Adverse drug reactions and Drug-drug interactions

Question 1

what are the different types of ADRs

Answer 1

Type A: Augmented Pharm. effect(Usually predictable and
dose dependant eh NSAIDs and Peptic ulcers
Type B: Bizarre or Idiosyncratic or Immunologic reactions
(Unpredictable, rare, and include allergy and
“pseudo-allergy”)
Type C: Chronic- long term use side effects- involves dose
accumulation (eg certain drugs and liver fibrosis)
Type D: Delayed- eg: carcinogens (with
immunosurpressants), teratogens (thalidomide)
Type E: End of treatment side effects:
-withdrawal- eg benzodiazepines
- rebound ie gets worse when drugs stopped (B-bloc
-adaptive reactions eg neuroleptics

Question 2

define an ADR

Answer 2

preventable or unpredicted medication events with harm to the patient

Question 3

how are ADRs classified

Answer 3

o Onset:
  -acute <1h
  -subacute 1-24h
  -latent: >2days
o severity:
  -mild: no change in treatment needed
  -moderate: change in therapy, add therapy, hospitaisatio
  -severe: disabling/life threatening- requires intervention
o type: (ABCDE)

Question 4

give an example of a pseudo-allergy

Answer 4

NSAIDS and bronchospasm (perhaps in asthma)

Question 5

what are the different types of drug-drug interactions

Answer 5

synergistic: ie potentiate each other effects (more than just adding their effects together)- 2 Anti biotics

overlapping toxicity eg ethanol and benzodiazepines

antagonistic effects

alteration in absorption: CHELATION ie irreversible binding in GI tract to metal ions (IRON and CALCIUM)

protein binding interactions- if two drugs both bing to one plasma protein, one will be displaced and therefore more will be in plasma=increased effect (important in WARFARIN)

drug metabolism/excretion: drugs could inhibit/induce enzymes involved in metabolism of other drugs

Question 6

what’s the main system involved in drug metabolism

Answer 6

CYP450 (most drugs can be metabolised by multiple isozymes and few only by one so inhibitors may have little effect as other isozymes can pick up the slack)

Question 7

what are the main CYP450 inducers

Answer 7

Rifampicin (antibiotic)
Carbamazepine (anticonvulsant or anti-epileptic drug)
St John’s Wort (hypericin is the compound that induces CYP450)- herbal product

takes hours/days (because we are waiting for new CYP450 to be synthesised)

Question 8

what are the main CYP450 inhibitors

Answer 8

-Erythromycin (macrolide antibiotics) and related antibiotics
-Cimetidine ( histamine H2 receptor antagonist that inhibits stomach acid production.)
-Fluoxetine and other SSRIs (Selective serotonin reuptake inhibitors )
-grapefruit juice
-Ritanovir and other HIV drugs
very rapid onset

Question 9

whats phase 1 metabolism

Answer 9

Oxidation, Reduction, Hydrolysis.

Question 10

whats phase 2 metabolism

Answer 10

Conjugation, Glucuronidation, Sulphation, Acetylation.

Question 11

whats the purpose of phase 1 and 2 metabolism

Answer 11

make the drug more POLAR – easier to excrete by kidneys

Question 12

what are the main isozymes in CYP450 (first two are probs most relevant)

Answer 12

CYP3A4, CYP2D6, CYP1A2, CYP2B6, CYP2C9, CYP2C19

Question 13

how can enzyme inducers cause ADRs

Answer 13

the drug will be metabolised faster so the effect will not last very long or if a pro drug is given there will be increased production of an active metabolite.

Question 14

How can enzyme inhibitors cause ARDs

Answer 14

drug not metabolised as quickly so increased and prolonged effect may result
or if it is a prodrug that was given it may not be turned into its active form
Accumulation of the compound in the body-bad

Question 15

what factors can affect ADRs

Answer 15

age
polypharmacy (use of multiple meds)
diet (eg grapefruit juice, vitamins and calcium )
renal function (decreased excretion)