IV Anesthetics, Opioids, LA, NMB Flashcards
how is propofol metabolized
fast! faster than hepatic blood flow so it also has extrahepatic metabolism eg plasma & lung
- pharmocokinetics and dynamics of propofol
- how to adjust for age of pt
- quick off b/c it is redistributing to skeletal mm and areas that are less well perfused (less hangover)
- dec dose in elderly (smaller central compartment/slower clearance)
- inc dose in kids (large Vd/fat + rapid clearance)
MOA of propofol
potentiateds Cl- flow thru GABA receptors
absolute and relative contraindications of propofol
- relative: egg allergy b/c propofol has egg white in it (but no EBM to back it up)…also caution with sulfa allergy b/c of the preservatives that propofol is kept in
- absolute: d/o of fat metabolism, caution in HLD, pancreatitis
CNS effects of propofol (& on EEG)
- ↓ CBF, ↓ ICP, ↓ CMRO2
- ↓ amplitude, ↑ latency, even burst suppression on EEG
- “feel good” b/c activates nucleus accumbens
CV effects of propofol
- ↓↓ BP 2/2 ↓ SVR (vasodilation - the most of the IV anesthetics!)
- inhibits the baroreflex so can really tank BP
- depresses myocardium/contractility
Resp effects of propofol
- resp depressant (inhibits central drive)
- inhibits aw reflex (could intubate with just propofol but would need a large dose that would drop BP a lot)
- inc apneic threshold (ventilatory response to CO2 dec)
GI effects of Propofol
- dec PONV (may dec serotonin in the area postrema)
induction dose of propofol
1-2.5 mg/kg
side effects of propofol
- pain on injection
- hypotn
- lipid emulsion –> bacterial growth
side effects and toxicity of barbs? (2 main ones)
- stimulates prophyrin –> AIP attacks
- chemical arteritis on accidental arterial injection
what problem can be encountered on injection of barbs?
may precipitate b/c it’s very alkaline & when it mixes with acidic NMB (roc) it can precipitate in IV –> “rock”
metabolism of barbiturates
slow hepatic oxidation –> more hangover effect
MOA of barbiturates
potentiates GABA (inc duration that Cl- channels r open), inhibits excitatory eg glutamate
CV effects of barbs (HR, BP)
- BP: dec via dec SVR (vasodilation & venodilation)
- HR: inc via baroreceptor unless that response is blunted (eg. BB) ** diff than propofol which blunts baroreceptor reflex
- myocardial depression
Resp effects of barbs (RR, hypoxic drive, apneic threshold)
- ↓ RR, ↓ TV –> apnea
- dec hypoxic drive (O2)
- inc apneic threshold (CO2)
CNS effects of barbs (and on EEG)
- vasoconstrictors - ↓ CBF, ↓ ICP, ↓ CMRO2
- can be used for focal CNS lesions
- on EEG dose dep’t burst suppression
main utility of barbiturates?
dec ICP in neuro cases; neuroprotection from focal cerebral ischemia
signif about onset and offset of barbiturates?
onset in 30 sec
offset takes awhile b/c half life is ~ 12 hrs and it takes 3-5 half lives before the drug is out of the body so it has signif “hangover” effect
why do pts wake up from anesthesia?
redistribution!!
beware barbiturates in these 4 settings
AS, hypovolemia, AIP, sepsis
where in the body is an anesthetic within 1-3 min?
within 10 min?
1-3: brain
10 : skel mm/lean tissue
which benzo works fastest and why
midazolam - most lipid soluble (gets into brain and spinal cord fast from the blood); action terminates from rapid redistribution
metab of benzos
all hepatic (oxdn which dec w/age, cirrhosis or other chronic liver dz) then renally excreted
mech of benzos
enhance GABA (inc freq of Cl- channel openings)–> hyperpolarization
CNS effects of benzos
- CNS: ↓ CMRO2, ↓ CBF, nc/↓ ICP
- prevent/control grand mal seizures
- amnesia, sedative, antianxiety effects
CV effects of benzos (on HR & BP)
- ↑ HR
- ↓ BP, ↓ CO, ↓ PVR slightly (midazolam > diazepam)
Resp effects of benzos
- minimal if given alone
- dec response to CO2
antagonism of benzos and dose
Flumazenil 8-15 ug/kg
- competitively binds GABA…(seff: anxiety, w/d, ↑ ICP, seizure, **n/v)… resedation may occur
which pt populations should i be careful with benzos
eldery
ppl who are altered already
unique feature of ketamine that sets it apart from other hypnotics
- ANALGESIA, “dissociative” amnesia (thalamus not synced w/limbic system), hypnosis
- low protein binding
metabolism of ketamine
P450 hepatic
MOA of ketamine
- inhibits excitatory NMDA receptor but also works on a bunch of other receptors in the body “dirty drug” aka can really mess you up
what other drug is good to give before induction with ketamine?
glycopyrralate b/c ketamine inc salivation. nb…glyco is used vs atropine b/c glyco doesn’t cross the BBB
why is ketamine’s use limited?
dissociative drug - dissoc b/w thalamus to limbic system. distorted visual/tactile sensations (but less in kids), experience delirium (give Versed)
CNS effects of ketamine (& on EEG)
- **vasodilator… ↑ ICP, ↑ CBF
- ? falsely high BIS
- ↑ amplitude but dec latency on EEG
CV effects of ketamine (BP, HR)
- ↑ SNS therefore small ↑ HR, BP, CO but beware use in critically ill pt with already decreased SNS stores. (ok in hypovolemic shock)
resp effects of ketamine (3)
- no resp depression
- bronchodilator (ok for - reactive aw dz)
- ↑ salivation may promote laryngospasm
induction dose of ketamine
1-2 mg/kg IV
4-6 up to 10 per Schell mg/kg IM
what situations is ketamine especially useful?
which are contraindications?
ggod: uncooperative pts,
ppl with reactive airways
- contra: pulm HTN ↑ PAP, inc IOP (b/c causes nystagmus)
what situation is etomidate especially useful for & why?
ppl with bad hearts b/c it is an IV hypnotic with minimal hemodynamic effects
metab of etomidate
ester hydrolysis (plasma & hepatic)
which drug should be utilized for pts with multiple allergies?
Etomidate
what effect can be observed during etomidate induction
myoclonus & pain @ IV on induction
MOA of etomidate
- potentiates GABA
- fast onset (bound to albumin, lipid soluble)
CNS effects of etomidate (& on EEG)
- vasoconstrictor… ↓ CBF, ↓ ICP, ↓ CMRO2
- ↑ amplitude but still ↓ latency on EEG (like Ketamine)
- contraindicated in seizure pts (can induce epileptiform activity on EEG)
CV effects of etomidate (on HR and BP)
- ***minimal - dec SVR but no effect on BP
- good drug for heart cases
- dec CBF & myocardial O2 demand
Resp effects of etomidate
- min resp depression (dec TV but inc RR)
what unique side effects does etomidate have (3)
- depresses endocrine system… inhibits 11-B-hydroxylase which inhibits cortisol and aldosterone synthesis
- worst PONV “vomidate”
- myoclonus
induction dose of etomidate
0.2-0.3 mg/kg IV
mech of dexmedetomidine
- a2 agonist on presynaptic terminal inhibits NE release –> sedation, dec MAC
main utility of dexmedetomidine
in ICU when want sedating pt but want them to be able to wake up and interact
MOA of opioids
bind opioid receptor (mu) to activate G protein –> ↓ excitatory NT (Ach, substance P)
where do opioids exihibit their MOA?
analgesia via binding receptors in the sensory neurons of peripheral nervous system, neuraxial: dorsal horn (inhibits passage of pain info), medulla (potentiates inhibitory pathways which modulate pain signals, & cortex (dec perception of pain & emotional response to it)
most potent opioids
- most potent = Sufentanil > Remi > Fentanyl > hydromorphone > morphine
most lipid soluble opioids
fentanyl, sufentanil > alfentanil… remembr bolus front-end and back-end graph
how are opioids metabolized?
what specific metabolites are active?
metab by liver (morphine –> M6G which is active; meperidine–>normeperidine –> seizures)
what is unique about codeine and tramadol?
they are prodrugs changed into active froms (morphine and another version of tramadol)
effect of opioids on circulation (HR and BP)
- ↓ HR via vagus nerve – esp fentanyl (so dec CO)…exception meperidine ↑ HR
- BP: ↓ from ↓ sympathetic tone (↓ venous and arterial P) but can have cardiac stability when used as single agent
seff of methadone & meperidine
prolong QT interval
unique about morphine re: seff
causes histamine release
respiratory effects of opioids re: RR, apneic threshold, hypoxic drive
- dec RR, dec MV via Mu receptor
- ↑ apneic threshold (↑ PaCO2)
- ↓ hypoxic drive
- histamine induced bronchospasm (more with morphine)
- chest wall rigidity (more with Fentanyl, rapid/hi doses… Tx: NMB)
opioid effects on CNS
- CNS: ↓ CMRO2, ↓ CBF, ↓ ICP; no effect on EEG
- sedative effects
- dec MAC
effect of opioids on eyes and GI
- miosis (stim edinger-westphal nucleus)
- GI: constipation from inc mm tone, sphincter of Oddi contraction (used to visualize on ERCP); chemoreceptor zone –> n/v
indications for opioids
- post-op shivering tx Meperidine 10-25 mg
- sedation, analgesia, anti-tussive
what is the opioid receptor antagonist
Naloxone (seff tachy, ventricular irritability, HTN, pulm edema…brief action 30-45 min)
describe Propofol infusion syndrome
- in peds/younger pt
- high infusion rate (>150-100 ug/kg/min) x hrs-days metabolic acidosis, bradyarrhythmia, cardiac arrest nonresponsive to tx, death.
- Mech? mitochondrial toxicity/lipid overload
contraindications to etomidate
- pt w/seizure hx
- pt w/AIP as can induce attack
how does myasthenia gravis change response to non-depolarizing NMB? how about depolarizing agents like SCh?
- MG have fewer ACh receptors on mm therefore….
- MG sensitive to NDMB
- MG resistant to Sux
how does myasthenic syndrome (Lambert-Eaton syndrome) change response to non-depolarizing NMB? how about depolarizing agents like SCh?
- LES has less ACh released at myoneural jxn but # of receptors is normal
- LES sensitive to both as already have underlying weakness present
Which benzo changes from water soluble to lipid soluble upon venous injection?
Midazolam
Which opioid depresses cardiac contractility the most?
Meperidine
Which drugs augment NDMB?
- inhaled gases
- aminoglycoside antibiotics (gentamycin, streptomycin, neomycin, tobramycin) + (Clindamycin, lincomycin) *Erythromycin is a macrolide and does not affect NDMB
- Mg
- IV local anesthetics
- Lasix
- Dantrolene
- CCB
- Lithium
Which drugs/states antagonize NDMB?
Calcium!!!! Also hyperPTH & hypercalcemia can be resistant to NDMB
Which anticholinesterase agents work the fastest of
edrophonium, pyridostigmine, neostigmine
Edro > neo > pyrido
- need to use atropine w/edro (atropine x BBB :( )
What is the effect of acute hyperkalemia on NDMB and depolarizing agents?
- NDMB: resistant
- Sux: sensitive b/c hyperkalemia hyperpolarizes cell membrane
what % of receptors can still be blocked when 5 sec head lift is sustained?
50%
effect of dexmedetomidine on HR and BP
- dec HR
- dec BP
effect of dexmedetomidine on RR?
minimal does not depress respiratory fxn
MOA of local anesthetics
- -inhibit VG-Sodium channels (at nodes of Ranvier) selectively when the nerves are actively firing so ↓ rate of depolarization… works at type A fibers (delta…pain, temp) and type c fibers (dorsal root…pain)
which nerve fibers are more sensitive to LA blockade?
- smaller, myelinated fibers are more sensitive to blockade (first things to go is sympathetics > pain > temp then touch)
- mantle fibers also more sensitive (outer surface of the nerve)
describe chemical properties of LA
all are weak bases
- B from crosses membrane
- BH+ is active @ sodium channels
how does pKa influence LA action?
- pKa closer to physiologic pH will have faster onset since molecule will have relatively more B form which can cross lipid membrane
- bicarb can be added to LA injection to speed onset of action
- onset of action proportional to pKa
how will inc protein binding of LA influence its action?
duration of action is prolonged w/inc protein binding
how are LA metabolized?
- ester: plasma esterases pseudochoinesterase) in blood…fast
- amide: liver p450…slow
at which injection sites do LA’s absorb the fastest?
IV > tracheal > intercostal
Seff of LA
*CNS develop before
CVS
- CNS excitatory: circumoral numbness 1st, blurred vision, then nervous/restless/agitated/twitching —> CNS depression, tonic-clonic seizures….
- then CV inhibitory: collapse and prolonged coding
Tx of seizures in LAST vs LAST in general
- benzos, hyperventilate (dec CO2 vasoconstricts cerebral vessels, dec CBF
- lipid emulsion
What is transient neurologic syndrome (TNS)? How to treat it
- 12-24 hrs post spinal anesthesia
- severe pain radiating down both legs but **NO sensory or motor deficits!
- moreso w/Lido
- Rx: NSAIDs
Cardiac effects of LA (contractility, vasculature…which LA is most cardiotoxic?
- inhibits Na channels so depresses contractility
- all are vasodilators except cocaine
- bupiv most cardiotoxic
MOA of cocaine?
inhibits NE reuptake –> adrenergic stim (HTN, ventricular ectomy, MI)…Tx NTG then maybe BB
which allergy can be observed with LA?
ester> amide b/c ester –> PABA (sunscreen)
which LA can cause methemoglobinemia and what is the rx for it?
- prilocaine (EMLA) + benzocaine
- oxidize the Fe in heme to 3+ state in which it can’t bind O2
- pulse ox falsely low twd 85%
- Tx: methylene blue 1 mg/kg
