Applied Pharmacology 5, Theraputic Index

Therapeutic index is a measure of how safe a drug is, comparing the effective dose with the toxic dose.

Notes
The therapeutic index (TI) (also called therapeutic ratio) is a comparison of the dose of a drug that causes the therapeutic effect to the amount that causes toxicity. This describes the margin of safety, accounting for the effective dose, toxic dose and even potential lethal dose. The related terms therapeutic window or safety window refer to a range of doses which optimize between efficacy and toxicity. This is always where we aim to be.

High (wide) TI is good for good safety profile, drug has low toxicity

Low (narrow) TI is more risky  (NTI drugs, narrow therapeutic index), drug more toxic
       
       TD    (toxic dose)
TI = -----
       ED    (effective dose)  

       TD50    (toxic dose)
TI = -----
       ED50    (effective dose)

Lethal dose
Toxicity effects
Adverse response threshold
Therapeutic window / range
Duration of action
Sub therapeutic range
Desired response threshold
Eg, anticoagulants, hypotensives, hypoglycaemics, analgesics, diuretics,


Low (narrow) Therapeutic Index drugs
Digoxin 2:1
Paracetamol (acetaminophen) 7 gram fatal dose
Lithium – nephrotoxicity, ataxia, discordination
Warfarin -
Gentamycin – nephrotoxic, auditory nerve damage - ototoxicity
Vancomycin - nephro
Phenytoin, fast uncontrolled eye movements, dizzy confused, poor coordination, slured speech
Antidepressants, tricyclics
Insulin,
AZT,

High (wide) TI drugs
NSAIDs
Benzodiazepines
Most antibiotics
Furosemide
SSRIs

Does not include any synergistic effects, e.g. diazepam and alcohol or diazepam and morphine, aspirin and warfarin, pharmacokinetic, pharmacodynamics effects, eg. Furosemide and ACEIs (oprils)

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