Adverse Drug Reactions

Question 1

What are adverse drug events

Answer 1

Preventable or unpredictable medication events with harm to the patient - due to medication errors and adverse drug reactions

Question 2

What are ADRs classifications based on?

Answer 2

Onset, Severity and Type

Question 3

What is a severe severity ADR

Answer 3

Disabling, life threatening, prolongs hospitalisation, causes congenital abnormalities, requires intervention to prevent further injurty

Question 4

What is a moderate severity ADR

Answer 4

Change in therapy required, additional treatment and hospitalisation

Question 5

What are different stages of onset ADR classification

Answer 5

onset: acute <1hr, subacute 1-24hr, latent >2 days
severity: mild, moderate, severe

Question 6

What is a type A ADR

Answer 6

Augument/extend the pharmacological effect: usually predictable and dose dependent and represents 2/3 of ARDs. Paracetamol has a threshold below which it has minimal side effects and then exceeding this the side effects rapidly increase and digoxin has dose dependant line for example

Question 7

What is a type B ADR

Answer 7

Bizarre - idiosyncratic or immunological reaction that is unpredictable, rare and includes allergy and ‘pseudo-allergy’ eg chloramphenicol, aplastic anaemia, ACE inhibitors, angiodema

Question 8

What is a type C ADR

Answer 8

Chronic - long term use side effects involving dose accumulation eg methotrexate and liver fibrosis

Question 9

What is a type D ADR

Answer 9

Delayed - delayed effects eg carcinogenicity (immunosuppressants) or teratogenicity (thalidomide)

Question 10

What is a type E ADR

Answer 10

End of treatment side effects eg withdrawal reactions, rebound reactions, adaptive reactions

Question 11

What is a withdrawal reaction? Give examples of drugs that cause this

Answer 11

Patient cannot make endogenous supply - opiates, corticosteroids and benzodiazepines are drugs that can cause this

Question 12

What is a rebound reaction? Give examples of drugs that cause this

Answer 12

Disease gets worse when drugs are stopped eg clonidine, beta blockers, corticosteroids.

Question 13

What are adaptive reactions? Drugs examples?

Answer 13

Adapted body reactions to drugs eg neuroleptics (tranquilisers)

Question 14

What are the different types of allergic reactions?

Answer 14

Type 1 – immediate, anaphylactic. IgE E.G. anaphylaxes with penicillin.
Type 2 – cytotoxic antibody. IgG, IgM E.G. methyldopa and HA.
Type 3 – serum sickness (antibody-antigen complex). IgG, IgM E.G. procainamide-induced lupus.
Type 4 – delayed-type hypersensitivity T-Cell E.G. contact dermatitis.

Question 15

What are examples of immunological ‘pseudo allergies’ - type B ADRs

Answer 15

Aspirin/NSAIDs cause bronchospasm: aspirin/nsaid inhibit COX so less prostaglandin synthesis and more leukotrienes made
ACE inhibitors -> cough/angiodema: ACEi inhibit production of AngII and stops the breakdown of inflammatory mediators such as bradykinin which stimulate the cough receptors of the lungs

Question 16

What are common causes of ADRs

Answer 16

• antineoplastics - cytotoxic drugs
• cardiovascular drigs
• NSAIDs/analgesics
• CNS drugs
  ^main 4
• Antibiotics
• Anticoagulants
• Hypoglycaemic
• Antihypertensives

Question 17

How does drug use affect ADR frequency

Answer 17

Increased individual drug use increases ADR frequency

Question 18

How are subjective reports of ADRs detected

Answer 18

The patient complaints are put on a yellow card system

Question 19

How are objective reports of ADRs detected

Answer 19

Direct observations of events and abnormal findings eg physical examination, lab tests and diagnostic features however rare events probs not found until after drug is marketed

Question 20

What is the yellow card scheme

Answer 20

A scheme introduced after thalidomide where it can be used voluntarily by any healthcare professional and includes bloods, vaccines and contrast media in order to report ADRs

Question 21

Why is drug drug interaction incidence difficult to ascertain?

Answer 21

• data for drug related hospital admissions do not differentiate out drug interactions, only ADRs
• lack of available comprehensive databases
• difficulty in assessing OTC drug use
• difficulty in determining drug contributions to interaction sin complicated patients
• sometimes the principle cause of ADRs is with specific drugs eg statins

Question 22

What is pharmacodynamics

Answer 22

Drugs effect on body eg receptor site dynamics leading to additive, synergistic, or antagonistic effects from coadministration

Question 23

What is pharmacokinetics

Answer 23

Body’s effect on the drug eg absorption, distribution, metabolism, excretion

Question 24

What are synergist actions of antibiotics

Answer 24

Use of two ABs will increase the effect of more than their seperate contributions OR they will antagonise each other

Question 25

What are two drugs that have overlapping toxicity

Answer 25

Ethanol and benzodiazepines

Question 26

What is chemiation

Answer 26

Irreversible binding in the GI tract for example, antibiotics to metal ions or calcium to form chelates that prevent absorption of the antibiotic

Question 27

What is a clinically significant example of protein binding interactions affecting pharmacokinetics

Answer 27

Warfarin is 99% albumin bound so anything to decrease that will increase the free warfarin so there is more anti coagulative effects

Question 28

What are the different ways drugs can undergo metabolism and then be excreted

Answer 28

They can either (1) be directly excreted, (2) undergo Ph1 metabolism and be excreted, (3) undergo Ph1 and Ph2 and then be excreted or (4) only undergo Ph2 and then be excreted

Question 29

What are pharmaceutical drug interactions

Answer 29

Drug interactions outside the body ie IV injections

Question 30

What are reactions in phase 1 metabolism

Answer 30

Oxidation, reduction, hydrolusis

Question 31

What are the reactions in phase 2 metabolism

Answer 31

conjugation (glutathione, amino-acid), glucuronidation, sulphation, acetylation and methylation

Question 32

Why can coadministration of a CYP450 inhibitor not affect metabolism rate?

Answer 32

Some isoenzymes can pick up the slack for the inhibited isoenzyme

Question 33

What are inhibitors of CYP450

Answer 33

``` Cimetidine Ciprofloxacin (and other related ABs) Fluoxetine (and other SSRIs) Erythromycin (and related ABs) Ritonavir (and other HIV drugs) Ketonazole Grapefruit juice ```

Question 34

What are inducers of CYP450

Answer 34

``` Rifampicin Phenobarbitone Carbamezepine Phenytoin St John's wort (hypericin) ```

Question 35

What are good drug elimination reactions?

Answer 35

Probenecid and penecillin where probenecid reduces excretion of penecillin and penecillin used to be expensive

Question 36

What is a bad drug elimination reaction

Answer 36

Lithium and thiazides where thiazides lead to toxic accumulation of lithium

Question 37

Where do drug elimination reactions almost always occur

Answer 37

In renal tubes

Question 38

What are examples of deliberate drug elimination reactions

Answer 38

- Levodopa + carbidopa can use lower doses of levodopa as carbidopa reduced peripheral metabolism. - ACEi + thiazides treat HF. - Penicillin’s + gentamycin treat severe staph. Infections. - Salbutamol + ipratropium beta-agonists and anti-muscarinics used in inhalers to treat asthma.