Drug Metabolism (Lecture V)

Where does metabolism occur?

• liver

• Kidney

• Lungs

• Plasma

• Intestinal mucosa

True or False: As drugs undergo metabolism, they become less lipid soluble and more polar.

TRUE

Biotransformation

enzymatic alteration of a drug

What happens in Phase I metabolism generally?

reactions unmask or introduce polar groups (-OH or -COOH)

What happens in Phase II reactions of metabolism generally?

reactions conjugate the drug to endogenous compounds

• usually water soluble and inactive

True or False: Chemical structure predicts metabolic transformation.

TRUE

When do phase II synthetic reactions occur?

When a drug or phase I metabolite contain a group suitable for combining with a natural compound to form a readily excreted polar metabolite

List 5 conjugating agents.

• glucuronic acid

• Glycine

• Cysteine

• Methionine

• Sulfate

• Acetyl

What is the toxic metabolite from acetaminophen oxidation resulting in toxicity?

NAPQI

Why do cats produce more NAPQI?

they are slow glucurindators

What does acetaminophen toxicity result in?

hepatotoxicity and methemogloinemia

What is one of the most common C/S of acetaminophen toxicity?

Cyanosis

How can you treat acetaminophen toxicity?

• Emesis (activated charcoal)

• N-acetylcysteine (mucomyst)

True or False: Decreased hepatic blood flow reduces the rate of metabolism.

TRUE

Decreased serum protein ____ drug availability for metabolism.

increases

Can some drugs induce enzyme synthesis?

Yes. Phenobarbital

Can some drugs inhibit microsomal emnzyme activity?

Yes. Chloramphenicol, Insecticides

When can microbial metabolism of a drug occur?

• after oral administration

• After passive diffusion of a non-ionized form of a drug from systemic circulation into the GI lumen

What are the two most common types of reactions from microbial metabolism?

Hydrolytic and reductive