Angina Pectoris Flashcards
Types of Angina and their description
Stable Agina
-Heavy pressing substernal discomfort during increased demand for o2
-major cause fixed narrowing of coronary arteries
myocardial ischemia during increased o2 demand
Unstable Angina
- Discomfort at rest
- major cause: formation of unstable non-occlusive thrombi lead to transient myocardial ischemia
Variant Angina (angiospastic angina)
-uncommon: discomfort at rest
-major cause: spasm in coronary artery
transient myocardial ischemia
Aim of Antianginal Drugs
Increased Perfusion of the myocardium
-dilation of coronary vasculature
Decreased metabolic demand
by reducing the cardiac workload
Why can’t use vasodilator for increasing perfusion of the myocardium
Coronary steal phenomenon due to
compensatory response in rearranging blood flow and growing of new blood vessel (collateral)
lead to further decrease in blood supply to the ischemic area which elevates angina symptoms
Name of Nitrates and their usage
Nitroglycerin, isosorbide dinitrate
Effective dilators of veins
-decreased amount of blood into the heart (decreased venous return) which decreased cardiac workload and thus myocardial O2 demand
Effective Dilators of Large Arteries
-mildly decreased peripheral vascular resistance (decreased blood pressure) decreased cardiac workload then myocardial O2 demand
Effective dilators of Collateral Coronary Artery
-improve distribution of coronary flow
Decreased coronary artery spasm
effective against variant angina
Mechanism of Action of Nitrates
Nitrate becomes Nitric Oxide NO then lead to the production of cyclic guanosine monophosphate (cGMP)
lead to dephosphorylation of myosin light chain which lead to relaxation
Precautious with use of nitrates
Effect of nitrate
-enhanced by phosphodiesterase 5 (PDE5) inhibitor e.g. sildenafil
-additive to that of stimulators of soluble guanylyl cyclase e.g. riociguat
lead to reflex tachycardia due to too much drop in BP
lead to increased in angina symptoms
Pharmacokinetics of Nitrates
Rapid metabolism in the liver -low oral bioavailability which sublingual route is preferred (dose administered via this sublingual route Is limited to avoid excessive effect which leads to brief duration of effect Rapid Onset -immediate relief Short duration of action Excretion of kidneys
Unwanted Effects of Nitrates
Tolerance (Tachyphylaxis)
- decreased response to nitrates due to frequently repeated or continuous exposure to nitrates (e.g. with long-acting nitrates isosorbide dinitrates or prolonged infusion or slow-releases forms of short-acting nitrates nitroglycerin
- avoid high doses
- administered with a nitrate-free period (8 to 12 hours each day usually at night with low physical activity low o2 metabolic demand )
Dependence
- withdrawal
- risk of coronary and digital arteriospasm
- Not to withdraw nitrates abruptly from a patient after chronic therapy
Adverse Effects
- headache
- postural hypotension
- tachycardia
Characteristics of Different Preparations of Nitrates (Sublingual and Oral)
Sublingual Administration
- fast onset
- short duration
- for fast relief and
- for prevention of anginal pain prior to exercise or stress
Oral administration
- prophylaxis against anginal episodes in patients with more than occasional angina
- higher doses and sustained-release preparations (due to low oral bioavailability and rapid metabolism)
Characteristics of Different Preparations of Nitrates (Cutaneous Transmucosal or Buccal, Intravenous )
Cutaneous Administration
- slow onset
- particularly useful for controlling nocturnal angina
Transmucosal or Buccal Administration
-for short-term prophylaxis of angina
-inserted under the upper lip above the incisors
–gradual release into the circulation for a prolonged period
,
Intravenous Administration
-allow rapid and safely titration of doses
-for relief of coronary vasospasm
Name of Calcium Channel Blockers and its effect
E.g. nifedipine and amlodipine, diltiazem, verapamil
Decreased force of contraction of the heart
-decreased cardiac workload and hence myocardial o2 demand
Effective vasodilators of Arteries and Arterioles
-decreased peripheral vascular resistance (decreased BP) thus decreased cardiac workload and myocardial o2 demand
Reduced Coronary Artery Spasm
-Effective against variant angina
Mechanism of Calcium Channel Blockers
Inhibit Voltage-Operated Calcium Channels (L-Type)
In the blood vessels
-decreased vasoconstriction and hence peripheral vascular resistance
In the heart
-decreased rate and force of contraction and thus cardiac output
Adverse Effects of Calcium Channel Blockers
Depends on Selectivity on Cardiac or Vascular Smooth muscle
- Drugs with vascular selectivity e.g. amlodipine, nifedipine
- -headache, flushing
- -hypotension which lead to decreased coronary perfusion and reflex tachycardia which both increased angina symptoms
- Drugs with cardiac selectivity e.g. diltiazem, verapamil
- -atrioventricular block which lead to heart failure
Name and effect of B-Blockers
Propanolol, metoprolol
Decreased force and rate of contraction of heart
- decreased cardiac workload and thus myocardial o2 demand
- increased duration of diastole and thus increased period of coronary flow and thus increased myocardial perfusion
Increased Coronary Artery Spasm
-avoided in variant angina
Adverse Effects of
b Blockers
Bronchospasm
-contraindicated in patients with asthma or other forms of obstructive airways disease
Hypoglycaemia
-cautious in patients with diabetes
Risk of Arrhythmia and Heart Failure
Risk of Vasospasm
-cautious in patients with severe peripheral vascular diseases or vasospastic disorders
Central Nervous System Disturbance
-cautious in patients with psychiatric disorders
Nicorandil and its effect
Possess Nitrate Like Vasodilator Properties
-which stimulate cGMP production
lead to effects enhanced by phosphodiesterase 5 (PDE 5 inhibitors and stimulators of soluble guanylyl cyclase]
Activate ATP Sensitive Potassium Channels
which increase potassium efflux
lead to vascular smooth muscle hyperpolarization
lead to vasodilatation
Both effect Dilate both arterial and venous vascular beds
[hemodynamic profile lies
in between that of nitrates
and dihydropyridine
calcium channel blockers]
which decrease Coronary artery spasm which is effective against variant angina
Adverse Effects of
Nicorandil
Headache, Hypotension and Tachycardia
[Same as nitrates
which contraindication of concurrent use of stimulators of soluble guanylyl cyclase or phosphodiesterase 5 (PDE 5 inhibitor]
Increased Risk of Gastrointestinal Ulcerations and Perforations
Trimetazidine and its usage
Inhibit Long Chain Mitochondrial 3 Ketoacyl Coenzyme A Thiolase 3
KAT) Enzyme [final enzyme in the free fatty acid β oxidation pathway] which
inhibit myocardial fatty acid oxidation thus shift to glucose oxidation for ATP production and increase efficiency of cardiac oxygen utilization
No Major Effect on Heart Rate or Blood Pressure
which can be used in patients with low heart rate or blood pressure
Adverse Effects of
Trimetazidine
Usually Mild e g gastrointestinal discomfort, muscle cramps, dizziness
Parkinson Syndrome [resolved after drug discontinuation]
which contraindicated in patients with Parkinson diseases or the related movement disorder, or with severely reduced kidney function
Ranolazine and its effect
Selectively Inhibit the Late Sodium Current in Heart which decrease sodium influx lead to decreased activation of Na ++/Ca 2 exchanger to remove Na
which decrease intracellular calcium concentration which decrease heart contractility which decrease cardiac work
No Major Effect on Heart Rate or Blood Pressure
which can be used in patients with low heart rate or blood pressure
Adverse Effects of
Ranolazine
Usually Mild e g nausea, dizziness, headache, constipation
Precautions with
Ranolazine
Metabolized by Liver Cytochrome P 450 CYP) 3A4 Pathway
- which lead to cautious in patients with hepatic dysfunction
- which lead to interactions with drugs [e g CYP 3 A 4 inducers or inhibitors]
Modestly Inhibit Potassium Current in Cardiomyocytes
- which risk of increased duration of action potential
- therefore cautious in patients with long QT syndrome
Ivabradine and its effect
Inhibitor of Hyperpolarization Activated Cyclic Nucleotide Gated (HCN) channels
-selectively inhibit I f current in the sinoatrial node (SA node)
-lead to decreased rate of spontaneous depolarization
-which decreases heart rate
thus decreased cardiac work and increased coronary perfusion
Adverse Effects of
Ivabradine
Bradycardia
-lead to dizziness, weakness or shortness of breath
Phosphenes (Flashes of Light), Blurred Vision
which is due to inhibition of Ih current in the retinal cells
Atrial Fibrillation
Contraindications for Ivabradine
Resting Heart Rate 60 smaller than Beats Per Minute Blood Pressure lower than 90 50 mmHg
Concurrent Diseases
- includes acute decompensated heart failure, sinus node dysfunction, pacemaker dependence [i.e heart rate maintained exclusively by the pacemaker]
- severe hepatic impairment
Concomitant Use of Strong CYP3A4 Inhibitors [e g azole antifungals (itraconzaole macrolide antibiotics (clarithromycin erythromycin)]
Pregnancy, Lactation or Women of Child Bearing Potential Not Using
Appropriate Contraceptive Measures
Non-Pharmacological Therapy of Angina
Coronary Artery Bypass Grafting (CABG)
Percutaneous Transluminal Coronary Angioplasty (PTCA)
Other Pharmacological Therapy of Angina
Anti Coagulant Drugs
Anti Platelet Drugs
Both reduces thrombi formation and prevent unstable angina
Lipid lowering drugs
which decreases Atheroma Deposition
