Drugs & Toxicology Flashcards
Reasons for TDM (drug factors) (5)
- overdose s/s similar to disease being treated
- very toxic in overdose
- narrow therapeutic index
- wide variation of therapeutic index (e.g. by variable pharmacokinetics, underlying conditions, DDI)
- ensure efficacy of the drug
Indications to start TDM (patient factors) (5)
- initiation / change of dosage
- suboptimal response despite compliance
- loss of control in previously stable patient
- additional drugs are given / polypharmacy
- confirm clinical diagnosis of toxicity
How many half-lives are required for a drug to reach steady-state concentration?
5 (so blood sampling should be taken afterwards)
Factors leading to a high / abnormal drug level (5)
- change in the form of medication –> affect bioavailability
- wrong dosage
- wrong sampling
- impaired excretion (e.g. renal impairment)
- DDI
Reasons for TDM for gentamicin (2)
- half-life is prolonged in renal impairment (2~3h to up to 100h)
- nephrotoxicity similar to GN septicaemia
TDM inclusion criteria for gentamicin (4)
- abnormal RFT
- > 60y
- concurrent use of nephrotoxic medication / contrast medium
- duration of planned therapy >5~7d
Sampling time for TDM of gentamicin
6~14h post-dose
What is the graph used to determine dosing interval of gentamicin?
Hartford nomogram
Reasons for TDM of phenytoin (3)
- non-linear dose-concentration curve (narrow therapeutic index)
- variable pharmacokinetics
(a) CYP substrate
(b) highly protein binding - CNS toxicity
Why TDM of phenytoin is indicated in pregnancy?
pregnancy –> ↑ protein level –> ↓ pheytoin conc. as it is highly protein bound
Sampling time for TDM of cyclosporine (what sample is taken?)
- C0 (pre-dose)
- C2 (2h post-dose)
(whole blood)
Therapeutic range of digoxin (HF and arrhythmia)
HF: 0.6~1.3
Arrhythmia: 1.2~2.6
When is digoxin effect potentiated? (4)
hypoK, hyperCa, hypoMg, hypothyroidism
DDI between digoxin and…
(a) Amiodarone
(b) Antibiotics
amiodarone –> ↓ elimination of digoxin
antibiotics –> ↓ gut metabolism of digoxin –> ↑ oral availability
Reasons for TDM of cyclosporine (4)
- narrow therapeutic index
- therapeutic index varying with organ transplanted and time from transplantation
- renal & hepatic toxicity mimic graft rejection
- ensure efficacy of drug
Reasons for TDM of digoxin (4)
- narrow therapeutic index
- conc. greatly varied by electrolytes
- toxicity (n/v, anorexia, colour vision distortion, arrhythmia) mimics chronic HF
- DDI (amiodarone, antibiotics)
Sampling time for digoxin
6h post-dose
Management of digoxin overdose (2)
digibind
correct electrolyte disturbance
Management of lithium overdose (2)
haemodialysis
correct water & sodium deficits
Comprehensive drug screening
(a) Indications (2)
(b) Sample
(c) Lab method
(a) poisoning of unknown cause / unexplained hypoK or hypoglycaemia
(b) urine
(c) mass spectrometry
Toxic metabolite of paracetamol (how is it detoxified in human body?)
NAPQI
(by glutathione conjugation in liver)
Toxic dose of paracetamol (lower threshold for which patients?)
> 150 mg/kg
(malnutrition, chronic alcoholics, CYP450 inducers)
Antidote for paracetamol poisoning (mechanism?)
IV N-acetylcysteine
(provide cysteine for glutathione synthesis / combine directly with NAPQI)
What is the graph that predict hepatotoxicity in acute paracetamol overdose? (sampling time?)
Rumack-Matthew nomogram
(>4h from intake)
4m in the name lolll
What is the usual acid-base disturbance in salicylate overdose?
respiratory alkalosis + metabolic acidosis
Treatment for salicylate poisoning
alkalinisation of urine
Metabolism of methanol (which metabolic is toxic?)
methanol –> formaldehyde –> formic acid (toxic) –> CO2
Osmolar gap abnormal range
> 10 mOsm/L
Management for methanol overdose (4)
- ethanol / fomepizole
–> inhibit alcohol dehydrogenase –> ↓ metabolism of methanol into formic acid - NaHCO3 (correct metabolic acidosis)
- Folic acid (↑ metabolism of formic acid)
- haemodialysis
Acute toxicity of Fe
corrosion to GI tract
Deficiency of which trace element gives impaired hair and nail growth?
Cu
Deficiency of which trace element gives impaired insulin effect?
Cr(III)
Deficiency of which trace element gives Keshan syndrome & Kashin-Beck disease?
Se
Deficiency of which trace element gives Acrodermatitis enteropathica?
Zn
Toxicity of which essential trace element gives pneumonitis?
Zn
What does most essential element toxicity present with?
dermatitis
Which heavy metals readily pass through the placenta? (2)
Pb, Cd
Management of heavy metal toxicity
remove from further exposure
chelation by penicillamine, BAL **except Cd
Forms of mercury (which is most selective to lipid-rich tissues like neurons?)
elemental (vapour), inorganic, organic
(organic)
Which heavy metal gives Mad hatter’s disease / Erethism?
Hg
Which heavy metal gives Pink disease / acrodynia?
Hg
Which heavy metal gives Itai-Itai disease? (what is it?)
Cd (disturbed Ca metabolism –> bone pain)
Which heavy metal is commonly found in seafood?
As (organic form)
Which form of As is toxic?
Inorganic
Which heavy metal gives peripheral neuropathy, intra-vascular haemolysis and renal toxicity?
As
