D. Metabolism

Proverbs 16:3

c. Metabolism (Biotransformation)

The initial pathway for drug elimination in which drugs become more hydrophilic, ionized (charged), polar, detoxified, and nontoxic is known as:

a. Distribution
b. Elimination
c. Metabolism (Biotransformation)
d. Excretion

b. Prodrug

An inactive drug that requires metabolic conversion to become pharmacologically active is called a:

a. Active metabolite
b. Prodrug
c. Xenobiotic
d. Conjugate

a. Clopidogrel

Which drug is a prodrug that requires metabolic activation?

a. Clopidogrel
b. Lisinopril
c. Captopril
d. Morphine

c. Lisinopril

• Captopril

• Enalaprilat

• Lisinopril

“CEL-active”

Which angiotensin-converting enzyme (ACE) inhibitor is active without metabolic conversion?

a. Enalapril
b. Clopidogrel
c. Lisinopril
d. Diazepam

a. Enalaprilat

Which is the active metabolite formed from enalapril?

a. Enalaprilat
b. Lisinopril
c. Captopril
d. NAPQI

b. Diazepam

Which active drug is metabolized into another active metabolite, oxazepam?

a. Codeine
b. Diazepam
c. Clopidogrel
d. Aspirin

c. Codeine

Which active antitussive drug is metabolized into the active analgesic morphine?

a. Diazepam
b. Clopidogrel
c. Codeine
d. Acetaminophen

c. NAPQI (N-acetyl-p-benzoquinoneimine)

Which toxic metabolite is produced from acetaminophen (APAP)?

a. Morphine
b. Oxazepam
c. NAPQI
d. Salicylic acid

b. N-acetylcysteine (NAC)

Which antidote is used in acetaminophen toxicity?

a. Atropine
b. N-acetylcysteine (NAC)
c. Flumazenil
d. Naloxone

c. Liver

• other sites: brain, lungs, intestines, kidneys

The primary site of drug metabolism is the:

a. Kidney
b. Lung
c. Liver
d. Intestine

• Brain

• Lungs

• Intestines

• Kidneys

Other sites of drug metabolism [4]

d. Kidney

Which organ is an extrahepatic site of drug metabolism?

a. Heart
b. Liver
c. Brain
d. Kidney

b. Renal dehydropeptidase

Imipenem is inactivated by this enzyme , and is protected from degradation by cilastatin?

a. Beta-lactamase

b. Renal dehydropeptidase

c. Cytochrome P450

d. Glucuronosyl transferase

a. Cilastatin

This drug inhibits renal dehydropeptidase, preventing the inactivation of Imipenem

a. Cilastatin

b. Clavulanic acid

c. Sulbactam

d. Tazobactam

c. First-pass effect

The initial metabolism of a drug before reaching the systemic circulation is known as:

a. Zero-order metabolism
b. Enterohepatic recycling
c. First-pass effect
d. Renal clearance

• Opioids

• Catecholamines (Epinephrine , Norepinephrine, Dopamine)

Example of Drugs with high first pass effect [2]

c. Phase I metabolism

The phase of metabolism also known as the functionalization:

a. Phase II metabolism
b. Phase III metabolism
c. Phase I metabolism
d. Enterohepatic circulation

c. Phase I metabolism

The phase of metabolism also known as the asynthetic phase is:

a. Phase II metabolism
b. Phase III metabolism
c. Phase I metabolism
d. Enterohepatic circulation

b. Phase II metabolism

The phase of metabolism also known as the conjugation:

a. Phase I metabolism
b. Phase II metabolism
c. Phase III metabolism
d. Phase IV metabolism

b. Phase II metabolism

The phase of metabolism also known as synthetic phase is:

a. Phase I metabolism
b. Phase II metabolism
c. Phase III metabolism
d. Phase IV metabolism

b. Unmask polar functional groups

The goal of Phase I metabolism is:

a. Increase protein binding
b. Unmask polar functional groups
c. Increase lipid solubility
d. Produce inactive conjugates

• Hydrolysis

• Oxidation

• Reduction

📌Mnemonic: “HOR”

Phase I metabolic reaction [3]

a. Acetic acid (vinegar) and salicylic acid

Hydrolysis of aspirin produces:

a. Acetic acid (vinegar) and salicylic acid
b. Morphine and codeine
c. Acetaldehyde and acetic acid
d. Oxazepam and diazepam

d. Salicylic acid

• dry granulation kasi prone sa hydrolysis

• if ma hydrolyze → acetic acid → vinegar odor

  

Hydrolysis of aspirin, from dry granulation process produces:

a. Acetic acid
b. Morphine
c. Acetaldehyde
d. Salicylic acid

b. Esters

• aspirin is also an ester

Which class of local anesthetics is more prone to hydrolysis?

a. Amides
b. Esters
c. Opioids
d. Barbiturates

b. Procaine, benzocaine, and cocaine

The local anesthetics that are esters and more prone to hydrolysis

a. Lidocaine, bupivacaine
b. Procaine, benzocaine, and cocaine
c. Xylocaine
d. Lidocaine

• Lidocaine

• Xylocaine

• Bupivacaine
  

The local anesthetics that are amides

[Multiple answer]

a. Lidocaine, bupivacaine
b. Procaine, and cocaine
c. Xylocaine
d. Benzocaine

a. oxidation

Remove H, add O

a. oxidation

b. reduction

d. CYP2E1

The CYP450 enzyme responsible for metabolism of:

• OH

• APAP

a. CYP3A4
b. CYP1A2
c. CYP2D6
d. CYP2E1

d. CYP2D6

The most studied CYP450 enzyme system

a. CYP2E1
b. CYP3A4
c. CYP1A2
d. CYP2D6

d. CYP2D6

Enzyme system responsible for metabolism of:

• Antipsychotics

• Antidepressants

• Codeine

a. CYP2E1
b. CYP3A4
c. CYP1A2
d. CYP2D6

a. CYP2D6

The CYP450 enzyme responsible for metabolism of:

• Codeine → Morphine

a. CYP2D6
b. CYP1A2
c. CYP2E1
d. CYP3A4

d. CYP3A4

The CYP450 enzyme responsible for metabolism of:

• Macrolide

• Amiodarone

• Cortisol

• Diazepam

• Grapefruit juice

a. CYP2D6
b. CYP1A2
c. CYP2E1
d. CYP3A4

a. Dehydrogenase

Non CYP mediated utilize this enzyme to induce metabolism reaction

a. Dehydrogenase

b. CYP450

c. Amylase

d. Dehydropeptidase

b. Alcohol dehydrogenase

[Alcohol metabolism]

Ethanol is converted to acetaldehyde by this enzyme
a. Aldehyde dehydrogenase
b. Alcohol dehydrogenase
c. Alcohol oxidase
d. Cytochrome P450

b. Aldehyde dehydrogenase

[Alcohol metabolism]

Acetaldehyde is converted to acetic acid by this enzyme
a. Alcohol dehydrogenase
b. Aldehyde dehydrogenase
c. Alcohol oxidase
d. Cytochrome P450

b. Aldehyde dehydrogenase inhibition

The mechanism of action of Disulfiram (Antabuse) is
a. Alcohol dehydrogenase inhibition
b. Aldehyde dehydrogenase inhibition
c. Alcohol oxidase inhibition
d. Cytochrome P450 inhibition

b. Acetaldehyde

Disulfiram inhibits aldehyde dehydrogenase, causing accumulation of
a. Ethanol
b. Acetaldehyde
c. Acetic acid
d. Methanol

b. Hangover symptoms

Increased acetaldehyde is responsible for
a. Improved mood
b. Hangover symptoms
c. Sedation
d. Analgesia

b. Alcohol use disorder

Disulfiram is used for
a. Opioid use disorder
b. Alcohol use disorder
c. Nicotine use disorder
d. Benzodiazepine use disorder

c. Prontosil

The drug converted from azoreduction

a. Chloramphenicol
b. Naloxone
c. Prontosil
d. Morphine

d. Chloramphenicol

The drug converted by nitroreduction

a. Naloxone
b. Prontosil
c. Morphine
d. Chloramphenicol

b. Aplastic anemia

If Chloramphenicol did not undergo nitroreduction, it will cause

a. Gray baby syndrome

b. Aplastic anemia

c. Hemolytic anemia

d. Agranulocytosis

d. Naloxone

The drug converted by carbonyl reduction

a. Prontosil
b. Chloramphenicol
c. Morphine
d. Naloxone

• Glucuronidation

• Glycine conjugation

• Glutathionylation

• Acetylation

• Sulfation

• Methylation

📌Mnemonic: GGGASM

Phase II Conjugation reactions [6]

a. Phase II

Addition of functional group/ conjugating moiety

a. Phase II

b, Phase I

d. Glucuronidation

The most common Phase II reaction with enzyme glucuronosyl transferase

a. Acetylation
b. Methylation
c. Sulfation
d. Glucuronidation

b. Glucuronosyl transferase

Enzyme in Glucuronidation Phase II reaction

a. Sulfotransferase

b. Glucuronosyl transferase

c. N-acetyltransferase

d. Glutathione S-transferase

b. Underdeveloped glucuronidation

Gray baby syndrome with Chloramphenicol occurs in neonates less than 1 month old due to
a. Underdeveloped renal excretion
b. Underdeveloped glucuronidation
c. Underdeveloped acetylation
d. Underdeveloped oxidation

c. Jaundice and kernicterus

The consequence of blocking glucuronidation leading to increased unconjugated bilirubin

a. Gray baby syndrome
b. Aplastic anemia
c. Jaundice and kernicterus
d. Lupus-like rashes

a. Gray baby syndrome

• Phase I nitroreduction: aplastic anemia

• Phase II glucuronidation: gray baby syndrome

The consequence of blocking glucuronidation associated with the use of Chloramphenicol

a. Gray baby syndrome
b. Aplastic anemia
c. Megaloblastic anemia
d. Lupus-like rashes

b. Aplastic anemia

• Phase I nitroreduction: aplastic anemia

• Phase II glucuronidation: gray baby syndrome

The consequence of blocking nitroreduction associated with the use of Chloramphenicol

a. Gray baby syndrome
b. Aplastic anemia
c. Megaloblastic anemia
d. Lupus-like rashes

• The senescent RBC release hemoglobin and can form globin or heme

• Heme become bilirubin and form unconjugated bilirubin (uncj bilirubin + albumin)

• In the liver, the uncj bilirubin + albumin undergo glucuronidation, forming conjugated bilirubin (non toxic)

• Blocking glucuronidation, increases unconjugated bilirubin= jaundice, kernicterus

Explain

d. N-acetyl transferase (NAT)

The enzyme responsible for Acetylation as a Phase II reaction

a. Glucuronosyl transferase
b. Glutathione transferase
c. Catechol-O-methyltransferase
d. N-acetyl transferase (NAT)

• Hydralazine

• Isoniazid

• Procainamide

• Sulfonamide

📌Mnemonic: “HIPS”

Drugs metabolized by acetylation include _____

a. Hydralazine, isoniazid, procainamide, sulfonamide
b. Heparin, insulin, penicillin, sulfonamide
c. Haloperidol, ibuprofen, propranolol, streptomycin
d. Hydralazine, ibuprofen, phenytoin, sulfonamide

d. Asians and Eskimos

Fast acetylators in NAT-2 polymorphism include ______ [2]

a. Caucasians and Egyptians
b. Caucasians and Eskimos
c. Asians and Caucasians
d. Asians and Eskimos

a. Caucasians and Egyptians

Slow acetylators in NAT-2 polymorphism include ______ [2]

a. Caucasians and Egyptians
b. Caucasians and Eskimos
c. Asians and Caucasians
d. Asians and Eskimos

• Genetic polymorphism — occurs in >1% of the population

• Genetic mutation — occurs in <1% of the population

Example:

Genetic polymorphism vs Genetic mutation

b. Increased risk of lupus-like rashes

The significance of NAT-2 polymorphism for Hydralazine in slow acetylators

a. Increased risk of aplastic anemia
b. Increased risk of lupus-like rashes
c. Increased risk of gray baby syndrome
d. Increased risk of kernicterus

b. Slow acetylators

Lupus-like rashes common in ______ acetylators of enzyme N-acetyl transferase

a. Fast acetylators

b. Slow acetylators

c. APAP

The drug metabolized by Glutathione conjugation

a. Catecholamines
b. Benzoic acid
c. APAP
d. Bilirubin

d. Catecholamines

The drug metabolized by methylation

a. APAP
b. Benzoic acid
c. Bilirubin
d. Catecholamines

c. Benzoic acid

The drug metabolized by glycine conjugation forming hippuric acid

a. Catecholamines
b. APAP
c. Benzoic acid
d. Bilirubin

a. Enzyme inducer

Cause under dosing (subtherapeutic)

a. Enzyme inducer

b. Enzyme inhibitor

b. Enzyme inhibitor

Cause overdosing (toxicity)

a. Enzyme inducer

b. Enzyme inhibitor

c. Rifampicin

The only antibiotic that is a CYP450 enzyme inducer

a. Chloramphenicol
b. Macrolides
c. Rifampicin
d. Fluoroquinolone

c. Azithromycin

The macrolide that is NOT a CYP450 enzyme inhibitor

a. Clarithromycin
b. Erythromycin
c. Azithromycin
d. Roxithromycin

b. CYP2C19

Clopidogrel is a prodrug activated by this enzyme into an active ADP inhibitor
a. CYP3A4
b. CYP2C19
c. CYP2D6
d. CYP1A2

b. Decreased active clopidogrel, increased inactive clopidogrel

Omeprazole inhibits CYP2C19, resulting in this effect on Clopidogrel
a. Increased active clopidogrel, decreased inactive clopidogrel
b. Decreased active clopidogrel, increased inactive clopidogrel
c. No effect on clopidogrel activation
d. Increased clopidogrel absorption only

b. Blood clot

The clinical consequence of Clopidogrel + omeprazole interaction, due to decreased active clopidogrel, is
a. Increased bleeding risk
b. Blood clot
c. Hypotension
d. Hyperkalemia

• Pantoprazole

• Rabeprazole

The alternative PPI to use instead of Omeprazole when a patient is on Clopidogrel

• a. Esomeprazole and Lansoprazole
  b. Pantoprazole and Rabeprazole
  c. Omeprazole and Esomeprazole
  d. Lansoprazole and Omeprazole

a. Omeprazole

• induce CYP1A

• inhibit CYP2C

This drug can be enzyme inhibitor or inducer

a. Omeprazole
b. Erythromycin
c. Azithromycin
d. Cimetidine

a. Valproic acid

The only anti-convulsant enzyme inhibitor

a. Valproic acid
b. Lithium
c. Clozapine
d. Carbamazepine

d. Carbamazepine

The enzyme inducer capable of inducing its own metabolism

a. Valproic acid
b. Lithium
c. Clozapine
d. Carbamazepine

b. Enzyme inhibitor

• Protease inhibitors

Antivirals for HIV (“-navir”) are __________

a. Enzyme inducer

b. Enzyme inhibitor