Week 9 - Pharmacokinetics Flashcards
What are the principles of drug formulation?
- Is the drug getting into the patient? (Pharmaceutical process)
- Is the drug getting to the site of action (pharmacokinetic process)
- Is the drug producing the desired pharmacological effect (pharmacodynamic process)
- Is the pharmacological effect translated into a therapeutic effect (therapeutic process)
What is the pharmaceutical process?
- Formulation of the drug
- – Solid or liquid
- – Solubility and acid stability in stomach must be considered
- Site of administration
- – May be focal (eye, skin, inhalation, etc.)
- – May be systemic (enteral [sublingual, oral, rectal] or parenteral [subcutaneous, intramuscular, intravenous])
What is oral bioavailability?
The proportion of a dose given orally (or by any route other than IV) that reaches the systemic circulation in an unchanged form
How can you measure oral bioavailability?
- Amount in blood
- Rate of availability
What is therapeutic ratio?
Maximum tolerated dose/minimum effective dose
What are the mechanisms of drug elimination?
- First pass metabolism
- – Blood from the gut reaches the liver by the portal system
- – The liver can metabolise the drug before it gets to the systemic circulation
- – Can be avoided by parenteral routes or sublingual/rectal routes
- Renal elimination via the glomerular filtrate
What is the volume of distribution?
The theoretical volume into which a drug has distributed, assuming that this has occurred instantaneously
- Calculation: amount given/plasma concentration at time 0
What else can drugs bind to?
Plasma proteins
- These interactions are important if:
- – The drug is highly bound to albumin
- – The drug has a small volume of distribution
- – The drug has a low therapeutic index
- Object (class I) drug: used at a dose which is lower than the number of available binding sites
- Precipitant (class II) drug: used at a dose which is greater than the number of available binding sites
- When a patient is taking 1 of the object drugs, adding on the precipitant drug will temporarily lead to higher free levels of the object drug, and hence higher risk of toxicity
What is first order kinetics?
When the rate of decline of plasma drug level is proportional to drug level
- The drug is used at a concentration which is lower than Km
- So metabolism is proportional to drug concentration
- It initially acts like first order kinetics until the enzyme become saturated
What is zero order kinetics?
When the rate of decline of plasma drug level is constant
- The enzyme is saturated
- The drug is used at a concentration which is much greater than Km
How long does it take to reach a steady state during drug administration?
Steady state will be reached within 5 half lives of that drug
- Irrespective of dose or frequency of administration
- If an immediate effect is necessary, a loading dose is needed
What is a loading dose?
A comparatively large dose given at the beginning of treatment to start getting the effect of a drug
When do drug interactions in metabolism matter clinically?
When:
- Drugs have a low therapeutic ratio
- The drug is being used at minimum effective concentration
- Drug metabolism follows zero order kinetics
Describe some drug interactions with warfarin
Potentiators of warfarin action
- Alcohol: inhibits metabolism
- Aspirin, sulphonamides, phenytoin: displacement from plasma proteins
- Broad spectrum antibiotics: reduced vitamin K synthesis by bacteria in gut
- Aspirin: reduced platelet function
Inhibitors of warfarin action
- Barbiturates, rifampicin: induces liver metabolising enzymes
What determines the effect of a drug?
The free level of the drug
