Drug toxicity

Question 1

Side effects

Answer 1

Effects of a drug that are not intended/adverse drug reactions - occur within therapeutic doses

Question 2

Drug toxicity

Answer 2

Harmful effects at therapeutic doses

Question 3

Augmented toxicity

Answer 3

Exaggeration of a drug’s normal effects when given at usual therapeutic dose - it is dose dependent

Question 4

Bizarre toxicity

Answer 4

Unexpected side effects

Question 5

Adverse effect of acetylcholinesterase inhibitors

Answer 5

Muscle weakness

Question 6

Adverse effect of B-adrenoreceptor antagonists

Answer 6

Heart block

Question 7

Adverse effect of general anaesthetics

Answer 7

Medullary depression

Question 8

Adverse effect of loop diuretics

Answer 8

Hypokalaemia

Question 9

Toxic response to aspirin

Answer 9

Tinnitus, metabolic acidosis

Question 10

Toxic response to carbamazepine

Answer 10

Drowsiness, visual changes

Question 11

Toxic response to digitoxin/digoxin

Answer 11

Bradycardia, nausea

Question 12

Toxic response to gentamicin

Answer 12

Otoxicity, renal toxicity

Question 13

Toxic response to phenytoin

Answer 13

Nystagmus, lethargy

Question 14

Toxic response to theophylline

Answer 14

Tremor, nervousness

Question 15

Antidote for paracetamol overdose

Answer 15

Acetylcysteine

Question 16

Immunogenic toxicity

Answer 16

• type of drug allergy
• LMW compounds can’t elicit allergic response themselves so bond with a macromolecule
• This conjugate is recognised as a foreign antigen
• T1 is immediate and IgE mediated e.g. penicillins
• T2 is cytotoxic - antigens on cell membrane, IgG/M/A activates complement and initiates cell lysis - e.g. thromcytopaenia (quinine)
• T3 occurs in serum when the complex is deposited on endothelial cells e.g. penicillins
• T4 is delayed and happens in the skin when sensitised T cells cause inflammation e.g. contact dermatitis

Question 17

Selective toxicity

Answer 17

Drugs like chemotherapy drugs that are toxic by design

Question 18

How does acetylcysteine work?

Answer 18

Acetylcysteine replenishes glutatione to reverse paracetamol overdose

Question 19

Stages of drug development

Answer 19

• Pre-clinical studies: basic pharmacology and toxicology profiles
• Phase 1 trials: pharmacokinetics, tolerability and side effects on small group of human subjects
• Phase 2 trials: people with the disease in question are used, investigate dose-response relationship and dosage protocol
• Phase 3 trials: RCT with thousands of participants
• Pharmacovigilance: long-term, ongoing monitoring of rare side effects

Question 20

Toxicity testing

Answer 20

• Acute toxicity: immediate side effects
• Subacute toxicity: side effects occurring within weeks
• Chronic toxicity: life-span of rats side effects

Question 21

Antidote for heparin toxicity

Answer 21

Protamine

Question 22

Activated charcoal

Answer 22

• Adsorbent
• Retained in GI lumen
• 10g charcoal/1g drug
• 50g dose 4hrly up to 24/36hours
• Overdose of carbamazepine/quinine/theophylline

Question 23

Why does aspirin overdose make you dehydrated?

Answer 23

Aspirin overdose makes body acidic = higher respiration rate to excrete more co2, kidneys excrete bicarbonate but also lose sodium and potassium → dehydrated

Question 24

Antidote for benzo overdose

Answer 24

flumenazil

Question 25

How does acetylcysteine work?

Answer 25

replenishes glutathione in paracetamol overdose (metabolism modifier)