Pharnacokinetics Flashcards
What is pharmacokinetics?
What the drug does in the body
What are the four main pharmacokinetic processes?
Absorption
Distribution
Metabolism (largely by liver)
Elimination (largely by kidney)
What are two main types of drug administration?
Enteral - delivery into internal environment of body (GI tract)
Parenteral - delivery via other routes (not GI)
Give three examples of enteral drug administration
Oral
Sublingual
Rectal
Give three examples of parenteral drug administration
Intravenous
Subcutaneous
Intramuscular
Where do drugs administrated orally get absorbed?
In the small intestine - constant GI movement- presenting drug molecules to GI epithelia.
What is the typical transit time for Drug Absorption in the Small Intestine?
3-5 hours
How are drugs absorbed at the molecular level? (4)
Passive Diffusion
Facilitated Diffusion
Primary / Secondary Active Transport
Pinocytosis
What molecules/drugs can be absorbed by passive diffusion?
Lipophillic drugs/steroids diffuse free,h across PM down concentration gradient
Weak acids/bases (protonated/deprotonated species) can diffuse across PM
What is absorbed by facilitated diffusion by solute carrier transport?
Molecules/solutes with net ionic charge (within GI pH range) cross the GI plasma membrane through a channel. Passive process based on electrochemical gradient
What are the two main types of solute carriers (SLC)?
OATs - organic anion transporters (For weak acids)
OCTs - organic cation transporters (for weak bases)
What two absorption processes can solute carriers be used in?
Facilitated diffusion
Secondary active transport
What is secondary active transport?
Transport driven by pre-existing electrochemical gradient (cotransport), does not utilise ATP directly
What factors effect drug absorption?
Physicochemical Factors
• GI length /SA
• Drug lipophilicity / pKa
• Density of SLC expression in GI
GI Physiology
• Blood Flow: e.g. Increase post meal
• GI Motility: e.g. Slow post meal
• Food /pH: Food can reduce/increase uptake
What is “first pass” metabolism?
The drastic reduction in concentration of drug reaching systemic circulation (affects therapeutic potential)
Give examples of where first pass metabolism occurs
Gut lumen - gut/bacterial enzymes
Gut wall/liver - metabolism by cytochrome p450s (phase 1 enzymes) and conjugating enzymes (phase 2 enzymes)
What does bioavailability mean?
Fraction of a defined dose which reaches its way into a specific body compartment (Circulation is the most common reference compartment, therefore when a medication is administered intravenously, its bioavailability is 100%.)
What is the most common bioavailability comparison?
Oral vs IV
What is drug distribution?
How drugs journey through the body to reach/interact sigh therapeutic and non-therapeutic targets and their interaction with other molecules
What are the stages of drug distribution?
Bulk food - large distance from arteries to capillaries
Diffusion - capillaries to interstitial fluid to cell membranes
Barriers to diffusion- interactions/permeability/non target binding
Capillary permeability differs depending on location in the body. What are the 3 main types of capillary permeability?
- Continuous - little transfer e.g.BBB
- Fenestrated - small fenestrations in the endothelium e.g. Small intestine and kidneys
- Sinusoid - incomplete basement membrane and intercellular gaps in endothelium e.g. Liver
What two major factors affect distribution of drugs?
Drug molecule lipophilicity/hydrophillicity - effects entry to cells
Degree of drug binding to plasma/tissue proteins e.g. Plasma proteins such as albumin and globulins. Binding to these proteins decreases free drugs available for binding
What are the three (simplified) main body fluid compartments?
Plasma Water - 3 Litres
Extracellular Water (Plasma Water + Interstitial) - 14 Litres
Total Body Water - Plasma Water + Interstitial Water + Intracellular Water - 42 Litres
Increasing penetration by drug into Interstitial and Intracellular Fluid compartments leads to what?
Decreasing Plasma Drug Concentration Increasing Vd (volume of distribution)