CVS - Nitrates, β-blockers, Cardiac Glycosides - Drugs used in IHD & Heart Failure Flashcards Preview

systemic pharmaco > CVS - Nitrates, β-blockers, Cardiac Glycosides - Drugs used in IHD & Heart Failure > Flashcards

Flashcards in CVS - Nitrates, β-blockers, Cardiac Glycosides - Drugs used in IHD & Heart Failure Deck (13):
1

Mechanism of action of nitrates

Nitroglycerin (glyceryl trinitrate)

Denitrated in smooth muscle and other cells - nitrite ion released & converted to NO - relaxes smooth muscle (no effect on cardiac/skeletal muscle)

2

PK - sublingual/oral/transdermal

Sublingual - immediate relief of acute symptoms, rapid onset (1-3 min), but not suitable for maintenance therapy (short duration of action, 20-30min)

Oral/Transdermal - slow onset, long duration of action, long term treatment, but leads to development of tolerance

3

Uses of nitrates

1. Symptomatic Relief of Angina
- vasorelaxation - venodilation - increased venous capacitance + decreased ventricular preload - less O2 consumption - reduced symptoms of angina
- vasorelaxation - arteriolar dilation - decreased afterload - less O2 consumption - reduced symptoms of angina
- Angina of effort: reduced preload & afterload
- Vasospastic Angina: relaxes epicardial coronary arteries SM, relieves coronary artery spasm
- Unstable Angina: unclear

4

Toxicity of nitrates (2)

1. Direct extensions of therapeutic vasodilation
- baroreflex - tachycardia
- venodilation - hypotension (orthostatic hypotension - syncope)
- vasodilation (meningeal artery) - headache
2. Tolerance

5

Mechanism of action of β-blockers

Competitively antagonizes effects of catecholamines at β-adrenoceptors - β1/2/3 receptors increase conversion of ATP to cAMP

1. Heart: mostly β1-receptors
- Increased cAMP synthesis - increased Ca influx across cell membrane & sequestration in cell - increased contractility + directly stimulates SAN to increase HR - reduces bp
- negative inotropic & chronotropic effects on the heart - useful in angina & CHF

2. Smooth Muscle: mostly β2-receptors
- increased cAMP - P of MLCK to inactive form - enhances relaxation & vasodilation

Local anaesthetic action - LA blockade of Na+ channels

6

Uses of β-blockers (5)

1. Hypertension
2. Ischemic Heart Disease - reduces frequency of angina episodes & improves exercise tolerance
3. Cardiac Arrhythmias
4. Glaucoma - decreased aq humour prod (cAMP regulated)
5. Hyperthyroidism - due to excessive catecholamine action

7

Toxicity of β-blockers + Contraindications (4+3)

1. Bradycardia, coolness of hands & feet in winter
2. CNS effects (mild sedation, vivid dreams)
3. Withdrawal Syndrome in patients with IHD/HTN
4. Erectile Dysfunction & worsening of claudication

1. AV Blockade (severe LV failure)
2. Diabetes (blocks β2R in liver - blocks glycogenolysis - hypoglycemia when taking insulin)
3. Asthma (blocks β2R in lungs - may produce airway resistance)

8

Approach to angina

Angina of Effort
- HTN - β-blocker or CCB; Normotensive - long acting nitrate

Vasospastic Angina
- Nitrates + CCBs

Unstable Angina
- Anti-platelet therapy, stenting, nitrates, β-blockers, CCBs

9

Approach to heart failure

- Positive Inotropic Drugs: glycosides, β-agonists, PDE inhibitors
- Vasodilators: PDE inhibitors, nitroprusside, nitrates, hydralazine, loop diuretics, ACEI
- Others: loop diuretics, ACEI, β-blockers, spironolactone, thiazides

10

Mechanism of action of cardiac glycosides

1. Inhibits Na+/K+ ATPase - increases intracellular [Na+] - reduces Ca efflux - more free Ca in sarcomere during systole - stronger systolic contraction
2. Mechanical effects: increased contractility - increased CO - reduced preload & afterload
3. Electrical effects: decreased QT & ST, inversion of T, increased parasympathetic activity - decreased AV conduction - increased PR interval + decreased ventricular rate

11

Uses of cardiac glycosides (2)

1. Heart Failure (systolic)
2. Atrial Fibrillation - usually only when diuretics & ACEI have failed, no effect on mortality but less hospitalizations & death

12

Toxicity of cardiac glycosides (4)

1. Cardiac - progressively severe dysrhythmia (AV junctional rhythm, premature ventricular depolarization, begeminal rhythm, AV block, AF, VF)
2. GI - anorexia, nausea, vomiting
3. CNS - headache, fatigue, confusion, blurred vision, aberrations of colour perception
4. Gynecomastia

13

Interactions of cardiac glycosides (5)

1. Hypokalemia - K+ & digitalis inhibit each other by binding to Na/K ATPase, hypokalemia enhances digoxin action
2. Hypercalcemia - increased intracellular Ca - facilitates toxic actions of glycosides (similarly, Hypomagnesia)
3. Quinidine, Verapamil - increase digoxin concentrations
4. Corticosteroids
5. K+ depleting diuretics