Principles of Drug Action Flashcards
What are the 4 components of the pharmacokinetic phase?
absorption, distribution, metabolism, elimination
Describe drug absorption.
movement of a drug into the bloodstream after administration, impacts bioavailability, must be both water and lipid soluble
Define bioavailability.
how quickly/how much of a drug reaches its intended target (how long it will take to begin effects)
What is the main determinant for how long it takes for a drug to take effect?
absorption
Describe passive and specialized transport.
passive: aqueous and lipid diffusion, concentration gradient is driving force (Fick’s)
specialized: facilitated, pinocytosis, active (requires specialized mechanism to cross cell membranes)
How is the movement of ions predicted?
Henderson-Hasselbalch equation (pH and drug dissociation constant determine the ratio of lipid to water soluble forms for weak acids and bases)
What is the general rule absorption in relation to weak bases and acids?
weak bases are absorbed faster in the small intestine where the pH is more basic
weak acids get absorbed faster in the stomach where the pH is acidic
Describe facilitated diffusion.
requires carrier membrane bound proteins, from high to low concentration, structure specific, saturable, competitive
Describe active transport and provide an example.
requires carrier protein, water soluble molecules, energy, is structure specific, saturable, and competitive
ex. pinocytosis
List some factors that affect absorption. (8)
drug concentration, solubility, size, ionization, surface area, presence of good circulation, bioavailability/ROA/form, additives
Describe absorption for the following enteral routes: mucus membranes in mouth and lower intestine, oral route, small intestines, pulmonary, topical, transdermal, eyes, and ears.
mouth - small surface area, highly vascular, avoids first pass phenomenon, rapid onset, limited types/doses
lower intestine - avoids most first pass, extensive vascularity, limited surface area, drugs need to be in solution
oral - low pH, rich blood supply, lipid soluble/non-ionized substances
small intestine - important for oral drugs, highly vascular, pH 7-8, peristalsis
pulmonary - rapid absorption, large surface area, rich blood supply, high permeability, many barriers, local/systemic effects
topical - epidermis barrier, more rapid absorption in dermis, local effects
transdermal - absorbed at steady rate
eyes - local effect
ears - local treatment
Describe distribution.
transport of drugs from the blood to the site of action, drugs can be distributed to site of action or not where they have no effect
List and describe factors that affect distribution. (6)
volume of distribution - degree of distribution of a drug into various body components and tissue (Vd = drug amount/plasma concentration)
CO and capillary permeability - affect regional blood flow and perfusion of tissues
plasma protein binding - decreases concentration of ‘free drug’, can act as storage mechanism and increase to toxic levels
tissue binding/affinity - lipid soluble have high affinity for fat tissue, long equilibration time
BBB - most drugs can’t pass
placenta - membrane lipid in nature, teratogenic effects
Describe the cumulative effect.
drug’s rate of loss from the body is less than the rate of absorption into the bloodstream, serum drug levels will continue to rise gradually
Define biotransformation.
process by which the body changes the chemical structure of a drug to another form called a metabolite
