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

Drug-drug and drug-disease interactions Flashcards

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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
combos - minimise side effects/ toxicity
loop diuretics cause potassium loss, prescribed with potassium sparing diuretic or antagonists in overdose
26
opiate overdose
naloxone
27
where do drug interactions occur?
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
what are the stages of pharmacokinetics
absorption distribution metabolism excretion
29
pharmacodynamic interactions
agonism antagonism non-selective nature of drug enhanced effect by other means
30
agonism
2 drugs of same/ similar class
31
antagonism
given the antagonist and agonist beta blockers and beta 2 agonists opiate analgesics and naloxone
32
non-selective nature of drug
interact with many receptor sub types | antidepressants
33
enhanced effect by other means
digoxin toxicity increased by hypokalaemia caused by a loop diuretic for example
34
absorption
changes in gut motility interfere with absorption and enterohepatic circulation altered P-glycoprotein activity
35
changes in gut motility
slow or speed it up e.g. opiates or metoclopramide
36
altered P-glycoprotein activity
transporter - alters how much is absorbed
37
metoclopramide
increases gastric emptying delivers drugs to small bowel quickly absorbed more rapidly
38
distribution
many drugs alter distribution by displacing another from plasma or tissue binding sites causes transient increase in unbound drug corrected by increased elimination
39
hepatic drug metabolism
2 phase metabolism
40
phase 1
CYP450 low substrate specificity metabolises wide range of drugs
41
phase 2
increases solubility and allows easier renal elimination
42
INR
ratio of pro-thrombin time compared between patient and normal
43
liver enzyme induction
enzyme inducing drug which increase CYP450 activity (anticonvulsants) break down more of the drug and increase drug metabolism
44
anticonvulsants
carbamezepine increases metabolism of warfarin so it is no longer effective
45
drugs that induce CYP450
increase metabolism of certain other drugs | may increase their own metabolism
46
CYP450 induction
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
st Johns Wort
effective herbal remedy for depression | induces CYP3A4 and increases metabolism of certain drugs
48
what does St Johns wort increase metabolism of?
oral contraceptives digoxin phenytoin (anticonvulsant) warfarin
49
CYP450 inducers
``` anticonvulsants antibiotics steroids alcohol weed cigarettes st johns wort HIV therapies ```
50
melaena
black poo caused by upper GI bleeding
51
macrolide antibiotics and warfarin
``` kill bacteria in gut vitamin K synthesis falls increases anticoagulant effect increased INR inhibit CYP450 enzyme system warfarin metabolism reduced and increased INR ```
52
CYP 450 inhibition
quick onset reduced metabolism of drugs increased effect and toxicity
53
CYP450 inhibitors
``` anti-arrhythmics antibiotics - erythromycin antidepressants HIV drugs statins ```
54
treatment failure or toxicity
CYP450 inducers = treatment failure and inhibitors = toxicity
55
QTc interval prolongation
people with elongated QT intervals are more prone to arrhythmias torsade des pointes
56
QT interval
between start of QRS complex to end of P wave
57
what causes prolonged QT intervals?
congenital malformations drugs genetic and acquired forms
58
what drugs prolong QTc interval?
anti-arrhythmics | any drug that impairs metabolism of a QTc prolonging drug
59
terfenadine
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
drugs and long QT syndrome
``` anti-arrhythmics antibiotics anti-fungals anti-histamines psychotropic drugs motility agents ```
61
drugs which often cause interactions
``` anticonvulsants anti-arrhythmics antidepressants antibiotics anticoagulants ```
62
hepatic disease
decreased clearance of hepatically metabolised drugs
63
renal disease
reduced clearance of renally excreted drugs
64
cardiac disease
reduced metabolism of drugs dependent on hepatic blood flow | cannot reach site of metabolism/ excretion
65
what foods commonly cause drug interactions?
grapefruit and cranberry juice
66
grapefruit juice
``` inhibits CYP450 isoenzymes reduces clearance of drugs amiodarone terfenadine simvastatin increases drug exposure ```
67
cranberry juice
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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