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LCRS Pharmacology and Therapeutics > Adverse drug reactions > Flashcards

Adverse drug reactions Flashcards

1
Q

What is the definition of an adverse drug reaction?

A

Preventable or unpredicted medication event with harm to the patient

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2
Q

What are ARDs classified on?

A

Onset
Severity
Type

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3
Q

How are ARDs classified based on onset?

A

Acute- within 1 hour
Sub-acute- 1 t o24 hours
Latent- >2 days

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4
Q

How are ARDs classified based on severity?

A

Mild- requires no change in therapy
Moderate- requires changes in therapy, additional treatment and hospitalisation
Severe- disabling or life threatening

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5
Q

What is a type A ADR?

A

Extension of the pharmacologic effect

Usually predictable and dose-dependent

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6
Q

What is the most common type of ADR?

A

Type A- it is responsible for at least 2/3s of ADRs

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7
Q

Give some examples of Type A ADRs

A

Atenolol will slow the heart down but if you give too much of it, it may cause complete heart block
Chronic use of NSAIDs can cause peptic ulcers

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8
Q

What is a type B ADR?

A

Idiosyncratic or immunologic reactions
Include allergy and pseudo allergy
Rare and unpredictable

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9
Q

Give some examples of type B ADRs?

A

Chloramphenicol can cause aplastic anaemia

ACE inhibitors can cause angioedema

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10
Q

What is a type C ADR?

A

Associated with long-term use

Involves dose accumulation

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11
Q

Give some examples of type C ADRs?

A

Methotrexate- liver toxicity

Antimalarials- ocular toxicity

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12
Q

What is a type D ADR?

A

Delayed effects- sometimes dose independent

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13
Q

Give some examples of type D ADRs?

A

Carcinogenicity- e.g. immunosuppression

Teratogenicity- e.g. thalidomide

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14
Q

What is a type E ADR?

A

Withdrawal reactions
Rebound reactions
Adaptive reactions

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15
Q

Give some examples of type E ADRs?

A

Withdrawal- opiates, benzodiazepines and corticosteroids
Rebound reactions- Clonidine, beta blockers and corticosteroids
Neuroleptics

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16
Q

What is clonidine used for and how does it have an effect?

A

Used as an anti-hypertensive- it is an alpha 2 agonist meaning that it reduces the release of noradrenaline from sympathetic neurones which leads to drop in blood pressure

17
Q

What can happen if you miss one or two doses of clonidine?

A

It could lead to a substantial increase in blood pressure

18
Q

How does the clonidine rebound occur?

A

Long term use of clonidine causes long term suppression of peripheral noradrenaline production which in turn leads to compensatory upregulation in adrenergic receptors on post-synaptic neurone
This upregulation in receptors means that when the inhibition of NA release by clonidine is removed, NA starts being produced again and has more receptors to act on and can cause a much greater effect > rise in BP

19
Q

What is the ABCDE classification?

A 
Augmented pharmacological effect
Bizarre
Chronic
Delayed
End of treatment
20
Q

What is the classification of allergies?

A

Type I- immediate, anaphylactic (IgE) e.g. anaphylaxis with penicillin
Type II- Cytotoxic antibody (IgG and IgM)
e.g. methyldopa and haemolytic anaemia
Type III- serum sickness (IgG and IgM)
e.g. procainamide induced lupus
Type IV- delayed hypersensitivity (T cell)
e.g. contact dermatitis

21
Q

What can aspirin/NSAIDs cause and how in terms of pseudoallergies?

A

Bronchospasm- they are inhibiting the production of prostanoids which are generally bronchodilators
Accompanied by increase in leukotriene production- generally bronchoconstrictors

22
Q

What do ACE inhibitors cause in about 20% of patients?

A

Cough- they stop the breakdown of kinins- these are present in the sensory nerves of the lungs. If it accumulates it causes coughing

23
Q

What common causes of ADRs are there?

A 
Antineoplastics
Cardiovascular drugs
NSAIDs/analgesics
CNS drugs
(Above 4 account for 2/3 of fatal ADRs)
Antibiotics 
Anticoagulants
Hypoglycaemic
Anti-hypertensives
24
Q

How are ADRs detected?

A 
Subjective report- patient complaint
Objective report- observation of event
Abnormal findings:
Physical examination
Laboratory test
Diagnostic procedure
25
Q

What is the yellow card scheme?

A

System for reporting adverse drug reactions

26
Q

What does additive effect mean in terms of drug interactions?

A

Two drugs add together

27
Q

What does synergistic effect mean in terms of drug interactions?

A

Two drugs potentiate each other’s actions to get a greater effect than expected
Antagonist effects- drugs that antagonise each others’ actions

28
Q

How can drug interactions alter absorption?

A

Chelation
Irreversible binding of drugs in the GI tract makes it difficult to absorb
e.g. tetracycline, quinolone, antibiotics, dairy products

29
Q

How do drug interactions affect protein binding effects?

A

Competition between drugs for protein or tissue binding sites
Increase in free (unbound) concentration may lead to enhanced pharmacological effects e.g. warfarin

30
Q

How do drug interactions affect drug metabolism?

A

It could be inhibited or enhanced by coadministration of other drugs. Some are metabolised by a single isozyme, most are metabolised by multiple isozymes

31
Q

Why is being metabolised by multiple isozymes useful?

A

If one of the isozymes is inhibited, the other isozymes could increase their activity to compensate for inhibited isozyme

32
Q

Which CYP450 isozymes do over half of drug metabolism?

A

CYP2D6 and CYP3A4

2D6 shows a great degree of variability

33
Q

Give some examples of CYP450 inhibitors

A 
Cimetidine (H2 antagonist)
Erythromycin and related antibiotics
Ketoconazole
Ciprofloxacin and related antibiotics
Ritonavir and the rHIV drugs
Fluotexine and other SSRIs
Grapefruit juice
34
Q

Give some examples of CYP450 inducers

A

Rifampicin
Carbamazepine
St John’s Wort (hypericin)

35
Q

How does the onset of inhibition and induction differ?

A

Inhibition- rapid

Induction- takes hours/days (need to produce new gene products/proteins)

36
Q

How does ADR risk change with increasing number of drugs?

A

It increases

LCRS Pharmacology and Therapeutics (33 decks)

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