Pharmacology - Melega Flashcards Preview

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Flashcards in Pharmacology - Melega Deck (41)
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1
Melega lectures

medical model of disease

diseases are related to underlying derangement of normal function

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Melega lectures

Quantal dose-response curves (d-r)

- 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)

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Melega lectures

ED50

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

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Melega lectures

TD50

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

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Melega lectures

LD50

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

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Melega lectures

TI

Therapeutic Index: TD50/ED50

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Melega lectures

Pharmacodynamics

what the drug does to the body

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Melega lectures

pharmacokinetics

what the body does to the drug ADME

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Melega lectures

efficacy (drug)

refers to magnitude of response on d-r curve

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Melega lectures

potency (drug)

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

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Melega lectures

full vs partial agonist

full: maximal efficacy, partial: partial efficacy

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Melega lectures

spare receptors

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

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Melega lectures

constitutive activity of receptors

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

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Melega lectures

Kd

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

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Melega lectures

4 main targets of drugs

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

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Melega lectures

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

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

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Therapuetic window

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

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Bioavailability

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

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Factors affecting drug absorption

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

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enteral vs parental

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

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4 ways drugs cross membrane

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

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First Pass Effect

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.

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Ion trapping (drug distribution)

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

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metabolism

Need for Drug metabolism

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

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metabolism

Main Categories of drug metabolism (2)

(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

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metabolism

CYP P450 Enzymes

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

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metabolism

Phase I: Alcohol metabolism

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)

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metabolism

Phase I: monoamine oxidase

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

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metabolism

Phase I: hydrolysis

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

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metabolism

prodrug

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)