Mid term Flashcards
Examples of drugs that are plant derived
digoxin, aspirin, morphine
semi synthetic drugs
have component of both synthetic and naturally occurring molecule
xenobiotics
compound that is foreign to the body
types of names of drugs
chemical name, generic name, brand name
5 rights of drug administration
right drug, right patient, right dose, right route, right time
oral administration
most common route; drugs must be metabolized in gut wall or liver prior to reaching circulation (first pass metabolism)
first pass metabolism
metabolizing of a drug that decreases the amount of active drug absorbed; metabolism of a drug before it reaches systemic circulation (ex: PO and PR); can be metabolized by enzymes in the intestines prior to undergoing further metabolism in liver prior to systemic circulation
sublingual administration
absorbed under the tongue; lots of vasculature making it a good way to administer medication that needs to enter bloodstream rapidly
transdermal administration
slow and continuous absorption through the skin
interosseous administration
injecting into bone marrow; substitute for inability to obtain IV access
intramuscular administration
delivered into muscle; muscle mass and perfusion can affect how quickly drug is absorbed
subcutaneous
delivered into subcutaneous fatty tissue directly below skin
Intravenous administration
fastest route to administer drugs; rapidly distributed
intrathecal
delivering drugs into spinal cord to reach CNS; released into CSF
intraperitoneal
peritoneum is semi-permeable and some people on dialysis may receive drugs this way
bioavailability
rate and extent of absorption; amount that reaches circulation
drug chemical/physiochemical properties affecting absorption
drug solubility/dissolution rate, size/surface area, polymorphism/amorphism, solvates/hydrates, salt form of drug, ionization stated, pKA/lipophilicity and GI pH
drug formulation factors affecting absorption
disintegration time, manufacturing variables, nature type and dose, ingredients, product age and storage conditions
patient factors that affect drug absorption
age, gastric emptying time, intestinal transit time, disease status, blood flow at absorption site, first pass metabolism, GI content (food)
pharmacokinetics of medication in body
- absorbed into circulation
- distributed to various tissues
- metabolized or broken down
- eliminated/excreted in urine or feces
absorption
transportation of unmetabolized drug from site of administration to the body circulation system
area of the body with the fastest drug absorption
duodenal mucosa because of the villi and microvilli which proved large surface area
overview of how drugs work
bind to a receptor -> activate cascade of intracellular effects -> results in change in cellular function -> cause physiological response of the drug
agonist
enhances activity; molecule capable of binding to and activating target protein; produce the desired effects by activating receptors
example of agonist
fentanyl binds to Mu, kappa, and delta receptors of CNS and PNS, activating them to produce desired affects such as analgesia and euphoria
antagonist
molecule that binds to target and prevents other molecules from binding to active receptor site
example of antagonist
atropine which is an antimuscarinic agent blocks muscarinic receptors of heart reversing vagally stimulated bradycardia
what happens when there is repeated receptor activation of a drug
desensitization of receptor response; decreased efficacy of drug
efficacy of a drug
extent that a drug can produce a response when all receptors/binding sites are occupied
potency of a drug
amount of drug necessary to produce an effect (more potent requires lower dosage)
therapeutic index
ratio of the drug that produces toxicity in half of the population to the dose that produces clinically desired response in half the population
as molecular weight approaches 500 daltons
skin permeation approaches zero
chiral atoms
carbon atom connected to 4 different substituents; creates asymmetric carbon atom that is not superimposable
R enantiomer of albuterol
right handed; creates the bronchodilation effect of when interacting with beta receptor
S enantiomer of albuterol
left handed; blocks metabolic pathways of R enantiomer and has slower rate of elimination causing accumulation in lungs = hyperreactivity and inflammation
polypharmacy
regular use of at least 5 medications
BEERS criteria
- reduce older adults exposure to potentially inappropriate medications; 2. educate clinicians and patients; 3. serve as tool for quality of care, cost, and patterns of drug use in older adults
pharmacokinetics
what the body does to a drug
phamarcodynamics
what the drug does to the body
distribution of drug depends on
blood flow, capillary permeability, binding of drugs to plasma proteins, binding of drugs to tissues, lipophilicity, volume of distribution
main source of drug metabolism
liver due to the enzymes present
how drugs can be metabolized
oxidation, reduction, hydrolysis, hydration, conjugation, condensation, isomerization
reasons for increased half life in indviduals
decreased renal/hepatic blood flow, decreased extracting of drug from plasma, decreased metabolism (ex: liver cirrhosis)
first order kinetics
rate of elimination is proportional to drug concentration; more drug = faster metabolism
zero order kinetics
rate of elimination is constant
examples of zero order kinetics
warfarin, heparin, aspirin, alcohol, theophylline, tolbutamide, phenytoin, phenylbutazone, ethanol
purpose of drug metabolism
make drug more hydrophilic and more water soluble to facilitate elimination
drug metabolized from and to
- toxic drug to nontoxic metabolite; 2. prodrug to an active drug; 3. active drug to inactive drug
phase 1 metabolism
oxidation, reduction, and hydrolysis reactions that converts drug to more polar molecule or converts lipid soluble to water soluble
most important enzyme in phase 1 metabolism
CYP450
CYP450
microsomal superfamily of isoenzymes that catalyzes oxidation of many drugs; can be induced or inhibited
phase 2 metabolism
conversion of parent drug to more polar (water soluble) inactive metabolites; renally excreted
CYP450 components
CYP3A4 and CYP206 which metabolize 50% and 25% of drugs
glomerular filtration
drugs enter kidney through renal arteries and divide to form glomerular capillary
proximal tubular secretion
represents primary kidney mechanism for eliminating hundreds of commonly prescribed meds
distal tubular reabsoprtion
passive process where drugs are reabsorbed into systemic circulation from lumen of distal tubules
normal glomerular filtration rate
120mL/min/1.73m3
pain
unpleasant sensory and emotional experience associated with actual or potential tissue damage
nocioceptive pain
to minimize and avoid damage from intense noxious stimuli; immediate attention and withdrawal
inflammatory pain
low threshold pain; tenderness discourages contact and movement reducing further risk of injury and promoting healing
neuropathic pain
lesion or disease of somatosensory nervous system; low threshold
CNS dysfunctional pain
no damage or inflammation; low threshold
pain therapies to close gate
massage, acupuncture, electrotherapy (surface nerve stim)
non-opioid analgesics
acetaminophen, ibuprofen, aspirin, anticonvulsants, antidepressants, topical agents, other NSAIDs
acetaminophen mechanism of action
interaction of cyclooxygenase and cyclooxygenase receptor pathway; acts on CNS cox receptors to block them and decrease prostaglandin synthesis = analgesic effect
acetaminophen mechanism of action (other way)
stimulates descending serotonergic pathway which regulates pain
acetaminophen dosage
pediatrics = weight based
adults = 325-975 (max 4g in 24 hours)
acetaminophen onset
30-60 minutes oral
5-10 minutes IV
peaks in about 4 hours
acetaminophen metabolism
undergoes both phase 1 and phase 2
primary metabolic pathway of acetaminophen
sulfation and glucuronidation leading to more water soluble metabolite to be excreted renally
rest of metabolic pathway of acetaminophen
metabolized by cytochrome P450 system to N-acetyl-p-benzoquinomine (toxic metabolite) which can bind to liver cells and cause injury; quickly bound to tripeptide glutathione inactivating metabolite and becoming more water soluble to be excreted renally
NSAID mechanism of action
works primarily on cyclooxygenase receptor
NSAID with PPI
reduce GI affects by decreasing overall stomach pH as method to reduce risk of gastritis and GI bleeding
gabapentin
anti-convulsant med that inhibits release of excitatory neurotransmitters; excreted unchanged through kidneys; used for seizure and neuropathic pain
pregabalin
inhibits excitatory neurotransmitter release, focal onset seizures, diabetic neuropathy, herpetic neuralgia, and fibromyalgia
amitriptyline
tricyclic antidepressant (TCA); inhibits norepi and serotonin reuptake into presynaptic neuron; prevents migraines headache and chronic pain
duloxetine
inhibits serotonin and norepi reuptake (SNRI); only metabolized in liver; GI side effects; moderate inhibitor of CYP3A4
opioids work how?
bind to specific receptors in CNS to produce effects that mimic action of endogenous peptide neurotransmitters
receptor families
- Mu (MOP)
- Kappa (KOP)
- Delta (DOP)
- Nociceptin (NOP)
naturally occurring compounds
morphine, codeine, thebaine, papaverine
semi-synthetic compounds
diamorphine (heroin), dihydromorphone, buprenorphine, oxycodone
synthetic compounds
pethidine, fentanyl, methadone, alfentanil, remifentanil, tapentadol
morphine mechanism of action
analgesic affect d/t sterospecific interaction with opioid receptors on membranes of neuronal cells on CNS
morphine actions
analgesia, euphoria, respiratory depression, cough reflex depression, miosis, emesis,
morphine
hydrophilic, metabolizes through conjug. in liver and p-glycoprotein, active metabolites renally eliminated, abuse deterrent formulas available
methadone
no active metabolites, racemic mix., metabolized by CYP450, lipophilic, can prolong QTC interval and cause torsades de pointes
fentanyl
100x more potent than morphine, greater lipophilicity and CNS penetration than morphine, metabolized by CYP3A4, no active metabolites
oxycodone
active metabolite is noroxycodone; metabolized by CYP2D6 and CYP3A4;less histamine and nausea; abuse deterrent fomulation available
oxymorphone
longer duration of immediate release than other opioids; oral bioavailability increases with food and alcohol; administered 1-2 hours after eating
hydromorphone
greater lipophilicity and CNS penetration than morphine; metabolized glucoronidation to H6G and H3G (renally excreted); abuse deterrent
codeine
prodrug; metabolized by CYP2D6 to active drug morphine; moderate to mild pain use; not for renally impaired, children under 12, children tonsils removal, obese w/ sleep apnea
hydrocodone
active metabolite is hydromorphone; metabolized by CYP2D6 and CYP3A4; abuse deterrent available
meperidine
not firs choice; active metabolite normeperidine which can accumulate with renal impairment = toxicity; naloxone does not work and can worsen seizure activity; dont use in elderly, liver/renal impairment, or chronic pain manage
tapentadol
Mu agonist and norepi reuptake inhibiter, treats nociceptive and neuropathic pain; metabolized by glucuronidation ; no CYP450 interact
tramadol
metabolized by phase 1 and 2 with CYP2D6, CYP2B6, CYP3A4
BUPRENORPHINE
mixed agonist-antagonist; partial agonist at mu and ORL-1 receptor, antagonist at kappa and delta receptor; long duration (very lipophilic); abuse deterrent available;
BUPRENORPHINE and naloxone
incompletely reversed
NALOXONE
antagonist at mu, kappa, and delta receptor (10x affinity for mu than kappa); half life 30-90 min; oral not effective
naltrexone
antagonist; similar to naloxone but longer duration (blocks effects of heroin 24 hrs-30 days); oral or injection
Benzodiazepines uses
CNS depressant, anxiolytic, hypnotic, anticonvulsant, amnesia, muscle spasm, withdrawal
benzodiazepine structure
central carboxamide group 7 membered heterocyclic ring w/ halogen or nitrogen (7th pos.)
Benzo receptor interaction
act at GABA (a specifically) allosterically causing increased action of GABA receptor
GABA receptor action
opens and allows Cl- ions in (hyperpolarizing) making neuron less likely to fire; results in calming effects
benzo metabolism
highly lipophilic = longer metabolize (need to become more water-soluble); majority of metabolism liver and CYP450
adverse side effects of benzos
dependence in high doses; drowsiness, confusion, ataxia, EtOH and of CNS depressants enhance, opioid use w/ benzo = sedation and resp. depress.
barbituates
used for alcohol withdrawal and seizure management; mainly replaced by benzos; no analgesic/may exacerbate pain
why were barbituates replaced
tolerance and physical dependence, lethal in OD, severe withdrawal
long acting barbituate
phenobarbital (> 1day)
short acting barbituate
pentobarbital (1-2 hours), secobarbital, amobarbital
low does barbituate effect
sedation, calming effect, reduce excitement
high dose barbituate
hypnosis, anesthesia, coma/death
barbituate receptor interaction
low doses enhance GABA and open Cl- channel for longer; high dose open GABA without GABA present; can block glutamate receptor
glutamate
excitatory neurotransmitter
barbituate metabolism
liver and CYP450; half-life 100-140 hours
anticonvulsant drug types
sodium channel blockers (carbamazepine), Ca blockers (depakote), unknown (keppra, gabapentin)
topiramate
anticonvulsant that decreases effects of oral contraceptives
CYP450 Induction
increase rate of hepatic metabolism
CYP450 inhibitor
block metabolic activity
stevens-johnson syndrome
disorder of skin and mucous membranes; usually reaction that resembles flu-like symptoms; painful rash/blisters where top layer dies and sheds; toxic epidermal necrolysis
antidepressants
used to treat depression by potentiating effects of norepinephrine or serotonin
norepinephrine
neurotransmitter and hormone; increases alertness, arousal, attention, constricts blood vessels, affects sleep wake cycle, mood, and memory
serotonin
monoamine neurotransmitter that acts as hormone, influences learning and happiness, regulates body temp., sleep, sexual behavior, hunger
90% of serotonin found where
GI tract cells
decreased serotonin
thought to cause anxiety and depression (mania sometimes)
types of antidepressants
monoamine oxidase inhibitors, tricyclic, tetracyclic and unicyclic, SARI’s, SSRI’s, SNRI’s
serotonin syndrome
life threateining condition from use of serotonergic drugs; AMS, autonomic hyperactivity, neuromuscular abnormalities
baclofen
antispasmotic that distributes to brain and spinal cord to cause muscle relaxation
oral baclofen
70-85% bioavailability; excreted by kidneys mainly; half-life of 3 hours; brain and spinal cord
intrathecal baclofen
allows for greater concentrations in spinal cord with lower levels in brain; half-life is about 5 hours
baclofen receptor interaction
agonist of GABA B (only one available)
GABA B
present in brain, ventral and dorsal horns, outside BBB, within sympathetic nervous system, some visceral tissues
why use baclofen
spasms due to MS, TBI, spinal cord injury or lesions
baclofen toxicity
hypothermia, bradycardia, hypotension, excess. saliv., HTN, tachycardia, depressed mental status, coma, seizures, resp. supress., N/V
migraine preventative drugs
beta-blockers (metoprolol), anti-epilectics (topiramate), tricyclic antidepressants (amitriptyline)
migraine abortive agents
ergot, triptans, ditans, calcitonin gene-related peptide (CGRP) receptor antagonists
why no triptan use with history of MI
side effects can mimic MI which could hide real MI symptoms
volume of distribution
