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Elderly dosage of prop?smallerkids dosage of prop?higherPONV dose of propofol?10-15 mg, then 10 mcg gttantipruritic dose of prop?10 mgAbsorption of prop?IV: highly lipophillicDistribution of prop?Rapid distribution and redistribution - leads to rapid awakeningMetabolism of prop?hepatic, and 1st pass pulmonary
glucuronidation (Phase II)Does prop have an active metabolite?yes, 4-hydroxypropofol, (1/3 hypnotic activity)How is prop excreted?Renalwhat does prop do to CNS activity?decreases (CBF, CMRO, ICP, CPP, IOP - should be used in these cases)
-less memory effects than thiopentalCan you give prop for sz?yesWhat does prop do to the CV system?decreases SNS > PSNS. decrease BP, CO, SVR. HR remains the same usually but can lower
no prolongation in QT intervalprop and respiratory effects-dose-dependent depression of ventilation
-decr TV and RR
-decr effect of chemorcpts: shift CO2 curve down and to rightShould you mix prop with lidocaine?no, oil dropletsWhen should you discard tubing of prop?12 hrswhen should you discard open vial of prop?6 hrsDoes prop shift CO2 curve to right or left?right (retain CO2) - decrease in central chemo responsePropofol syndrome occurs whendrip on for >48hrs
dose >4mg/kg/hr
prop in sepsis ptswhat is the first thing you should do when you expect propofol syndrome?Turn of the dripsigns of propofol syndrome?refractory bradycardia, acidosis, rhabdo, renal failure, hyperlipidemia
brugada's sign: RBB
cloudy urine and plasma may be first clue!Etomidate MOAGABA allosteric agonist
-enhances affinity of GABAwhat is Etomidate is most commonly used forinduction agentEtomidate induction dose0.2-0.4 mg/kgEtomidate OOA60 secondsEtomidate DOA5-15 minEtomidate absorption-water solubility in acidic solutions
-provides lipid solubility at physiological pH
-transmucosal route - bypasses hepatic metabolismEtomidate distribution-large Vd with considerable tissue uptake
-weak base. 99% unionized at physiologic pH (this accounts for rapid onset)
-prompt awakening reflects primarily the redistribution from brain to inactive tissue sites
-largely protein boundEtomidate Metabolismliver and plasma esterasesEtomidate excretionrenal mostly/bileEtomidate increase or decr. ICP?-decr CBF, CMRO2, and ICPMajor thing that can happen with etomidate on inductionmyoclonus (looks like sz)
-more than any other induction agentHow can you prevent myoclonus with etomidate?premed
(dex, midaz, roc, lidocaine)If your pt is hypovolemic should you give them etomidate?NO, decrease SVR and associate decr BPshould you use etomidate in compendated heart dx?
-dont use in aortic or mitral stenosisok to use as long as they are not hypovolemicshould you use etomidate in aortic and mitral vavle dx?noDoes etomidate cause resp. depressiondose dependent
-transcient effect (3-5 min)Does etomidate release histamine?noMajor contraindication to etomidateadrenal cortical suppression
hypovolemic patientsWith Etomidate, TV ________ and RR _______decreases, increasesrisk of PONV with etomidate?yes
-highest risk PONV for induction agentIndications for etomidate-CV dx, sz duration potential, etomidate > than prop and thiopental in prolonging the sz duration potentialContraindications for etomidate-peds (neural apoptosis)
-sz disorder
-adrenal suppression
-acute int. porphyria
-mitral and aortic stenosisWhat is the one thing that ketamine provides that other induction agents do not?analgesia (also has hypnotic/amnestic/sedative properties)ketamine MOA-Non GABA sedative hypnotic. NMDA Receptor noncompetitive antagonist.
-Blocks afferent signals of pain perception to the thalamus and cortex and limbic system.
-binds allostericKetamin3 induction doseIV: 1-2 mg/kg
IM: 4-8 mg/kg
PO: 10 mg/kgketamine analgesic doseIV: 0.2-0.5 mg/kgKetamine maintenance doseIV: 15-45 mcg/kg/min (1-3 mg/min)Does ketamine have an active metabolite?yes norketamine (potent - may contribute to analgesia).Ketamine PK (OOA, DOA, Vd)high lipid solubility, rapid onset, short DOA, not significantly protein bound. Vd = 2.5-3.5 L/kgKetamine excretionkidneysEsketamineavailable for tx of therapy resistant depression. It produces more intense analgesia, more rapid metabolism and recovery, less salvation, lower incidence of emergence rxns than R ketamine.When should you use ketamine?- use in pts with shock, hypovolemia, cardiomyopathy, trauma, bronchospasm, painWhat pts should you be cautious about using ketamine in?-TBI pts
-PTSD (can cause hallucinations/delirium in all pts)
-hx of sz
-ocular surgery (causes nystagmus)
-open globe
-PTSD
-acute intermittent porphyriaFlumazenil MOA-competitive antagonist at GABA receptor
-Antagonizes the benzo component of ventilatory depression that is present during combined administration of a benzo and opioid
-short duration and half life make the possibility of resedation. Especially in overdose
-dependent on amount of free benzo to exert its actionAdult dose of flumazenil0.2 mg IV (max 1 mg)Peds does of flumazenil0.01 mg/kg (max 0.2 mg)Half life of flumazenil40-80 minutesDistribution of flumazenilweak base
Vd = 0.5 L/kg
Lipophilic
Protein binding: 50%metabolism/excretion of flumazenil99% metabolized (1% excreted in urine)
-dependent on hepatic blood flow
-metabolites (de-ethylated free acid and its glucuronide conjugate)
-Renal excretion
-hepatic metabolism, no active metabolitesWhen should you not use flumazenil-sz disorders
-benzo dependent ptsMorphine MOAbinds primarily to the mu receptor, opioid agonistMorphine adults IV dose2-10 mgMorphine peds IV dose0.01-0.1 mg/kgmorphine OOA15-30 minmorphine DOA4 hoursMorphine half life120 minutesMorphine absorptionpoorly lipid soluble. High degree of ionization at physiologic pHmorphine metabolismextensive first pass metabolism.
conjugation by the liver, renal metabolism significant (20%)Morphine metabolitesMorphine 6 glucuronide acts at mu receptors, causes ventilatory depression and analgesia more potent than morphine. Can accumulate in the liver
M3G and M6Gmorphine excretionkidneysDoes morphine release histamineYes, May lead to a decrease in SVR and blood pressure. Careful using with asthmatics.does morphine cause respiratory depression?yes, dose-dependent
-incr airway resistance
-skeletal muscle rigiditywhat does morphine do the CBFdecr CBFwhat does morphine cause the pupils to do?constrict, miosisHow do you treat sphincter of oddi spasm?2 mg glucogon IVWhat if your pt starts to flush/itch with morphine?Flushing and pruritis that is NOT an allergic rxn (naloxone gtt or prop 10-15 mg antidote)what does morphine do to the GU system?urinary retention and frequencyAlfentanil MOAPrimarily acts on mu, mu produces analgesia. synthetic opioid agonistUses for Alfentanil?-use for brief stim, "stuns" patient; acute and transient stim
-ex: retrobulbar block (eye)
-use for "rapid onset and offset of intense analgesia"
-NOT GOOD for use in a drip- difficult to titrate to effectPotency of Alfentanil compared to fentanyl?1/5 to 1/10 as potent as fentanyl, and ⅓ durationDose of alfentanil15-30 mcg/kg15 mcg of alfentanil does what?blunts stim to laryngoscopy20 mcg/kg of alfentanil does what?blunts catecholamine response to noxious stimInduction/unconsciousness dose of alfentanil150-300 mcg/kghow much alfentanil do you need when combined with IA?25-150 mcg/kgOOA of alfentanil?fastest of opioids- effect site time 1.4mins
Small Vd (crosses BBB)
Low pKa (~90% nonionized)metabolism of alfentanil?96% metabolized by CYP in ~60min: affected by cirrhosis but NOT by renal failureHypotension and N/V of alfentanil compared to sufentanil and fentanylmore hypotension and less N/V in alfentanilWhat could happen on induction with alfentanil?reflex coughingwhat pt population should you avoid using alfentanil in?parkinsons and dystoniaRemifentanil MOASelective mu agonist. Unique d/t ester linkage. Opioid agonist mu selectivewhat cases would you use remifentanil in?use in cases that benefit from rapid drug onset effect, precise titration
-intense but limited stim (laryngoscopy)
-long operation, where quick recovery is desired
-ex: can bolus to drill into head (mayfield)Remifentanil IV dose0.25-1 mcg/kg
IBW dosing!!!Remifentanil dose combined with other agents0.05-0.2 mcg/kgOOA of remi1.1 minutesDOA of remirecovery complete within 10 minutesDo you dose remi off of IBW or TBW?IBW dosingContext sensitive half time of remi4 minutes, independent on infusion durationHow is remi metabolized?nonspecific tissue esterasesIs renal or hepatic failure going to change metabolism of remi?
PChE disorders wont affect it eithernoRemi is synergistic with what IV medicationpropShould you use remi with a seizure pt?remi can induce sz like activityRemi CV effectshypotension/bradycardiaHow can you prevent remi hyperalgesiaMg, nitrous, ketamineWhen you cut of a remi drip what is important to do?make sure a long acting opioid is on boardShould you use remi for epidural or spinalnoAcetaminophen - exerts its analgesic effect by?-activation of serotogenic pathways
-antagonisms of NMDA, substance P and NO pathways
-exact MOA unknownDoes acetaminophen have anti-inflammatory effects?nopeIndication for acetaminophenNon opioid analgesics; antipyretic and analgesic but NO ANTI INFLAMMDose of acetaminophen (q4-6hrs)325-600mg PO
1000 mg q6 IVRectal does of acetominophen10-20 mg/kg q6Max dose per day of acetominophen4000 mg/daymax dose per day of acetominophen in chronic alcholism2000 mg/kdayAcetominophen absorptioncomplete and rapid oral bioavailabilityAcetominophen metabolism-liver - number 1 cause of liver failure d/t damage from metabolite depleting natural antioxidantsacetominophen excretionurine and bileIbuprofen MOA and classNSAID
Inhibit biosynthesis of prostaglandins by preventing substrate arachadonic acid from binding to cox enzyme active site = all our drugs hit cox 1 and 2
-non-selective, reversible inhibition of the cyclooxygenase enzymes COX-1 and COX-2ibuprofen indicationsnon opioid analgesicibuprofen dosenot on slides, but 200-400mg up to 3 times a day
max: 1,200mg in 24hr (OTC)
Max: 3,200 in 24hr (prescription strength; 800mg Q4)ibuprofen Vdlowibuprofen bound to proteins90%ibuprofen plasma half life.25-70 hoursibuprofen absorptioncomplete rapid oral bioavailabilityibuprofen metabolismliveribuprofen excretionurine and bileDosing of ibuprofen in renal ptslowerShould you use ibuprofen in children?no (especially under 6 months, can close PDA)How soon should you stop ibuprofen before surgery?2 days priorwhat can ibuprofen do to plts?-plt dysfunction due to acting on cox 1 receptorWhat SE does ibuprofen have on the GI systemupper GI ulcers d/t cox1 inhibitionCV effects of ibuprofendisruption in pro and anticoag factors balanceWhat should you watch out for in a pt with nasal polyps or asthmahypersensitivity (especially with NSAID admin)
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