopercanncenotttake ers aloneand k ADR:- luminousphenomena If current is a pacemaker that activates n inward Na+/K+current cells of the SA node

Agents Agents that that improve improveprognosis prognosis - -Aspirin Aspirin / /other antiplatelet antiplatelet agents - -ACE ACE inhibitors inhibitors - -Statins Statins - - - -blockers blockers other agents Halt Halt progression progression Prevent Prevent acute acuteinsult Improve Improvesurvival survival insult

Memory matrix In the following table indicate increase,decrease or no effect with signs , , respectively Drug/Class HR BP Wall Tension Contract- ility O2 Suppl y Beta-blockers CCBs Verap/Dilt Dihydropyridines Nitrates Ranolazine