Pharmacokinetics III

Question 1

What is the first pass metabolism?

Answer 1

Extent of metabolism occurring before drug reaches systemic circulation

Question 2

Describe the first pass metabolism

Answer 2

Drug orally taken
Absorbed from GI tract into portal circulation
Metabolised in liver
Fraction enters systemic circulation (bioavailability)

Question 3

Describe the chemical transformation within the body

Answer 3

Needed to change drug into 2 major ways:
Reduce lipid solubility
Alter biological activity

Question 4

Why study metabolism?

Answer 4

Genetic differences
Age
Elderly patients
Nutritional status
Metabolites

Question 5

Describe the metabolic reactions of drug

Answer 5

Excreted, Inactivatedm Toxic metabolite, Prodrug

Active metabolite

Question 6

Describe the summary of metabolic reactions

Answer 6

Phase I reactions
Phase II reactions
Induction of drug metabolism
Inhibition of drug metabolism

Question 7

Describe how phase I reactions chemically alter basic structure of a drug

Answer 7

Oxidative/Reductive reactions - Alter/create new functional groups
Hydrolytic reactions - Cleave esters/amides to form functional groups
More water soluble - More activty
Some phase I metabolites may cause toxicity

Question 8

Describe phase II reactions

Answer 8

Conjugation reactions where drug/metabolite couples to endogenous substrate
Conjugate is active
More water soluble keeps it in the blood
Eliminated more rapidly by kidneys

Question 9

Name examples of phase I metabolism enzymes

Answer 9

Cyctochrome P450
Monoamine oxidase
Alcohol dehydrogenase

Question 10

Describe phase II metabolism

Answer 10

Adds group to drug
Forms many drugs but few conjugates
Mechanisms occur: Glucuronidation, Sulfation, Acetylation

Question 11

What is glucuronidation?

Answer 11

Addition of glucuronide

Question 12

What is sulfation

Answer 12

Addition of sulfate

Question 13

What is acetylation

Answer 13

Addition of acetyl groups

Question 14

Describe enzyme induction in terms of clinical significance

Answer 14

Decrease efficacy of drugs - Co-administered drugs stimulate metabolism eg oral anticoagulants/oral contraceptive pill
Osteomalacia - Barbiturates/Anti-epileptics stimulate Vit D3 metabolism eg decreases Ca stores
Increased dose requirement of benzodiazepines/analgesics in smokers

Question 15

Describe how the induction of drug metabolism lead to increased cytochrome P450 synthesis

Answer 15

Barbiturates, herbicides, nicotine, steroids, pesticides

Question 16

Describe the characteristics of an unfinished drug course

Answer 16

Therapeutic levels only acheived by increasing dose many times
Presence of another drug increase clearance
Changes in plasma levels means loss in efficacy
Toxic effects appeared gradually
Increased drug clearance reversible
Enzyme induction causes faster metabolism

Question 17

Describe inhibition of drug metabolism

Answer 17

Drug interaction - When one drug inhibits metabolism of another

Question 18

What are the 2 types of drug inhibitions?

Answer 18

Inhibition of cytochrome p450 eg binding to haem

Inhibition of other specific metabolic pathways

Question 19

Describe what is caused due to inhibition of drug metabolism

Answer 19

Increased plasma drug levels
Prolongation of pharmacological effects
Toxic effects

Question 20

What are the routes of excretion?

Answer 20

Kidney, lung, liver (bile), faeces, breast milk, tears/saliva/sweat, hair, skin

Question 21

What are the 3 processes of renal excretion?

Answer 21

Passive tubular reabsorption (IN)
Active tubular secretion (OUT)
Glomerular filtration (OUT)

Question 22

Describe passive tubular reabsorption

Answer 22

Common for lipophilic drugs

Occurs in distal tubule

Question 23

Describe active tubular secretion

Answer 23

Free/bound drug molecules available

Occurs in proximal tubule

Question 24

Describe glomerular filtration

Answer 24

Only free molecules filtered

Occurs on bowmans capsule

Question 25

What is clearance?

Answer 25

Volume of plasma cleared per unit time (ml/min)

Question 26

What is a zero order process?

Answer 26

Rate of drug elimination is constant

Question 27

Describe zero order process

Answer 27

Drug elimination half life is proportional to the plasma drug conc
Clearance is inversely proportional to the drug conc

Question 28

Describe maintenance dose aka css

Answer 28

With continuous drug administration, plasma drug concentration increases until it reaches steady-state condition
Rate of drug elimination is equal to the rate of drug administration (takes 405 drug half lives to achieve CSS)