Pharmaceutical Priniciples Flashcards
Define pharmacokinetics
Study of time course of drug concentration in body
What body dues to drag
Name the 6 aspects of pharmacokinetics
Lad-met Liberation Absorption! (Bioavailability) Distribution! Vd Metabolism! (Half life) Excretion! (Clearance) Toxicity
Bioavailability formula?
Auc oral / AUC IV
Name 3 important factors that influence bioavailability
- Absorption: how much reaches target site. Poor absorption = low bioavailability
- first pass metabolism: metabolism of drug prior to reaching systemic circulation by gut wall, intestinal flora and liver. Highly metabolised. = low bioavailability
- Food interactions: May influence absorption or metabolism
Define steady state
Drug absorption = elimination and Cp (plasma conc) plateaus
How many t1/2 take to reach steady state for first order kinetic drugs?
4-5
Volume of distribution formula?
Vd = total amount drug in body (mg) / drug Cp (mg/l)
Define low Vd (4)
<15 l. Mostly confined to systemic circulation Higher Cp Faster metabolism/ elimination Eg penicillin
Define high Vd (5)
>40 L Spread throughout body Lower Cp Slower metabolism /elimination Eg tricyclic antidepressants
Importance of volume of distribution?
Determine loading dose.
Define half life
Time necessary for Cp of drug to decrease by half
Why is half Life important?
Used to determine steady state (time course of drug accumulation and elimination ) and dosing interval
How calculate loading dose from volume of distribution?
Vd x cp
Name 3 important factors that influence half life
- Elimination rate - high clearance reduce half life
- volume of distribution- direct relationship
- patient factors- genetics, food or drug interactions
How does a short half life affect duration of action, dosing frequency, compliance, steady state and side effects?
- Short duration
- increased dosing
- lower compliance
- steady state reached earlier
- side effects disappear faster: short washout
How does a long half life affect duration of action, dosing frequency, compliance, steady state and side effects?
- Longer duration
- decreased dosing
- higher compliance
- steady state reached later
- side effects disappear slower:long washout
Define first order kinetics and how t1/2 , concentration and decline applies
Constant fraction of drug eliminated per unit of time
• T1/2 constant
• Concentration independent
• doubling dose doubles Cp
• undergoes exponential decline - will not accumulate, predictable, never completely disappear but reach clinically insignificant conc
• most drugs
Define zero order kinetics and how t1/2 , concentration and decline applies
Constant amount of drug eliminated per unit time
. T 1/2 variable
• concentration dependant due to saturable kinetics.
• high Cp require more time to clear thus T1/2 increase
• linear decline - saturable parameters, ADME are rate limiting factors, will eventually completely disappear
• only few drugs eg phenytoin, alcohol
name 3 examples of drugs that follow zero order kinetics
- Phenytoin
- alcohol
- Aspirin
Formula for clearance?
Cl (L /h) = rate of elimination (mg/h) / drug cp (mg/l)
What is the relationship of clearance to vd and T1/2
Cl (L/h) = (0,693 x Vd ) / t1/2
How calculate clearance of Iv drugs?
Cl (L/h) = dose / area under curve
How calculate clearance of oral drugs?
Cl (L/h) = (bioavailability x dose ) / area under curve
Why is clearance important?
Determine maintenance dose at steady state and indicate route of elimination when compare hepatic and renal blood flow
Maintenance dose rate formula?
Maintenance dose rate (mg /h ) = cl (L /h) x CSS (conc steady state) (mg /L)