Unit 1 - Basic Principles of Pharmacology

Question 1

drug action VS drug effect

Answer 1

molecular action is invisible

pharmacologic effect shoes visible response

Question 2

define selectivity

Answer 2

selectivity: property of drug to cause a specific effect

- few drugs produce a single effect

Question 3

primary VS secondary effects

Answer 3

primary: desired
secondary: “side effects” that may or may not be desired

Question 4

pharmokinetics VS pharmodynamics

Answer 4

kinetics: time course of drug absorption, actions, and elimination
dynamics: types of drug actions

Question 5

what are the types of pharmodynamics?

Answer 5

physiochemical actions - simple chemical interactions
-ex: antacids, antiseptics not very specific
receptor interactions - interaction of drug with physiologic receptors (most drugs are macromolecules)

Question 6

drug-receptor interactions

Answer 6

cause molecular events to occur in each cell

-enough of events cause change in cell function resulting in change in tissue function

Question 7

information on drug receptors

Answer 7

• 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

Question 8

when is a maximal response achieved?

Answer 8

related to number of drug receptor interactions and physiologic capacity of tissue (healthy VS diseased)

Question 9

what are 5 types of receptors and examples?

Answer 9

membrane-bound: neural synapse, ion channels
enzymes: intracellular or extracellular
structural macromolecules: microtubules
intracellular macromolecules: steroid receptors, RNA
cell membrane: change electrical potential, fluidity

Question 10

receptor amplification and transduction

Answer 10

drug-receptor interactions last fractions of seconds and activate G protein activity that lasts for seconds

Question 11

information on G proteins

Answer 11

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

Question 12

receptor theory

Answer 12

structure-activity relationships

• 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

Question 13

log dose response curve characteristics

• threshold
• slope
• maximal asymptote

Answer 13

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

Question 14

receptor occupancy

Answer 14

intensity of response is proportional to fraction of receptors occupied

• effect = Emax * [D] / KD + [D]
• where Kd = EC50

Question 15

intrinsic activity

Answer 15

ability to stimulate receptor once bound

• relates to structure and influences efficacy and potency
• greater intrinsic activity = greater efficacy (brings to Emax)

Question 16

spare receptors

Answer 16

not all receptors need to be occupied to achieve Emax

-less efficacious agonists need to occupy more receptors than highly efficacious agonists

Question 17

secondary receptors

Answer 17

outside of target tissue(s), may mediate other effects (side effects)

Question 18

receptor regulation

Answer 18

a cell can up or downregulate a population of receptors by changing the total number of receptors or their sensitivity

Question 19

difference between binding site and effector portion

Answer 19

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

Question 20

what are the two ways of quantifying agonism?

Answer 20

efficacy and potency

Question 21

what is efficacy? what does it depend on?

Answer 21

ability of drug to activate effector portion of receptor once drug is bound to receptor
-depends on structure of the drug

Question 22

what is potency? what does it depend on?

Answer 22

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)

Question 23

types of noncompetitive antagonism

Answer 23

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

Question 24

filtration

Answer 24

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

Question 25

micropinocytosis

Answer 25

active process where drug is transported in pinched off packets of single layer membrane

Question 26

what are characteristics of weak electrolyte drugs?

Answer 26

nonionized forms - diffuse - lipid soluble - concentration gradient ionized forms - do not diffuse both weak acids and bases

Question 27

what does the ratio of ionized to nonionized forms estimate?

Answer 27

ease of absorption at a particular pH can be predicted

Question 28

are weak acid or weak base drugs absorbed better in the stomach?

Answer 28

weak acids | -weak bases generally stay in the GIT

Question 29

what are 4 considerations for routes of administration?

Answer 29

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

Question 30

what are advantages and disadvantages of oral drug routes?

Answer 30

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

Question 31

what is the "first pass" effect

Answer 31

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

Question 32

what are advantages and disadvantages of rectal drugs?

Answer 32

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

Question 33

what are advantages and disadvantages of sublingual drugs?

Answer 33

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)

Question 34

what are advantages and disadvantages of intravenous drugs?

Answer 34

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

Question 35

what are advantages and disadvantages of intraarterial drugs?

Answer 35

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

Question 36

what are advantages and disadvantages of intramuscular drugs?

Answer 36

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

Question 37

what are advantages and disadvantages of subcutaneous drugs?

Answer 37

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

Question 38

what are advantages and disadvantages of intrathecal drugs?

Answer 38

(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

Question 39

what are advantages and disadvantages of topical drugs?

Answer 39

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

Question 40

what are advantages and disadvantages of inhaled drugs?

Answer 40

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

Question 41

what is bioavailability and how is it measured?

Answer 41

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

Question 42

how do you predict plasma concentration of a drug? what if there's significant limitations in bioavailability?

Answer 42

usually Cp = Dose / Vd (where Cp = concentration in plasma, and Vd = volume of distribution) -but if bioavailability problems, then Cp = (F x Dose) / Vd

Question 43

what is the limiting step in oral drugs?

Answer 43

dissolution

Question 44

why is measuring bioavailability important?

Answer 44

1. drugs that are potent in small doses 2. drugs given for serious illness 3. changes in drug manufacturer

Question 45

what are enteral and parenteral factors affecting absorption?

Answer 45

enteral: form of drug, food in stomach, illness, blood flow - absorbed quickest to slowest: solution > suspension > capsule > tablet > timed release parenteral: blood flow, heat, cold, illness (wafer, rods, injection in oil, transcutaneous patch)