Basic Concepts in Drug Therapy

receptor (AKA target)

-component of a cell or organism that interacts with the drug and initiates the chain of events leading to the drugs observed effects

pharmacodynamics

-the way drugs exhibit their effect and their mechanisms of action on the target

pharmacokinetics

-amt of time in which drug is in contact with target

-incl drug absorption, distribution, metabolism and excretion

Types of receptors

-surface receptors: molecule binds the receptor, changes it's shape and causes direct effect

-2nd messenger receptors: trigger a cascade of chemical reactions: indirect

selective drug

-one that elicits only the response for which it is given

non-selective drug

-a drug that interacts with more than one target or receptor producing undesirable effects in addition to the desired effect

-side effects

agonist

-exhibits effects similarly to a naturally occurring molecule

-types: partial and full

antagonist (blocker)

-inhibits the effect to a naturally occurring molecule

-types: competitive, irreversible (not coming off receptor), reversible (med wears off or new med is applied)

Full agonist

-drug capable of fully activating the effector system when it binds the receptor

-ex: morphine

partial agonist

-produces less than the full effect, even when it has saturated the receptors

-in the presence of full agonist a partial agonist acts as an inhibitor

-ex: buprenorphine (used for opioid maintenance)

competitive antagonists

-drugs that bind to, or close to, the agonist receptor in a reversible way w/o activating the effector system for that receptor

-in presence of competitive agonist, the dose-response curve for an agonist is shifted to higher doses but the same max effect is reached

-the agonist, if given in high enough concentration, can displace the antagonist and fully activate the receptors

-ex: naloxone/Narcan

irreversible antagonist

-downward shift of the max, with no shift of the curve on the dose axis unless spare receptosr are present

-cannot be overcome by adding more agonist

-ex: aspirin

direct action (non-receptor mechanism)

-act directly

-don't req receptors

-ex: H2O2 on a wound

metabolites

-may have effects or side effects

chelation

-binding of drug to molecules

receptor desensitization/down-regulation

-account for the reduced effect of many drugs with continual treatment

-occurs with increased stimulation

-down-regulation of receptors leads to increased sensitivity in remaining receptors even though the overall effect is desensitization

receptor supersensitivity

-blocking receptor can cause an increase in the number of receptors

-up-regulation of receptors leads to decreased sensitivity in each receptor, but overall increase in sensitivity because there are more

Agonist+Competitive antagonist

-causes the entire curve to shift to the right

-must increase the dose of the agonist to achieve the same effect

Agonist+antagonist

-shifts curve downward

-attenuates the max effect of the agonist

Efficacy

-greatest effect agonist can produce if dose is taken to highest tolerated level

What determines efficacy

-mainly determined by nature of the drug and the receptor and its associated effector system

Which has lower max efficacy: partial or full agonists

-partial

Potency

-does of a drug necessary to prod response

What determines potency

-affinity of receptor for the drug

-number of receptors available

Therapeutic Index

-ratio of TD50/ED50

-greater TIs considered safer

-OTCs have greatest TIs

-prescription drugs usually have lower TI's

-some drugs have TIs very close to 1

Therapeutic window

-dosage range btwn minimum effective therapeutic concentration/dose and max toxic concentration/dose

-TD50-ED50