Pharmacology - Melega

Question 1

Melega lectures

medical model of disease

Answer 1

diseases are related to underlying derangement of normal function

Question 2

Melega lectures

Quantal dose-response curves (d-r)

Answer 2

• plots the fraction of population that responds to a given dose: response is recorded as either ‘present’ or ‘not present’ (it either occurs or does not occur). Log dose (x) vs %maximal response (or individuals responding)

Question 3

Melega lectures

ED50

Answer 3

amount of drug that produces a therapeutic response in 50% of the people taking it

Question 4

Melega lectures

TD50

Answer 4

amount of drug that produces a toxic response in 50% of the people taking it

Question 5

Melega lectures

LD50

Answer 5

amount of drug that produces a lethal response in 50% of the people taking it

Question 6

Melega lectures

TI

Answer 6

Therapeutic Index: TD50/ED50

Question 7

Melega lectures

Pharmacodynamics

Answer 7

what the drug does to the body

Question 8

Melega lectures

pharmacokinetics

Answer 8

what the body does to the drug ADME

Question 9

Melega lectures

efficacy (drug)

Answer 9

refers to magnitude of response on d-r curve

Question 10

Melega lectures

potency (drug)

Answer 10

Refers to effective concentration that produces 50% of its maximal response (EC50) when comparing two drugs with the same efficacy.

Question 11

Melega lectures

full vs partial agonist

Answer 11

full: maximal efficacy, partial: partial efficacy

Question 12

Melega lectures

spare receptors

Answer 12

even after brief introduction of irreversible antagonist, maximal efficacy still reached (bc cell had spare receptors that became activated)

Question 13

Melega lectures

constitutive activity of receptors

Answer 13

receptor isomerization between active and inactive forms. receptors have some activity even in absence of agonist

Question 14

Melega lectures

Kd

Answer 14

Kd is a measure of drug affinity (tendency to bind) for the receptor. Lower Kd = higher affinity since Kd=Koff/Kon

Question 15

Melega lectures

4 main targets of drugs

Answer 15

(1) ligand gated ion channels (2) G coupled proteins (3) enzymes (4) transporters

Question 16

Melega lectures

How does Exposure to Drug-Agonists Affect Receptor Function and Receptor Number

Answer 16

Short term: reduction in response tachyphylaxis. Long term response: decrease in receptor #. “receptor down regulation” less synthesis

Question 17

Therapuetic window

Answer 17

the range of doses that produce a therapeutic response, without unacceptable side effects; - an index of drug safety. Seen on a plasma drug vs time graph

Question 18

Bioavailability

Answer 18

the fraction of administered drug that reaches the systemic circulation. AUCoral/AUCiv x100 = % bioavailability

Question 19

Factors affecting drug absorption

Answer 19

(1) route of administration (2) membrane diffusion (3) metabolism (first pass effect)

Question 20

enteral vs parental

Answer 20

via GI tract (oral and rectal); easy, but first pass effect reduces bioavailability. Not GI tract (IV, sub-cutaneous etc), for drugs not easily absorbed. good for drugs that are poorly absorbed in GI

Question 21

4 ways drugs cross membrane

Answer 21

(1) diffusion (gradient) (2) facilitated diffusion (3) active transport (4) pinocytosis

Question 22

First Pass Effect

Answer 22

The intestinal & hepatic degradation or alteration of a drug taken by mouth, after absorption, removing some of the active substance from the blood before it enters the general circulation.

Question 23

Ion trapping (drug distribution)

Answer 23

only neutral molecule can diffuse across the membrane. Once inside the weak base dissociates and is “trapped” inside. Thus ions can enter but not exit. How much diffuses depends on pH of solution and pka

Question 24

metabolism

Need for Drug metabolism

Answer 24

Drugs are usually lipophilic (important for absorption). This makes them hard to excrete. Metabolism makes them more hydrophilic

Question 25

# metabolism Main Categories of drug metabolism (2)

Answer 25

(1) Phase 1 functionalization reactions: polar substrate is introduced via oxidation, reduction, hydrolysis. GOAL: make metabolites more H2O soluble. (2) Phase II reactions: Conjugate reactions. GOAL: make metabolites even more H2O soluble.A substrate (parent drug or phase I metabolite) is coupled to an endogenous compound such as glucuronic acid, glycine, or sulfate

Question 26

# metabolism CYP P450 Enzymes

Answer 26

Most important enzyme system for Phase I. Catalyze oxidation of organic substances (monooxygenase rxn). p450 embedded in ER of cells. Highest concentration found in Liver (GI, skin, lung etc also). Metabolism and detoxification of compounds enterring the body p.o

Question 27

# metabolism Phase I: Alcohol metabolism

Answer 27

alcohol dehydrogenase: alcohol to aldehyde (oxidation). Then oxidized again to carboxylic A. Side effect of excessive alcohol: decreased NAD+ levels and increased NADH. Increase in NADH pathways and decrease in NAD+ pathways (extremely dangerous if taking acetaminophen like tylenol which will then overwhelm liver)

Question 28

# metabolism Phase I: monoamine oxidase

Answer 28

MAO: non p450 phase I oxidation. Amines--\>aldehydes

Question 29

# metabolism Phase I: hydrolysis

Answer 29

Esterases are present in plasma and other tissues; they rapidly metabolize esters and amides to carboxylic acids. Ex:For short term anesthesia, succinylcholine is administered by infusion; its neuromuscular blocking effect is terminated rapidly by hydrolysis by plasma cholinesterase

Question 30

# metabolism prodrug

Answer 30

Drug is inactive before metabolism and is activated by metabolism. Designed to overcome delivery problems. 30% or all prescription drugs are prodrugs. Some metabolites of active drugs also are active (longer pharmacological action)

Question 31

# metabolism CYP p450: induction and inhibition

Answer 31

Induction: increase in p450 synthesis. protein synthesized so delayed effect--\> higher metabolism and decreased drug effect. Inhibition: competition with other drugs for active site of p450. reduces metabolism and increases drug action

Question 32

# metabolism Factors affecting individual differences in drug metabolism

Answer 32

Age: less p450 in older people (lower the dose for elder;y). Genetic differences (EM and PM extensive and poor metabolizers). Environment (other drugs health etc)

Question 33

# metabolism alcohol metabolisma and polymorphism

Answer 33

Asians often have a atypical type two ALDH (aldehyde dehydrogenase- second enzyme in pathway) leading to build up in acetaldehyde (nausea, tachycardia, and flushing)

Question 34

# B1W4Melega4-Pharmacokinetics bioequivalence

Answer 34

two drugs are bioequivalent if bioavailabilities are similar after administration (same dose)

Question 35

# B1W4Melega4-Pharmacokinetics Volume of distribution: Vd

Answer 35

Vd(L/Kg) = D(mg/kg)/C(mg/L) D=dose,C=plasma concentration. Def. Theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Therefore the dose required to give a certain plasma concentration can be determined if the VD for that drug is known.

Question 36

# B1W4Melega4-Pharmacokinetics Clearance

Answer 36

Cl= rate of elimination/plasma concentration. Clearance as a ratio is a constant. Most commonly measured as renal clearance but can also be liver clearance or total clearance when everything is summed

Question 37

# B1W4Melega4-Pharmacokinetics relation of 1/2life, clearance, and Vd

Answer 37

T1/2 = .693 Vd/Cl, since Cl = K x Vd and .693/K = T1/2

Question 38

# B1W4Melega4-Pharmacokinetics steady state concentration (Css)

Answer 38

input=output, no net change in concentration

Question 39

# B1W4Melega4-Pharmacokinetics loading dose

Answer 39

an initial higher dose given to push blood concentration into therapuetic range early on and after which a maintenance dose can be prescribed. loading dose = Vd x C(desired)

Question 40

# B1W4Melega4-Pharmacokinetics capacity limited elimination

Answer 40

saturation of enzyme or transporter

Question 41

# B1W4Melega4-Pharmacokinetics zero order kinetics

Answer 41

drug eliminated at a constant rate