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Questions and Answers
What is the term used to describe the process by which the body changes drug molecules?
What is the term used to describe the process by which the body changes drug molecules?
Which of the following enzymes are specifically involved in drug metabolism?
Which of the following enzymes are specifically involved in drug metabolism?
Where are microsomal enzymes predominantly located in the body?
Where are microsomal enzymes predominantly located in the body?
Which organ is most associated with the metabolism of drugs due to the presence of microsomal enzymes?
Which organ is most associated with the metabolism of drugs due to the presence of microsomal enzymes?
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Which of the following is NOT a function of drug metabolism?
Which of the following is NOT a function of drug metabolism?
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What is the primary role of drugs in relation to living organisms?
What is the primary role of drugs in relation to living organisms?
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What is meant by the elimination of drugs from the body?
What is meant by the elimination of drugs from the body?
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Which of the following statements about drugs is correct?
Which of the following statements about drugs is correct?
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What characterizes the substances categorized as drugs?
What characterizes the substances categorized as drugs?
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How do drugs typically leave the body?
How do drugs typically leave the body?
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What enzyme is responsible for the reduction of azo and nitro compounds?
What enzyme is responsible for the reduction of azo and nitro compounds?
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Which compound is mentioned as being converted to sulfonamide through reduction?
Which compound is mentioned as being converted to sulfonamide through reduction?
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What functional groups are mentioned in the context of reduction reactions?
What functional groups are mentioned in the context of reduction reactions?
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Which acid is directly mentioned in the conversion to gentisic acid?
Which acid is directly mentioned in the conversion to gentisic acid?
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What type of reaction primarily occurs when salicylic acid is converted into gentisic acid?
What type of reaction primarily occurs when salicylic acid is converted into gentisic acid?
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What type of reactions are involved in Phase-II metabolism?
What type of reactions are involved in Phase-II metabolism?
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Which reaction is NOT part of Phase-I metabolism?
Which reaction is NOT part of Phase-I metabolism?
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Which of the following processes introduces an oxygen atom into a drug molecule?
Which of the following processes introduces an oxygen atom into a drug molecule?
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What is one of the key processes of Phase-II metabolism?
What is one of the key processes of Phase-II metabolism?
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Which of the following describes a reaction that removes a hydrogen atom from a drug molecule?
Which of the following describes a reaction that removes a hydrogen atom from a drug molecule?
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What is the role of acetyl transferase in drug metabolism?
What is the role of acetyl transferase in drug metabolism?
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Where is acetyl transferase predominantly found in the body?
Where is acetyl transferase predominantly found in the body?
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What is the precursor molecule formed when acetic acid is activated by CoA?
What is the precursor molecule formed when acetic acid is activated by CoA?
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Which compounds are primarily involved in the conjugation process mentioned?
Which compounds are primarily involved in the conjugation process mentioned?
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What does the term 'acetylation' refer to in the context of drug metabolism?
What does the term 'acetylation' refer to in the context of drug metabolism?
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What explains the vulnerability of fetuses or neonates to drug toxicity?
What explains the vulnerability of fetuses or neonates to drug toxicity?
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What is a common consequence of poorly developed kidneys in neonates related to drug metabolism?
What is a common consequence of poorly developed kidneys in neonates related to drug metabolism?
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How does aging affect drug metabolism in the elderly?
How does aging affect drug metabolism in the elderly?
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Which factors can negatively affect drug metabolism?
Which factors can negatively affect drug metabolism?
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What is a characteristic of slow acetylators, related to drug metabolism?
What is a characteristic of slow acetylators, related to drug metabolism?
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Study Notes
Drug Distribution
- Drugs penetrate to sites of action via blood vessels
- Distribution is through various body fluid compartments (plasma, interstitial fluid, trans-cellular)
- Apparent Volume of Distribution (VD): Theoretical volume needed to contain the total amount of drug in the body to create the same concentration in plasma. A measure of how drug is distributed in body. It's an apparent rather than real volume
- Factors affecting rate of distribution
- Protein Binding:
- Drugs bind reversibly to plasma proteins.
- Only unbound drug is active and can leave the plasma to sites of action.
- Protein binding reduces drug diffusion and delays metabolism. High protein bound drugs act longer (e.g. phenylbutazone). Low protein bound drugs act shorter(e.g. thiopental sodium)
- Plasma Concentration of Drug (PC)
- Concentration of free drug in plasma varies
- After intravenous (IV) administration, plasma concentration falls rapidly
- After oral administration, plasma concentration rises and falls gradually.
- Sublingual administration demonstrates plasma concentration that rises sharply and decreases gradually.
- Protein Binding:
Drug Clearance
- Clearance: Volume of plasma cleared of the drug by metabolism and excretion per unit time.
- Protein binding reduces the amount of drug available for filtration at the glomeruli, and hence delays excretion and reduces clearance.
Barriers to Drug Distribution
- Physiological barriers in the body prevent uniform distribution
- Blood-brain barrier (BBB): Some drugs like thiopental sodium cross but not dopamine
- Placental barrier: Non-ionized drugs with high lipid/water partition coefficient can cross e.g. alcohol, morphine
Drug Affinity to Certain Organs
- Drug persists in certain tissues even if plasma concentration is low.
- e.g., Mecaprine concentration in the liver is significantly higher than plasma.
- Iodine is concentrated in the thyroid.
Drug Metabolism
- Drugs are chemically transformed by the body from one form to another to eliminate or increase excretion
- Biotransformation or drug metabolism: body's process of changing drug molecules
- Enzymes responsible for metabolism
- Microsomal enzymes (e.g., glucuronyl transferase, dehydrogenase, hydroxylase, cytochrome P450) found in liver, kidneys, gastrointestinal tract (GIT)
- Non-microsomal enzymes (e.g. esterases, amidases, hydrolases) in the cytoplasm and mitochondria of various organs
- Types of Biotransformation
- Phase I: Oxidation, reduction, and hydrolysis, converting the drug to a more polar metabolite
- Phase II: Conjugation reactions, e.g., glucuronidation, sulfate conjugation, acetylation, glycine conjugation, methylation
Cytochrome P450 (CYP)
- A family of isoenzymes
- Drugs bind to CYP and are oxidized or reduced
- CYP3A4 accounts for more than 60% of clinically prescribed liver-metabolized drugs
- Cytochrome P450 enzyme induction: Some drugs stimulate their own and other drug metabolisms (e.g. phenobarbital, rifampin, phenytoin, carbamazepine, griseofulvin, cigarette smoke)
- Cytochrome P450 enzyme inhibition: Some drugs reduce the activity of hepatic drug-metabolizing enzymes increasing active drug levels (e.g. alcohol, allopurinol, grapefruit juice, cimetidine, amiodarone, ciprofloxacin, clarithromycin, erythromycin, fluoxetine, isoniazid, metronidazole, verapamil, oral contraceptives)
Phase II Reactions (Conjugation Reactions)
- Synthesize drugs with endogenous substances (glucuronide, sulfate, glycine, methylated compounds, amino acids)
- Ex:
- Glucuronidation
- Sulfation
- Acetylation
- Glycine conjugation
- Methylation
Variations in Drug Metabolism
- Fetus/neonates: Their livers and metabolizing enzymes are under-developed and have a less developed blood-brain barrier, making them vulnerable to drug toxicity
- Elderly: Hepatic enzymes and other organs deteriorate, affecting drug metabolism. Men generally metabolize faster than women
- Diseases (e.g., hepatitis, cardiac, pulmonary) affect drug metabolism
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Description
This quiz covers the fundamentals of drug distribution, including how drugs penetrate to sites of action via blood vessels and the role of different body fluid compartments. Key concepts such as Apparent Volume of Distribution and factors affecting drug distribution, including protein binding and plasma concentration, are explored.
