Cardiovascular system pharmacology-Ischemic Heart Disease
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| What is myocardial stunning? | The reversible reduction of function of heart contraction after reperfusion not accounted for by tissue damage or reduced blood flow
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| The calcium combines with calmodulin to form: | a complex that converts the enzyme myosin light-chain kinaseto its active form (MLCK)
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| Beta2 agonists may cause relaxation in smooth muscle by: | accelerating the inactivation of MLCK
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| Calcium influx is inhibited by | CCBs, leading to muscle relaxation
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| Organic nitrates release | Nitric oxide
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| What is the function of nitric oxide? | Activation of guanylyl cyclase and increases formation of cGMP
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| What is the function of cGMP? | Smooth muscle relaxation by activating kinases that increase myosin phosphatase activity and decrease myosin phosphate levels
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| α 1-Adrenoceptor agonists activate | phospholipase C (PLC)
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| What is the function Phospholipase C (PLC)? | Increased formation of inositol triphosphate (IP3) from phosphatidyl inositol bisphosphate(PIP2), leading to increased release of calcium from the sarcoplasmic reticulum
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| Function of B2 receptor agonists: | Increased formation of cyclic adenosine monophosphate (cAMP), which activates kinases that inhibit myosin light-chain kinase
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| What is the prototype of nitroglycerine? | Nitroglycerine
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| What is the function of Nitroglycerine? | Nonspecific smooth muscle relaxant
General vasodilation
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| How is nitroglycerine administered? | Usually, sublingual
But can be administered by many routes
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| Onset of action of nitroglycerine? | 1-3 minutes, Peaks at 10 minutes
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| DOA of nitroglycerine: | 15-30 minutes
Until reductase in the liver breaks down the drug
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| How long does arteriolar vasodilation last? | 5-10 minutes
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| How long does venous vasodilation last? | 30 minutes
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| Function of arteriolar vasodilation: | Decreases systemic blood pressure (afterload) and causes reflex tachycardia and increased contractility (the last two are deleterious effects)
Might increase MVO2
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| Function of venous vasodilation: | Decreases venous return (preload) and decreases MVO2
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| Side effects of Nitroglycerine: | Headache
Hypotension
Tachycardia
Increased intraocular and intracranial pressures
Methemoglobinemia
Tolerance: only for the arteriolar effects
Withdrawal: in workers in ammunition industry
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| Functions of Beta Adrenergic Blockers | Cause subjective and objective improvement
Decreased number of anginal episodes
Nitroglycerine consumption
Enhanced exercise tolerance
Improved ECG
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| Advantages of taking Beta adrenergic blockers: | Prevent actions of catecholamines, so more effective during exertion
Do not dilate coronary arteries
Do not increase collateral blood flow
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| Functions of CCBs: | Beneficial in vasospasm
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| Harmful effects of CCBs: | Can affect platelets aggregation
May be dangerous in the presence of heart failure and in patients susceptible to hypotension
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| Side effects of CCBs: | Hypotension
Headache
Dizziness
Flushing
Peripheral edema.
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| Function of Dipyridamole: | Inhibits the uptake of adenosine and inhibits adenosine deaminase enzyme
Thought to be a good coronary dilator
Increases the blood flow to the normal area
Still used as an antiplatelet drug
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| Other solutions for ischemic heart disease: | ACEI
Anticoagulants and/or Thrombolytic Therapy
Cholesterol Lowering Agents
Angioplasty
Surgery
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| Newer anti-anginal drugs: | Metabolic modulators
Direct bradycardic agents
Potassium channel activators
Rho-kinase inhibitors
Sulfonylureas
Thiazolidinediones
Vasopeptidase inhibitors
Nitric oxide donors
Capsaicin
Amiloride
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| What is the newer metabolic modulator? | Ranolazine
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| What is the newer bradycardiac agent? | Ivabradine
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| What is the newer Potassium channel activators? | Nicorandil
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| What is the newer Rho-kinase inhibitor? | Fasudil
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| Newer sulfonylurea? | Glibenclamide
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| Newest Nitric oxide donor: | L- arginine
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| Additional Effects of CCBs: | A direct effect on HR and contractility (decrease)
Indirect effect (from high doses)
Increase HR and contractility (reflex)
Enhance collateral vessel diameter
The ratio of epicardial to endocardial blood flow/endo is increased
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| Nifedpine is not used in | cardiac arrhythmias , unlike verapmil which is effective in almost everything
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