Pharmacology Flashcards

Question

pH and charge

Answer 1

charged molecules DO NOT cross bio membranes well membrane are lipid, charges increase water solubility important for weak acids and bases - shift amout charged as a function of pH

Answer 2

weak acid only passes in HA form, not in charged form at low PH (sick, acidemic) - in HA form, more passes over membrane Pka = 3 at higher pH (physio) - most is chargd form and doesn't move across membrane, most is in blood

Answer 3

pH pH \> pKa - deprotonated forms mostly A-, B (acids stay in blood, bases cross)

Answer 4

couldn't revive after overdose gave a bolus of fat - cause drug to diffuse from tissue into blood because it became fatty - took all drug away from the heart increase BP

Answer 5

normally, acid in eq between tissues, plasma, urine if make uring really basic, make aspirin become uncharged and drag it out of tissues urine [ASA} increases as a function of pH

Answer 6

drugs that move slowly into compartments move slowly out of compartments extravascular compartment can serve as a reservoir to maintain high blood concentrations following chronic administration

Answer 7

digoxin overdose - lives in heart give Fab - big and can't leave blood but binds free digoxin and drags all of the drug into blood from heart

Answer 8

phase I - redox - reactive species made phase II - conjugation - reactive conjugates made phase II - elimination phase II can happen before phase I, can skip a phase or 2

Answer 9

prepare lipophilic drugs for the addition of functional groups or add the groups - convert to active/inactive/less active/prodrug to drug oxidation hydrolysis reduction dehydrogenation dealkylation

Answer 10

primarily CYP450 Phase I

Answer 11

phase 1 i.e. aspirin ASA + H2O --\> Salicylic acid (effect) + acetic acid (inactive)

Answer 12

3 phase I reactions, no phase II ethanol --\> acetylaldehyde --\> acetic acid (easily eliminated, not active) ethanol --\> acetyl aldehyde: CYP2E1, ADH (alcohol dehydrogenase, CATALASE acetylaldehyde --\> acetic acid : ALDH (aldehyde dehydrogenase)

Answer 13

Conjugation after Phase I or parent drug itself enhance solubility allowing increased renal and other pways to elimination detoxification - reduce toxic effects of parent/metabolized drug

Answer 14

most common phase II addition of glucuronic acid helps drug get out - doesn't always make it inactive morpine: add in diff spots, metabolites still a little active, some pain relief but not a lot

Answer 15

cytochromes - class of hemoproteins that transfers electrons between oxidized Fe3+ and reduced Fe2+ forms of iron predominatly responsible for Phase I drug metabolism

Answer 16

on smooth ER most in liver some in kidney some in intestine (in enterocytes of SI - contribute to "first pass" metabolism)

Answer 17

the concentration of a drug is greatly reduced before it reaches the systemic circulation After a drug is swallowed, it is absorbed by the digestive system and enters the hepatic portal system. It is carried through the portal vein into the liver before it reaches the rest of the body. The liver metabolizes many drugs, sometimes to such an extent that only a small amount of active drug emerges from the liver to the rest of the circulatory system. This first pass through the liver thus greatly reduces the bioavailability of the drug.

Answer 18

drugs, chemicals, hormones that undergo biotransfrmation via CYP450 depends on Km - if small, enzyme requires only a small amount to become saturated

Answer 19

alters enzyme activity resulting in decreased metabolism of substrate most common cause of drug-drug interactions can result in increased or decreased bioavailaiblity of a drug i.e. grapefruit

Answer 20

alters enzyme activity causing increased metabolism of substrate nuclear receptor mediated! gene transcription - more enzymes, more activity enhance druge effect beceuase increasted activity of prodrug to active druge decrease effect by enhanced elimination

Answer 21

concetration of substrate at which 50% max activity of the enzyme small Km - substrate only needs a small amt of substrate to be saturated large Km - need a lot to reach max V for substrate of CYP450 enzyme

Answer 22

low Km - ADH - at low amount, use ADH high Km - CYP2E1 - in alocholics, use mostly, metabilize better at high concentrations

Answer 23

depends on many properties i.e. S-warfarin and R-warfarin - work in diff CYP450

Answer 24

lowers cholesterol but can cause liver and muscle damage grapefruit juice in small intestine - inhibits CYP34A mediated first-pass metabolism - cause serious liver and muscle problems because severe statin toxicity

Answer 25

considered normal normal amt of enzyme and ddrug response

Answer 26

at least one gene isn't working normally less enzyme than normal may be less response OR more side effects

Answer 27

variants in both genes much less enzyme/not at all high risk for side effects, or may need higher drug if it needs to be broken down before it works

Answer 28

extra copies of CYP genes --\> more enzymes than normal may break some drugs down so quickly that don't work at usual doses may neeed a lower dose if it has to be metabolized before it works

Answer 29

enzyme activity is different in different regions i.e. codeine, needs to be broken down into morphine to work, no effect for poor metabilizers, toxic effect for ultrarapid metabolizers

Answer 30

sit on cell surface and actively pump drug out of cell ATP can move drugs against concentration gradient has inducers and inhibitorsactivel extrudes drugs back into intestinal lumen, also BBB, kidneys, liver bile ducts if inhibit - more intracellular = toxicity

Answer 31

PHASE II - sulfation/glucuronidation --\> detox and elim PHASE I - oxidation via CYP450 to NAPQI --\> phase II to detox and elim at therapeutic concentrations - Phase II reactions if overdose - make too much NAPQI, can't detox - toxicity to hepatocytes, poisn liver - centrally located holes in cells

Answer 32

GPCR hyperpolarizes post-synaptic neurons inhibits presynaptic nt release

Answer 33

abilinty of drug to bind its biological compartment how it gets on its receptor Kd = [L][R]/{LR] Ka = 1/[Kd}

Answer 34

high affinity! it will bind a greater number of a particular receptor at a lower concentration than a low affinity drug

Answer 35

low affinity

Answer 36

all will ultimately have the same effect but which has ED50 at the lowest dose

Answer 37

effect is notbinding once binding occurs what is the effect

Answer 38

median effective concentration how much is needed for 50% max effect - find where effect is 50% and drop down

Answer 39

provides max effect at given receptor

Answer 40

same efficacy but can never get 100%

Answer 41

drug that sits on R and does nothing if have agonist, can occupy and prevent agonist from working

Answer 42

if constituitively active - does opposite - gives decreased signaling up to 100%

Answer 43

noncovalent binding i.e. ibuprofen

Answer 44

permanent alteration i.e. aspirin at COX1

Answer 45

A and I acting at same site as increase antagonist - act at same site + reversible mass action - inhibits less - shift EC curve to the right! have to give more agonist

Answer 46

allosteric - binds and takes it out - doesn't mater if increase [agonist] pseudo-irreversible also

Answer 47

competitive (bind at same site) but noncompetitive! binds so tightly that it looks like non comp

Answer 48

smoking cessation drug partial agonist! withdrawl attenuation: stronger potency but partial agonist - relieves craving and withdrawl blocks nicotine induced domaminergic activation: partial agonist - if take nicotine with it, block reward

Answer 49

adaptation such that exposure to a drug induces changes that result in a decrease of one or more effects over time, or the nee for a higher dose to maintain an effect many mechanisms: desensitistation, internalization, downregulation

Answer 50

LD50/ED50 average!

Answer 51

window between efficacy and no toxicity ED50-LD1 (where 1 person dies)

Answer 52

very small TW - experiemental! keep between 2-3 need to test between benefit and hemorrhage

Answer 53

in a chiral environment, stereoisomers may have steroselective protein binding, transport, receptor, enzyme interactions ----\> diff effects i.e. Methodone is chiral

Answer 54

when EC50 \< Kd between the biologican resoinse you want and all of the receptors that are avaiable if EC50 = Kd - if you remove one receptor you will decrease efficacy

Answer 55

Kidney and liver

Answer 56

break in membrane bilayer - passive how big, soluble

Answer 57

FIRST ORDER filtration process how much drug is in concentration, in the system - into kidneys! more in blood --\> more scooped out - certain PERCENTAGE of total drug (dilution of remaining drug passes through the kidney again) percent/time concentration dependent

Answer 58

percent/unit time concentration dependent

Answer 59

slope of the line when drawn in natural logs how much you are removing - percent/time

Answer 60

.693/k(e) elimination constant! how much it takes for 1/2 of drug to be gone helps to dose medication correctly

Answer 61

ZERO ORDER limited number of enzymes - a certain amount of a drug can be broken down by unit time doesn't matter how much there is - concentration independent

Answer 62

enzymes - when concentration of drug is low - function based on blood flow and metabolize a certain percent per time (FIRST ORDER) and then when get overwhelmed (massive overdose) they switch to ZERO ORDER and are at capacity - metabolize a certain amount

Answer 63

analogous to the Vd - amount of blood that is totally removed of a drug in a unit of time Cl = rate of elimination/Cp (plasma concentration) vol/time total body clearance is sum total of all routes of elimination

Answer 64

when drug concentration remains relatively constant over time absorbtion and elimiation rates are equal! SS = absorption/elimination = rate in/rate out usually - 5 half lives to get steady state

Answer 65

dosing interval! how often you have to give a drug over a period time

Answer 66

first order process (like kidneys!) blood in, drug out remove certain amt in 4 hours factors favoring elim: small Vd, low protein binding, water soluble, molecular weight is small calculate how long patient needs to stay on HD to bring drug concentration down to an acceptible amount

Answer 67

decrease amount of drug absorbed enters enterohepatic ciruclation if IV drug - can still leave through feces