Disposition of Drugs - Exam 3 Flashcards
disposition of drugs describes the
study of the movement of drugs in the body across biological membranes from the time of absorption to elimination
disposition of drugs also known as
pharmacokinetics
what are the 4 stages of drug disposition
absorption, distribution, biotransformation (metabolism), and excretion
7 factors that affect disposition of the drug
biological cell membranes, [gradient], pump mechanisms, site of administration, total body water, plasma protein binding, disease
4 properties of the cell membrane
phospholipid bilayer, proteins & carbs, cell junctions, aqueous pores
4 mechanisms of transport of drug across cell membrane
passive diffusion, facilitated diffusion, active transport, pinocytosis
properties of passive diffusion
most common, no energy required, [high] -> [low], hydrostatic pressure differences, H2O can carry small H2O soluble substances with it i.e.: eating a tablet
transmembrane passive diffusion
through aqueous protein channels in cell membrane
paracellular passive diffusion
filtration through intracellular aqueous pores, tissues with barrier mechanism (tight junctions) i.e.: BBB
simple diffusion passive diffusion
movement through lipid membrane
the majority of drugs move through the body via
simple diffusion
properties of facilitated diffusion
carrier-mediated, [high] -> [low], faster than passive diffusion, no energy required, saturable, i.e.: glucose transport via insulin in muscle
properties of active transport
carrier mediated, [low] -> [high], requires energy, symporter, antiporter, saturable, selective, competitive inhibition by co-transporters
most abundant active transport pump in the body
primary active transport
example of primary active transport pump
Na K ATPase
example of secondary active transport pump
Na glucose transporter in renal tubules
pinocytosis also known as
“cell drinking”
what is pinocytosis
endocytosis where drug engulfs the drug molecules dissolved in H2O
example of drug transport via pinocytosis
aminoglycoside antibiotics that can cause renal damage/toxicity
2 examples of aminoglycosides
amikacin & gentamicin
3 factors affecting simple diffusion
[gradient], lipid solubility, degree of drug ionization
lipid membrane effect on drug diffusion
limits it
higher lipid solubility of a drug =
faster crossing cell membranes (lipophilic)
lipid partition coefficient
solubility of drug in lipid : solubility of drug in H2O
non-lipid soluble drugs dependent on
molecular size (smaller the molecule = faster the transport through membrane pores)
drugs cross biological membranes in what form
non-ionized
rate of drug diffusion depends on
degree of ionization (nonionized form of drug : ionized form of drug or N/I)
3 factors degree of ionization depends on
pH of drug, pKa of drug, pH of environment in vivo (blood, stomach)
how is pH determined in environment
number of protons (H+)
pH of a drug depends on
whether it acts like an acid or a base in a solution
most drugs act as
weak acids/bases (weak electrolytes)
pH of cell surface in stomach
7
pH of stomach (gastric juice, HCl)
2
what is pKa
pH at which 50% drug ionized & 50% nonionized
most drugs act as weak acids/bases with pKa between
3 and 11
higher N/I caused by
higher pKa of weak acid & lower pKa of weak base
a weak basic drug is expected to
be excreted in milk in large quantities
