drug toxicity

Question 1

definition of drug toxicity

Answer 1

Drug toxicity definition –
Side effects are effects of a drug that are not the intended effects – some well know some are not also called adverse effects. These tend to occur within therapeutic doses( normal range)
Drug toxicity is reserved for effects seen at very high doses way above the the therapeutic doses and also the harmful effects at therapeutic doses due to mechanism of action such as cancer drugs

Question 2

augmented

Answer 2

over sedation or over suppression

Question 3

bizarre

difference between minimum effective and max tolerance dose

Answer 3

happen at any dose prior to exposure

Minimum effective dose is when you start to see a reponse
Maximum tolerated ose beyond which see side ffects

Question 4

adverse effect of loop diuretics

Answer 4

hypokalaemia

bED50 effective dose 50
LD50 – lethal dose 50

Question 5

what does a narrow therapeutic index mean

Answer 5

Narrow therapeutic index drugs are drugs where small differences in dose or blood concentration may lead to serious therapeutic failures and/or adverse drug reactions that are life-threatening or result in persistent or significant disability or incapacity

Question 6

paracetamol overdose over 10 grams results in a depletion of what leading to liver failure

Answer 6

glutathione

Typ1 – immediate ige mediated, urticaria, oedema, bronchoconstriction eg penicillin
Type 2 – cytotoxic – antigen on cell membrane Igg,m,a activate complement and cell lysis eg thrombocytopenia ( quinine) , haemolytic anaemia ( methyldopa or penicllin)
Tyep 3 immune complex in the serum/plasma, complex deposited on endothelial cells eg serum sickness penicllins
Type 4 – cell mediated , delayed, mostly in skin , inflialtion of sensitiised t cells local inflammation and irritation , eg contact dermatitis nd stevens johnson syndrome

Question 7

antidote for paracetamol overdose

Answer 7

N-acetylcysteine and this works by replenishing glutathione

Question 8

treatment for warfarin overdose

Answer 8

Vitamin k and fresh frozen plasma FFP

Question 9

treatment for heparin toxicity

Answer 9

Protamine

Question 10

treat methemoglobinemia( form of hb)

Answer 10

Methylene blue and vit c

Question 11

testing the drugs and clinical trials each stage

Answer 11

Drug development – pre-clinical studies (basic pharm and tox profiles)
Phase 1 clinical trials – pharmacokinetics, tolerability and side effects
Phase 2 clinical trials – larger trials – inviting people with actual disease and want to treat as desired condition – dose response relationship and dosage protocol
Phase 3 clinical trials
Pharmacovigilance – phase 4 trial – long term on going monitoring of much rarer side effects that you would not have seen in thousands of participants

Question 12

how can toxicity be reduced

Answer 12

Toxicity can be reduced by minimising further drug absorption , maximisign drug elimination, negating effects with antidotes( if one exists)

Gastric aspiration and lavage
Considered up to hour psot ingestion of drug not absorbed by activated charcoal eg lithium and iron salts
Rarely used

Question 13

what can we use in carbamazepine and quinine and theophylline overdose

Answer 13

charcoal - 50g dose of 4 Horus up to 24-36 Horus

Question 14

What is the mechanism of action to increase elimination of salicylates at toxic levels?

Answer 14

Alkalinize the urine – treatment for this toxicity is sodium bicarbonate which will alkaline the urine which will augment the bodys ability to excrete the salicyclic acid

Question 15

What is the mechanism of the drug used to treat a patient that has taken toxic levels of TCAs? (tricyclic antidepressants)

Answer 15

Plasma alkalinisation – use sodium bicarb.

Question 16

What is used to treat benzodiazepine toxicity

Answer 16

Flumazenil (Romazicon) is a competitive benzodiazepine receptor antagonist that can be used as an antidote for benzodiazepine overdose.