[LADME] Metabolism - Phase II

Proverbs 16:3

Phase II

This phase is also known as CONJUGATION phase.

Conjugation

Phase II is also known as ________ phase.

● Glucuronidation

● Acetylation

● Glutathione conjugation

● Amino acid conjugation

● Sulfonation / Sulfation

● Methylation

→Mnemonic “GAGA” si “SM”

[PHASE II]

Phase II reactions include _____ [6]

Glucuronidation

[PHASE II]

This reaction involves the enzyme, UDP-Glucuronosyl transferase.

UDP-Glucuronosyl transferase

[PHASE II]

Enzyme involved in GLUCURONIDATION:

Glucuronidation

[PHASE II]

This is the MOST COMMON phase 2 reaction in ADULTS.

Glucuronidation

[PHASE II]

These drugs undergo ______ reaction:

● Morphine

● Acetaminophen

● Bilirubin

● Thyroxine

● Chloramphenicol

● NSAIDs

● Morphine

● Acetaminophen

● Bilirubin

● Thyroxine

● Chloramphenicol

● NSAIDs

→Mnemonic: "MAB” “TCN”

[PHASE II]

Drugs that undergo GLUCURONIDATION [6]

bilirubin

[PHASE II]

Neonates lack glucuronidation, which can lead to increased _______ in the body, causing kernicterus and mental retardation.

Acetylation

[PHASE II]

This reaction involves the enzyme, N-acetyltransferase.

N-acetyltransferase

[PHASE II]

Enzyme involved in ACETYLATION:

Acetylation

[PHASE II]

This reaction is involved in GENOTYPIC VARIATION.

Slow acetylators

[PHASE II]

These acetylators have DECREASED or ABSENT N-acetyltransferase (NAT) activities, leading to DRUG-INDUCED adverse drug reactions.

Drug-induced ADRs

[PHASE II]

Slow acetylators have DECREASED or ABSENT N-acetyltransferase (NAT) activities, leading to __________.

Fast acetylators

[PHASE II]

These acetylators have INCREASED N-acetyltransferase (NAT) activities, leading to DECREASED drug activity.

decreased drug activity

[PHASE II]

Fast acetylators have INCREASED N-acetyltransferase (NAT) activities, leading to __________.

● Hydralazine

● Isoniazid

● Procainamide

● Dapsone

● Sulfa drugs

→Mnemonic: “HIP” “DS”

[PHASE II]

Drugs that undergo ACETYLATION include ______ [5]

Acetylation

[PHASE II]

These drugs undergo ______ reaction:

● Hydralazine

● Isoniazid

● Procainamide

● Dapsone

● Sulfa drugs

Isoniazid (INH)

[PHASE II]

Acetylation:

This drug is combined with vitamin B6 (pyridoxine) to prevent peripheral neuropathy.

Isoniazid (INH)

[PHASE II]

Acetylation:

This drug undergoes PHASE II first before PHASE I.

● Fast acetylators = HEPATOTOXICITY

● Slow acetylators = PERIPHERAL NEUROPATHY

[PHASE II]

Acetylation:

Adverse effects of ISONIAZID for fast and slow acetylators include:

Glutathione conjugation

[PHASE II]

This reaction involves the enzyme, Glutathione-S-transferase (GST).

Glutathione-S-transferase (GST)

[PHASE II]

Enzyme involved in GLUTATHIONE CONJUGATION:

Glutathione conjugation

[PHASE II]

This reaction is responsible for paracetamol toxicity.

< 4 g or 8 tabs per day

[PHASE II]

Maximum dose of paracetamol per day

IV form of NAC (N-acetylcysteine)

[PHASE II]

The toxic metabolite of paracetamol, NAPQI, decreases glutathione in the body. To resolve this, _________ is used.

Sulfonation/Sulfation

[PHASE II]

This is the MOST COMMON phase II reaction in NEONATES.

Sulfonation/Sulfation

[PHASE II]

This reaction involves the enzyme, SULFOTRANSFERASE

Sulfotransferase

[PHASE II]

Enzyme involved in SULFONATION/SULFATION:

● Acetaminophen

● Minoxidil

[PHASE II]

Drugs that undergo SULFONATION/SULFATION [2]

Sulfonation/Sulfation

[PHASE II]

These drugs undergo ______ reaction:

● Acetaminophen

● Minoxidil

Chloramphenicol

[PHASE II]

This drug causes bone marrow suppression in neonates, causing aplastic anemia and gray baby syndrome.

Methylation

[PHASE II]

This reaction involves the enzyme, methylase.

Methylase

[PHASE II]

Enzyme involved in METHYLATION:

Methylation

[PHASE II]

This is a MINOR pathway in drug metabolism.

Methylation

[PHASE II]

This is more important in the synthesis of ENDOGENOUS compounds (e.g. melatonin and epinephrine).

● Melatonin

● Epinephrine

[PHASE II]

Methylation is more important in the synthesis of ENDOGENOUS compounds. These include _____ [2]

Amino acid conjugation

[PHASE II]

This reaction involves the enzyme, amino acid transferase.

Amino acid transferases

[PHASE II]

Enzyme involved in AMINO ACID CONJUGATION:

Benzoic acid

[PHASE II]

Drugs that undergo AMINO ACID CONJUGATION:

Amino acid conjugation

[PHASE II]

Benzoic acid undergo _____ reaction.

Benzoic acid

[PHASE II]

Amino acid conjugation:

This drug is metabolized to hippuric acid (hippurate), which was first isolated from horse urine.

Glycine

[PHASE II]

Amino acid used in amino acid conjugation