Flashcards in Unit 1 - Basic Principles of Pharmacology Deck (45):
drug action VS drug effect
molecular action is invisible
pharmacologic effect shoes visible response
selectivity: property of drug to cause a specific effect
-few drugs produce a single effect
primary VS secondary effects
secondary: "side effects" that may or may not be desired
pharmokinetics VS pharmodynamics
kinetics: time course of drug absorption, actions, and elimination
dynamics: types of drug actions
what are the types of pharmodynamics?
physiochemical actions - simple chemical interactions
-ex: antacids, antiseptics not very specific
receptor interactions - interaction of drug with physiologic receptors (most drugs are macromolecules)
cause molecular events to occur in each cell
-enough of events cause change in cell function resulting in change in tissue function
information on drug receptors
-macromolecules, particularly proteins, on or in a cell, or free in plasma or extracellular fluid
-specific and present as part of normal biochemical and physiologic mech, and usually interact with endogenous compounds
-function as both ligand binder and effector
-each cell in a tissue contains a large population of receptors that are easily accessible to drugs
when is a maximal response achieved?
related to number of drug receptor interactions and physiologic capacity of tissue (healthy VS diseased)
what are 5 types of receptors and examples?
membrane-bound: neural synapse, ion channels
enzymes: intracellular or extracellular
structural macromolecules: microtubules
intracellular macromolecules: steroid receptors, RNA
cell membrane: change electrical potential, fluidity
receptor amplification and transduction
drug-receptor interactions last fractions of seconds and activate G protein activity that lasts for seconds
information on G proteins
GTP binding proteins regulate activity of distinct effector proteins in cell
-there can be multiple GPRO in a single cell
-act as switches that are turned on by receptor and turn themselves off in a few seconds
-several drugs can stimulate different receptors but ultimately influence same effector PRO through mediation of GPRO that is shared by different receptors so stimulus averaging/modulation is achieved
-structure of drug determines how it will fit into the receptor
-better fit has better stimulation
-subtle changes in structure among a class of drugs can greatly influence drug's effects
log dose response curve characteristics
threshold: beginning of the curve
-dose of agonist at which response starts
-may relate to affinity of agonist for receptor
slope: rate of rise of response on steep portion of a curve
-log of EC50 also relates to affinity
maximal asymptote: top of the curve, represents E max for that particular agonist
intensity of response is proportional to fraction of receptors occupied
-effect = Emax * [D] / KD + [D]
-where Kd = EC50
ability to stimulate receptor once bound
-relates to structure and influences efficacy and potency
-greater intrinsic activity = greater efficacy (brings to Emax)
not all receptors need to be occupied to achieve Emax
-less efficacious agonists need to occupy more receptors than highly efficacious agonists
outside of target tissue(s), may mediate other effects (side effects)
a cell can up or downregulate a population of receptors by changing the total number of receptors or their sensitivity
difference between binding site and effector portion
effector portion needs to be bound in order to exert effect, but if binding site not bound, then weaker agonist
-if only binding site bound, then it's an antagonist
what are the two ways of quantifying agonism?
efficacy and potency
what is efficacy? what does it depend on?
ability of drug to activate effector portion of receptor once drug is bound to receptor
-depends on structure of the drug
what is potency? what does it depend on?
relates to amount of drug that is needed for an effect
-depends on biologic system (receptor density, efficacy of stimulus-response mechanisms of tissue) and interaction of drug with receptor (affinity and efficacy)
types of noncompetitive antagonism
I - changes effector, does not change binding of drug to ligand site OR alters effector site so even if ligand binds to the receptor, it cannot initiate effect
II - changes binding site for agonist by directly binding to it or by attaching to a different portion of receptor and altering agonist binding site
passive process that's driven by hydrostatic pressure
-drugs dissolved in moving fluid is transported through pores in a membrane or channels betweenc ells
-drug molecule size will be limiting
active process where drug is transported in pinched off packets of single layer membrane
what are characteristics of weak electrolyte drugs?
nonionized forms - diffuse
ionized forms - do not diffuse
both weak acids and bases
what does the ratio of ionized to nonionized forms estimate?
ease of absorption at a particular pH can be predicted
are weak acid or weak base drugs absorbed better in the stomach?
-weak bases generally stay in the GIT
what are 4 considerations for routes of administration?
1. planned use of the medication - for patients to give at home VS clinical setting
2. clinical setting - acute VS chronic (may want to closely monitor drug effect and titrate dose VS daily dosing for long term effects)
3. rapidity of onset of desired action (heart attack must be treated quickly)
4. specific target organ that the drug is intended to reach
what are advantages and disadvantages of oral drug routes?
pros: ease, safety, self-administration, cheap, prolonged absorption causing prolonged effect
cons: absorption may be slow, variable, and unpredictable; drug may be irritating, destroyed by gastric acid/enzymes, completely metabolized on first pass of liver; not available to comatose, vomiting patients
what is the "first pass" effect
1. drug is administered by mouth
2. drug enters GI tract
3. active drug is absorbed from stomach and SI
4. high blood concentration of free drug is in hepatic portal vein (before liver metabolism)
5. low blood concentration of free drug is in systemic arterial or venous circulation
what are advantages and disadvantages of rectal drugs?
pros: useful for infants, comatose, vomiting patients, and foul-smelling, distasteful drugs destroyed in upper GIT; avoids immediate liver metabolism; for local action in the rectum
cons: poor compliance, erratic/incomplete absorption; possibility of rectal irritation
what are advantages and disadvantages of sublingual drugs?
pros: bypasses liver when first absorbed, and rapid absorption
cons: drugs must be soluble in saliva, not too distasteful, have appropriate pKa for rapid absorption; tablets must be small (diffusible, small nonionized)
what are advantages and disadvantages of intravenous drugs?
pros: rapid effect, can watch response and titrate dose, all dose enters circulation, for when oral route not available, for when drugs are too irritating (if given im or sc), in large volumes of fluid, infusions and continuous monitoring, for hypertonic solutions
cons: cost, skill in administration, danger of infection, possible anaphylactic reaction, danger of embolus formation due to air, drug preciptation, and RBC agglutination, adverse CV effects if administration too rapid, and painful
what are advantages and disadvantages of intraarterial drugs?
pros: administration of radioopaque material for visualization of circulatory tree
cons: as for IV administration
-cost, skill in administration, danger of infection, possible anaphylactic reaction, danger of embolus formation due to air, drug preciptation, and RBC agglutination, adverse CV effects if administration too rapid, and painful
what are advantages and disadvantages of intramuscular drugs?
pros: when oral route is not available; absorption is less variable than with oral route and less painful and more rapid than with sc route; possible to slow absorption to prolong effect
cons: pain, sterile techniques, possible local necrosis, lag period before effect onset, accidental IV injection possible; not used after antigoagulant administration
what are advantages and disadvantages of subcutaneous drugs?
pros: absorption slower than after im, and effect more prolonged, but has all the pros of im administration
-when oral route is not available; absorption is less variable than with oral route and less painful and more rapid than with sc
cons: has all the cons of im administration
-pain, sterile techniques, possible local necrosis, lag period before effect onset, accidental IV injection possible; not used after antigoagulant administration
what are advantages and disadvantages of intrathecal drugs?
(injection into spinal fluid)
pros: when local effect on CNS required and other route unsatisfactory (b/c of BBB)
cons: skill, danger of spinal cord injury
what are advantages and disadvantages of topical drugs?
pros: for local action on or under skin/membrane; non-invasive
cons: difficult to absorp through skin, and danger of excessive absorption through membranes and systemic toxicity
what are advantages and disadvantages of inhaled drugs?
pros: rapid absorption for systemic action; high concentration attainable for local effect; self administration possible
cons: possible excessive absorption and systemic toxicity; poor regulation of dosage; irritation of pulmonary
what is bioavailability and how is it measured?
fraction of dose available for biologic action (usually in regards to oral drugs)
=AUC oral / AUC iv X 100 where AUC = area under curve
-the higher the AUC, the higher the bioavailability
-this impacts the size of the dose given orally to achieve desired plasma level
how do you predict plasma concentration of a drug? what if there's significant limitations in bioavailability?
usually Cp = Dose / Vd (where Cp = concentration in plasma, and Vd = volume of distribution)
-but if bioavailability problems, then Cp = (F x Dose) / Vd
what is the limiting step in oral drugs?
why is measuring bioavailability important?
1. drugs that are potent in small doses
2. drugs given for serious illness
3. changes in drug manufacturer