Pharm 1

Zyrtec known as

serotine

Benadryl

diphenhydramine

Claritin

loratadine

hydroxyzine

the other gen 1

Allegra

fexofenadine

pharmkinetics

actions of the body on the drug

ADME

1. absorption:

2. distribution

3. metabolism/biotransformation

4. elimination/ excretion - without this step every medication would be toxic cause there is no way to leave. Majority is excreted through the kidneys

pharmdyanmics

the drug actions on the body

routes of administrations

1. oral: PO, has some most of the complicated pathways of absorption and there is differences all the times EX. if the medication is take with food or not. could make a different if a medication is affective or has side affects.

   1. Can be enteric coated prevents stomach acid from dissolving.

   2. extended-release coating that controls the drug release that allows slower absorption and prolonged duration of action and good for drugs with half short life (could take the drug multiple times a day but then adherence would go down) each bead as its own capsule for the coating- which means it can not be cut in half. After bariatric surgery modified coated drug does not work well.

   3. Sublingual/ buccal- placement of drug in cheek and gum

2. Parenteral” introduces drug into systemic circulation

   1. IV administration: does not need absorption because going into blood supply and is the most rapid

   2. intramuscular

   3. subcutaneous

   4. intradermal- normally for diagnostic test ex TB

other routs

oral inhalation nasal prep

topical

transdermal

rectal- good for when patients always vomit

bb

look back to see what miss

barriers to drugs crossing cell membrane

1. lipophilic v hydrophilic- lipids drugs cross more easily

2. size ionization- large molecules may struggle to penetrate membrane-

   1. pH difference affects the drug ionization, if the drug has a charge on it will have a hard time

+

absorption

drugs movement form site of administration into the blood

1. passive diffusion- goes with concentration gradient

2. facilitated diffusion

3. active transportation- needs proteins and energy

4. endocytosis - the cell engulfing the drug and used for very large molecules Ex. vit B 12

factors that influence absorption

1. dissolution rate (pH of drug and absorption site): increase dissolution means increase absorption

2. blood flow to the absorption site: increase perfusion means increase absorption

3. total SA

4. lipophilicity

5. expression of P-glycoprotein (pump things outside the cells so it kicks the drugs back out): increase P-glycoprotein means decrease absorption

how pH affects absorption example: drug A has pKa 7.8 at which site will absorption of drug be able to readily pass through the membrane: Mouth 7.0, stomach 2.5, duodenum 6.1, jejunum 8.0-

acids ionize in basic media while bases ionize in acidic media. When it is non ionized it absorbs the easiest.

IN pH gradients the acidic drugs accumulate on the alkaline side while that basic drug accumulate on the acidic side

Answer= the last one

Bioavilability

amount of active drug that reaches systemic absorption varies depending on the route of action (IV=100) other drugs it depends on the med meaning changes in doses based on the RoA

F - abbreviated to capital F

bioequivalence

when 2 products are equal in rate and extent to which active ingredients avliavble at site of drug testing exam brand v generic name of drugs

first pass metab

% of the drug that is metabolized by the liver before making it to the site of action- can further reduce the bioavailability

rectal first pass?

50% of drug absorbed will bypass the first pass system

Distribution

the transport of a drug at the site of absorption to various tissue in the body. Influenced by:

-CO

-blood flow

-capillary permeability

-lipophilicity

-volume of distribution

-binding to proteins

protein binding

albumin is the most prevalent protein in the plasma and the most important of the proteins to which it binds- when drug is bonded to albumin it is not having any effect on the body.

only unbounded (free) drug molecules ca leave the vascular system

protein bound molecules are too large to fit through the pores in the capillary wall

ex: pt with liver disease or kidney - has less albumin- important to keep in mind

crossing the BBB

can no be ionized or pilar

volume of distribution

theoretical concept that is the best way to gage how medication has moved around the body

amount of drug in the body over concentration in the blood

important for:

1. dosing decisions

2. where the drug is accumulation

3. how fast the drugs is being cleared

4. how concern you should be for toxicity

drug has a high molecular weight and bound to albumin, the drug will likely have a blank apparent volume of disruption

low- not able to get into body easily so dominator is larger because the drug is stuck in the blood stream

what are characteristics of a medication that remains in the bloodstream

large size

charges

plasma protein bound- more acidic compounds

ex: heparin anticoagulation that needs to work with clotting factors

metabolism

breakdown of a drug so it can be eliminated from the body

most drugs metab takes place in liver performed by cytochrome P450

substrate

the drug upon which an enzyme acts on

phase 1 metab

lipophilic drugs to hydrophilic polar substrates utilizes the p450 system, enzyme that breaks down drugs

enzyme induction

increase CYP 450 enzyme and decrease concentration of the drug which means you have to up the dose due to the decrease expected drug concentration

enzyme inhibition

results in decrease CYP 450 enzyme activity and increase concentration causing that there will be more of the drug taking the affect causing toxicity

drugs that have gone through phase 1

may go through phase 2 might not

drugs can jump to phase 2

phase 2= conjugation reactions happens when the metabolites are still lipophilic to be excreted so they do conjugation to make them polar and water soluble - sometimes the drug become inactive or active during phase 1

ex pro drugs are not active until phase one metabolism

usually after phase 2 the drug will become inactive

in liver disease which phase of drug breakdown is mostly affected

Phase 1 is more affect

so pt with liver disease needs medication that is breakdown mainly though phase 2

Drug A is metabolized by CYP3A4 while Drug B is an inducer what effect may occur, what actions should be considered

decrease concentration of drug A, increase the dose of Drug A

special consideration around metabolism

1. Age: infants do not have full metab capability until 1 year, older adults decrease ability

2. liver disease

3. drug tolerance

Excretion

kidney is the most important organ from drug excretion

others: biliary, fecal, breast milk, sweat, salvia, expiration

clearance= efficiency of drug removal decrease clearance (kidney disease) means decreased execration may need a lower dose to increase half life

renal excretion

1. GFR - only unbounded drug is filtered (drug enters with the blood and dependent on the GFR duh filtration step)

2. PCT: actively secreted into the tubules to increase drug loss

3. DCT: drugs can be reabsorbed back into systemic circulation. Happens for lipid soluble drugs, pH and ionization of drug can impact extent

how to determine pt renal function

creatine clearance used the CrCl equation to measure volume of blood plasma cleared per unit time

need the age, mass, sex, creatin serum levels

she will give you the equation on exam do not have to memorize this specific equation

normally 120 mL per min- but normal alternates

pt with renal disease needs drug x what would likely occur

increase affect because unable to filter and decrease the dosage - what

loading dose

large initial dose to achieve plateau more quickly

mechanical dose

rate of drug administration equal to rate of elimination at a steady state, smaller dose to maintain plateau

discontinuouation

94% of the drug is gone after 4 half lives

drug had half life of nine hours when will drug reach steady state

45 hours

takes 4-5 half life to achieves steady state

pharmacodynamics def again

what the drug does to the body

therapeutic affect + adverse effects

usually do not do novel activities- new interactions

drugs normally activate/ inhibit a pathway of something happening. Altering the pace.

Mechanism of action

effect happens when the drug (ligand) bind to the receptor

our body had endenous ligands

receptors are on or in a cell and when a drug binds an effect occurs

drugs act as signals

receptor family types

1. ligand gated ion channels: remain close until activated by agonist, once open there can be an exchange of ions (aka action potential)

2. G protein- coupled receptors =: extracellular ligand binding cause intracellular G protein interactions, cause further action within the cell by second massagers

3. enzyme linked receptors: extracellular receptor, when the ligand bind to receptor it changes the shape of the receptors that triggers intracellular cascade reaction

4. intracellular: primary targets are transcriptions factors that regulate gene expression inside the cell because they are lipid soluble and can enter the cell

when they do not like lipids ligands interact with receptors on the cell surface

onset of action is affect by

route of administration and drug dosage

think IV is quick

duration of action depends on

dosage

how it distributed

metab rate

execration rate

dose response relationship

how increase dose increase the effect

at a point (platue) no matter how much we increase dose no change in effect

flat

linear

platue

MEC min effective concentration

plasma drug level less than therapeutic effect will not occur

toxic concentration

no more therapeutic effect and can cause harm (platue phase)

therapeutic range

in-between the MEC and toxic concentration (linear part of the curve)

ED 50

dose at which 50% people who took it had theurputic response

LD50

50% who took this dose died

TI

the ration of a drug LD50 to ED 50 reflects a drugs safety, the larger the ration the difference between the therapeutic dose and lethal those means that larger T1 reflect greater safety

Narrow TI

need labs to monitor to make sure that the dose is affective and not at lethal range the periodic labels allow for opportunists for fine tunning the dose

simple occupancy th

intensity of the response is proportional to the numbers of receptors occupied

a max response will occur with all available receptors have been occupied - when all receptors are bonded that is the max result of the drug

modified occupancy th

the intensity of response is no proportional to number off receptors occupied influenced by drug-receptor interactions:

1. affinity: the strength of the attraction between drug and receptor

2. intrinsic activity: the ability of a drug to activate the receptor after binding

potency

comparing drugs

how much of the drug is required to get the desired result

efficacy

what is the maximal response this drug can produce think absolute value

greater efficacy> greater potency

beyond the max point the efficacy does not increase it will only increase adverse effects and toxicity

potency v. efficacy

1. Potency refers to the amount of drug needed to produce a specific effect.

   1. Efficacy is the maximum effect a drug can achieve, regardless of dose.

ended on slide 27

biggest category for substances involved in human exposure

analgesics - over the counter and prescription medication mostly from people not using there medication correctly

what to looks for with a poison patient

puiple size size, RR(might have to manually retake, temp, skin, tremor, ankle, clonus

hemodialysis

can help speed up elimination if the toxin has low protein binding, small Vd, water soluble, small molecular weightur

urinary alkinalinization

pee more acidic

activated charcoal

best used within an hour of ingesting toxin, can cause some poison to absorb to the charcoal- very porous (high surface area) which is why it is so effective

important to test bowel sounds for obstruction because will worsen

only work on substances but not on heavy metals, alc, corrosive, iron, hydrocarbons inorganic minerals

activated charcoal can still have some benefit after the one hour window

gastric emptying

forceful vomiting must be one 1-3 hours not used as much because many toxins are more harmful on the way up

whole bowel irrigation

uses laxative medication - profound laxative effect meaning all content of GI tract will be evacuated do not use with absent bowel sounds, cardiovascular, renal, or electrolyte imbalance

simulates GIT motility

dermal decontamination

contaminated clothing should be completely removed and double bagged to prevent contamination others and for lab testing

skin should be thoroughly cleaned in general water in copious amounts is the decontaminant of choice for skin irrigation

mixing heavy metal chemicals and water not good cause metalic forms can be active

common pharm toxins

acetaminophen

opioids

benzo

organophosphate

methemoglobinemia

in the reading: methanol, isopropanol, cyanide, iron, lead- is material you are responsible for

acetaminophen

too much NAPQI normal byproduct of hepatotoxic metabolite glutathione in liver detoxify NAPQI but when too much liver unable to keep up

max dose= 4000mg/day

S: abdominal pain, jaundice

labs 4-24 post inject will determine need for N Acetylcysteine (antidote)

intreated can mean acute liver failure, common, death, encephalopathy- could take weeks

Rumack-Matthewnomogram to determine the next step

Review of action potential

1. resting state- cell is neg

2. trigger

3. sodium- makes the cell positive

4. potassium- potassium leaving the cell causing the cell to become neg

5. hyperpolarization: too much potassium leaves

opioid

cause hyperpolarization means that the neurons are not firing as much:

repressed RR

lower HR

reduce consciousness

constipation

pinpoint pupils

Narcan- naloxone opioid receptor antagonist - is pretty short acting so may need multiple administration may be needed - they are not going to feel well with antidote because they will feel withdraw symptoms

opioid the same receptor with a higher affinity means it kicks of the opioid that are currently on that receptor.

exitatory pathways

like Ach

stimulate ion movement= depolarization of post synaptic membrane

inhibitory pathways

GABA

BB

organophosphate posining

inhibits AchE the enzyme that breaks down Ach means there will be an overstimulation of acetylcholine

DUMBELLSS- cholinergic effects

medication- atropine is a muscarinic agnost?

acquired methemoglobinemia

oxidize hemoglobin means the hemoglobin can not bind and release oxygen well can be caused by a variority of chemicals and medication. Giving supplemental O2 will not help these patients they need methylene blue (dont have to know mech) know that can turn pt urine green or blue

anyone works on a farm what should you think

organophosphate poisoning

pinpoint pupils, tearing, bradycardia, excessive saliva and tears- choleric effects

you should give atropine

NAC

can be over the counter as well used for aceteophinophine regimen

main factors for individual drug response

• drug factors- like the route

• clinical factors

• environmental

• genetic

range means one person med work greats and in another they dead

liver disease

reduce albumin means more free drug which is more active drug

acid base imbalance

change in blood, urine ph affects if the drug is in the ionized or not ionized state so affects where it can be absorbed. An imbalance can cause the chemical to get stuck in a specific tissue.

genetic variant and genetic polymorphism

variant- changes to DNA sequence -both rare and common

polymorphisms- a variant that is common in the population - more than 1 %- example different blood type

can influence how drugs are metabolized

SNP single nucleotide polymorphism

one letter difference in the DNA sequence (most common variation in DNA) To be a SNP must be present in more than 1% of population

PGx variants

PGx variants are typically found in 3 main types of genes:

1. drug metab enzyme genes

2. drug transport releated genes

3. immune system genes- predisposed hypersensitivity to a drug

star represent a specific variant of the allele

start 1& no function

star 17 increased expression means they would be a rapid metabolizer