Benzos And Barbs Flashcards
5 effects benzos
Anxiolysis, anterograde amnesia, anticonvulsant, sedation, spinal level muscle relaxation
Benzos DONT do what 3 things
Produce enough muscle relaxation for surgery, alter amt of muscle relaxant required, or induce hepatic enzymes
Benzos safer in which ways (3)
Less tolerance and abuse potential than barbs and opioids. Greater margin of safety in OD. Have a specific antagonist.
Benzos MOA 2. Don’t do what.
Facilitate action of GABA at GABAa, increase affinity of GABAa for its receptor. DONT activate the GABAa receptor
What does affinity for gaba a receptor do 4
Enhances opening of cl gated ch, inc cl conductance, hyperpolarizes post-synaptic membrane, inc resistance of post synaptic membrane to excitation
3 things that block gaba a receptor
Etoh, benzos, propofol
Generally benzos are what two things
Highly lipid soluble and protein bound (albumin)
Versed: solubility, potency, metabolism
Water soluble. 2-3x >than diazepam. Extensive hepatic 1st pass effect.
Versed: duration, t 1/2
Short (rapid redistribution), 1-6.5 hrs
Versed
How metabolism occurs
Hydroxylation from lipid to water soluble compounds in liver- 1 and 4 hydroxy-midazolam. Conjugated and excreted in urine
Versed: renal failure does not alter what
Vd, t 1/2, or clearance
Versed CNS effects: potent 2, decreases 2
Potent anticonvulsant and amnestied. Decreases CBF and CMRO2
Versed CNS effects: does not do what. Preserves what
Does not produce isoelectric EEG, does not attenuate ICP response to laryngoscopy. Preserves cerebrovascular resp to CO2
Versed respiratory effects: ventilation effects, decreases what 2
Dose dep vent dec. Hypoxemia/hypoventilation enhanced w/ presence of opioid. Depresses swallowing reflex and dec a/w activity.
Versed CV effects: decreases what, what doesnt change
Dec SVR at induction dose (BP decreases after). CO unchanged. Doesnt prevent HR/BP changes w intubation.
Versed dose: premedication in peds, max dose
0.25-0.5 mg/kg PO. Max dose 20 mg
Versed dose: IV sedation in adults. As high as what.
1-2.5 mg. 5 mg.
Versed dose: induction, timing
0.1-0.2 mg/kg over 30-60 secs
Diazepam: solubility, duration, solvents
Lipid soluble, prolonged duration. Propylene glycol and benzyl alcohol
Diazepam: pH, injection is what, binding, PO is what
6.6ish. Painful IV/IM. Protein bound. Rapid GI absorption.
Diazepam: metabolism
Oxidation & n-demethylation to desmethyldiazepam*, oxazepam, and temazepam by hepatic microenzymes. Conjugated to glucaronic acid, renal excretion
Diazepam: what happens to desmethyldiazepam
Oxidized, conjugated, and excreted in urine
Valium: ___ inhibits CP450 system
Cimetidine
Diazepam and desmethyldiazepam e 1/2t
D- 21-37 hrs if healthy, inc w age
DM- 48-96 hrs
Valium compared to versed: cv effects
Minimal changes in SVR, BP, CO (<20% decrease)
Valium doses: premedication PO
10-15 mg
Valium doses: premedication IV, reduces what
0.2 mg/kg, MAC
Valium doses: induction
0.5-1 mg/kg IV
Valium doses: anticonvulsant IV, how it works
Inhibits activity in hippocampus and limbic system. 0.1 mg/kg IV
Ativan: potency, metabolites
5-10x stronger than valium (strongest of all benz0s), inactive metabolites
Ativan: t 1/2, metabolism influence, solvent
10-20 hrs. Less affected by liver/age/other drugs. Propylene glycol
Ativan: premedication PO dose, onset
50 mcg/kg (max 4 mg). Slow onset limits usefulness, 2 hrs to peak concentration
Flumazenil: how it works
Specific competitive benzo antagonist w high affinity for benzo receptors
Flumazenil: duration
30-60 min
Flumazenil: dose, timing, max
0.2 mg iv. Wait 2 min. 0.1 mg subsequent at 60 sec intervals. Max 3 mg
Flumazenil: can dx what/how, gtt dose
Coma, dose 5 mg. Gtt: 0.1-0.4 mg/hr (0.5-1 mcg/kg/min)
Flumazenil: antagonizes what. Postop pts dont experience what
Depression of ventilation and sedation. Dont experience acute anxiety/stress response
Flumazenil metabolism
Hepatic metab renal excretion
Barbiturates: highly what, purpose. Derived from what
Highly alkaline to be bacteriostatic. All derived from barbituric acid: urea+ Malonic acid
Barbiturates with which substitutions are sedative/hypnotic
2 and 5 carbons
Barbiturates: what diff pts of structure do
Branch chain at 5 inc hypnotic activity. Phenyl at 5- anticonvulsant (phenobarb). Methyl radical= convulsants (methohexital).
Barbs: sulfuration = what, and as inc what
Fat soluble. As lipid solubility inc: shorter duration, more rapid onset, inc potency
Barbs: which chain more potent, which isomers more potent
Long branched chain > potent that straight chain. Levo isomers > potent than dextro isomers.
Barbs: only available as what. Oxygen vs sulfur at # 2 leads to
Racemic mixtures. O2- oxybarbiturate. S- thiobarbiturate.
Relative potency of barbiturates
Thiopental and thiamylal about 1. Methohexital 2.5
Barb MOA
Dec GABA dissociation, enhances gaba activity. Mimics gaba (directly activates cl ch) at receptor. Depresses RAS
Barb MOA: how it affects BP, muscle relaxation fx
Hypotension by dec transmission in sympathetic ganglia. Dec postsynaptic membrane activity to ach- some muscle relaxation but not enough for sx
Barbs: onset, metab, binding
Rapid (redistribution), terminates quickly, extensive metab, highly protein bound
Barbs: fat: blood partition coefficient, ionization
- PK 7.6
Metabolism of oxybarbs and thiobarbs. What terminates activity
Oxy- hepatic. Thio- hepatic and some extra. Side chain oxidation at c#5 to carboxylic acid
Barbs: metabolism
De sulfuration, hydrolysis opens ring, to water soluble pts. Renal excretion mainly
Barbs: t 1/2 tpl. Prolonged in what. T 1/2 methohexital
TPL- 11.6. Prolonged in pregnancy d/t protein binding. Meth- 3.9 hrs
Barbs CNS fx: decreases what
LOC, cerebrovasocontriction, reduces CBF, ICP, and CMRO2. Also decreases IOP
Barbs CNS effects: EEG, paradoxical ___, methohexital does what
Isoelectric EEG. Excitement. Myoclonus and hiccups
Barbs CNS: Doesn’t effect what, small doses do what
Doesnt effect SSEP monitoring or cause skel muscle relaxation. Small doses can cause pain
Barbs: CV effects.
Dec SNS outflow, vasodilation, dec preload, SBP dec, HR increases if normovolemic. Myocardial depression minimal
Barb: if SNS not intact, hypovolemia, or large dose given for ICP what happens
Significant dec in BP, myocardial depression
Barbs: if rapid iv admin what happens. Oral barbs produce minimal what
Histamine release. Oral= min cv fx
Barb resp fx
Dose dep depression of medullary and pontine centers. Dec response to hypoxia and hypercapnia. Apnea.
Barb resp fx: depression of what is incomplete
Laryngeal and cough reflexes
Barb: if not a large enough dose what can happen
Stage 2 like response during a/w manipulation, inc risk of laryngospasm and bronchospasm
Barb: chronic use does what to metab, which most potent at this
Hepatic enzyme induction. Phenobarb most potent.
Barbs: inc metabolism of what 5
Oral anticoags, phenytoin, TCAs, corticosteroids, vit k
Barbs: DONT GIVE TO WHICH PTS and why
Porphyria. Stim d amino acid synthetase
Barbs: readily crosses what, what happens to sz pts, does what iv
Placenta. Metab drugs 2x as fast (esp muscle relaxants). Venous thrombosis
Barbs: tolerance and allergies
Tolerance rapidly- dose req inc 6 fold. Allergy rare but high mortality
Barbs: nv incidence
Higher than midaz and propofol. Lower than etomidate, ketamine, and volatiles
Barbs: TPL adult dose, dec dose in whom
3-5 mg/kg IV. Elderly, 1st trimester preg
Barbs: TPL dose peds and infants
5-6 mg/kg peds, 7-8 mg/kg infants
Barbs: methohexital dose adults and peds
1-2 mg/kg iv. 20-30 mg/kg pr peds
Duration of single iv induction dose of barbs
5-8 min
Drugs to not mix w barbs: general 4 and why
Opioids, catecholamines, NMBs, versed (all acidic)
Drugs to not mix w barbs: 6 specific
Pancuronium, vecuronium, atracurium, alfentanil, sufentanil, midazolam
Barbs: if __ solution too ___, precipitates. Use what w reconstituting powder
LR, acidic. Sterile water or NSS
Barbs: intra arterial injection tx general 4
NSS dilution. Pnehoxybenzamine. Heparin or urokinase. Brachial plexus or stellate ganglion block.
Barbs intra arterial injection: 2 specific
Papa Ernie 40-80 mg in 10-20 ml nacl, 5-10 ml lidocaine 1%
Porphyrins: 6
Hgb, myoglobin, catalase, peroxidase, resp and p450 liver cytochromes
How porphyrin attack starts
Decrease in heme concentration. Drugs most commonly. Also hormone flux, menstruation, NPO, dehydration, stress, infection
S/s porphyria crisis
Abd pain, NVD, tachycardia, htn (ans instab), na/k/mg disturb, skel muscle weakness, resp failure, seizure
Drugs to avoid w porphyria
Ketamine, etomidate, barbiturates
