chemicals and drugs even natural compounds when taken in inappropriate doses (overdose) may cause systemic derangements, heart is a prime site of attack of such abuses. this presentation deals with "chemical" substances bringing about toxic manifestation in Heart.

1. CARDIAC TOXIC CHEMICALS
-An Overview
-by Namrata Mohan

2. Chemicals That Can Induce
Cardiotoxicity
Can Be Grouped as-:
Pharmaceutical Chemicals
•Antiarrythmic Agents
•Inotropic Drugs
•CNS acting Drugs
•Local Anesthetics
•Anthracyclines and other Neoplastic Agents
•Antimicrobials .........etc
Natural Products

3. ALCOHOLIC CARDIOMYOPATHY
• Alcohol abuse causes multiple physical and
chemical changes in the body that affect many
internal organs, including the heart. Alcoholic
cardiomyopathy damages the heart in several
ways:
• The damaged heart muscle cannot pump enough
blood to the rest of the body.
• When the left ventricle cannot pump out all the
blood, the heart enlarges to hold the extra blood.
• Blood pressure increases to make up for reduced
heart production. This causes further strain on
the heart and blood vessels.
• Eventually, the heart muscle, valves, and blood
vessels may fail from the damage and overwork.

4. MECHANISM OF DRUGS
(nutshell)
•production of toxic oxygen free radicals accumulate in the heart
because of the high levels of cardiolipin Cardiac tissue limited capacity
to deal with free radicals (because of low levels of antioxidant
enzymes).
• cause lipid peroxidation of membranes leading to vacuolation,
irreversible damage, and myocyte replacement by fibrous tissue also
associated with a decrease of the endogenous antioxidant enzymes,
such as glutathione peroxidase (responsible for the scavenging of free
radicals) Mitochondria are particularly susceptible to free radical
damage.
•Apoptosis Elevated calcium accumulation in mitochondria
Modulation of cardiac gene expression.

5. Anti-Arrythmic Drugs-
HERG is a gene that controls influx of potassium,
drugs that block HERG lead to prolonged QTc
symdrome.
Antiarrythmics Class Ia and II
Anti-infectives
•Fluoroquinolones
•Erythromycin
•Pentamidine
•Ketoconazole and other Azole antifungals
AntiHistamines- terfenandine , Astemizole
(Removed from Market)

6. Serotonin Syndrome
• Its not an idiopathic drug reaction; its a
predictable consequence of excess
serotonergic antagonism of CNS and
peripheral receptors.
• Clinical triad- Mental status changes,
Autonomic hyperactivity, neuromuscular
abnormalities
• Drugs- SSRI’s, SNRI’s, MAOI’s etc.

7. ANTHRACYCLINES
• Anthracyclines were originally isolated from
Streptomyces peucetius for use as cytotoxic antibiotics.
found to have broad anti-tumor activity –first line for
hematological and solid tumors Inhibit DNA and RNA
synthesis & prevent DNA repair by action on
topoisomerase II
• Doxorubicin
• Duanorubicin
• Idarubicin
• Mitoxantrone