Med Safety and Delivery Methods- Pharm Lec 1,2 & 3

what are some safety processes for rx prescribing? (generic)

clear writing

avoid error prone abbreviations

LASA meds

black box warnings

REMs

pregnancy considerations

antimicrobial stewardship

what is one way to mitigate mixups on LASA meds?

include the purpose on the rx for pharmacy

what does REMS stand for

risk

evaluation

mitigation

safety

What are REMS programs

drug safety program to help with making sure that medications with serious safety concerns are being prescribed appropriately→ benefits outweigh the risk

what is antimicrobial stewardship

help clinicians appropriately prescribe abx

help develop guidelines and educate

what is the definition of a drug

substance that affects the function of the body

what is pharmacology

science of drugs

• what they are

• what they do

• how they work

what is the definition of the mechanism of action

how the drug produces the reaction → the biochemical rxn

involves molecular targets

what is an antagonist-agonist receptor

ligand (drug) binds to a receptor while simultaneously blocking a separate receptor from being activated

competitive vs non competitive inhibitors

competitive- drug and substrate compete for binding site

non-competitive- drug binds and alters binding site so substrate cannot bind

what 3 things affect the pharmacologic profile of a drug

dose- quantity/route

timing- when and how often

response- predicted vs individual

what 4 routes of administration go straight to the circulatory system

buccal/SL

rectal

IV

Inhalation- circ and tissues

what is an elixir

flavored liquid with added sugar and/or ethanol→ for constipation

what is a suspension

liquid with sediment; must shake to disperse

delayed release vs extended release

delayed release- med delayed to release till past the stomach into SI

extended release- controlled continuous release of medication over a period of time

what routes of administration absorb faster than others?

buccal, SL, solution, suspension

what routes of administration absorb slowest?

enteric coated tablets, regular tablets

what is a bolus

fast 2-3 IV admin

what is a slow IV push

slower than bolus, over a few minutes

what is an IV piggyback

you add the medication on to IV fluids already running, for short periods of time

what is a continuous IV infusion

med in fluid bag, runs all day

subcu vs IM

subcu:

• 2ml dose

• slower absorption

• less painful

IM

• 5mL dose

• more painful

• faster absorption

what is the big con of inhaled meds?

imprecise technique- people do it wrong a lot

what is the target of a transdermal patch?

not the skin! the circulatory system

pros of topical therapy

avoid systemic effects

easy admin

con of topical vehicles

accidental transfer

localized irritation

what is a paste

ointment and powder mixed!

adheres better than powder, less greasy than ointment

in what situation/are would you use a ointment

to hold moisture in, very dry areas, thickened skin, occlusive properties

in what situation/are would you use a cream

most versatile! all areas, spreadable, dry skin

in what situation/are would you use a gel

hairy areas, cooling effect, for face too

in what situation/are would you use a lotion

more watery and spreadable than cream so good for large areas

hairy areas bc lighter than cream

in what situation/are would you use a solution

“thinner” lotion

easy to spread, hairy areas

in what situation/are would you use a foam

hairy area, not for hydrating purposes→ for sensitive or oily areas

in what situation/are would you use a spray

large areas, cooling effect, hard to reach areas

what area of skin is most permeable?

mucous membranes

scrotum

eyelids/face

what area of the skin is the least permeable

nails

palms and soles

what is absorption

how the drug gets into the body

everything that happens before the drug enters systemic circulation

ex of absorption

drug gets in via skin, go tract, bloodstream, etc

what is distribution

where the drug goes in the body

what is metabolism

how the drug is processed and broken down

where are the sites of metabolism

liver, kidneys, gi tract

what is excretion

where the drug is eliminated

what is pharmacokinetics

what the BODY does to the drug

what are the 4 components of pharmacokinetics

absorption, distribution, metabolism, excretion

how are iv drugs absorbed?

they aren’t, they go directly into systemic circulation

drug is taken orally and makes its way to the stomach

what phase is the drug in?

absorption

what is bioavailability

the percent of a drug that gets into systemic circulation

what drug has the highest bioavailability

IV drugs

what is first pass metabolism

the portion of the drug that is inactivated by the liver prior to any of the drug reaching the bloodstreamwh

what type of drug is most affected by first pass metabolism?

oral meds

when does distribution start

once drug gets into vascular space

where can drugs be distributed too

fat, muscle, tissue, interstitial space, remain in blood and bind (albumin) vs not bind

what is the volume of distribution

the volume of body where drug travels to

high volume of distribution means

drug has spread to many different parts of the body

low volume of distribution means

the drug stays in the blood and does not redistribute to other tissues

what case would we adjust the dose of a medication for the first pass effect?

cases where the liver isn’t doing its job

what are some properties that would increase the volume of distribution of a drug?

small molecule size

uncharged

highly lipid soluble

dec protein binding

what are some patient factors that influence Vd?

age

sex/gender

hydration - low hydration=low Vd

water distribution- kidney failure, CHF→ all inc Vd

body weight

if you have a patient with kidney failure how will that affect Vd?

inc vd; more fluid in body means the drug can distribute further

what is a loading dose?

larger dose prescribed to ensure that enough drug reaches the site of action

what is used to calculate the loading dose?

the vd, we are looking at if a drug naturally has a high Vd or if not, they may need a loading dose to ensure drug reaches intended site of action and has the effect we want WHEN we want it

how does protein binding affect Vd?

proteins can bind up drug (albumin) → bound drugs can’t do their jobs→ drug can’t get to site of action → low Vd

In what cases would you want to give a patient a loading dose?

drug has low vd

we need to get drug to a certain site of action FAST

what happens to Vd if pt is malnourished

less proteins to bind drug→ more unbound drug→ more of an effect→ higher Vd→ can be good or bad

where does absorption occur?

GI tract, everything before systemic circulation reached

where does distribution occur?

vascular system→ to other tissues

what are the 2 big components of distribution

protein binding and volume of distribution

what routes of drug admin are subject to first pass effect?

oral meds

what routes of drug admin are NOT subject to first pass effect?

IV, buccal, transdermal, rectal, inhalational

what is a half life of a drug?

time required for serum concentrations of a drug to decrease by one half after absorption and distribution are done.

what is it called when the drug concentration is consistent in the body?

steady state

how many half lives does it take for a drug to reach steady state (usually)?

3-5

where does metabolism happen?

liver usually

gi tract wall, kidneys, lungs, blood

what is the definition of metabolism?

the irreversible transformation of drug into daughter compounds

what performs the transformation of drug to daughter components

enzymes

cytochrome P450

3 ways drugs can be metabolized

active→ inactive form

inactive→ active form (prodrug)

lipid form of drug → something more excretable, makes more polar for excretion

what type of enzyme is responsible for most drug metabolism rxns

cytochrome P450 enzymes

how can drugs affect CYP450 enzymes

can induce them and inhibit them

what are membrane transporters

proteins that help with actively transporting drugs across cell membranes

how do we get CYP enzymes?

they are genetically encoded

where can we find membrane transporters

intestines, liver, kidneys, and blood brain barrier

what is excretion?

removal of substance from body

where does excretion occur?

kidneys

what are some extrinsic factors that can impact pharmacokinetics?

smoking, diet, alcohol use, other drugs, environment

what are some patient factors that can affect elimination?

kidney function- blood flow to kidney? efficiency of kidney?

Creatinine clearance

measures how efficient kidneys are → normal kidneys filter creatinine out from blood into urine efficiently, if the kidneys are messed up then they won’t filter creatinine out well

measures how much blood the kidneys can filter creatinine out of in 1 minute- 120 mL/min

what would be the next course of action if you gave an active parent drug to a patient but the CYP enzymes were induced by other drugs?

you would need to increase the amount of drug you are giving that the CYP enzymes are acting on

what would be the next course of action if you gave an active drug to a patient but the CYP enzymes were inhibited by other drugs?

you would need to reduce the dose of the active drug the CYP enzymes are acting on

what are some membrane transport super families

P-glycoprotein

organic anion transporters

what are the 2 biggest reasons you would adjust a dose for a patient

kidney and liver function

what is pharmacodynamics

what the DRUG does to the BODY

drug receptor complex def

drug binds receptor and then there is a response

what is pharmacogenetics

single gene effect on how a drug works in the body

what is pharmacogenomics

many genes effect on how a drug works in the body

wild type allele

most common or reference type allele

*1

variant or polymorphic allele

the “unusual” alelle

the reason why someone may have an issue

homozygous alleles

two identical allelesh

heterozygous alleles

2 different alleles

phenotype

the observable characteristics of a person

hair, eye color etc

what are some phenotype examples of pharmacokinetics

metabolism: ultrarapid, normal, intermediate, poor