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Renal system > Drug-drug and drug-disease interactions > Flashcards

Drug-drug and drug-disease interactions Flashcards

1
Q

what is drug interaction?

A

modification of one drug’s action by another drug

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2
Q

what do drugs include?

A 
prescribed drugs
herbal remedies
OTC medications
dietary factors
lifestyle factors - smoking and alcohol
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3
Q

what do drugs interact with?

A

drugs

disease

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4
Q

variation in drug response

A

physiological changes
genetics
drug-drug interactions
disease state

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5
Q

variation in drug response - physiological changes

A 
age
sex
pregnancy
size
weight
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6
Q

variation in drug response - genetics

A

ethnicity

enzymatic

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7
Q

variation in drug response - disease state

A 
hepatic
renal
GI
cardiac
CNS
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8
Q

individual variations to drugs

A

variability in the effect of a drug can occur in different individuals or the same individual on a different occasion

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9
Q

what can variability cause?

A

loss of efficacy

unexpected side effects

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10
Q

what are the types of drug response variability?

A

different concentrations of drug reaching site of action - pharmacokinetic
different degree of response to the same drug concentration - pharmacodynamic
different unpredictable response - idiosyncratic

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11
Q

the effects of youth

A

drug metabolism is slower - immature organ function
renal excretion is less efficient
drug sensitivity changes - receptor numbers
physiological factors

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12
Q

effects of elderly

A 
drug metabolism is slower - failing organ function
renal excretion is less efficient
drug sensitivity changes
poly-pharmacy 
co-morbidities
body fat to mass
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13
Q

pregnancy and drug response

A

decrease in plasma protein binding
increased plasma volume and ECF
increased cardiac output
increased renal blood flow and GFR (increased renal drug elimination)

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14
Q

pharmaco-genetics

A

how different individual genotypes relate to different drug responses

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15
Q

pharmaco-genomics

A

pharmacogenetics applied to the whole human genome

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16
Q

ethnicity and drug responses

A

genetic differences account for some variations

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17
Q

ACE inhibitors in Afro-caribbeans

A

reduced hypotensive effect

increased angioedema

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18
Q

alcohol

A

some groups less tolerant of alcohol

altered ethanol metabolism

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19
Q

idiosyncratic reactions

A

usually harmful reaciton in tiny % of patients
unexpected and unusual
often genetic and immunological basis

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20
Q

beneficial drug interactions/ combinations

A

enhanced effect
reduce metabolism
minimise side effects/ toxicity

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21
Q

harmful drug interactions

A

15% of adverse drug reactions

certain groups at high risk

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22
Q

who are at high risk of harmful drug interactions?

A

elderly
hepatic/ renal disease
polypharmacy
patients taking drugs with narrow therapeutic ranges

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23
Q

combos - enhanced drug effect

A

triple therapy for TB reduces development of resistance

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24
Q

combos - reduced metabolism of drugs

A

L-dopa and peripheral dopa decarboxylase inhibitor reduces peripheral breakdown to maximise CNS effect in parkinson’s

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25
Q

combos - minimise side effects/ toxicity

A

loop diuretics cause potassium loss, prescribed with potassium sparing diuretic
or antagonists in overdose

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26
Q

opiate overdose

A

naloxone

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27
Q

where do drug interactions occur?

A

pharmaceutical level - chemical interaction when mixed
pharmacokinetic level - interference with absorption, distribution, metabolism and excretion
pharmacodynamic level -drugs may interfere with others at site of action

28
Q

what are the stages of pharmacokinetics

A

absorption
distribution
metabolism
excretion

29
Q

pharmacodynamic interactions

A

agonism
antagonism
non-selective nature of drug
enhanced effect by other means

30
Q

agonism

A

2 drugs of same/ similar class

31
Q

antagonism

A

given the antagonist and agonist
beta blockers and beta 2 agonists
opiate analgesics and naloxone

32
Q

non-selective nature of drug

A

interact with many receptor sub types

antidepressants

33
Q

enhanced effect by other means

A

digoxin toxicity increased by hypokalaemia caused by a loop diuretic for example

34
Q

absorption

A

changes in gut motility
interfere with absorption and enterohepatic circulation
altered P-glycoprotein activity

35
Q

changes in gut motility

A

slow or speed it up e.g. opiates or metoclopramide

36
Q

altered P-glycoprotein activity

A

transporter - alters how much is absorbed

37
Q

metoclopramide

A

increases gastric emptying
delivers drugs to small bowel quickly
absorbed more rapidly

38
Q

distribution

A

many drugs alter distribution by displacing another from plasma or tissue binding sites
causes transient increase in unbound drug
corrected by increased elimination

39
Q

hepatic drug metabolism

A

2 phase metabolism

40
Q

phase 1

A

CYP450
low substrate specificity
metabolises wide range of drugs

41
Q

phase 2

A

increases solubility and allows easier renal elimination

42
Q

INR

A

ratio of pro-thrombin time compared between patient and normal

43
Q

liver enzyme induction

A

enzyme inducing drug which increase CYP450 activity (anticonvulsants)
break down more of the drug and increase drug metabolism

44
Q

anticonvulsants

A

carbamezepine increases metabolism of warfarin so it is no longer effective

45
Q

drugs that induce CYP450

A

increase metabolism of certain other drugs

may increase their own metabolism

46
Q

CYP450 induction

A

200+ drugs induce CYP450
relatively slow onset
new enzyme production required
induction can persist after withdrawal whilst enzyme levels normalised
removing an inducer will disturb equilibrium and so may reduce CYP450 activity, causing build up of drug

47
Q

st Johns Wort

A

effective herbal remedy for depression

induces CYP3A4 and increases metabolism of certain drugs

48
Q

what does St Johns wort increase metabolism of?

A

oral contraceptives
digoxin
phenytoin (anticonvulsant)
warfarin

49
Q

CYP450 inducers

A 
anticonvulsants
antibiotics
steroids
alcohol
weed
cigarettes
st johns wort
HIV therapies
50
Q

melaena

A

black poo caused by upper GI bleeding

51
Q

macrolide antibiotics and warfarin

A 
kill bacteria in gut
vitamin K synthesis falls
increases anticoagulant effect
increased INR
inhibit CYP450 enzyme system 
warfarin metabolism reduced and increased INR
52
Q

CYP 450 inhibition

A

quick onset
reduced metabolism of drugs
increased effect and toxicity

53
Q

CYP450 inhibitors

A 
anti-arrhythmics
antibiotics - erythromycin
antidepressants
HIV drugs
statins
54
Q

treatment failure or toxicity

A

CYP450 inducers = treatment failure and inhibitors = toxicity

55
Q

QTc interval prolongation

A

people with elongated QT intervals are more prone to arrhythmias
torsade des pointes

56
Q

QT interval

A

between start of QRS complex to end of P wave

57
Q

what causes prolonged QT intervals?

A

congenital malformations
drugs
genetic and acquired forms

58
Q

what drugs prolong QTc interval?

A

anti-arrhythmics

any drug that impairs metabolism of a QTc prolonging drug

59
Q

terfenadine

A

anti-histamine in body rapidly changed to fexofenadine
another drug - anti-fungal for example blocks conversion to fexofenadine, causing build up of terfenadine which is a potent calcium channel blocker in heart which causes cardiac effects.

60
Q

drugs and long QT syndrome

A 
anti-arrhythmics
antibiotics
anti-fungals
anti-histamines
psychotropic drugs 
motility agents
61
Q

drugs which often cause interactions

A 
anticonvulsants
anti-arrhythmics
antidepressants
antibiotics
anticoagulants
62
Q

hepatic disease

A

decreased clearance of hepatically metabolised drugs

63
Q

renal disease

A

reduced clearance of renally excreted drugs

64
Q

cardiac disease

A

reduced metabolism of drugs dependent on hepatic blood flow

cannot reach site of metabolism/ excretion

65
Q

what foods commonly cause drug interactions?

A

grapefruit and cranberry juice

66
Q

grapefruit juice

A 
inhibits CYP450 isoenzymes
reduces clearance of drugs 
amiodarone
terfenadine
simvastatin
increases drug exposure
67
Q

cranberry juice

A

used for treatment of urinary sepsis
inhibits bacterial adherence to urothelium
inhibits CYP2C9 isoform
decreases clearance of warfarin
increases risk of haemorrhage
dont drink excessive amounts when on warfarin

Renal system (17 decks)

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