Adsorption, Distribution, Metabolism, Elimination Flashcards
What is the core concept of drug absorption?
The process by which a drug moves from its site of administeration to the systemic circulation
What four physiological processes govern the time course of a drug?
- Adsorption
- Distribution
- Metabolism
- Excretion
What does absorption involve?
Drugs crossing cell membranes e.g lipid bilayers
What are the three ways that drugs can cross cell membranes?
- Passive diffusion through a lipid
- Solute carrier-mediated transport
- Diffusion through aqueous pores
What chemical and physical factors affect drug uptake?
- The drugs physiochemical properties
- Dissolution in water is affected by molecular size and degree of hydrophobicity
- Drug diffusion across membranes is influenced by the concentration gradient
What biological factors affect drug uptake?
- Vascularity and local blood flow to the absorption site
- Gastric content
- Surface area for absorption
- Local pH
- Local enzymes in the gut wall and liver
- Specific transport systems in the GIT allow absorption of nutrients
How might you by-pass drug absorption?
the iv route
What is the iv drug route useful for?
- Rapid effects
- Fluid therapy
- Precise dosing
- Administration of short-acting drugs
- Administration of irritant drugs
How might you be able to modify absorption through formulation?
- Depot injections (e.g particle size)
- Controlled/ Sustained release products
What is drug distribution?
The reversible passage of drugs between tissues, organs and compartments
By what mechanism do drugs move around the body?
Bulk flow in the blood
What influences drug distribution?
Degree of reversible binding to proteins in plasma, only unbound drugs can distribute into tissues
What does distribution between different drug compartments depend on?
- Physiochemical characteristics of the drug
- local pH
- Blood flow
- Transport mechanisms
- Disease Process
- Protein binding within compartments
What does individual variation in drug response refer to?
The concept that there are differences in response between individuals in the same drug dosage
What is drug metabolism?
The chemical transformation of a drug into one or more products within the body
Where does drug metabolism predominantly occur?
In the liver, cytochrome p450 plays an important role
What is the phase 1 reaction?
CYP450 enzymes introduce a reactive chemical group, producing a metabolite more reactive than the original drug
What is the phase 2 reaction?
Anabolic- involves conjugation, produces inactive, polar products readily excreted in the urine
What is the major factor that accounts for differences in drug effects across species?
Biotransformation
What is drug interaction?
The process by which a substance alters the action and/or kinetics of a drug
What may drug interactions result in?
effects that are either beneficial or deleterious
What is drug elimination?
The removal of a drug through the body via metabolic and/or excretory processes
What is the main route of drug elimination?
Via the kidneys, thus renal function has a major influence on drug plasma concentrations
