Pharmacokinetics Flashcards
Absorption
Process by which drug enters a system in circulation followed by illustration of mouth inhalation, through skin or injection
Passage of drug from site of administration into plasma
What are the 4 main mechanisms for movement of small molecules?
Passive diffusion through lipid- conc gradient, best small and hydrophobic
Facilitated passive diffusion- molecules more polar, charged, carried molecule, with conc gradient
Active transport
Pinocytosis
Acidic drug best absorbed at which levels?
Acidic environments
What is sublingual administration?
Placing drug under tongue, to dissolve, absorb into blood stream through tissue there
What is transdermal administation?
Through skin to bloodstream
What are the factors affecting absorption from GI tract?
Particle size and formulation- liquid dissolve more quickly
Physiochemical factors- molecular sizing
Gut content- faster absorption on empty
GI motility- gastric emptying determines how quickly drug delivered to small intestine
Splanchnic blood flow- reduced in heart failure, give reduced absorption
What is IV administration?
Direct administration into plasma
Bioavailability
The fraction of the administered dose that reached the systemic circulation as the parent drug
Reason for incomplete bioavailability for oral admin
Incomplete absorption and loss in faeces
How does bioavailability of a drug affect the dose
Poor bioavailability will need a higher dose
Distribution
Process by which drug is transferred reversibly between the plasma and the tissues
Distribution is dependent on which 2 factors
Blood flow
Lipid solubility - lipid soluble more likely to cross blood brain barrier causing less side effects
Why are lipid soluble drugs more likely to be more slowly released from body
Tissue store of lipid soluble drug will be higheer resulting in slower elimination
Oral distribution of drug
Gradual increase in blood
Even filling of all compartments
IV distribution of drug
Rapid rise of drug in blood
Rapid rise in vessel rich
Slow rise in intermediate and poor vessel
Drug redistributed from vessel rich so become equal
Volume of distribution
Theoretical volume necessary to contain total amount of an administered drug at same conc that is observed in blood plasma
Volume of distribution equation
total amount of drug in body/ plasma conc
Low volume distribution drugs
Large, water soluble
Stay within plasma
High volume distribution drugs
Small lipid soluble
Distribute into all compartments
What is principle site of drug metabolism?
Liver
What does liver do?
Aim to make drug more soluble for elimination via kidneys
Metabolism of drug affected by 3 factors
Enzyme induction or inhibition
Blood flow to liver
Genetic variation in enzymes
How do enzyme inhibitors affect activity of drug?
Increase activity
How do enzyme inducers affect activity of drug?
Reduce activity
Pro-drug
Drug that is metabolised after administration to a pharmacologically active metabolite
adminstered inactive form, reduces undersirable effects
Larger molecules are excreted how?
By bile (removed in faeces)
Smaller moelcules are excreted how?
Renally (urine)
What is first order drug elimination
Metabolism rate is proportional to drug plasma conc
Drug conc drops by fixed percentage in given time
What is zero order drug elimination?
Metabolism removes fixed amount of drug in given period
Half life of drug
Time it takes for plasma conc or amount of drug in body to be reduced by 50%
Clearance equation
Rate of elimination from body/ drug conc in plasma
Cl total equation
Cl renal + clearance non renal
Repeated administration
Drug administration of fixed dose at regular time interval through given route
Drug drug interactions
When one drug affects the activity of another when 2 are given in combination
Therapeutic index equation
Dose resulting in toxicity/ dose giving therapeutic response
High TI indicates what toxicity
Low risk of toxicity
Low TI or narrow indicated what
High risk of toxicity
