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Pharm > Adverse reactions to drugs > Flashcards

Adverse reactions to drugs Flashcards

1
Q

Define adverse drugs event

A

preventable or unpredicted medication event—with harm to patient

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2
Q

ADR can be classified according to what

A

Onset
Severity
Type

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3
Q

Classify ADR according to onset of event

A 
Acute 
Within 1 hour
Sub-acute 
1 to 24 hours
Latent 
>  2 days
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4
Q

Classify ADR according to severity

A 
Severity of reaction:
Mild
requires no change in therapy
Moderate
requires change in therapy, additional treatment, hospitalisation 
Severe
disabling or life-threatening
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5
Q

What might be the consequences of a sever ADR

A

Results in death

Life-threatening

Requires or prolongs hospitalisation

Causes disability

Causes congenital anomalies

Requires intervention to prevent permanent injury

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6
Q

Outline type A ADR

A

extension of pharmacologic effect

usually predictable and dose dependent

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7
Q

Give examples of type A ADR

A

e.g., atenolol and heart block, anticholinergics and dry mouth, NSAIDS and peptic ulcer

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8
Q

Differentiate the ADR with paracetemol and digoxin

A

Digoxin the ADR steadily increases, throughout the therapeutic window

With paracetemol, there is low ADR throughout the therapeutic window, but dramatically increases following even a small amount over the therapeutic dose

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9
Q

Outline type B ADR

A

idiosyncratic or immunologic reactions

includes allergy and “pseudoallergy”

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10
Q

Give examples of type B ADR, including pseudoallergy

A

e.g., chloramphenicol and aplastic anemia,

PSEUDOALLERGY: ACE inhibitors and angioedema

Aspirin/NSAIDs – bronchospasm

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11
Q

Differentiate the commonality of type A and type B ADR

A

A- 2/3 of ADR

B- very rare and unpredictable

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12
Q

Outline type C ADR

A

associated with long-term use

involves dose accumulation

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13
Q

Example of type C ADR

A

e.g., methotrexate and liver fibrosis, antimalarials and ocular toxicity

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14
Q

Give an example of acute onset ADR

A

Anaphylaxis

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15
Q

Outline type D classification of ADR

A

delayed effects (sometimes dose independent)

carcinogenicity

teratogenicity

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16
Q

Type D. What is carcinogenecity. Give an example

A

Cancer causing (immunosuppressant)

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17
Q

Type D what is teratogenecity. Give an example

A

Damage to foetus… thalidomide

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18
Q

Outline type E reactions

A

Withdrawal reactions

Rebound reactions

“Adaptive” reactions
`

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19
Q

Give examples of withdrawal reaction (type E)

A

Opiates (cold turkey), benzodiazepines (can lead to fitting), corticosteroids

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20
Q

Give examples of rebound reactions (type E)

A

Clonidine, beta-blockers, corticosteroids

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21
Q

Give example of adaptive reactions

A

Neuroleptics (major tranquillisers)

Movement reactions (i.e. the EPS)

reactions don’t go away when you remove the drug, and can get worse

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22
Q

When are antimalarial drugs given

A

In some rheumatic disease

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23
Q

Outline rebound reactions with clonidine

A

BP reduces during

But missing a couple of doses results in rebound

You end up worse than before you started

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24
Q

Memoire for dverse drug reactions

A 
A     Augmented pharmacological effect
B	Bizarre
C	Chronic
D	Delayed
E	End-of-treatment
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25
Q

Classify the 4 hypersensitivity reactions

A

I- Immediate, anaphylactic

II- cytotoxic antibody (IgG, IgM)

III- serum sickness (IgG, IgM)

IV- delayed hypersensitivity (T cell)

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26
Q

Give an example of a drug allergy associated with each hypersensitivity type

A

I- anaphylaxis with penicillins

II- methylopa and haemolytic anaemia

III- procainamide-induced lupus

IV- contact dermatitis

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27
Q

……

A

…..

28
Q

…..

A

…….

29
Q

…..

A

……

30
Q

Give examples of pseuoallergies

A

Aspirin/NSAIDs – bronchospasm

Block COX and thus prostanoids….. more leukotrienes produced.

They are pro-inflammatory and bronchoconstrictor

Only happens in a minority of patients, but NSAIDs not used

ACE inhibitors – cough/angioedema

Pharmacoloical… due to build of bradykinin which causes cough, swelling of tongue, lips, etc.

Bradykinin is pro-inflammatory.

Not in everyone (ethnic differences)

THESE ARE PHARMACOLOGICAL NOT ALLERGIC

31
Q

Which drugs are most common cause of ADRs

A

Antineoplastic, CVS, NSAIDs/Analgesics, CNS drugs

account for 2/3 of fatal ADRs

Also: 
ABs, 
Anticonvulsants, 
Hypoglycaemics, 
Antihypertensives

are common causes of ADRs

32
Q

All cuases of ADR

A 
Antibiotics
Antineoplastics*
Anticoagulants
Cardiovascular drugs*
Hypoglycemics
Antihypertensives
NSAID/Analgesics*
CNS drugs*
33
Q

Why is there lots of ADR with CVS and CNS drugs

A

Cos so many take them

34
Q

What causes increase in ADR

A

Giving more drugs

35
Q

How are ADR detected

A

Subjective report
-patient complaint

Objective report:

  • direct observation of event
  • abnormal findings
36
Q

What abnormal findings might help with ADR

A

physical examination
laboratory test
diagnostic procedure

37
Q

What is the problem with ADR detection

A

Stastically, large numbers needed to detect rare events

1 in 100 needs 300 to detect
1 in 100 X 3 needs 650 people to detect

ie rare events will probably not be detected before
drug is marketed

38
Q

What is the yellow card scheme

A

for established drugs only report serious adverse reactions
(fatal, life-threatening, needing hospital admission, disabling)

for “black triangle “ drugs (newly licensed, usually <2 years) report any suspected adverse reaction

39
Q

Who can yellow card scheme be used by

A

can be used by doctors, dentists, nurses, coroners and
pharmacists, and members of the public

voluntary

40
Q

What should happen if ADR is suspected

A

Should be confirmed (high probability)

Estimate frequency

Inform prescribers

41
Q

Why is it hard to work out drug drug interactin

A

Data for drug-related hospital admissions do not separate out drug interactions, focus on ADRs

Lack of availability of comprehensive databases

Difficulty in assessing OTC and herbal drug therapy use

Difficulty in determining contribution of drug interaction in complicated patients

Sometimes principal cause of ADRs with specific drugs
eg statins

42
Q

Outline the three types of drug interactios

A

Pharmacodynamic
Related to the drug’s effects in the body

Pharmacokinetic
Related to the body’s effects on the drug

Pharmaceutical
- drugs interacting outside the body (mostly
IV infusions)

43
Q

What does pharmacodynaic drug interaction relate to

A

Related to the drug’s effects in the body

Receptor site occupancy

44
Q

What does pharmacokinetic drug interaction relate to

A

Related to the body’s effects on the drug

Absorption, distribution, metabolism, elimination

45
Q

Outline pharmacodynamic drug interactions

give examples

A

Additive, synergistic, or antagonistic effects from co-administration of two or more drugs

Synergistic actions of antibiotics

Overlapping toxicities - ethanol & benzodiazepines

Antagonistic effects - anticholinergic medications (amitriptyline and acetylcholinesterase inhibitors)

46
Q

…..

A

…

47
Q

….

A

….

48
Q

What are the pharmacokinetic drug interactions

A

Alteration in absorption

Protein binding effects

Changes in drug metabolism

Alteration in elimination

49
Q

Give an example of alterations in absorptions as a cuase of drug drug interactions

A

Chelation
Irreversible binding of drugs in the GI tract

Tetracyclines, quinolone antibiotics (i.e. those used for COMPLICATED gastric ulcer!!!)

can bind to:

  • ferrous sulfate (Fe+2), - antacids (Al+3, Ca+2, Mg+2),
  • dairy products (Ca+2)

So that you absorb less of these ions and you absorb NO antibiotic!

50
Q

Outline protein binding interactions

A

Competition between drugs for protein or tissue binding sites
Increase in free (unbound) concentration may lead to enhanced pharmacological effect

51
Q

Why have protein binding interactiosn been overestimated

A

Many interactions previously thought to be PB interactions were found to be primarily metabolism interactions
PB interactions are not usually clinically significant

but a few are

52
Q

Give an example of a clinically significant protein binding interactions

A

PB interactions are not usually clinically significant

but a few are (mostly with warfarin)

53
Q

How can a drug be handled by the kidney

A
  1. Excreted unchanged by kidney (furesomide)
  2. Phase 1 reaction in liver / kidney. Excreted OR in kidney:
  3. Phase 2 reaction (with or without previous phase 1) nand excreted by kidney
54
Q

Examples of phase 1 metabolism

A

Oxidation
Reduction
Hydrolysis

55
Q

T/F Phase I must happen before Phase II

A

F

56
Q

Examples of phase II metabolism

A

Conjugation:

Glucoronidation
Sulphation
Acetyation

57
Q

Outline drug metaboism interactions

A

Drug metabolism inhibited or enhanced by coadministration of other drugs

Phase 2 metabolic interactions (glucuronidation, etc.) occur, research in this area is increasing

58
Q

T.f most drugs are metabolised by a single isoenzyme predominantly

A

Few examples of clinically used drugs
Examples of drugs used primarily in research on drug interactions

Most drugs metabolized by more than one isozyme

59
Q

What is the problem with targeting CYP 450

A

If co-administered with CYP450 inhibitor, some isozymes may “pick up slack” for inhibited isozyme

60
Q

Give examples fof CYP 450 inhibitors

A

Cimetidine

Erythromycin and related antibiotics

Ketoconazole etc

Ciprofloxacin and related antibiotics

Ritonavir and other

HIV drugs

Fluoxetine and other SSRIs

Grapefruit juice

61
Q

Give examples of CYP 450 inducers

A

The “usual suspects”
Rifampicin

Carbamazepine

(Phenobarbitone)

(Phenytoin)

St John’s wort (hypericin)

62
Q

Differentiate change in CYP450 activity

A

Inhibition is very rapid… due to enzyme inhibiton

Induction takes hours/days (new enzyme synthesis and protein making etc.)

63
Q

Outline the drug elimintation interactions with examples

A

Almost always in renal tubule

  • probenecid and penicillin (good),
  • lithium and thiazides (bad)
64
Q

Explain - probenecid and penicillin (good)

A

Good

Giving probenecid with penicillin allows you to give smaller doses of penicillin as the probenecid reduces elimintation of the penecillin

65
Q

Exmplain - lithium and thiazides (bad)

A

the thiazide will increase the excretion of sodium at the expense of the lithium

Lithium retained and circulating levels increased

66
Q

Give examples of deliberate drug interactions

A

levodopa + carbidopa

salbutamol + ipratropium

ACE inhibitors + thiazides

penicillins + gentamicin (particulary staphylococcal)

Pharm (33 decks)

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