nurs 116 lecture 2

stopped at half-life

where are most po drugs absorbed?

where are most po drugs absorbed?

>90% absorbed by villi in sm int (duodenum, jejenum)

GI mucosa absorption drugs to known

amy ate caffeine with pie

alcohol

aspirin (ASA)

caffeine

warfarin (coumadin)

phenytoin (dilatin)

what is distribution?

transportation of drug to target tissue

factors affecting distribution

1. *blood flow to the tissue (ex. CO, BBB, injury)

2. size of tissue

3. molecular characteristics (lipohilicity, size, ionization)

4. PPB

% of blood flow to organs at rest from most to least

1. liver (25%)

2. kidney/muscles (20%)

3. brain (18%)

4. skin (7%)

5. bone marrow/heart (5%)

what allows for selective transport of substances through BBB?

p-glycoprotein pump

where is the exception of the BBB?

the hypothalamus. it is needed to relay info about toxicity to chemoreceptors

structure of BBB

endothelial cell —> basement membrane —> astrocytes with tight junctions

what binds to albumins?

acidic drugs like ASA

what binds to alpha-1-acid glycoprotein

basic drugs

what does PPB do to distribution?

decreases it

characteristics of PPB

competitive, reversible, saturable

unbound vs. bound drugs

unbound = effective

bound = not effective

drugs extensively bound (>90) - worthless imps need fat dumplings

warfarin

ibuprofen

naproxen

furosemide

digitoxin

volume of distribution (vd)

estimates how extensively a drug is distributed into tissue

-assumes total drug equally reaches tissue

-relative comparison ONLY

vd calculation

drug dose/plasma concentration

metabolism/biotransformation

an enzymatic chemical conversion to prepare the drug/substance for excretion

what does biotransformation cause?

termination of drug action

what are other metabolizing organs?

lungs, kidneys, mouth (saliva)

what does the liver contain for biotransformation?

hepatic microsomal enzymes

-P450 system

types of biotransformation metabolization

1. active drug to inactive metabolite

2. active drug to active metabolite

3. inactive drug to active metabolite (prodrug)

example of prodrug

codeine —> morphine

T or F: kids can have codeine

F

phase 1 metabolism

-hydrolysis, reduction, oxidation

-remove hydrogen and add oxygen (polar metabolite)

-CYP450 enzyme group

main CYP450 enzyme groups

1. CYP3A4/5 - 50% of drugs use

2. CYP2D6

3. CYP2C8/9

4. CYP1A2

what metabolized acetaminophen?

CYP 3A4/1A2

CYP 3A4/1A2 inducer vs. inhibitor for acetaminophen

inducer: tobacco

inhibitor: some antibiotics

phase 2 metabolism

-conjugation (side chain addition) and polarization

acetaminophen phase 2 metabolism

acetaminophen —> phase 1 —> n-acetyl-p-benzo (NAPB) —> hepatoxic —> phase 2 —> glutathione enzyme conjugation —> inactive metabolite

consequence of tylenol overdose

depletes glutathione which lets the hepatoxic metabolite to build up in the tissue

what is the primary organ of excretion?

kidney

other excretory pathways

saliva, bile, lungs

biliary excretion pathway

drugs —> bile —> duodenum —> lg int —> feces

what % of unchanged drugs does the kidney excrete?

30%

general pathway of kidney excretion

afferent —> glom capsule —> efferent

ideal molecular characteristics for renal excretion?

ionization, hydrophilicity, small size

excretion + PPB?

not excreted

excretion + metabolisation?

excreted only if metabolized/unchanged throughout

excretion + urinary pH?

pH of filtrate is changed for excretion

acid in alkaline filtrate (vice versa)

ionized —> secreted —> excreted

example of urinary pH being changed for excretion?

ASA (acidic) + NaCO3 admin to pt = ionized —> excrete

factors affecting renal excretion

molecular characteristics, cardiac output, renal function

what is normal GFR function

125 mL/min

write out the cockcroft-gault formula for estimating creatinine clearance

CrCL (ml/min) = (((140-age) x lean body weight (kg))/(serum creatinine (mg/dL) x 72)) x (0.85 if female)

what is clearance (cl)

rate of elimination of drug in an hour

1st order elimination kinetics

most drugs, readily metabolized in the liver

elimination proportionate to the drug serum (mg/dL or L)

how is Cl calculated (1st order)

elimination/peak plasma concentration (mg/dL/hr)

zero order elimination kinetics

rate of elimination is constant

zero order drugs

every ass poops

-etoh

-aspirin (ASA)

-phenytoin (dilantin)

what is half-life

time required for cmax drug plasma concentration to decrease by 50%

T or F: if a drug has a long half-life, it takes a short time to be excreted

F

why is half-life important?

guidelines for frequency of drug administration

how long does it take for a drug to be >90% cleared?

4 x halflife

zero order kinetics saturable drug examples

alcohol

aspirin, phenytoin (in excess)

drug-receptor binding factors

saturable

increases or suppresses existing processes

blocks the receptor

recepter affinity

strength/length of binding

specific, saturable, reversible

what type of drugs perform a necessary action, but negatively affect the cell?

cytotoxic drugs that kill cells for cancer tx

do antagonists have efficacy?

most don’t. they only block receptors

drug A is 20mg and drug B is 10mg. which one is more potent?

drug B

what is an agonist

mimics an endogenous substance

binds readily for very good effects

what does morphine mimic?

endorphins

primary agonist

extensively & successfully binds to existing receptor

partial agonist

maximum response is smaller even if all receptors occupied

lower efficacy

what’s the issue with using a partial agonist?

in the presence of a full agonist, it acts as an antagonist

what does buprenorphine act as an antagonist to?

morphine b/c they go for the same receptors

inverse agonists

induce opposite effect of the naturally binding substance

caffeine properties

inverse agonist

mostly hydrophilic, lipophilic enough to have an effect

does not bind to alpha/beta receptors

what receptors does caffeine bind to for an inverse effect?

adenosine receptors, which are used for a calming effect

what type of -gonist is naxalone?

antagonist. stronger affinity to opioid receptors, so it knocks it off for a short time to reverse OD

6 major types of receptors

g-protein (GPCR)

ion channels

nuclear receptors

intracellular enzymes

transmembrane enzymes

non-enzyme (JAK-STAT)

majority of ion channels that drugs bind to?

voltage gated channels

lidocaine

closed ion channels that prevent pain transfer

nuclear receptors

aka steroid receptors

most bind in cytoplasm = change cell fx via DNA

example of nuclear receptor ligand

hormones

example of enzyme binding (insulin)

insulin binds to cell membrane receptors to stim transmembrane enzyme tyrosine kinase —> activate cellular glucose uptake

JAK-STAT receptors used by what?

interferons

drug tolerance

aka down regulation: receptor de-sensitization or decreased number of viable receptors

most common

drug resistance

drug is less effective bc of PK changes

ex. increased drug metabolism —> less bioavailable —> less effective

T or F: drug resistance = antibiotic resistance

NO

antibiotic resistance

bacteria acquires resistance