Session 2

Question 1

List the factors affecting drug absorption

Answer 1

First pass metabolism:
Gut lumen - gastric acid, enzymes
Gut wall - P-glycoprotein efflux
Liver
Drug formulation
Food (lipid soluble > water soluble)
Vomiting
Malabsorption (Coeliac's disease)

Question 2

List the factors affecting drug distribution

Answer 2

Protein binding:
Albumin - acidic drugs
Globulins - hormones
Lipoproteins - basic drugs
Hypoalbuminaemia
Pregnancy
Renal failure
Displacement by other drugs

Question 3

Explain the terms ‘bioavailability’ and ‘volume of distribution’

Answer 3

Bioavailability - fraction of an administered dose of unchanged drug that reaches the systemic circulation, IV = 100%
Volume of distribution - measure of how widely a drug is distributed in body tissues
Vd = dose/[drug]t0

Question 4

List the factors affecting drug metabolism

Answer 4

Metabolism dependent on CYP enzymes

Can be influenced by drugs (inducers/inhibitors)

Question 5

List some common CYP450 inducers

Answer 5

Phenytoin
Carbamazepine
Barbiturates
Rifamiicin
Alcohol (chronic)
Sulphonylureas, St John's Wort

Question 6

List some common CYP450 inhibitors

Answer 6

Omeprazole
Disulfiram
Erythromycin
Valproate
Isoniazid
Cimetidine, Ciproflaxin
Ethanol (acute)
Sulphonamides 
Grapefruit juice

Question 7

List the factors affecting drug excretion

Answer 7

Unbound/bound drugs

Urine flow rate

Question 8

Recognise the equations used for clearance and drug half life

Answer 8

Clearance = urine conc x urine flow rate/plasma conc
Half life is indirectly proportional to clearance
It takes 4-5 half lives to reach a drug’s steady state

Question 9

Understand the difference between linear and non-linear kinetics

Answer 9

Linear (1st order) - rate of elimination is proportional to drug level
Non-linear (0 order) - rate of elimination is constant and does not vary with drug concentration, no half life calculable therefore drug monitoring essential

Question 10

List some common zero order drugs

Answer 10

Alcohol
Phenytoin
Warfarin
Heparin
Aspirin (high dosage)
Theophylline, tolbutamide
Salicylates

Question 11

Appreciate how steady stage therapeutic levels in plasma (CpSS) are reached and how loading doses are employed to reach CpSS more rapidly

Answer 11

4-5 doses = steady state

Loading dose = Vd x [drug]target

Question 12

Understand the basic concepts relevant to pharmacodynamics

Answer 12

How do drugs work - interact with endogenous proteins (agonise/antagonise/unconventional mechanisms)
Where do drugs work - receptors ion channel, transporter enzymes

Question 13

Define the terms ‘specificity’ and ‘selectivity’

Answer 13

Specificity - target drugs against specific receptor subtitles and specific organs
Selectivity - less chance of interaction with different targets therefore fewer undesirable side effects

Question 14

Define ‘affinity’, ‘efficacy’ and ‘potency’ and appreciate the idea of a therapeutic window

Answer 14

Affinity - tendency of a drug to bind to a specific receptor type
Efficacy - ability of a drug to produce a response when the receptor is occupied
Potency - dose required to produce the desired biological response
Therapeutic index - relationship between concentrations causing adverse and desirable effects (TD50/ED50)
Therapeutic window = treatment while still safe

Question 15

Describe, with examples, pharmacokinetic and pharmacodynamic drug interactions

Answer 15

CYP450 inducers/inhibitors

Question 16

Understand induction and inhibition of the cytochrome P450 system

Answer 16

Induction - enzymes become more active causing drug to be processed quicker –> drug ineffective at treatment
Inhibition - enzymes inhibit activity causing drug to remain in body for longer –> drug has a larger effect (toxic?)

Question 17

Outline how cardiac, renal and hepatic disease cause disease-drug interactions

Answer 17

Cardiac - decreased cardiac output, low perfusion of organs
Renal - low GFR= decreased clearance of drugs
Hepatic - decreased CYP enzyme activity

Question 18

Recognise circumstances in which drug interactions are most likely to occur

Answer 18

Polypharmacy
Extremes of age
Co-morbidities
Drugs with a narrow therapeutic index
Drugs used near their minimum/maximum effective concentration

Question 19

List some important drug-food interactions

Answer 19

Grapefruit juice (CYP450 inhibitor) - decreased clearance of simvastatin, amiodarone
Cranberry juice (CYP2C9 isoform inhibitor) - decreased clearance of warfarin, increased risk of haemorrhage 
*used as a UTI treatment as inhibits bacterial adherence to urothelium

Question 20

Recognise the main routes of drug administration into the body

Answer 20

Oral
IV
SC
IM
Parenteral
PR
Transdermal