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principles of disease > drug interactions > Flashcards

drug interactions Flashcards

1
Q

define drug interaction

A

modification of a drug’s effect by prior or concomitant administration of another drug/herb/food/drink

occurs when the pharmacological effect of 2 or more drugs given together isnt just a direct function of their individual effects

aren’t always detrimental

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2
Q

type of drug interactions

A 
drug-drug
herbal-drug
food-drug
drink-drug
pharmacogenetic interactions
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3
Q

the object drug

A

the drug whose activity is affected by the interaction

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4
Q

the precipitant

A

the agent which precipitates such an interaction

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5
Q

factors that can modify drug action

A

food, smoking, alcohol and herbs as well as other drugs

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6
Q

epidemiology of drug-drug interactions

A

2.3-3.0% of hospital patients
9.2-70% of GP patients
significant interactions - 1%

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7
Q

drugs involved with serious interactions

A

potent with a narrow therapeutic index - small change in blood levels can induce profound toxicity
e.g. lithium, digoxin, warfarin, erythromycin

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8
Q

foods that interact with warfarin

A

vegetables: asparagus, broccoli, cabbage, onions
herbals: ginseng, green tea
misc: avocado, fish oils, liver

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9
Q

susceptible patients to drug-drug interactions (5)

A
  • polypharmacy
  • elderly and young
  • critically ill
  • undergoing complicated surgical procedures
  • chronic conditions: liver disease, renal impairment, diabetes, epilepsy, asthma
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10
Q

mechanism of drug interactions (3)

A

pharmaceutical
pharmacokinetic
pharmacodynamic

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11
Q

pharmacokinetic drug interactions

A

ADME
one drug can alter the ADME of another drug
there is marked inter-individual variation in these processes - possible to predict potential interactions but not in which patient

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12
Q

types of pharmacodynamic interactions (5)

A

antagonistic
additive/synergistic
interactions due to changes in drug transport
interactions due to fluid and electrolyte disturbance
indirect interactions

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13
Q

mechanisms of absorption interactions (4)

A

formation of insoluble complexes
altered pH
altered bacterial flora
altered gut motility

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14
Q

absorption interactions: interaction in the GI tract

A
  • complex
  • most interactions result in changes in absorption rate (rather than extent of absorption)
    delayed absorption is important when a drug has a short half life or when we want high plasma levels rapidly
    moset interactions result in delay in absorption and can be avoided if 2-4 hrs are left between administration of the drugs
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15
Q

absorption interactions: drug binding in the GI tract

A

some drugs bind to each other in the GI tract
e.g. tetracycline and erythromycin complex bind with Fe, Ca and Mg
cholestyramine resin used to bind cholesterol in the GI tract also binds to a variety of drugs e.g. warfarin

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16
Q

absorption interactions: changes in pH

A
  • absorption is affected by the degree of ionisation which is dependent on pH
    H2 agonists, proton pump blockers and antacids reduce H+ and so increase pH
17
Q

absorption interactions: changes in bacterial flora

A

usually found in the large bowel
broad spectrum antibiotics destroy normal gut flora
may lead to failure of OCP

18
Q

absorption interactions: GI motility

A

most oral medicines are absorbed in the S intestine
gastric emptying is the rate limiting step
many drugs delay gastric emptying (anticholinergics tricyclic anti-depressants, opiates) and some increase it and accelerate absorption of paracetamol

19
Q

distribution interactions

A

protein binding displacement occurs when there is a reduction in the extent of plasma protein binding of a drug caused by the presence of another drug
results in increased bioavailability of the displaced drug
only the unbound drug is pharamcologically active
common interaction but patients are protected by increased metabolism and excretion
significant in drugs with >95% plasma protein binding (narrow therapeutic window)

20
Q

metabolism interactions

A

occur when one drug induces or inhibits the metabolism of another
drugs (such as erythromycin, clarithromyciin, cimetidine etc) inhibit the cytochrome system
some drugs can also induce the C P450

21
Q

metabolism commonly occurs in the …

A

liver via the cytochrome P450 system

22
Q

metabolism interactions: inhibition of the cytochrome P450 system

A

these drugs inhibit the metabolism of a small group of drugs metabolism by the C P450 system:
cimetidine = warfarin, diazepam
metronidazole = warfarin, alcohol
omeprazole = phenytoin, warfarin

23
Q

metabolism interactions: inducers of cytochrome P450 system

A
  • Drugs such as barbiturates, carbamazepine, phenytoin, rifampicin and tobacco smoke are potent inducers of cytochrome P450
  • The effects of enzyme induction aren’t seen for 2-3wks
  • The effects of induction depend on age, disease, genetics and concurrent drug therapy
24
Q

metabolism interactions: common examples of inducers of cytochrome P450 system (drugs)

A

phenytoin: warfarin, steroids, OCP
rifampicin: warfarin, OCP

25
Q

elimination/excretion interactions

A

most drugs are excreted in urine/bile

changes in GFR or tubular secretion with effect excretion

26
Q

elimination/excretion interactions: examples

A
  • Digoxin and lithium are toxic agents that are eliminated by the kidney - Verapamil/diltiazem and digoxin (CCBs inhibit excretion)
  • Loop diuretics and lithium (loop diuretics increased tubular reabsorption)
27
Q

what are pharmacodynamic interactions

A

occurs when the pharmacodynamic actions of a drug are changes due to presence of another drug acting directly on the same receptor or indirectly on different receptors

28
Q

types of pharmacodynamic interactions

A 
direct 
indirect - agonism 
antagonistic - direct/indirect 
synergistic 
additive/multiplicative
29
Q

pharmacodynamic interactions: indirect agonism

A

CNS depression, benzodiazepines and tricyclics or alcohol, warfarin and NSAIDs (indomethacin), atenolol and verapamil

30
Q

pharmacodynamic interactions: direct antagonism

A

beta blockers such as atenolol will block actions of agonists e.g. bronchodilators such as salbutamol

31
Q

pharmacodynamic interactions: indirect antagonism

A

NSAIDs and antihypertensive medication

NSAIDs and treatment for heart failure

32
Q

pharmacodynamic interactions: synergistic

A

when 2 drugs with the same pharmacological effect acting on the same receptor are given concurrently

33
Q

which CP450 is responsible for the genetic variation in the metabolism of warfarin

A

CYP2C9

34
Q

rifampicin increases metabolism of ciclosporin by inducing …

A

CYP3A4

35
Q

St John’s wort increases metabolism of ciclosporin by induing

A

CYP3A4

principles of disease (40 decks)

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