Pharmaceutical Chemicals: Toxicology of Cardiac Drugs

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Questions and Answers

What is the mechanism of cardiotoxicity caused by catecholamines?

Through oxidative stress (correct)

Through blockade of cardiac Na+ channels

Through their action on the sympathetic nervous system

Through Ca2+ channel blockade

What is a common adverse effect of the anticancer drug Adriamycin?

Acute arrhythmia

Prolonged QRS duration

QT prolongation

Severe cardiac toxicity (correct)

What is the classification of antiarrhythmic drugs based on?

Route of administration

Primary mechanism of action (correct)

Chemical structure

Therapeutic indication

What is the effect of blockade of cardiac Na+ channels?

Reduced conduction velocity Signup and view all the answers

Which of the following is a selective COX-2 inhibitor?

Rofecoxib Signup and view all the answers

What effect can high circulating concentrations of catecholamine cause?

Cardiac myocyte death Signup and view all the answers

What is the primary mechanism of action of Class I antiarrhythmic agents?

Blockade of Na+ channels Signup and view all the answers

Which of the following CNS-acting drugs can have considerable effects on the cardiovascular system?

General anaesthetics Signup and view all the answers

What is a common effect of cardiac toxicity caused by Rofecoxib?

QT prolongation and increased risk for sudden cardiac death Signup and view all the answers

What is a common adverse effect of tricyclic antidepressants?

Postural hypotension Signup and view all the answers

What is a mechanism of cardiac toxicity of tricyclic antidepressants?

Blockade of peripheral α-adrenergic receptors Signup and view all the answers

What is the primary mechanism of cardiotoxicity of digitalis?

Blockade of Na+ channels Signup and view all the answers

Which ion currents are depressed by tricyclic antidepressants in cardiac myocytes and Purkinje fibers?

Inward Na+ and outward K+ currents Signup and view all the answers

What is a prominent adverse cardiovascular effect of antipsychotic drugs?

Orthostatic hypotension Signup and view all the answers

What is a common effect of catecholamine-induced cardiotoxicity?

Increased systolic arterial blood pressure Signup and view all the answers

What is a cardiac effect of phenothiazines?

Negative inotropic actions Signup and view all the answers

What is a mechanism of cardiac toxicity of catecholamines?

Increased myocardial oxygen demand Signup and view all the answers

Which of the following is a cardiovascular effect of clozapine?

Tachycardia Signup and view all the answers

What is a cardiac effect of general anesthetics?

Reduced cardiac output Signup and view all the answers

How does halothane affect cardiac myocytes?

Causes a negative inotropic effect Signup and view all the answers

What is a mechanism of cardiac toxicity of NSAIDs?

Inhibition of COX-1 Signup and view all the answers

What is a difference between non-selective NSAIDs and selective COX-2 inhibitors?

Non-selective NSAIDs inhibit both COX-1 and COX-2 Signup and view all the answers

What is a mechanism of cardiac toxicity of antipsychotic drugs?

Direct effects on the myocardium Signup and view all the answers

What is a cardiovascular effect of general anesthetics?

Sensitization of the heart to epinephrine Signup and view all the answers

Study Notes

Cardiac Toxicity

Cardiac drugs can cause cardiotoxicity, either related or not related to their therapeutic action.
Examples of cardiac drugs that can cause acute arrhythmia include digitalis, quinidine, and procainamide.
Catecholamines may cause cardiac toxicity through oxidative stress, rather than by their action on the sympathetic nervous system.

Non-Cardiac Drugs

The cardiotoxicity of non-cardiac drugs limits their uses.
Examples of non-cardiac drugs that can cause cardiac toxicity include:
- Adriamycin, an anticancer drug that can produce severe cardiac toxicity.
- Rofecoxib, a selective COX-2 inhibitor used as an anti-inflammatory drug, which can cause QT prolongation and increase the risk for sudden cardiac death.

Antiarrhythmic Agents

Antiarrhythmic drugs have historically been classified based upon a primary mechanism of action, including:
- Na+ channel blockers (class I)
- β-adrenergic blockers (class II)
- K+ channel blockers (class III)
- Ca2+ channel blockers (class IV)
However, this classification is artificial because most drugs have multiple mechanisms of action.

Class I Antiarrhythmic Agents

Class I antiarrhythmic agents are primarily Na+ channel blockers, including:
- Disopyramide
- Flecainide
- Lidocaine
- Mexiletine
- Procainamide
- Quinidine
Blockade of cardiac Na+ channels results in a reduction of conduction velocity, prolonged QRS duration, and decreased automaticity.

Catecholamines

High circulating concentrations of catecholamine may cause cardiac myocyte death.
Catecholamines and related drugs have been shown to induce cardiac myocyte hypertrophic growth in vitro.
Catecholamine-induced cardiotoxicity involves increased heart rate, enhanced myocardial oxygen demand, and an overall increase in systolic arterial blood pressure.

CNS Acting Drugs

Some CNS-acting drugs have considerable effects on the cardiovascular system, including:
- Tricyclic antidepressants (TCAs)
- General anaesthetics
- Opioids
- Antipsychotic drugs

Tricyclic Antidepressants

TCAs, including amitriptyline, doxepin, imipramine, and protriptyline, have significant cardiotoxic effects, particularly in cases of overdose.
The effects of TCAs on the heart include:
- ST-segment elevation
- QT prolongation
- SVT and VT
- Sudden cardiac death
TCAs also cause postural hypotension due to peripheral α-adrenergic blockade.

Antipsychotic Drugs

The most prominent adverse cardiovascular effect of antipsychotic drugs is orthostatic hypotension.
Phenothiazines (e.g., chlorpromazine and thioridazine) may exert direct effects on the myocardium, including:
- Negative inotropic actions
- Quinidine-like effects
ECG changes induced by these drugs include:
- Prolongation of the QT and PR intervals
- Depression of the ST segment
Clozapine can produce substantial elevations in heart rate (tachycardia) through anticholinergic actions.

General Anesthetics

General anesthetics, such as desflurane, halothane, isoflurane, and methoxyflurane, have adverse cardiac effects, including:
- Reduced cardiac output by 20% to 50%
- Depression of contractility
- Production of arrhythmias
These anesthetics may sensitize the heart to the arrhythmogenic effects of endogenous epinephrine or to β-receptor agonists.

Anti-inflammatory Agents

NSAIDs, including aspirin, Ibuprofen, and Diclofenac, are nonselective NSAIDs that inhibit both COX-1 and COX-2.
Inhibition of COX-1 is associated with GI toxicity because COX-1 exerts a protective effect on the lining of the stomach.
Selective COX-2 inhibitors, such as rofecoxib, celecoxib, and valdecoxib, have been developed.

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Description

This quiz covers the toxic effects of cardiac drugs, including digitalis, quinidine, and procainamide, which can cause cardiotoxicity and arrhythmia. It also explores the role of catecholamines in cardiac toxicity through oxidative stress.