Intro to Pharm Sciences Principle of Toxicology

Question 1

Toxicology

Answer 1

The study of the undesirable effects of drugs or chemicals and the mechanisms or conditions regulating their occurrences

Question 2

Toxicity Reactions: Classifications based on exposure time

Answer 2

Acute: Less than 24 hours

Sub-acute: Several days to 4 weeks

Chronic: Months or years

Question 3

Acute toxicity

Answer 3

Rapid onset

Usually seen after a large, single dose

Examples: Cyanide, barbiturates, and methanol

Question 4

Sub-acute toxicity

Answer 4

Due to frequent exposures to a small dose that is not toxic by itself

Drug accumulates in the body due to impaired metabolism or excretion

Example: Acetaminophen in patients with liver disease –> Hepatotoxicity

Question 5

Chronic toxicity

Answer 5

Due to repeated exposure over a long time

Slow elimination half-life

Elimination is rapid, but drug causes an accumulating injury

Question 6

Toxicity Reactions: Classification based on outcome

Answer 6

Organ toxicity

Hepatotoxicity (Liver)

Nephrotoxicity (Kidney)

Cardiotoxicity (Heart)

Neurotoxicity (Neurons in CNS or spinal cord)

Carcinogenicity (Induction of cancer)

Teratogenicity (Induction of abnormalities in the growing fetus)

Phototoxicity (Toxicity due to exposure to sunlight)

Question 7

Stepwise approach to treat drug overdose/poisoning

Answer 7

1. Stabilization: (Airway, breathing, and circulation)
2. Treatment: Lower drug concentration at the site of action or drug-target interaction

a. Decontamination: Prevention of further drug absorption

b. Enhanced elimination: Accelerated removal of drug/poison

c. Focused therapy: Use of antidotes - Pharmacological agents

Question 7

Drug overdose/poisoning: Types

Answer 7

Intentional (Suicide)

Accidental:

Pediatric: Accidental ingestion of medications by children

Drug abuse: Abuse of drugs for recreational purposes

Iatrogenic: Taking a higher dose than prescribed

Occupational

Environmental

Question 8

Stabilization

Answer 8

Airway is closed: Endotracheal intubation

Breathing is depressed: Supplemental oxygen to prevent hypoxia

Circulation - No pulse or BP: CPR

Question 9

Decontamination

Answer 9

Preventing or reducing the absorption of a drug/poison after ingestion reduces the severity of toxicity

Four common methods

a. Induced emesis: Ipecac syrup to induce vomiting and empty stomach

b. Gastric lavage: Wash and remove contents of stomach

c. Activated charcoal: Adsorption of poison in the GI tract

d. Whole bowel irrigation: Purging of contents through the GI tract

Question 9

Enhanced elimination

Answer 9

Refers to accelerated removal of drug or poison from the body - Used when most of the drug or poison is already absorbed into the blood

Four common methods

a and b. Hemodialysis and hemoperfusion: Direct removal from the blood

c. Multi-dose activated charcoal: Removal through stools

Forced Diuresis: Removal through urine

Question 10

Hemodialysis

Answer 10

Blood is circulated through a membrane that allows only small molecules to pass through in dialysate and cleanses the blood

Most effective for drugs that are low MW, water-soluble, and with minimal protein binding

Question 11

Hemoperfusion

Answer 11

Blood percolates through a charcoal cartridge - allows for drug adsorption into the column, cleansing the blood

Useful for drugs that lipid soluble or highly protein bound

Not effective for drugs with large Vd because most of the drug is in the tissue instead of the blood

Question 12

Multi-dose activated charcoal

Answer 12

Repeated doses of activated charcoal which attract drug molecules across capillary bed of intestines to the AC for adsorption and interruption of enterohepatic recirculation, leading to less reabsorption of the drug

Net effect is greater drug excretion in the stool

Most effective for slowly absorbed drugs and drugs that undergo enterohepatic cycling

Question 13

Forced Diuresis

Answer 13

For drugs filtered in the urine

Using either ascorbic acid or sodium bicarbonate based on whether it is a base or an acid

Question 14

Receptor antagonism

Answer 14

Blocks receptors where drug takes action

Example: Naloxone and opioids

Question 15

Enzyme inhibition

Answer 15

Adding a molecule to fight for a certain enzyme, stopping the metabolism of the drug or molecule

Example: Ethanol and Methanol, ethanol using alcohol dehydrogenase before methanol can

Question 16

Chemical antagonism

Answer 16

Binding to form water-soluble complexes, preventing metal toxicity

Example: Deferoxamine and iron

Antibodies binding drugs in serum and extracellular fluid

Example: Digibind and digoxin, preventing digoxin poisoning

Question 17

Enhanced drug metabolism

Answer 17

Using other drugs/molecules to metabolize drugs/molecules that are in too high of a quantity to be safe

Example: Acetaminophen and N-Acetylcysteine (NAC), preventing liver toxicity

Question 18

Normal Activated Charcoal

Answer 18

More effective than induced emesis and gastric lavage

Primary method of decontamination of ingested poisons

Will not bind to metals and alcohols, those will be with Whole Bowel Irrigation