2.6 - Metabolism

Question 1

Biotransformation/ Chemical Change

Answer 1

Metabolism

Question 2

Goal:

To convertdrugs into the following forms:

Answer 2

– Inactive
– Polar
– Non-toxic/ Less Toxic
– Easily excreted

Question 3

Exceptions

Answer 3

• Prodrug
• Formation of Toxic Metabolites
• Active ➡️ Active

Question 4

Inactive parent molecule metabolized to become active

Answer 4

Prodrug

Question 5

Ex: Prodrugs

Answer 5

• ACEIs — EXCEPT 
 - Captopril
 – Lisinopril
 – Enalaprilat IV
• Clopidogrel
• Dipivefrinn (EPI)

Question 6

Formation of Toxic Metabolites

Answer 6

APAP ➡️ NAPQI

Question 7

Active ➡️ Active

Answer 7

Diazepam ➡️ Oxazepam

Question 8

Organs

Answer 8

• Liver — dominant
• Kidneys
• Plasma
• GIT
• Placenta

Question 9

– For PO drugs

– Initial metabolism of drugs before enterig the syatemic circulation

Answer 9

First Pass Effect/ Pre-systemic Metabolism

Question 10

GIT ➡️ Portal Circulation ➡️ Liver

Answer 10

Effect: ⬇️Oral Bioavailability

Question 11

Ex: First Pass Metabolism

Answer 11

• Propranolol
• Opioids
• Catecholamines
• Felodipine
• Lidocaine

Question 12

2 Phases of Metabolism

Answer 12

• Phase 1

* Phase 2

Question 13

– Functionalizariin/ Asynthetic

Answer 13

Phase 1

Question 14

Goal of Phase 1:

Answer 14

To add/ unmask FUNCTIONAL groups

Question 15

Phase 1

Answer 15

• Oxidation
• Reduction
• Hydrolysis

Question 16

– Dominant Phase 1

– 2 enzymes

Answer 16

Oxidation

Question 17

2 Enzymes

Answer 17

• CYP Mediated

* Non CYP Mediated

Question 18

CYP1A2

Answer 18

• Caffeine
• Acetaminophen
• Theophylline

Question 19

CYP2C19

Answer 19

• PPIs
• Propranolol
• Clopidogrel

Question 20

CYP2C9

Answer 20

• S-Warfarin

* Phenytoin

Question 21

CYP2D6

Answer 21

• Codeine
• Antidepressants
• Antipsychotics

Question 22

CYP3A4,5,7

– responsible for metabolism > 50% of commercial drugs

Answer 22

• CCBs
• Azoles
• Macrolides
• Anti-HIV
• Antineoplastics

Question 23

Non CYP mediated

Answer 23

• MAO
• Alcohol Dehydrogenase
• Aldehyde Dehydrogenase

Question 24

Reduction

Answer 24

• Nitroreduction
• Carbonyl reduction
• Azo reduction

Question 25

Nitroreduction

Answer 25

Chloramphenicol

Question 26

Carbonyl reduction

Answer 26

* Methadone | * Naloxone

Question 27

Azo reduction

Answer 27

Prontosil

Question 28

Hydrolysis

Answer 28

* Ester | * Amide

Question 29

Ester

Answer 29

* ASA * ACEIs * Ester-tyoe local anesthetics

Question 30

Amide

Answer 30

* Procainamide | * Lidocaine

Question 31

Conjugation/ Synthetic

Answer 31

Phase 2

Question 32

Phase 2

Answer 32

* Glucuronidation * Acetylation * Muscellaneous

Question 33

Goal:

Answer 33

Addition of a POLAR Conjugate

Question 34

– dominant Phase 2 (adults) – Uridine-5'-diphosphoglucuronosyl transferase – Poorly expressed in neonates

Answer 34

Glucuronidation

Question 35

``` – N-acetyltransferase – Substrates: - Hydralazine - Isoniazid - Procainamide ```

Answer 35

Acetylation

Question 36

Miscellaneous

Answer 36

* Glycine Conjugation * Methylation * Sulfation — dominant Phase 2 (neonates)

Question 37

Enzyme Induction/ Inhibition

Answer 37

* Enzyme Induction | * Enzyme Inhibition

Question 38

Stimulates activity of enzymes

Answer 38

Enzyme Induction

Question 39

GOSPRC

Answer 39

* Griseofulvin * Omeprazole * St. John's Wort * Phenytoin, Phenobarbital * Rifampicin * Cigarette, Chronic Alcoholism

Question 40

Consequences

Answer 40

* Prodrug * Toxic Metabolite * Inactive Metabolite

Question 41

Prodrug

Answer 41

⬆️Efficacy; ⬆️Toxicity

Question 42

Formation of Toxic Metabolites

Answer 42

⬆️Toxicity

Question 43

Inactive Metabolites

Answer 43

⬇️Efficacy

Question 44

Reduce Enzyme Activity

Answer 44

Enzyme Inhibition

Question 45

MEDVICKGA

Answer 45

* Metronidazole * Erythromycin * Disulfiram, Diphen, Diltiazem * Valproic Acid, Verapamil * Isoniazid, Indinavir * Cimetidine, Cipro, Chloram * Ketoconazole * Grapefruit * Acute Alcoholism

Question 46

Consequences

Answer 46

* Prodrug | * Active Parent — Inactive

Question 47

Prodrug

Answer 47

⬇️Efficacy

Question 48

Active Parent — Inactive

Answer 48

⬆️Efficacy; ⬆️Toxicity