Clinical Pharmacology

Question 1

What is the quantal dose response relationship?

Answer 1

plotting the fraction of the population that responds to a given dose of drug against the drug dose which generalises the effect of a drug to a population rather than an individual

Question 2

What are the different 50% responses of significance in the quantal dose response?

Answer 2

ED50
TD50
LD50

Question 3

What is the ED50?

Answer 3

the median effective dose in 50% of the population

Question 4

What is the TD50?

Answer 4

the median toxic dose in 50% of the population

Question 5

What is the LD50?

Answer 5

the median lethal dose in 50% of the population, often not recorded in humans

Question 6

Give an example of drug interactions that can be beneficial

Answer 6

b-blockers + ACE inhibitors = decreased BP and hypertension

Question 7

What kinds of interactions can result in adverse effects?

Answer 7

pharmacokinetic

pharmacodynamic

Question 8

When does the risk of adverse reaction go significantly up?

Answer 8

when taking 12 drugs or more - 20% chance and up

Question 9

What are pharmacodynamic interactions?

Answer 9

Drug A modifies the pharmacological effect of Drug B without affecting its concentration in tissues

Question 10

What are pharmacokinetic interactions?

Answer 10

Drug A modifies the concentration of Drug B that reaches its site of action

Question 11

How might pharmacokinetic interactions occur?

Answer 11

through ADME

Question 12

How might pharmacokinetic interactions affect absorption?

Answer 12

increasing or decreasing the rate of emptying the stomach

enterohepatic recycling such as with the pill

Question 13

Give an example of a drug that increases stomach emptying

Answer 13

metoclopramide

Question 14

Give an example of a drug that decreases stomach emptying

Answer 14

atropine

Question 15

How do antibiotics affect the absorption of the pill?

Answer 15

gut bacteria normally release the pill from the conjugated form released in the bile and allow reabsorption. Antibiotics prevent this

Question 16

How might pharmacokinetic interactions affect distribution?

Answer 16

drugs bound to plasma proteins may be displaces by a second drug increasing their free concentration

Question 17

When does plasma protein binding matter with drug interactions?

Answer 17

with drugs that are extensively protein bound or have a low therapeutic ratio

Question 18

Why does plasma protein binding only have little significance?

Answer 18

Cp drives elimination

Question 19

Give an example of a drug with low therapeutic ratio

Answer 19

phenytoin

Question 20

How might pharmacokinetic interactions affect metabolism?

Answer 20

may induce hepatic enzymes decreasing the efficacy of another drug
may inhibit enzyme that metabolises another drug

Question 21

How might pharmacokinetic interactions affect excretion?

Answer 21

drugs may share a common transporter e.g. in the proximal tubule of the nephron

Question 22

Why does taking viagra and organic nitrates result in collapse?

Answer 22

organic nitrates cause vasodilation via NO and viagra potentiates this response by inhibiting PDEs causing severe hypotension

Question 23

Why does taking warfarin and flucanazol cause blood in the urine?

Answer 23

flucanazol inhibits CYP3A4 which metabolises warfarin

hence anti-coagulant effect is enhanced and causes blood in urine

Question 24

What may cause a Cp to be higher than desired?

Answer 24

excessive dosage and/or decreased clearance

Question 25

What factors may cause a Cp to be higher?

Answer 25

``` normal variation saturable metabolism genetic enzyme deficiency renal/liver failure old age/young age enzyme inhibition ```

Question 26

What may cause a Cp to be lower than desired?

Answer 26

dose too low and/or increased clearance

Question 27

What factors may cause Cp to be lower?

Answer 27

``` normal variation poor absorption high first pass metabolism genetic hyper-metabolism enzyme induction non-compliance ```

Question 28

How may enzymes be inhibited?

Answer 28

competitively - higher Km | non-competitively - lower Vmax

Question 29

What are some example enzyme inhibitors?

Answer 29

cimetidine erythromycin fluoextine

Question 30

What are some example enzyme inducers?

Answer 30

alcohol phenobarbiton phenytoin

Question 31

What causes impaired drug metabolism in liver disease?

Answer 31

decreased enzyme metabolising capacity | decreased liver blood flow

Question 32

How is drug dosage adjusted in liver disease?

Answer 32

for high Cl drugs | for low Cl drugs

Question 33

What is hypoproteinemia?

Answer 33

reduced synthesis of blood plasma proteins

Question 34

What is significant about hypoproteinemia in liver disease?

Answer 34

increases toxicity of highly bound drugs such as phenytoin

Question 35

What effect does reduced clotting factor synthesis have in liver disease?

Answer 35

increases sensitivity to oral anti-coagulants i.e. warfarin

Question 36

What is cholestasis?

Answer 36

flow of bile to the duodenum is compromised

Question 37

what may occur as a result of hepatic encephalopathy?

Answer 37

deterioration of brain function which may be precipitated by several drug class i.e. sedatives and opioids

Question 38

What may occur as a result of ascities?

Answer 38

accumulation of fluid in the peritoneal cavity associated with severe liver disease may be worsened by drugs that cause fluid retention i.e. NSAIDs

Question 39

What is used to measure renal impairment?

Answer 39

clearance of creatinine as a measure of GFR

Question 40

How are drugs adjusted for in renal impairment?

Answer 40

reducing the size of individual dose or increasing the time interval between doses

Question 41

Why may a loading dose be necessary in renal impairment?

Answer 41

T1/2 is increased for drugs cleared by the kidney which prolongs the time to Cpss

Question 42

What are the grades of renal impairment?

Answer 42

mild - 20-50 ml.min moderate - 10-20 ml.min severe

Question 43

How is dosing carried out in children?

Answer 43

by body weight and surface area

Question 44

What is particularly problematic in neonates?

Answer 44

inefficient renal filtration relative enzyme deficiencies inadequate detoxifying systems

Question 45

What are important considerations when prescribing for the elderly?

Answer 45

renal elimination tends to be impaired metabolism is usually impaired both lower overall clearance

Question 46

What are the main issues in prescribing for pregnancy?

Answer 46

teratogenicity if drug is absorbed orally, assume it crosses the placenta benefits have to outweigh risks