Pharm_01.txt

area of pharmacology concerned with the use of chemicals in the prevention, diagnosis, and treatment of disease

area of pharmacology concerned with the undesirable affects

the effects of the body on the drug

actions of the drug on the body

receptors in the body

• can differ in their affinity for the receptor
• different rates of metabolism

• 100-1000
• drugs smaller then 100 are not selective enough
• larger then a 1000 are poorly absorbed and distributed

• covalent; very strong, usually irreversible
• electrostatic bonds; weaker, between a cation and anion
• weak interactions; van der waals, hydrophobic bonds

if the drug results in activation after binding

if the action of the drug is inhibition

bind to the the receptor not at the active site but elsewhere that causes a conformational change that increases or decreases the affinity of the receptor for its substrate

• drugs can bind to nonregulatory molecules in the body, does not produce any effect.
• can play a large role in buffering the concentration of a drug because bound drug does not contribute to the drugs concentration gradient

• absorption
• distribution
• elimination

movement of a drug into and within the biologic environment

• the movement of a molecule through the watery extracellular and intracellular spaces
• most capillaries of the body have small water filled pores that allow for passive diffusion

the passive diffusion of molecules through membranes and lipid structures

• inhibits transport of uric acid, pcn, and other weak acids in the nephron
• used to increase the the excretion of uric acid in gout
• metabolism of nucleic acid purene

found to cause cancers to become drug resistant by transporting the drug out of the cell

allows very large or insoluble molecules to enter the cell

• used to predict the rate of movement across a barrier
• takes into account the permeability coefficient, aream thickness of the barrier
• rate= concentration difference x area x (permeability coefficient / thickness)
• shows drug absorption is faster through organs with the largest surface area; small intestine

• unchanged particles are more lipid soluble
• charged particles are more water soluble

• protonation of a weak base ionizes it
• protonation of a weak acid is neutral and lipid soluble

most drugs are filtered freely but lipid soluble drugs are easily reabsorbed

• aspirin is a weak acid
• accelerate excretion by alkalinizing the urine, give bicarb
• the alkaline urine will cause the acid the deprotonate and become charged and excreted

• pyrimethamine, amphetamine
• give ammonium chloride to acidify the urine and protonate the weak base

the amount of drug absorbed divided by the amount given

when a drug is taken orally it is absorbed into the hepatic circulation and subjected to deactivation by the liver

• the high blood levels of the drug are reached very quickly
• 100% bioavailability

• anticoagulants such as heparin
• can cause bleeding and a hematoma in the muscle

most will avoid the hepatic circulation but some of the drug will tend to migrate upward to the superior rectal veins and will be carried to the portal vein by the inferior mesenteric veins

a faster blood flow increases absorption through the subcutaneous and intramuscular administration

• size; the larger the organ the more drug in can absorb because the concentration in the organ does not rise too much. Skeletal muscle is a very large organ and keeps a large blood to tissue concentration gradient
• blood flow; well perfused tissue will achieve a higher concentration sooner
• solubility; the solubility on the tissue will influence concentration in the perivascular extracellular space. if the drug absorbs into cells readily then more drug will be absorbed into the extra cellular space out of the vasculature
• Binding; binding of a drug to macromolecules increases the drugs concentration in that compartment. Example is warfarin, it strongly binds to albumin which restricts its diffusion out of the vascular compartment

• administered as inactive compounds that must be metabolized to become active
• levadopa, minoxidil

• drug can bind irreversibly to its receptor
• metabolised
• phenoxybenzamine, an irreversible alpha antagonist, is eliminated by binding alpha receptors

• the rate of elimination is directly proportional with the drugs concentration
• the higher the concentration the more eliminated per unit time
• half life is constant regardless of the amount of drug in the body
• This is most drugs in clinical use

• the rite of elimination is constant regardless of concentration
• occurs with drugs that saturate there elimination mechanism at clinical doses
• ethanol