Pharmacokinetics Flashcards
What is the journey of a drug?
Administered, absorbed Distributed Metabolised Excreted Voided/Removed
List some administration routes for drugs
Dermal Intramuscular Subcutaneous Intraperitoneal Intravenous Inhalation Ingestion
What are the two pathways that drugs move throughout the body via
Bulk flow transfer and diffusion transfer
What is bulk flow transfer
drugs that move via the blood
What is diffusion transfer
When drugs move molecule by molecule over short distances
What pH are most drugs
Most drugs are either weak acids or weak bases
What are factors that affect drug distrubution
Extracellular binding (plasma protein binding)
Regional blood flow
Capillary permeability
Localisation in tissues
What are the two major routes of excretion?
Kidney and liver
What happens to drugs in the kidneys
- Glomerulus - Bioactive drug filtered but drug protein complexes aren’t bc too big
- Proximal tubule is where active secretion of acids and bases happens - some lipid soluble drugs reabsorbed
- Proximal and distal tubules - lipid soluble drugs reabsorbed
Why might intravenous sodium bicarbonate increase aspirin excretion
Sodium bicarb increases urine pH so ionises aspirin. This means it’s less lipid soluble and less reabsorbed from the tubule, increasing it’s rate of excretion
- pH partition hypothesis
What are other routes of excretion other than the kidney and liver?
Skin Lungs GI secretions Saliva Sweat Milk Genital secretions
What is biliary secretion?
Concentrate large molecular weight molecules
What does the liver do to excrete drugs
Biliary secretion and active transport systems into bile
What leads to drug persistance?
Enterohepatic cycling
What is first order kinetics (most drugs)
Amount of drugs decreases at a rare that is proportional to the conc of drugs remaining in the body
What is zero order kinetics?
Amount of drug decreases at a rate independent of the conc of drug remaining in the body.
What does zero order kinetics imply about the metabolic process
A saturable, usually enzymatic, metabolic process
What is bioavailability
Proportion of the administered drug that is available within the body to exert its pharmacological effect
What is the apparent volume distribution?
The volume in which a drug appears to be distributed - indicator of the pattern of distribution
What is the biological half life?
Time taken for the conc of drug (in blood/plasma) to fall to half its original value
What is blood plasma clearance
The vol of blood plasma cleared of a drug in a unit of time (if made up of multiple steps, is the sum of these steps)
What methods are used to cross lipid barriers in the body?
Diffusing through the lipid
Diffusing through aq pores in the lipid (polar only
Carrier molecules
Pinocytosis
What is the pH partition hypothesis?
in order to undergo passive diffusion, the drug best diffuses in it’s unionised form
- when the pH of the environment is below the pKa of the drug in question, the majority of the drug is unionised and thus readily diffuses
What is ion trapping?
If the pH of the environoment is too far above the drug’s pKa then the drug can become ‘ion trapped’ as it is mainly in ionised form and therefore isn’t passively diffused much
Why is the fact most drugs are either weak acids or weak bases significant to think about?
Because non polar substances can freely dissolve in non polar substances eg lipid membranes, but since they aren’t neutral, they exist in both ionised and non ionised forms in a dynamic equilibrium
What does the ratio of the ionised to un-ionised drugs depend on?
pH of the environment and pKa of the molecules
What is enterohepatic cycling?
Drugs/metabolites are excreted into the gut, reabsorbed and taken back to the liver to be excreted again
