Antianginal Drugs. Drugs That Increase Regional Blood Flow Flashcards
Determinants of coronary blood flow (and therefore oxygen supply)
HR Perfusion Pressure Size: Lumen of coronary arteries Ventricular Contractility Ventricular Wall Stress
Principle of Antianginal Drugs
Reduce oxygen demand or enhance oxygen supply to myocardium
Molecular Mode of Action of Organic Nitrites and Nitrates
NO activates guanylyl cyclase–> cGMP–> PKG–>MCLP (dephosphorylation) –> relaxation
Haemodynamic Effects of Nitrates
Low dose: venodilation
decrease preload, decrease ventricular end diastolic volume and pressure–> decrease O2 demand
High dose: venous pooling and arterial vasodilation
decrease TPP–> reduce O2 demand
General:
coronary blood flow increases
redistribution of flow to damaged region due to dilation of collaterals
Antianginal Actions of Nitrates
Reduction of cardiac O2 consumption
Redistribution of flow
Improved subendothelial perfusion
Relief of coronary vasospasm
Non Vascular Effects of Nitrates
Increased relaxation of heart
Inhibition of platelet aggregation
Bronchodilation
Relaxation of SM GIT
Tolerance of Organic Nitrates
Mechanism and Cause
Monday Morning Disease
Mechanism:
depletion of vascular SH stores–> impaired NO release
oxidative stress–> enhanced No degradation
Cause:
Frequent or continuous exposure
Monday Morning Disease
tolerance ceased during weekend
headache, flushing, orthostatic hypotension, reflex tachy, methemoglobin formation
Mechanism of Action on SM relaxation by NO
NO is a endogenous activator of soluble guanylyl cyclase–> formation of cGMP from GTP
Activation of cGMP–>PKG—>MLCP–> deP of Myosin LC–> relaxation
P of IP3 R–> decrease Ca conc–> relaxation
Drugs that can reverse tolerance of organic Nitrates
SH compounds and other antioxidants Vasodilators B Blockers ACE Inhibitors Diuretics
Drug List: Organic Nitrates and Nitrites
Nitroglycerin
sublingual or transdermal patch: fast and no first pass
metabolised in liver
T1/2: 3 min only for acute symp relief
Side effects: headache, flushing, loss of consciousness, tissue hypoxia
Isosorbide Dinitrate
longer duration than nitroglycerin T1/2: 45 min
sublingual
metabolised to isosorbide mononitrate
Isosorbide Mononitrate
active first metabolite of iso.. dinit..
less activity but longer duration T1/2: 3-6 hrs
excellent bioavailability
excreted renally
Ca Channel Blockers: How antianginal
decrease O2 demand:
arterial vasodilation (decrease after load)
negative chrono and Inotropic
decrease blood and oxygen supply by dilation
Ca Channel Blocker
Drug List
Verapamil Nitrendipin Amlodipine Nimodipine Nifedipine Diltiazem
Beta Blockers
How Antianginal
Reduce metabolic demand of myocardium
negative chrono and Inotropic
USELESS IN PRINZMETAL
DRUG INTERACTION: Verapamil and Beta Blocker
Beta Blocker
Drug List
B1 as cardio selective
metoprolol atenolol bisoprolol nevivolol celiprolol
Drug categories increasing regional blood flow
A Blocker
5HT2 R Antagonists
Ca Channel Blockers
Synthetic Prostaglandins
Phosphodiesterase Inhibitors
Penile as well
Nicotinic Acid (th of vasospasm) L Arginine (vasodilation, precursor of NO)
