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59 Cards in this Set
- Front
- Back
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ANGINA PECTORIS:
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Angina is the ischemic chest pain that is felt when the oxygen supply to the myocardium is insufficient for its needs. It is a symptom of ischemic heart disease
Often presents as a radiating chest pain (to the arm and jaw) and can be brought on by exertion If the myocardial ischemia is sufficiently severe and maintained for a sufficient period of time, death of tissue (injury and infarction) can occur |
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ANGINA: UNDERLYING PATHOLOGY
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Oxygen supply to the myocardium is reduced due to:
- Coronary arteriosclerosis - Transient platelet aggregation and formation of a thrombus in the coronary arteries - Coronary vasoconstriction due to accumulation of potent vasoconstrictors at sites of endothelial injury - Coronary artery spasm of unknown cause |
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ANGINA: UNDERLYING PATHOLOGY cont...
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Excess sympathetic activity (eg: during exercise) can precipitate/exacerbate anginal pain by increasing the myocardial oxygen demand
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ANGINA: UNDERLYING PATHOLOGY cont...
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Narrowing of the artery pic
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TYPES OF ANGINA
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Stable angina
Unstable Angina Variant angina |
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STABLE ANGINA
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- Classic Angina, Angina of Exercise
- Predictable chest pain brought upon by exertion - CAUSE: Fixed narrowing of the coronary vessels by an atheroma |
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STABLE ANGINA
TREATMENT STRATEGIES
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Prevent recurrence of angina with drugs that improve oxygen supply & reduce myocardial oxygen demand
- Long-acting nitrates - β blockers (Non-selective or β1 selective) - Calcium channel blockers Treat underlying atherosclerosis eg. with Statins Prophylaxis against thrombosis eg with aspirin or clopidogrel |
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UNSTABLE ANGINA
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- Crescendo, Angina at rest
- Occurs at rest or with minimal physical activity - Sudden onset, often occurs prior to an episode of acute myocardial infarction (AMI) - The chest pain is more severe, lasts longer - CAUSE: Reduced coronary perfusion due to thrombus or plaque obstructing coronary blood flow |
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Treatment of unstable angina in the context of acute coronary syndrome (ACS)
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pic
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Management of ACS
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- GOAL: To relieve chest pain and prevent progression to irreversible myocardial injury
- Manage unstable angina by reducing myocardial demand & improving coronary perfusion β blockers , nitrates - Opioids to reduce anginal pain and prevent excessive sympathetic activation (CNS effect) |
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Management of ACS cont...
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- Anticoagulants & Antiplatelet drugs to interfere with formation or progression of the thrombus
- Evaluate the type of myocardial infarct (NSTEMI or STEMI) - Evaluate the necessity for surgical intervention: angioplasty or percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) -- More potent anti-platelet agents ( GpIIB/IIIa blockers -- Thrombolytics to open blocked arteries (recommended in STEMI) |
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Therapeutic Management Post-ACS
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Short term:
- Antiplatelet agents (clopidogrel, GPIIb/IIIa blockers) - Antiarrythmic agents Long term: - Manage reversible risk factors with life style modification - ACE inhibitors, beta-blockers - Antiplatelet agents (to prevent reocclusion) - Statins |
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VARIANT ANGINA
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- Vasospastic, Prinzmetal
Occurs at rest - Cyclical: Pain at the same time of the day (usually early morning) - Chest pain can be accompanied by ventricular arrythmias - Cause: Coronary vasospasm -- Coronary arteries are usually free of a fixed obstruction -- Occurs about few cms away from an infarct site |
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VARIANT ANGINA
TREATMENT STRATEGIES
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GOAL : Relieve chest pain & minimize
myocardial damage - Nitrates - Calcium channel blockers - Treatment is slowly tapered off over 6-12 months |
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ANTI-ANGINALS: DRUG CLASSES
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- Organic Nitrates
- Beta blockers - Calcium Channel Blockers |
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ORGANIC NITRATES
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AMYL NITRITE (used to treat cyanide poisoning)
GLYCERYL TRINITRATE (Nitroglycerin) Nitrobid® ISOSORBIDE DINITRATE, ISDN (Isobid®) ISOSORBIDE MONONITRATE, ISMN (Ismo®) |
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NITRATES: CLINICAL USES
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- Termination of an acute anginal attack
- Prophylaxis of stress induced attacks - Long term prophylaxis against recurrent attacks - For patients with frequent symptoms - For patients who are not responsive to or intolerant of β blockers (Asthma, diabetes), or Ca++ channel blockers (recent MI) - Treatment of cyanide poisoning (Amyl Nitrite followed with methylene blue) |
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NITRATES:THERAPEUTIC ACTIONS
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1. Reduce myocardial oxygen consumption by reducing work load
Peripheral venodilation (reduces preload) Peripheral arteriolar Dilation (reduces afterload) |
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NITRATES:Therapeutic actions
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2. Increase oxygen supply to the ischemic area
Nitrates dilate coronary arteries - To redistribute coronary flow towards ischemic areas via collaterals - To oppose the coronary spasm in variant angina |
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Coronary Circulation
Nitrates vs Dipyridamole
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pic
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Nitrates: Signal transduction
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pic
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Nitrates: Signal transduction flow chart
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pic
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NITRATES:ADVERSE EFFECTS
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- Throbbing Headache (meningeal artery vasodilation) Orthostatic Hypotension Syncope
- After few days of therapy, tolerance develops to headache & hypotension) should resolve Dose can be reduced for nitrate induced syncope |
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NITRATES:ADVERSE EFFECTS
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- Dizziness,
- Flushing - Nausea - Reflex Tachycardia - Large IV doses of nitroglycerine can cause methemoglobinemia |
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Tolerance to Nitrates
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- Tolerance to the vasodilatory effects of nitrates may develop with continuous exposure to nitrates
- More likely with nitrate formulations with longer half-lives or with transdermal patches of nitroglycerine - Can be overcome by providing a daily ‘nitrate-free interval’ in the night |
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ORGANIC NITRATES
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AMYL NITRITE (used to treat cyanide poisoning)
GLYCERYL TRINITRATE (Nitroglycerin) Nitrobid® ISOSORBIDE DINITRATE, ISDN (Isobid®) ISOSORBIDE MONONITRATE, ISMN (Ismo®) |
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NITRATES: CLINICAL USES
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- Termination of an acute anginal attack
- Prophylaxis of stress induced attacks - Long term prophylaxis against recurrent attacks - For patients with frequent symptoms - For patients who are not responsive to or intolerant of β blockers (Asthma, diabetes), or Ca++ channel blockers (recent MI) - Treatment of cyanide poisoning (Amyl Nitrite followed with methylene blue) |
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NITRATES:THERAPEUTIC ACTIONS
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1. Reduce myocardial oxygen consumption by reducing work load
Peripheral venodilation (reduces preload) Peripheral arteriolar Dilation (reduces afterload) |
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NITRATES:Therapeutic actions
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2. Increase oxygen supply to the ischemic area
Nitrates dilate coronary arteries - To redistribute coronary flow towards ischemic areas via collaterals - To oppose the coronary spasm in variant angina |
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Coronary Circulation
Nitrates vs Dipyridamole
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pic
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Nitrates: Signal transduction
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pic
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Nitrates: Signal transduction flow chart
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pic
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NITRATES:ADVERSE EFFECTS
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- Throbbing Headache (meningeal artery vasodilation) Orthostatic Hypotension Syncope
- After few days of therapy, tolerance develops to headache & hypotension) should resolve Dose can be reduced for nitrate induced syncope |
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NITRATES:ADVERSE EFFECTS
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- Dizziness,
- Flushing - Nausea - Reflex Tachycardia - Large IV doses of nitroglycerine can cause methemoglobinemia |
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Tolerance to Nitrates
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- Tolerance to the vasodilatory effects of nitrates may develop with continuous exposure to nitrates
- More likely with nitrate formulations with longer half-lives or with transdermal patches of nitroglycerine - Can be overcome by providing a daily ‘nitrate-free interval’ in the night |
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Monday-Morning Sickness
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- Tolerance also develops to the adverse effects of nitrates
- Recognized in workers at explosive factories who after a weekend of “nitrate-free” period experience headaches, low blood pressure etc the first day back at work |
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Nitrates: Contraindications
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Do not prescribe phosphodiesterase (PDE) inhibitors (Sildenafil, Tadelafil) to patients taking nitrates
- PDE inhibitors prevent breakdown of cGMP and prolong the effects of nitrates. Combining these two classes of drugs can lead to hypotensive shock Concurrent use of migraine medication ( methysergide, bromocriptine) may increase blood pressure & decrease effects of nitrates |
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NITROGLYCERINE: PHARMACOKINETICS
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pic
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Comparison of action duration of Nitrites:
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pic
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Nitrates: Classification based on duration of action
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pic
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Nitrate formulations: Important considerations
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- Sublingual tablets, or translingual sprays are preparations of choice for quick relief during exertion
- Long acting nitrates (ISDN, ISMN) become useful when the number, severity and duration of anginal attacks increase Schedule 10-12 hrs nitrate free interval |
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Nitrate formulations: Important considerations
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Sublingual tablets are volatile and lose potency when exposed to air & light
- Stored in a cool dry place - Should be kept in the original amber bottle Can only be used for a maximum of 6 months after the container has been opened Monitor expiration date strictly & expired SL preparations should be replaced |
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Nitroglycerin, either directly or through reflexes results in which one of the following effects?
1. Decreased heart rate 2. Decreased venous capacitance 3. Increased after load 4. Increased cardiac force 5. Increased diastolic intramyocardial fiber tension |
4. Increased Cardiac Force (indirectly by causing vasodilation)
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β blockers-Clinical uses
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- Stable Angina: First choice to prevent recurrence of symptoms
- Unstable Angina -- Acutely, slows progression of the MI and reduces mortality --- With the first appearance of chest pain, i.v β1 blockers are recommended followed by long-term oral use in high risk patients -- Chronic use to reduce recurrence of angina, arrythmia - Not useful in variant angina (minimal effect on coronary vasospasm) |
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β-blockers: Therapeutic actions
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- Beneficial effects are mediated by β1antagonism
- Prevents exertion induced increase in heart rate & cardiac contractility and subsequently cardiac output - Decreases systolic blood pressure especially if hypertension is present - Overall effect is to reduce the myocardial oxygen demand produced by exertion |
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β-blockers: Side effects
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- Bradycardia
- Bronchospasms (switch to β1 selective) - Fatigue - Depression - Rebound hypertension if stopped suddenly Use with caution in: - Asthma - Diabetes (masks symptoms of hypoglycemia in diabetics) |
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L-type Calcium channel Blockers in Angina
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pic
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L-type calcium channel blocker types
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Dihydropyridines (Preferentially block vascular L-type channels)
- Nifedipine (Adalat®, procardia®) - Bepiridil (Vascor) Phenylalkylamines (Preferentially block cardiac L-type channels) - Verapamil (Isoptin®) Benzothiazepines (Block both cardiac & vascular L-type channels) - eg Diltiazem (Cardizem) |
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Calcium channel blockers: Clinical uses
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- Prophylactic therapy in stable & vasospastic angina
- Particularly useful in atherosclerotic angina when combined with nitrates - Hypertension - PSVT - Migraine (Verapamil,amilodipine) - Reynaud’s disease - Stroke (Nimodipine,amilodipine) |
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Calcium channel blockers: Therapeutic actions in Angina
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- Block calcium entry via the L-type channels during membrane depolarization in cardiac and vascular smooth muscle to reduce myocardial workload (preload & afterload)
-- Decrease heart rate & contractility -- Dilate peripheral vasculature - Relieve coronary vasospasm |
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NIFEDEPINE IN ANGINA
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- Variant Angina: Very effective in relieving coronary vasospasm
- In acute anginal attacks - Causes both veno & vasodilation: Reduces afterload more then preload Adverse effects: - Headache, - Flushing , Ankle edema, Reflex tachycardia (Less than nitrates) - Constipation (effect on GI smooth muscle) - Gingival hyperplasia |
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BEPIRIDIL (VASCOR)
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- Blocks both Na+ and Ca++ channels
- Used in chronic stable angina - Not a first line drug Side effects: -- Heart failure when combined with β blockers (Similar to verapamil & Diltiazem) -- Torsades & other arrythmias -- Agranulocytosis |
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VERAPAMIL IN ANGINA
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Stable Angina, Variant angina
Therapeutic actions: Decreases cardiac workload & oxygen demand - Slows heart rate - Slows conduction through AV node - Decreases contractility |
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VERAPAMIL: Side effects
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Constipation & Gingival hyperplasia
Sinus bradycardia High doses can cause - Myocardial depression - Heart failure - Vascular effects (edema, headache hypotension & reflex tachycardia) |
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VERAPAMIL: Contraindications
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Do not combine with β blockers: Can cause AV block
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DILTIAZEM
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Properties are b/w Nifedepine & Verapamil
Clinical Uses: - Stable angina & variant angina Side effects: - Sinus bradycaria - AV block, Heart failure (When used in combination with beta blockers) - Peripheral effects (hypotension, edema) |
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Calcium channel blockers: Side effects
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Side effects
- Constipation - Sinus Bradycardia - Gingival hyperplasia - Higher doses (Heart failure, AV nodal block, Depressed myocardial contractility) - Nausea - Edema - Flushing, Dizziness - Reflex tachycardia |
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Which one of the following drugs often causes tachycardia?
1. Diltaizem 2. Isosorbide dinitrate 3. Propranolol 4. Verapamil |
2. Isosorbide dinitrate
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Treatment of angina in patients with concomitant diseases
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pic
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