Principles of pharmacokinetics Flashcards
First pass effect
-metabolism from the gut and liver
Gut absorption
- absorbed by active transport, passive diffusion and pore filtration
- factors influencing the absorption of drugs include intestinal motility, gastric emptying,ph, intestinal flora, area available for absorbption, blood flow and presence or absence of food
- p-glycoprotein transports some drugs- inhibted by grapefruit juice
IM administration
- lipid soluble drugs are rapidly absorbed
- drugs of low molecular weight are better absorbed
Protein binding
- distribution of a drug depends on how protein bound it is
- it is the unbound fraction (free) that can be active
- plasma protein binding is usually reversible
- highly protein bound drugs such as phenytoin are most prone to interactions mediated by this mechanism
- principle protein binding for acidic drugs is albumin with alpha 1 acid glucoprotein is the primary binding protein for alkaline drugs
Blood brain barrier
- affecte by fever, head injury, hypoxia, hypercapnia, retrioviruses, inflammation, vasculitis, hypertension, cerebral irradiation and aging
- unionised molecules and less protein bound so they are transported across the barrier easily
- small, lipophilic molecules or those with transporters
Bioequivilance
-measure of comparability of plasma levels of two different formulations of the same active compound when given at same dose and the same route of administration
Half life
refers to the time taken for the plasma concentration of a drug to halve
First order kinetics
when a constant fraction of drug is cleared per unit time
- the higher the amount of drug present the faster the elimation
- rate depends on concentration
- not dependent on any other rate-limiting step
- constant half life
Zero order kinetics
- constant amount of drug is cleared per unit time- not fraction
- the body only clears a fixed amount of the drug regardless of concentration
- increasing the dose might result in serious toxicity
- half life depends on dose
Loading dose
help to achieve steady state more rapidly
Steady state
when rate in is the same as rate out and the plasma level is constant
Changes in pregnancy
- delayed gastric emptying
- decreased GIT motility
- increased volume of distribution
- decreased drug-binding capacity
- decreased albumin level
- induced liver metabolic pathway
- increased GFR and renal clearance
Changes in elderly
- decrease in body water and increase in fat-longer half life
- decreased plasma protein binding
- hepatic metabolism remains the same but blood flow may reduce
- decreases in renal blood flow and reduce Cr clearance and GF
- absorption remains the same
- decreased number of brain acetylcholine postsynaptic receptors and acetylcholinesterase also decreased
Neonates
- neonates have a higher proportion of total body water and extracellular body water
- neonates have a lower proportion of adipose tissue
- eGFR Is lower in those under 5 months
- neonates have lower gastric acidity and increased gastric emptying time
- more permeable BBB
- lower plasma conc of albumin
Renal impairment
-use benzos with caution- halve dose of lorazepam
0imipramine and amitriptyline can be given with usual dosage
-halve dose of citalopram
-dont use sertraline
-haloperidol can be used normally
-dont use amisulpride
-lithium best avoided
