Pharmacokinetics Flashcards
What is pharmacokinetics?
What the body does to a drug
What are the main components of pharmacokinetics?
Absorption
Distribution
Metabolism
Elimination
What factors affect pharmacokinetics?
Bioavailability Half-life Drug elimination Intra-subject variability Drug-drug interactions
What is bioavailability?
Measure of drug absorption into body compartment where it can be used
What is the bioavailability of IV drugs?
100%
What factors affect bioavailability?
Absorption
- formulation
- age
- food
- vomiting
- malabsorption
First pass metabolism
What is first pass metabolism?
Metabolism before reaching systemic circulation
What factors affect distribution?
Blood flow
Lipophilicity
Hydrophilicity
Protein binding
What is Vd?
Volume of distribution
= how widely a drug is distributed in the body
How is Vd calculated?
Dose/[drug]plasma
What does a small Vd show?
Drug confined to plasma and extracellular fluid
What does a large Vd show?
Drug distributed throughout tissues
How are Vd and t1/2 related?
t1/2 is proportional to Vd
What are the main routes of administration?
Enteral
Parenteral
What does enteral mean?
Via the GI tract
What are examples of enteral routes?
Oral
Sublingual
Rectal
What does parenteral mean?
Not via the GI tract
What are examples of parenteral routes?
IV
SC
IM
What is a pneumonic for drug administration?
Oi It is sir
What are the routes for drug administration?
Oral Intravenous Intramuscular Transdermal Intranasal Subcutaneous Sublingual Inhalation Rectal
What are the main processes of drug absorption?
Passive diffusion
Facilitated diffusion
Primary/secondary active transport
Pinocytosis
What type of drugs use passive diffusion?
Lipophilic drugs
Weak acids/bases
What type of drugs use facilitated diffusion?
Drugs with a net ionic charge
What molecules are used for facilitated diffusion?
SLCs(solute carriers)
- OATs (organic anion transporters)
- OCTs (organic cation transporters)
What factors affect drug absorption?
GI length /SA Drug lipophilicity Density of SLC expression in GI tract Blood flow GI motility First pass metabolism
What is the effect of first pass metabolism?
Reduces availability of drug reaching systemic circulation
How is biovailability calculated?
Area under graph ([plasma] against time)
What are the main mechanisms of drug distribution?
Bulk flow
Diffusion
What factors affect drug distribution?
Lipophilicity
Hydrophilicity
Degree of drug binding to plasma/tissue proteins
How does lipophilicity affect distribution?
Lipophilic drugs can move freely across membrane barriers
How does hydrophilicity affect distribution?
Needs more help crossing membrane barriers
Relies on
- capillary permeability
- local pH
- presence of OAT/OCTs
How does drug protein binding affect distribution?
Only free drugs can bind to target sites
Where does most drug metabolism occur?
Liver
What molecules metabolise drugs?
Phase I + II enzymes
What carries out phase I metabolism?
Cytochrome P450 enzymes
What happens when drugs are metabolised?
Ionic charge is increased
What else does phase I metabolism do?
Activates prodrugs
What carries out phase II metabolism?
Hepatic enzymes
What happens in phase II metabolism?
Ionic charger is further increased
What is the effect of phase II metabolism?
Enhances renal elimination
What factors affect drug metabolism?
Age
Sex
General health
CYP450 inducers/inhibitors
What drugs are CYP450 inducers?
Carbamazepine Rifampicin Barbiturates Phenytoin St John's Wort
What drugs are CYP450 inhibitors?
Sodium valproate Ciprofloxacin Sulphonamide Cimetidine/omeprazole Antifungals Amiodarone Isoniazid Erithromycin/clarithromycin Grapefruit juice
What is the main route of drug elimination?
Kidney
What are other routes of drug elimination?
Bile Lung Breast milk Sweat Tears Genital secretions Saliva
What are the 3 processes involved with renal excretion?
Glomerular filtration
Active tubular secretion
Passive tubular reabsorption
What happens in glomerular filtration?
Unbound drug enters tubule
Where does active tubular secretion occur?
PCT
What happens in the PCT?
High expression of OATs + OCTs
Carry ionised molecules
Lipophilic molecules pass back into blood
Where does passive tubular reabsorption occur?
DCT
What happens in the DCT?
Passive reabsorption of lipophilic drugs
What is clearance?
The volume of plasma that is completely cleared of the drug per unit time
How is total body clearance calculated?
Hepatic clearance + renal clearance
What is the unit for clearance?
ml/min
What is t1/2?
Half life
The amount of time over which the concentration of a drug in plasma decreases to one half og the concentration when it was first measured
How is t1/2 calculated?
t1/2 = (0.693xVd)/Cl
How many half lives does it take to clear a drug?
5
