pharm 3 toxicity

toxicity

being noxious -drug or substance out of therapeutic range and eliciting change in the body

administration

drug form, route of drug admin, drug interactions all can influence patient response to toxicity

pharmacodynamics

onset, peak, and duration -therapeutic range -side effects, adverse reactions -assess reactions to see possible cause -all effect patient response

clinical factors

age, weight, gender, ethnicity, present health disorders, other disease entities, client drug compliance can all effect patient response -these especially can impact metabolism

pharmacokinetics

absorption, distribution, metabolism (t1/2), excretion

genetic differences and ADME

different ethnicities metabolize things different and its important to know that when giving drugs -genetic polymorphisms

genetic polymorphisms in liver enzymes

eg. decreased CYP2D6 enzyme = reduced metabolism of specific drugs, risk of toxicity + reduced metabolism of prodrugs (codeine) risk of low efficacy

pregnancy category A

appropriate human studies no risk -like maternal vitamins

pregnancy category B

insufficient human studies but animal research suggests safety or animal studies show issues but human studies show safety

pregnancy C

insufficient human studies, but animal studies show problems or no animal studies, and insufficient human studies -risk vs benefit which one out weighs other and is there any other drugs that can be used

pregnancy D

human studies, with/without animal research shows fetal risks, but the drug is important to some women to treat their conditions -risk vs benefit which one out weighs other and is there any other drugs that can be used

X

fetal risks are evident; there are no situations where the risk/benefit justifies use

altered GI fx

during pregnancy -delayed GI emptying, drugs take longer to absorb -decreased acidity

higher blood volume

up by 50% during pregnancy, higher CO due to blood flow to placenta -higher HR, decreased PPB, higher GFR = higher elimination of drugs

during pregnancy

most drugs cross into placenta and into breastmilk -high Vd drugs; A & D characteristics

not during breastfeeding

when you can’t have ibuprofen and opioids

pediatric pharmacotherapy

calculated by body mass -per kg of body weight -blood volume way less -caregiver dependent

teens

curious, usually use for cramps, sport injuries, skin problems -need to educate on STIs and

organ fx young

neonates and young infants have lower liver and renal function -need to check -creatinine clearance, liver enzymes, urine volume/hr

decreased organ fx

GI: decreased peristalsis, acidity, elimination -renal: decreased GFR -Lung: shallower resps

older adult

lower albumin (affects PPB), decreased CO (distribution), lower total body water due to lower muscle mass and diff. metabolism -risk dehydration: lower GFR - toxicity risk

polypharmacy

adding onto drugs to maintain state of wellness, happens in older adults -need to determine which ones are actually necessary

common toxicities

ASA, acetaminophen, opioids (oxycodone, fentanyl), benzodiazepines (xanax, valium), alcohol (ETOH), THC, cocaine -adhd meds

medication errors

dose errors, crushing of tablets meant for sustained release, late charting, rushing

A & B

assess patency, effort, rate, colour -Et tube? -O2?

C

assess perfusion quality, LOC, pulses, skin, BP -IV fluids (extra volume for CO), sympathomimetics (like epi, F or F response stimulated)

D

assess for dysfunctions and treat as needed -apnea, seizures, cardiac arrhythmias, hyperthermia

E

identify the drug/substance and initiate treatment -focused

identify drug/substance

health history, lab toxicology (urine, serum) -physical assessment of S&S using toxidromes

toxidromes

symptoms from toxic amount of substance in body

ASA toxidromes

confusion, tachycardia, tachypnea, hyperthermia, diaphoresis (sweating), vomiting

Acetaminophen toxidromes

abdominal pain (liver), loss of appetite, nausea/vomiting, diaphoresis (sweating), somnolence (drowsiness)

opioid toxidromes

bradypnea/apnea, bradycardia, somnolence/coma, pupils constricted -slows things down

cocaine and other stimulants

agitation, tremors, tachycardia, tachypnea, hyperthermia, diaphoresis, pupils dilated, tremors, nervousness -stimulated nervous system

cannabis toxicity

neurocognitive effects -lots of signs and symptoms

cannabis toxidrome

VS changes (tachycardia, hypertension), seizures, nausea/vomiting, acute psychosis -LOC changes: agitation, coma, stupor -sns and f or f stimulant

inhale cannabis

15-30 min onset, bioavailability 50%

PO cannabis

1-2 hour onset (variable), can possibly last 8 hrs, bioavailability 5-20% -can take more and more to enhance effects

THC

causes CNS and VS instability

CBD

modulates effect of THC at receptors -stimulates vital signs

toxicity treatment

algorithms to determine steps, use ADME -stabilize patient with supportive treatments

seizure tx

use benzodiazepines to calm brain -gaba enducer

hypertension tx

use antihyperintensives

intubation

respiratory depression tx

antipsychotics

treatment for psychosis

adsorption

prevent absorption from happening -bind before enters circulation or try to bind while in circulation

charcoal

tylenol, ASA, and benzodiazepines easily bind to this for adsorption for treatment of toxicity

activated charcoal

binds drug to surface carbons -enteral route (GI) of administration (won’t work once not in GI) and eliminated via stool

induce metabolism

give substance or administer enzyme or precursor to enzyme to enhance metabolism

glutathione

tylenol toxicity depletes this liver enzyme -hepatotoxic NAPB causes liver failure

NAC

a glutathione enzyme precursor -enhances phase 2 metabolism -IV and PO -(n-acetylcysteine/acetylcysteine

alcohol toxidrome

• slow or irregular breath

• low body temp

• vomiting

• seizures

• unconsciousness and can’t be woken up

ADH

liver and GI metabolized by alcohol dehydrogenase -phase 1 -turns into to acetaldehyde

ALDH

metabolizes acetaldehyde into acetic acid -it can now be eliminated from body

certain groups

make acetaldehyde but it shuts off phase 1, which stops alcohol from being metabolized -higher alcohol in blood -can cause nausea, flushing, and high HR

chronic alchohol use

depletes vitamin B during metabolism

drug dose dependent

CNS alcohol effect

GABA agonist

-alcohol -it binds in its place and mimics effects -has a calming effect -very high affinity -enhances inhibitory effects of GABA

glutamate inhibitor

alcohol inhibits this major excitatory neuron, suppressing it and giving it a calming effect

diuresis

alcohol inhibits ADH causing this -excess production of urine -causes dehydration and electrolyte imbalance -piece that leads to hangover

tolerance

chronic use of alcohol leads to this -down regulation -GABA receptors #’s increase, requiring more and more alcohol to create the same effect

metadoxine

Tx drug for alcohol -induces alcohol dehydrogenase (ADH) metabolism -through IV

increase elimination

via GI, kidneys, and blood (hemodialysis)

elimination via GI

activated charcoal increases GI elimination of charcoal bound drug

elim via kidneys

alkalization to induce acidic drug excretion -can be riskier, need to make basic to intolerable limits -sodium bicarb

sodium bicarb

Tx drug to ionize acidic substances -IV -like ASA toxicity

elim via blood

hemodialysis -active removal from blood -IV line and feeding into machine that does job of kidneys

antagonism

block off a specific receptor = cessation of drug -for opioid and benzo toxicity -needs to have higher affinity than og substance -need to know onset of action

narcan

opioid receptor antagonist -no other effects on body so its safe to give -just have to give frequently enough to be effective -IV

Flumazenil

GABA receptor antagonist -for benzodiazepine toxicity -IV