Lecture 9 - Pharmacology and toxicology Flashcards
What is forensic toxicology?
Application of toxicology for purposes of the law.
What is dose-response? and how is it calculated?
The response on the y axis, is plotted against log[dose] on the x axis.
What is each abbreviation for dose-response?
NOEL - no observed effect.
ED50 - Effective dose for 50% of those tested
TD50 - Toxic dose for 50% of those tested
LD50 - Lethal dose for 50% of those tested
What is tested for post-mortem toxicology?
Blood
Vitreous humor
Urine
Bile
Liver
(Others can be lung, spleen, stomach contents and hair)
What are the key questions for P-MT?
- Were drugs taken? - chemical analysis of collected samples, help case.
- How much was taken? - comparison to known standards, presence of metabolites will help know known amount, can apply pharmacokinetic parameters to help determine the amount.
- When was it taken? - ratio of metabolites to parent drug, pharmacokinetic parameters may also help
- Cause of death? - use known toxic and lethal doses, need case info
What are the cautions?
Caution required in applying pharmacokinetic parameters:
– Inter-individual variation
– Disease
– End-stage organ failure near time of death
As elimination falls, half lives are longer and blood concentrations increase
Hepatic failure – drugs metabolised in the liver may accumulate
Renal failure – drugs metabolised in the kidney may accumulate
Effects of polypharmacy
What is polypharmacy?
The administration of multiple drugs
What are the 2 effects of polypharmacy
- Positive - desired interactions
- Negative - ineffective therapy and excessive toxicity
Common uses in elderly and drug abusers.
Why is polypharmacy bad?
- Death can occur due to mixing of drugs or accidental overdose
- Can make the cause of death hard to determine
- Failure to correctly diagnose symptoms
- Can be caused by the drugs themselves or
their metabolites and their reactions with
other drugs
What usually happens in cases of the elderly?
- More susceptible to polypharmacy issues because illness is more common
- Complimentary and alternative medicines are increasingly popular
- Multiple pharmacy use
- Multiple heath care providers
- Prescribing cascade
- Ageing alters pharmacokinetics - therefore there may be increased or altered effects
What are the effects of ageing on absorption?
Rate of absorption may be delayed but bioavailability is unchanged.
Absorption through the skin may increase as ageing skin can be thin and frail.
What are the effects of ageing on distribution?
Decreased body water – decreased distribution for hydrophilic drugs
Decreased lean body mass – decreased
distribution for drugs that bind to muscle
Increased fat stores – increased distribution for lipophilic drugs
Decreased albumin in plasma – increased % of unbound or free drug
Increased α1-acid glycoprotein in plasma –
decreased % of unbound or free drug
What are effects of ageing on metabolism?
Metabolism of drugs by the liver may be
reduced due to:
– Decreased hepatic blood flow
– Decreased liver size and mass
- Decreased phase I metabolism
- Stability of phase II – therefore drugs
undergoing phase II hepatic metabolism are generally preferred in the elderly due to
inactive metabolites.
What are the effects of ageing on elimination?
Decreased kidney size
Decreased renal blood flow
Decreased number of functional nephrons
Decreased filtration rate
Reduced elimination leads to drug
accumulation and toxicity
What are 2 ways prevent polypharmacy in elderly?
- Lower drug doses to achieve same effects with advancing age and complications with lack of adherence to drug regimens
To prevent polypharmacy;
- Increased knowledge on which drugs cause problems in the elderly
- Increased knowledge of contraindications
