Week 2: Introduction to Drug Interactions

Question 1

Likelihood and significance of drug interactions

Answer 1

Increasing amount of drugs being taken will increase the likelihood of a drug interaction
Not all drugs interactions are clinically significant

Question 2

Potential clinical significance

Answer 2

When a therapeutic combination could lead to an unexplained change or complication in the patients condition

Question 3

What is a drug interaction?

Answer 3

An interaction is said to occur when the effects of one drug are changed by the presence of another drug, herbal medicine, food, drink, medical conditions or environmental chemical agent

Question 4

What is the effect of a drug interaction?

Answer 4

Additive or increased exposure/effects of one or more drugs
Decreased exposure or effects of one or more drugs causing decreased effectiveness
Antagonism of the effects of one or more drugs

Question 5

Clinically important drug interactions

Answer 5

Drugs with a narrow therapeutic index

Drugs with a steep dose-response curve

Question 6

Drug-Disease interactions examples

Answer 6

Tricyclic antidepressant and history of postural hypotension
Long term use of NSAID for osteoarthritis and chronic renal failure
Anticholinergic drugs to prevent extrapyramidal side effects of antipsychotic drugs
Long term prescription of long half life benzodiazepine to treat insomnia, dementia or anxiety

Question 7

Drug-Food and Drug-Herb interaction examples

Answer 7

Alterations of drug absorption
Grapefruit juice inhibits intestinal CYP3A4
Vitamin K and Warfarin
Herbal products with anticoagulant and anti platelet properties

Question 8

What is pharmacokinetics?

Answer 8

The effects of the drug on the body

Absorption, distribution, metabolism and excretion

Question 9

What is pharmacodynamics?

Answer 9

The effects of the body on the drug

e.g. receptor interactions

Question 10

What is Cmax?

Answer 10

The maximum concentration of the drug in the bloodstream from a dose

Question 11

What is Tmax?

Answer 11

The time it takes for the drug to reach Cmax

Question 12

What is the half life?

Answer 12

The time it takes for half of the concentration within the bloodstream to clear from the body

Question 13

What does area under the curve of a concentration time graph indicate?

Answer 13

The total exposure to the drug that the body receives `

Question 14

What is absorption?

Answer 14

The routes of drug administration
Drug travels through the gut to liver to veins to heart to lungs to heart then to arterial circulation
The route of administration impacts the time for drug action to occur

Question 15

What is distribution?

• 4 main compartments of the body
• Volume of distribution calculation

Answer 15

Movement of drug between compartments of body (blood/plasma, fat, extracellular fluid, intracellular fluid)
Free drug can move between bound drug is localized to that compartment to eventually reach equilibrium across all compartments
The Vd = total amount of drug in body/concentration of drug in plasma

Question 16

What is metabolism?

- First pass metabolism

Answer 16

Metabolism of the drug often occurs in the liver
FIrst pass metabolism refers to oral drugs entering the liver before distribution therefore are metabolized before having an effect on the body thus a reduction in dose reaching the circulation occurs

Question 17

What is a cytochrome p450 enzyme?

• Processes
• Phases

Answer 17

Metabolite within the liver to metabolis various forms of drugs
Processes include: Oxidation, Hydrolysis and Hydroxylation
The two phases are metabolism for drug activation and metabolism for drug excretion

Question 18

What is excretion?

- Clearance formula

Answer 18

Irreversable removal of drug from body
Most drugs excreted by kidneys (nephron to collecting duct to urine)
Clearance = (Concentration of drug in urine x Rate urine produced) / Concentration of drug in plasma

Question 19

What are the order of kinetics?

Answer 19

First order - Excretion rate dependent on plasma concentration
Zero order - Excretion rate independent of plasma concentration (metabolite to excrete)

Question 20

What are the 4 pillars of Quality of Medicines (QUM)

Answer 20

Safety
Efficacy
Judiciousness
Appropriateness

Question 21

Pharmacokinetic changes in elderly

Answer 21

Renal function often deteriorates - influences excretion

Measured by creatinine clearance

Question 22

Pharmacodynamic changes in elderly

Answer 22

Altered sensitivity to drugs due to changes in drug receptors and target organ responses
Reduced physiological reserves and impairment of secondary compensatory mechanism predisposes to adverse effects

Question 23

What is polypharmacy?

- Superpolypharmacy

Answer 23

Multiple drugs
Increased risk of drug interactions and adverse effects
Superpolypharmacy - +10 drugs
Can also occur by misdiagnosing symptoms as new disease when it is adverse effects of current medication

Question 24

What is adherence?

- How is it maximised

Answer 24

The extent to which a person’s behaviour corresponds with agreed recommendations from health care provider
Maximise by building a therapeutic alliance with patient

Question 25

What is hepatic impairment?

Answer 25

Acute or chronic liver dysfunction impairs patients ability to metabolize drugs and thus eliminate them

Question 26

What are some factors that influence the action of drugs within the body?

Answer 26

The action of some drugs can be influenced by genetics, extreme heat (Queensland)

Question 27

What are the 4 stages of prescribing and therapeutic decision making?

Answer 27

The 4 stages are information gathering, decision making, communication and review/monitor/follow up

Question 28

What is teratogenic exposure?

Answer 28

Exogenous agent that can modify any embryonic of fetal functional or structural development

Question 29

What factors affect the teratogenicity and placental transfer of a drug?

Answer 29

Gestational timing of dose (which trimester mother is in)
Size of dose/administration route
Lipophilicity

Question 30

What proves a drug is a teratogen?

Answer 30

Produces deformities in >2-3% exposed mothers

Consistent pattern of deformities

Question 31

Define Category A drugs for pregnant women

Answer 31

Drugs which have been taken by a large number of pregnant women and women of childbearing age without any proven increase in frequency of malformation or other direct or indirect harmful effects on fetus

Question 32

Define Category B1 drugs for pregnant women

Answer 32

Drugs which have been taken by only a limited number of pregnant women and women of child bearing age, without an increase in frequency of malformation or other direct or indirect harmful effects of fetus
Studies in animals have not shown evidence of an increased occurrence of fetal damage

Question 33

Define Category B2 drugs for pregnant women

Answer 33

Drugs which have been taken by only a limited number of pregnant women and women of child bearing age without an increase in the frequency of malformation or other direct or indirect harmful effects of fetus
Studies in animals are inadequate or may be lacking, but available data show no evidence of an increased occurrence of fetal damage

Question 34

Define Category B3 drugs for pregnant women

Answer 34

Drugs which have been taken by only a limited number of pregnant women and women of child bearing age, without an increase in frequency of malformation or other direct or indirect harmful effects on the fetus
Studies in animals have shown evidence of an increased occurrence of fetal damage (significance in humans is uncertain)

Question 35

Define Category C drugs for pregnant women

Answer 35

Drugs which have caused or may be suspected of causing harmful effects on fetus or neonate without causing malformations
These effects may be reversible

Question 36

Define Category D drugs for pregnant women

Answer 36

Drugs which have caused, are suspected to have caused or may be expected to cause an increase incidence of fetal malformation or irreversible damage
These drugs may have adverse pharmacological effects

Question 37

Define Category X drugs for pregnant women

Answer 37

Drugs which have such a high risk of causing permanent damage to fetus that they should not be used in pregnancy or when there is the possibility of pregnancy