3. Pharmacodynamics, Drug Interaction, and Toxicology Flashcards
What are the conventional mechanisms of action of drugs?
Interactions with endogenous proteins - cell surface receptors, nuclear receptors, enzymes, ion channels, transporters, signal transduction proteins etc.
What is the unconventional mechanism of action that vinca alkaloids and colchicine utilise?
Disruption of structural proteins
What is the unconventional mechanism of action that streptokinase utilises?
Being enzymes
What is the unconventional mechanism of action that cyclophosphamide utilises?
Covalently linking to macromolecules
What is the unconventional mechanism of action that antacids utilise?
Reacting chemically with small molecules
What is the unconventional mechanism of action that infliximab and drugs for heavy metal poisoning utilise?
Binding to free molecules/atoms
What is the ideal standard for a drug?
Acts at one site (selective) and performs one certain action (specific). This isn’t realistic, real drugs have side effects.
Give an example of drug selectivity
Penicillin targets an enzyme involved in bacterial cell wall synthesis, but not human cell wall synthesis.
Give an example of drug specificity
Adrenergic receptors - Beta 1 in heart, Beta 2 in lungs
What is affinity?
Drug tendency to bind to specific receptor types
What is efficacy?
Ability of drug to produce a response as a result of receptors being occupied
What is potency?
Dose required to produce the desired biological response
What is the therapeutic index?
The relationship between concentrations of a drug causing overdose and concentrations causing the desired effect.
Is a higher or lower therapeutic index better?
Higher as that means there is a larger margin of safety.
What is the therapeutic window?
The range of doses that can be used to treat a pt with a specific drug while remaining safe
Name some drugs with a narrow therapeutic window.
Warfarin
Digoxin
Aminophylline
Aminoglycoside abx
When drugs interact, at what levels can they interact?
Absorption
Distribution/Protein binding
Metabolism
What can be altered to affect GI absorption of a drug?
P-glycoprotein activity (active transporter)
Which drugs is protein binding interactions most relevant for?
IV drugs
Drugs with a short haf life
Drugs with a narrow therapeutic window
What classes of drugs are the usual suspects for drug interactions?
Anticonvulsants Antibiotics Anticoagulants Antidepressants/psychotics Antiarrhythmics
What other “DDI” is important to remember?
Drug Disease interactions
What diseases should we look out for when thinking about drug interactions?
Renal, kidney, and liver disease
Why is renal disease important in drug metabolism?
If cleared by kidneys or affect functioning of the kidneys (nephrotoxic), renal disease decreases GFR so clearance is decreased, so can predispose to toxicity.
What is the classic example of drug interactions in hepatic disease?
Opiates in cirrhosis -> accumulation of small doses -> coma. Reduced clearance so drug half life increases.
Why is cardiac disease important wrt drug interactions?
Reduced CO -> reduced organ perfusion, and an increased response to hypotensive aagents
What does grapefruit juice interact with, and how?
Inhibits CYP450 isoenzymes affecting simvastatin, amiodarone, and terfenadine among others.
What does cranberry juice interact with, and how?
Inhibits CYP2C9 isoform -» warfarin, anticoagulants. High risk of haemorrhage.
