PH3110 - How human biology influences drug handling and action 1 Flashcards
What is pharmacokinetics?
The study of what the body does to a drug
What is pharmacodynamics?
The study of what the drug does to the body
What is the therapeutic window?
Minimum effective dose to minimum toxic dose
What effect does pharmacokinetics have on the therapeutic window?
Provides information on the dosage regimen to achieve a given ‘window’ of plasma drug concentration
What effect does pharmacodynamics have on the therapeutic window?
Provides information on the effect likely to be achieved with regards to a given ‘window’ of plasma drug concentrations
What are the effects of drugs?
Stimulation (e.g. adrenaline)
Depression (e.g. quinidine)
Irritant (e.g. deep heat)
Replacement (e.g. insulin)
Cytotoxicity (e.g. antibiotics, chemotherapy)
What are the three classifications of a response to a drug?
Clinical (subjective vs objective)
Surrogate endpoint (e.g. blood pressure - risk factor for CV event)
Biomarker (e.g. PSA in prostate cancer)
What is the difference between subjective and objective clinical responses to a drug?
Subjective - e.g. 1 - 10 in pain score
Objective - e.g. measuring a parameter (e.g blood sugar)
What type of receptors can be used as drug targets?
Cell surface and intracellular receptors
Enzymes
Structural proteins
What is the relationship between Dose and Concentration?
Pharmacokinetics
Relationship changes with time
What is the relationship between Concentration and Effect?
Pharmacodynamics
Relationship DOES NOT change with time
What is the relationship between concentration and response?
Michaelis Menten curves
What is the equation for the Michaelis Menten curve?
E = Emax x C / Ec50 + C
What is the EC50 of a drug?
The concentration of drug that gives 50% of the maximum response
What is the concentration-effect rule?
Concentration and effect relationship does not change with time
If the concentration is 40, then effect on body is the same whether drug is being absorbed or eliminated. E1=E2
What is the difference between efficacy and potency?
Efficacy is the maximum effect of a drug (Emax)
Potency affords comparison between a set of drugs and indicates the doses of drugs required to produce the same effect
Why is concentration used, rather than dose?
Concentration (exposure) in body gives rise to effect
Concentration drives effect
Proportionality between dose and concentration
What is the problem with using dose in epilepsy medication?
Massive variation in concentration due to pharmacokinetics. Epilepsy is controlled with plasma concentrations between 10-20mg/L
Why aren’t plasma concentrations routinely monitored?
Limited pharmacokinetic variability
Wide safety margins (e.g. antibiotics)
Cost
Plasma concentrations correlates poorly with response
- tolerance
- multiple active species
- time delays
Single dose therapy (e.g. salbutamol after an asthma attack)
Duration vs intensity
What are multiple active species?
Conversion of parent drugs to active metabolites (e.g. codeine -> morphine)
Alprenolol more active when given orally than IV
- first pass metabolism doesn’t occur so less active formed
- higher concentration in blood but less effect
