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Quantative Pharmacology > Clinical Pharmacology > Flashcards

Clinical Pharmacology Flashcards

1
Q

What is the quantal dose response relationship?

A

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

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2
Q

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

A

ED50
TD50
LD50

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3
Q

What is the ED50?

A

the median effective dose in 50% of the population

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4
Q

What is the TD50?

A

the median toxic dose in 50% of the population

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5
Q

What is the LD50?

A

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

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6
Q

Give an example of drug interactions that can be beneficial

A

b-blockers + ACE inhibitors = decreased BP and hypertension

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7
Q

What kinds of interactions can result in adverse effects?

A

pharmacokinetic

pharmacodynamic

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8
Q

When does the risk of adverse reaction go significantly up?

A

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

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9
Q

What are pharmacodynamic interactions?

A

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

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10
Q

What are pharmacokinetic interactions?

A

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

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11
Q

How might pharmacokinetic interactions occur?

A

through ADME

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12
Q

How might pharmacokinetic interactions affect absorption?

A

increasing or decreasing the rate of emptying the stomach

enterohepatic recycling such as with the pill

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13
Q

Give an example of a drug that increases stomach emptying

A

metoclopramide

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14
Q

Give an example of a drug that decreases stomach emptying

A

atropine

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15
Q

How do antibiotics affect the absorption of the pill?

A

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

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16
Q

How might pharmacokinetic interactions affect distribution?

A

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

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17
Q

When does plasma protein binding matter with drug interactions?

A

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

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18
Q

Why does plasma protein binding only have little significance?

A

Cp drives elimination

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19
Q

Give an example of a drug with low therapeutic ratio

A

phenytoin

20
Q

How might pharmacokinetic interactions affect metabolism?

A

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

21
Q

How might pharmacokinetic interactions affect excretion?

A

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

22
Q

Why does taking viagra and organic nitrates result in collapse?

A

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

23
Q

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

A

flucanazol inhibits CYP3A4 which metabolises warfarin

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

24
Q

What may cause a Cp to be higher than desired?

A

excessive dosage and/or decreased clearance

25
Q

What factors may cause a Cp to be higher?

A 
normal variation
saturable metabolism
genetic enzyme deficiency
renal/liver failure
old age/young age
enzyme inhibition
26
Q

What may cause a Cp to be lower than desired?

A

dose too low and/or increased clearance

27
Q

What factors may cause Cp to be lower?

A 
normal variation
poor absorption
high first pass metabolism
genetic hyper-metabolism
enzyme induction
non-compliance
28
Q

How may enzymes be inhibited?

A

competitively - higher Km

non-competitively - lower Vmax

29
Q

What are some example enzyme inhibitors?

A

cimetidine
erythromycin
fluoextine

30
Q

What are some example enzyme inducers?

A

alcohol
phenobarbiton
phenytoin

31
Q

What causes impaired drug metabolism in liver disease?

A

decreased enzyme metabolising capacity

decreased liver blood flow

32
Q

How is drug dosage adjusted in liver disease?

A

for high Cl drugs

for low Cl drugs

33
Q

What is hypoproteinemia?

A

reduced synthesis of blood plasma proteins

34
Q

What is significant about hypoproteinemia in liver disease?

A

increases toxicity of highly bound drugs such as phenytoin

35
Q

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

A

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

36
Q

What is cholestasis?

A

flow of bile to the duodenum is compromised

37
Q

what may occur as a result of hepatic encephalopathy?

A

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

38
Q

What may occur as a result of ascities?

A

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

39
Q

What is used to measure renal impairment?

A

clearance of creatinine as a measure of GFR

40
Q

How are drugs adjusted for in renal impairment?

A

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

41
Q

Why may a loading dose be necessary in renal impairment?

A

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

42
Q

What are the grades of renal impairment?

A

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

43
Q

How is dosing carried out in children?

A

by body weight and surface area

44
Q

What is particularly problematic in neonates?

A

inefficient renal filtration
relative enzyme deficiencies
inadequate detoxifying systems

45
Q

What are important considerations when prescribing for the elderly?

A

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

46
Q

What are the main issues in prescribing for pregnancy?

A

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

Quantative Pharmacology (9 decks)

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