Metabolism/ Biotransformation

Question 1

Biotransformation

Answer 1

Converts lipid soluble and non-polar compounds to water soluble and polar compounds so they’re easily excreted and absorbed

Question 2

What happens when a substance isn’t converted to a water-soluble form?

Answer 2

Remains in body for a long period of time –> toxic reaction

Question 3

Active drug to inactive

Answer 3

Majority of drugs
Inactivation or pharmacological inactivation
Ex: phenobartbital to hydrocyphenobarbital

Question 4

Active drug to more active

Answer 4

Bioactivation or toxicological activation (could cause toxicity)
Ex: codeine to morphine, malathion to malaxon

Question 5

Inactive (pro-drug) to active metabolite

Answer 5

Pharmacological activation
Given because active compound isn’t always stable
ex: enalapril to enalaprilat or phenacetin to acetaminophen

Question 6

Active drug to equally active metabolite

Answer 6

No change in pharmacological activity
ex: digitoxin to digoxin, diazepam to nordiazepam

Question 7

Active drug to active metabolite

Answer 7

Having entirely different pharmacological activity
ex: iproniazed (antidepressant) to isoniazid (anti tubercular)

Question 8

________ is the primary site of metabolism

Answer 8

LIVER

Question 9

Where is most drug metabolizing activity found in the cell?

Answer 9

Smooth ER and cytosol

Question 10

Microsomal drug metabolizing enzymes

Answer 10

In lilophilic membranes of the SER
Most imp: glucuronide conjugation
Inucible by drugs, diets

Question 11

Non-microsomal drug metabolizing enzymes

Answer 11

In cytoplasm, mito, body fluids (liver, GI, plasma)
All conjugative reactions
Non-inducible

Question 12

Phase 1 pathway of biotransformation

Answer 12

Functionalization = reduction, hydrolysis, oxidation

Question 13

Reduction

Answer 13

Addition of hydrogen to the drug molecule

Question 14

Hydrolysis

Answer 14

Cleavage of drug molecules by taking up a molecule of water

Question 15

Oxidation

Answer 15

Introducing polar functional groups (OH) by microsomal enzymes (MFO or CYP-450)

Question 16

Phase 2 pathway of biotransformation

Answer 16

Conjugation (synthetic)
Attachment of polar molecules to parent drugs or their phase 1 products forming a highly polar product

Question 17

The _______ of the conjugate (metabolite) determines mainly its route of excretion

Answer 17

Molecular weight

Question 18

Low molecular weight conjugates are excreted mainly in the __________

Answer 18

Urine

Question 19

Where are high molecular weight conjugates excreted?

Answer 19

Bile (glutathione, glucoroinide)

Question 20

Glucurodination

Answer 20

Conjugation with glucoronic acid
Most common
Except in CATS and FISH
Only conjugation by hepatic microsomal enzymes

Question 21

Sulfation

Answer 21

Conjugation with sulphate
Non-microsomal enzymes
Important in CATS

Question 22

ACETYLATION

Answer 22

Conjugation with acetyl group
Drugs having amino group are acetylated
DOGS and FOXES don’t
Sulfonamides metabolize by acetylation

Question 23

Methylation

Answer 23

Methyl (-CH3) conjugation
More important for biosynthesis (epinephrine)

Question 24

Glutathione

Answer 24

Meracapturic acid formation
Tripeptide- glutamic acid, cysteine and glycine
Conjugates with electrophilic substrates like superoxides, epoxides and toxic intermediates

Question 25

Animo acids

Answer 25

Glycine
Ornithine in BIRDS
EX; SALICYLIC ACID, NICOTINIC ACID AND CHOLIC ACID

Question 26

THIOSULFATE

Answer 26

Detoxification of cyanide

Question 27

Induction of enzymes

Answer 27

Cytochrome P-450 and glucuronyl transferase drugs induce enzymes
Enhanced metabolism of co-administered drugs

Question 28

Inhibition of enzymes

Answer 28

By enzyme degradation or deceased enzyme synthesis
Decrease in metabolism of drugs