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errors and drugs > Drug interactions > Flashcards

Drug interactions Flashcards

1
Q

What is a drug interaction

A

Clinically meaningful alteration in effect of one drug as a result of co-administration of another drug, food or chemical (precipitant)

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2
Q

What types of durug interactions increase effect

A

Summative
Synergistic

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3
Q

When are drug interactions only clinically relevant often

A

When narrow therapeutic index

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4
Q

How common are drug interactions

A

15-65% potnetial
Actually around 6%
hospital admission 4-8%
Reduced efficacy 8%

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5
Q

How does polypharmacy increase DDI

A

2 drugs - 13%
4 drugs - 38%
>7 drugs - 82%

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6
Q

What is a pharmacodynamic interaction

A

Drugs act on same target site of clinical effect

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7
Q

What are pharmacokinetic DDIs

A

Altered drug concentration at target site of clinical effect eg ADME

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8
Q

What is pharmacodynamic DDI causes resp depression

A

opiates and benzos

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9
Q

What pharmacokinetic DDI causes COCP failure

A

Antibiotics

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10
Q

How can synergistic DDIs be beneficial

A

Increase effect eg antimicrobial efect of rifampacin and isoniazid at mycobacterim TB

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11
Q

What effect does alcohol and benzos have

A

Increased action at GABA - sedative effect on CNS

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12
Q

What drug antagonises salbutamol

A

atenolol - bronchoconstrictor - beta adrenoreceptors

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13
Q

How does naloxone work

A

Antagonist at opioid receptor (which morphine is endogenous agonist) - reverses sedative effect of morphine

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14
Q

What is danger os sildenail and isosorbide mononitrate

A

Markedly increased hypotnesion = can be extermely dangerous esp if cardiac problems/IHD

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15
Q

Mechanisms which can alter rate and extent of absorption

A

pH
Gastric emptying and intestinal motility
Physio-chemical interaction

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16
Q

What happens to absorption when pH lowered eg antacid

A

Reduced absorption - more ionisation, can’t cross membrane of cell

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17
Q

What happens to drug absorption if pH of stomach increased

A

eg alcohol
Less ionisation and faster absorption

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18
Q

What drugs delay gastric emptrying

A

opiate analgesics - morphine, pethidine
Antimuscarinics eg atropine, propantheline
TCAs eg impiramine - side effect

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19
Q

What drugs increase rate of gastric emptying

A

Metoclopramide
Muscarinic agents eg bethanechol

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20
Q

What is the clinical significance of decreased gastric emptying

A

Lower peak concentration
BUT prolonged duration

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21
Q

What drugs do antacids make insoluble therefore reduce absorption

A

Tetracyclines
Quinolones
Iron
Bisphosphonates

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22
Q

What drug can be used to reduce absorption of acidic drugs in overdose

A

Cholestyramine

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23
Q

Examples of acidic drugs that overdoses can be treated with cholestyramine if uick

A

Digoxin, warfarin

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24
Q

How does activated charcoal stop absorption

A

Adsorbs toxins to surface, not absorbed by digestive system so excreted in faeces

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25
Q

What are distribution interactions

A

Displacement of plasma protein bound drugs by another drug - increased free drug conversion
Danger is from toxicity

26
Q

What drugs have high protein binding

A

Warfarin, statins, amiodarone, diazepam, NSAIDs, heparin, furosemide tolbutamide, phenytoin, sulphonamides

27
Q

When does distribution DDI become significant

A

normally minor - compensation increase in metabolism and excretion free drug
IF 2nd mechanism eg drug also inhibits metabolism of old drug
Produces toxicitiy

28
Q

What drug interacts with phenytoin in distribution interaction

A

Valproate
Also inhibits metabolism

29
Q

What two cardiac drugs can interact distibutionally causing toxicity

A

Digoixin and quinidine/verapamil/amiodarone

30
Q

mechanism of digoxin toxicity when given with quindien

A

Quinidine displaces digoxin from cardiac receptors
Increase plasma concentration of digoxin -> toxiciity
ALSO decreases excretion of digoxin

31
Q

Effect of CYP450 inducers vs inhibitors on effect of drugs

A

Inducers increase metabolism -> reduce effect of drug
INhibitors slow metabolism -> enhanced effect

32
Q

Why does induction OF cyp450 take days to weeks?

A

Need an increase in actual enzymes - liver grows and blood flow increases, increased clearance of everything

33
Q

Why is inhibition immediate of CYP450

A

Blocking exisitng CYP450s - dont need more time

34
Q

Examples of CYP450 inducers

A

CRAPGP

Phenytoin
Carbamazepine
Barbituatesn(phenobarbitone)
Rifampicin
Alcohol - chronic
St johns wort
Grisefolun

35
Q

Exmaples of CYP450 inhibitors

A

Cimetidine
Erythromycin/clarithromycin
Ciprofloxacin
Sulphonamides
Isoniazids
Verapamil
Metronidazole
Omeprazole
Grapefruit juice
Alcohol - acutely
Amiodarone
Antifungals

36
Q

What drug can baribituates induce

A

Warfarin (reduced effect)

36
Q

What drug can rifampacin induce (reduce effect)

A

Theophylline

37
Q

What drug can phenytoin induce

A

COCP

38
Q

What need to watch for when stopping medication

A

If its a CYP450 inducer - may increase effect of other drug

39
Q

How can wtihdrawal of carbamazepine affect warfarin

A

Higher dose of warfarin due to inductino by carbamazepine (normal blood levels as increased clearnace)
If carbamazepine stopped acutely + reaplced by valproate (inhibitor) warfarin clearance falls, blood levels above therapeutic index -> haemorrhage

40
Q

What drugs will st johns wort interfere with

A

CYP450 inducer - makes below less effective
Warfarin
COCP
SSRI - serotonin syndrome
Ciclosporin - transplant failure
Theophylline
Digoxin
Carbamazepine
Phenytoin

41
Q

What enzyme do grapefruit and cranberry juice block

A

CYP3A4 in gut wall and liver

42
Q

What drugs do grapefruit and cranberry juice interact with

A

Drugs metbaolised by CYP3A4
CCBs
Benzos
Simastatin - myopathy

43
Q

Why can COCP be less effective with antibiotics

A

Enterohepatic recycling - oestrogen from liver -> gut in bile -> free oestrogen by bacteria
Antibiotics reduce bacteria and therefore amount of free oestrogen released from the gut

44
Q

Precautions with COCP and antibiotics

A

None if antibiotic not inducer and no N/V - short course
Long course - gut recolonised

45
Q

What drug can inhibit active tubular secretion of acidic drugs

A

Penicillin, methotrexate

46
Q

What drugs inhibit tubular secretion about digoxin

A

Quinidine and verapamil

47
Q

What does interaction between lithium and thiazide diuretics?

A

Lithium retained in tubules -> increased and potnetial toxicity

48
Q

What can NaCl and spirinolactone cause

A

Hyperkalaemia
Potassium sparing and adding potassium

49
Q

What effect do some antibiotics (ciprofloxacin, clarith/erythromycin) have on theophylline

A

CYP450 inducers -> theophylline toxicity

50
Q

Theophylline toxicity symptoms

A

Dizziness, hypotension
Seizures, cardiac arrhtyhmias, death

51
Q

What enzyme causes interaction between methotrexate and trimethoprim and what do they cause

A

Dihydrofolate reductase enzyme inhibitors folate deficiency (bone marrow supression)

52
Q

Steps when DDI

A

Understand pharmacolgoy
Avoid combination - alternative
Adjust dose
Monitor therapy - clinical (signs), therapeutic eg drug conc, measure marker for interaction eg U+Es
Continue medication

53
Q

What antibiotics increase effect of warfarin and shld be avoided

A

Erythromycin
Metronidazole

54
Q

What drugs that increase bleeding risk (GI) avoid with warfarin

A

Aspirin or NSAIDs
PPI cover

55
Q

What antibiotics increase effect of CBZ and what do when given

A

Erythromycin, clarithromycin, fluconazole

56
Q

What do you do when NSAID/diuretic is prescribed with lithium and why

A

Decrease lithium dose by 50% They increase Li levels in blood (confuse with sodium in tubules and retain)

57
Q

What drugs avoid with COCP as makes ineffective

A

Carbamazepine
Rifampacin
Can increase dose of

58
Q

What drugs can interact with SSRIs and cause serotonin syndrome or hypertensive crisis

A

St Johns Wort
Triptans
MAOI

59
Q
A

errors and drugs (8 decks)

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