Pharm Flashcards
half life of benzos in order: alprazolam, diazepam, lorazepam, midazolam, temazepam
midazolam 1.5-2.5hrs (6x potent than diaz)
alprazolam 6-24hrs
temazepam 10hrs
lorazepam 11-22hrs (10x potent than diaz)
diazepam 40 - 100hrs
PRIS (propofol infusion syndrome) signs
- metabolic lactic acidosis
- rhabdomyolysis
- refractory bradycardia
- cardiac failure
- renal failure
- hyperkalemia
- hypertriglyceridemia
- hepatomegaly / fatty liver
- pancreatitis
4mg/kg/hr for > 48hrs
What does ED-95 mean?
The dose of NMB needed to reduce twitch height by 95%. The dose for tracheal intubation is typically 2x ED95.
Rank midazolam from greatest bioavailability to least
IV > SQ > IM > sublingual > intranasal > rectal > oral
What drugs are metabolized by CYP 3A4
acetaminophen alfentanil dexamethasone fentanyl lidocaine methadone midazolam propofol (3A4, mostly 2B6) sufentanyl
*note: midazolam inhibits 3A4, may slow down metabolism of other drugs
What drugs inhibit CYP3A4
grapefruit antifungal drugs protease inhibitors mycin ABX protease inhibitors SSRI
What drugs increase activity of CYP3A4
rifampin rifabutin tamoxifen glucocorticoids carbamazepine barbiturates St. John's
what metabolizes codine to morphine?
CYP 2D6
morphine = active metabolite of codine
**inhibits 2D6 = SSRI, quinidine
If someone is on SSRI, what narcs do you want to avoid?
oxycodone (prodrug) –> oxymorphone
codine –> morphine
hydrocodone –> hydromorphone (more potent)
**SSRI inhibits CYP 2D6 –> responsible for converting to active metabolite morphine
*note: hydromorphine –> hydromorphone-3-glucuronide (no analgesic effects), accumulation causes neuro-excitation (agitation, restless, myoclonus)
what drugs are cleared by ester hydrolysis
esmolol
remifentanyl
succinylcholine (butylcholinesterase)
Kidney elimination of: pancuronoum, vec, roc
pancuronium 85%
vecuronium 20-30%
rocuronium 10-20%
neostigmine elimination
50% renal excretion
1/2 life increases from 77 –> 180min in renal failure
low dose vs high dose dopamine receptors?
low dose: 0.5-3mcg/kg/min –> activates D-1 –> vasodilate renal, mesenteric, coronary arteries
moderate: 3 - 10 mcg/kg/min –> stim a-1, stim b-1 –> NE release at nerve terminals
high> 10mcg/kg/min
What pH and temp conditions encourage hoffmann elimination?
- increased pH and increased temp –> faster hoffmann elimination
- note: intubating dose of cisatracurium (0.1-0.15 mg/kg),
cisatracurium: intubation dose, duration, half-life
intubating dose (0.1 - 0.15 mg/kg)
duration 30-60mins
half-life 25mins
contraindications to suggamadex (gamma-cyclodextrin) use?
pediatric pts renal failure (>95% kidney excretion) didn't use roc or vec reversal of roc/vec in ICU pts known hypersensitivity to suggamadex or components
*suggamadex is line-incompatible with zofran, ranitidine, verapamil
what eye drops can cause sux to last much longer?
echothiophate = anticholinesterase –> miosis
inhibits pseudocholinesterase
95% reduction in butylcholinesterase
what diuretics are potassium-sparing?
the K+ STAEs Spironolactone Triamterene Amiloride Eplerenone
nicardipine: type of drug, metabolism, preload/afterload effects, 1/2 life, elimination
CCB --> dilates coronary and peripheral arteries (+) ionotropic effect --> increases HR liver = prolonged in liver failure 1/2 life = 3-13mins elimination = bile, feces
ARTERIOLAR vasodilation –> decreased afterload w/o affecting preload
How to deal with hypotension 2/2 ACEi/ARB
1st line = phenylephrine, ephedrine, glyco
2nd = norepinephrine, vasopressin (no data for)
**giving bolus 0.5-1U vasopressin is equivalent to giving 30min of 0.03U/min. Can decrease cardiac output, decrease gastric perfusion, lactic acidosis
What effects do acetylcholinesterase inhibitors have on succinylcholine?
AChI inhibit plasma butyrlcholinesterase –> prolonged SUX duration
Why does excessive dosing of AChI (neostigmine) cause weakness?
extra ACh –> pre-synaptic / post-synaptic desensitization/ inactivation of Na channels –> prevents depolarization
nitroprusside: MOA toxicity, preload/afterload effects
1) cyanide –> cytochrome c oxidase –> inhibits aerobic respiration –> metabolic gap lactic acidosis
2) cyanmethemoglobin –> can’t carry oxygen
3) thiocyanate –> CNS toxicity
arterial and venous dilator –> decreases preload and afterload
what immunosuppressant drug prolong’s NDNMB?
cyclosporine
also has nephrotoxic and neurotoxic effects
metabolized by CYP3A4 (if patient uses St. John’s wort, increases metabolism –> subtherapeutic levels of drug –> organ rejection)
how do you calculate time constant for equilibrium of an anesthesia circuit
volume or capacity of circuit / FGF
S/E fospropofol?
paresthesias
onset ~4mins since has to be metabolized by endothelial and hepatic alk phosphatase to active drug
onset and duration of H2 blockers
cimetidine: onset 1 - 1.5hr, duration 3-4hrs
ranitidine: onset 1hr, duration 9-10hrs
famotidine: onset 1 hr, duration 10-12hrs
meperidine: use, MOA, metabolism, elimination, S/E
MOA: synthetic opiod, binds to mu and kappa receptor
use: pain, post-op shivering
metabolism: liver –> normeperidine (no analgesia, CNS excitatory effects)
1/2 life meperidine : 2.5 - 4hrs
1/2 life normeperidine: 15-30hrs
elimination: liver and kidney
S/E: normeperidine –> CNS excitatory / neurotoxic–> Sz. Don’t use in pt’s taking MOAi. Normeperidine inhibits serotonin reuptake –> serotonin syndrome
- be careful in pts with renal/liver failure as normeperidine accumulate
- *Libby Zion died of phenylzine (MOAi) + meperidine
anaphylaxis vs anaphylactoid reaction?
anaphylactic: IgE/type 1 –> mast cell degranulation and histamine release. Need priming/sensatization event. Triggers = muscle relax, latex, ABX
anaphylactoid: direct stimulation of histamine release (mechanism does not involve IgE). Triggers = protamine, IV contrast, opiods, thiopental, d-tubocurarine
clinically indistinguishable
metoclopramine: use, MOA,
Rx: gastroparesis, nausea PPX
MOA: dopamine antagonist (chemoceptor triggers zone in CNS) and serotonin antagonist (anti-nausea), peripheral cholinergic agonist (increase gastric emptying, reduced gastric fluid, increased LES tone, opens pyloric sphincter).
S/E: don’t use in parkinson pts, can cause extra-pyramidal effects (Rx: benadryl, benztropine)
What are methemoglobin-inducing drugs?
prilocaine benzocaine quinine metoclopramide sulfonamides dapsone chloral hydrate
What are EMLA contraindications?
- allergy to amides
- class 3 anti-arrhythmic: amiodarone, bretylium, satolol, dofetilide
- methymoglobinemia
- infants (<12mo) on methymoglobin-inducing agents
What over the counter herbs/supplements increase bleeding risk?
Gingko = PLT aggregation in vitro Ginger = inhibit thromboxane synthase --> thromboxane --> PLT aggregation + vasoconstriction Garlic = PLT aggregation Vit E = PLT aggregation Echinacea when on warfarin
What are the effects of different receptors of opiods: mu, kappa, delta
u1: analgesic
u2: respiratory, GI/constipation, dependence
u3: anti-inflammatory, unknown
kappa: analgesia, dysphoria
delta: resp, GI, dependence, GU
contraindication to using ACEi
aortic stenosis
bilateral/single renal artery stenosis
pregnancy (teratogen)
angioedema
list order of NMB prolongation with gas?
des > sevo > iso > halo > TIVA
DISH? but out of order so DSIH
Rank fluoride ion production in halogenated agents from most to least
methylflurane > sevo > enflurane > iso > des
MSEID
What can you determine from:
- solubility or blood:gas coefficient
- oil: gas coefficient
- why does NO2 have a faster onset than desflurane?
- less soluble, lower blood:gas –> faster FA/Fi ratio
- oil: gas –> potency. higher coefficient, higher potency, lower MAC (takes less % of drug to get the job done)
- desflurane has a lower blood:gas so you’d think it’d be a faster onset than NO2. The difference is NO2 is delivered in very high concentration
signs of nitroprusside toxicity
- elevated MVO2
- tachyphylaxis
- metabolic acidosis
What does pre-treatment of NDNB before SUX help with?
- fasiculations, increases in ICP, intragastric pressure
note: it will NOT prevent increased intra-ocular pressure. No not use sux with open eye injuries.
2-chloroprocaine: onset, half life, duration, elimination
- onset = 6-12 mins
- half-life = 45 seconds
- peak = 10-20 mins
- duration = 30-60 mins –> 60-90 w/ epi
- eliminated by plasma cholinesterases; prolonged with plasmacholinesterase deficiency
Which volatile agents are a/w lowest seizure potential?
desflurane
isoflurane
all agents decrease seizure potential though
What volatile agent increases cerebral perfusion the most?
halothane
Which volatile agent increases CMO2 brain?
NO2
don’t use in neuro cases!
How does cirrhosis affect paralytic dosing?
- cirrhosis –> increased volume of distribution –> increase intubating dose of roc, vec,
- clearance depends on hepatic metabolism –> longer duration (roc, vec, pan)
- sux degradated by pseudocholinesterase. If cirrhosis, less production –> sux lasts longer (increases from 3min –> 9 min)
barbiturates: considerations
decreases cardiac output
myocardial suppression
venous pooling
decreased sympathetic output
respiratory depression
induces ALA synthase: pts w/ porphyria can have acute porphyria attack
- do not do intra-arterial injection –> crystalizes –> thrombosis/vasospasm
Etomidate: considerations
Adrenal suppression: 11-b-OH, 17-a-OH
- N/V (30%)
- thrombophlebitis / pain on injection
ketamine: considerations
- increases ICP, intra-ocular pressure –> do not use if cranial masses or open-globe
opiods: consideration
- DO NOT develop tolerance to miosis and constipation
- renal failure –> risk of toxicity w/ morphine and meperidine
- decreases cerebral blood flow
- N/V, biliary cholic, constipation
- better than gas at mediating stress response!
meperidine: considerations
- atropine-like structure –> vasolytic effects
- local anesthetic effects 2/2 Na channel interactions
- serotonin syndrome if pt on MOAi or SSRI
- can be fatal
- good for post-op shivering
methadone: MOA, 1/2 life, considerations
- mu agonist, NMDA antagonist
- lipid soluble, long 1/2 life (15-60hrs)
- large 1/2life variability 2/2 CYP differences
fentanyl vs. alfentanyl
compared to fentanyl, alfentanyl has…
- 4x faster onset
- 1/4 the duration
- 1/4 the potency (need 4x the dose of fentanyl)
ketamine: considerations
- factors that increase incidence of emergence delirium: age, female, personalities (excentric), on multiple meds
- airway reflexes remain intact (cough, gag)
- reverse emergence delirium with physiostigmine –> increases ACh in the brain. Theory that emergence delirium may represent an anticholinergic response in the brain
- S/E: nystagmus, pupil dilation, salivation, increases ICP
Which CV drugs can be given IM?
atropine glyco ephedrine epinephrine phenylephrine hydralazine vasopressin (minimal vasoactive effects)
ephedrine: considerations
alpha, beta agonist
indirectly releases NE
can give IM
be careful in someone taking MAOi’s –> trigger release of accumulated catecholamines –> exaggerated response
Which ABX prolong NMB?
aminoglycosides polymyxins tetracyclins linomycin clindamyin
MOA: decreases prejunctional ACh release –> less ACh –> less AP
- depresses post-functional receptor sensitivity
list volatile anesthesics in order of potency
most potent
Halothane –> iso –> enflurane –> ether –> sevo –> des –> NO
HIEESD
What volatile anesthetic uptake Fi/Fa is most affected by change in cardiac output?
low cardiac output states readily allow uptake of blood-soluble anesthetic agents like iso
F
faster rate of increase if CO is lower for iso compared to des
What drugs are known to activate NMDA antagonist
ketamine
mag sulfate
nitrous oxide
opiods: methadone, tramadol
nesiritide: moa
recombinant form of human BNP
- vasodilation
- natriuresis
- diuresis
nitroglycerine: MOA, preload/afterload effects
direct acting vasodilator
cGMP production
venous dilation–> pooling –> decreased preload
