IV Anesthetics Flashcards
pKa of Thiopental and methohexitla
10-11
MOA of Barbituates
Potentiates GABAa Channel activity
Increasing the duration of GABA is active opning Cl channels
But directly activates GABA at higher doses
How are Barbituates metabolized and what does their metabolism produce?
Hepatic Metabolism by Oxidation
Producing Porhyrins
What are theh two barbituates seen in Anesthesia
Methohexital (Brevital)
Thiopental
Which Barbituate is cleared faster?
Methohexital is cleared faster than Thiopental
What is Methohexital mostly used for ?
Methohexital is used for ECT therapy becasue it lowers the seizure threshold
What are barbituate consideration with induction using barbiturates?
Age weight and mostly Cardiac Output
Vd changes with age
CNS effects of Barbituates
Dose dependant CNS depression
Decrease everything
CMRO2
CPP
CBF
ICP
EEG
NO ANALGESIA
Respiratory effects of Barbituates*
Histamine release (Asthma concern)
Resp Depression
Dose dependant depression of medullary and pountine vent centers
(Decrease in CO2 response)
Lose reflexes at high doses
CV effects of barbituates
thiopental and how
Thiopental causes 5-10 decrease in BP
This is due to vasodilation and depression of medullary vasomotor centers and decrease SNS outflow to CNS
BUT compensated by 15-20 BPM HR increase
Dosing of Thiopental
3-5 mg/kg IV
Induction Dosing of Methohexital
1-1.5 mg/kg IV
Name the Structure
Propofol
2,6 Diisopropylphenol
What is propofol used for
Sedation induction maintenance of anesthesia
What are the lipid emulsion components in Propofol
and in genenric forms?
10 % soybean oil
2.25 % Glycerol
1.2 % purified Egg Lecithin
Generic–> Sodium Bisulfate
Ph and pKa of Propofol
Diprivan and generic
pH- 7-8.5 Generic- 4.5-6.4
pKa- 11
How often do you need to Change syringe and tubing for prop
syringe- 6 hours
Tubing- 12 hours
Propofol dosing
Induction
Maintanence
Sedation
Antiemetic
Antipuritic
Induction- 1-2.5 mg/kg bolus
Maintanence- 100-300 mcg/kg/min
Sedation- 25-75 mcg/kg/min or
10-20 mg bolus
Antiemetic- 10-15mcg/kg/min
Antipuritic- 10 mg
MOA of Propofol
Direct GABAa agonist
Changes conductance of Cl causing neuronal hyper polarization
Does not effect spinal motor neuron excitability
What IV anesthetic is ideal for spine/neuro cases?
Propofol does not effect spinal neuron excitability
Precedex. Can be woken up for test easily
Propofol kinetics time to awake and why
Time to awake is dose dependant but usually 5-15 minutes
Rapid distribution throughout VRG
Propofol distribution half life
2-4 minutes
Propofol Elimination half-life
1-5 hours
Propofol clearance
25 ml/kg/min
Propofol protein binding
98 %
Does Propofol have analgesia properties
NO!
Neuro effects of Propofol
Decrease everything
CMRO2
CBF
ICP
IOP
BIG DROP IN CPP
Burst surpression in EEG
How much does propofol decrease blood pressure by?
What parameters go down (CO SVR SNS CI SV)
roughly 25-45 %
Decreases everything!
Respiratory effects of PROP
Dose dependant decrease in RR
Decrease Vt
Increase apnea time
Decrease sensitivity to CO2
Small Bronchodilation
What does prop do to urine and why
Turns urine green (Phenols) and Cloudy (uric Acid)
What does propofol not do?
Does not
Enhance NMBAs
cause MH
Affect Corticosteroid synthesis
Affect hepatic or renal function
What are people allergic to in propofol?
Diisopropyl side change and phenyl nuclei
Preservatives
What are key clinical characteristics of PRIS
EKG changes (widening QRS and arrythmias)**
Refractory Bradycardia**
Severe metabolic Acidosis
Rhabdo
Fever
Hyper K
Hypotension**
HLD
Hypoxia
Cardiac Failure
Hepatic Problems
RF
Risk Factors for PRIS
High dose for long term
Dose >5mg/kg/hr
>48 hours of use
High-fat low-carb intake
Inborn errors of mitochondrial fatty acid oxydation
Concomitant Pressors or steroids
Management of PRIS
D/c Prop
Supportive measures (50% mortality)
Pacing
glucogon
CRRT
Phosphodiesterase inhibitor
increase gas exchange
Fospropofol
MOA
Dose
Onset
Duration
Prodrug of Prop metabolized by Alkaline phosphate (lower onset and increase duration)
Dose- Bolus 6.5 mg/kg
Maintanence 1.6 mg/kg
onset- 5-13 minutes
duration 15-45 minutes
Benefits and drawbacks of Fosprop
No burning. Less allergic reaction.
No bacterial growth concern
Benefits of Etomidate
minimal hemodynamic effects
d/t Alpha2B adrenoceptors mediates compensatory increase in BP
Unless severe aortic or mitral valve disease
Minimal Cardiorespiratory depression
Propblems with Etomidate
Burn on injection
Supresssion of adrenocortical function
Contributes to Acute porphyries
increase post op NV
Involentary Myoclonus
MOA of Etomidate
R isomer is a selective modulator of GABAa
Etomidate onset
duration
Dose
0.2-0.4 mg/kg
onset 30-60s
Duration 5-15 minutes
Metabolism of Etomidate
Hepatic transformation by ESTER HYDROLYSIS to inactive metabolites
small amount excreted unchange in urine
highly protein bound 77%
Etomidate CNS effects
Dose dependant CNS depressions within one arm-brain circulation
NO ANALGESIA
CBF CMRO2 IOP decreased
Excitatory muscle contraction
Adrenocortical effects of Etomidate
Inhibition of 11BHydroxylase–>stops formation of cortisol from cholesterol
Lasts for 24 hours after first dose
CNS Effects of Benzodiazepines (5)
Anxiolysis
Antegrade Amnesia
Sedation
Hypnosis
Anticonvulsant
Dose dependant CNS depression
Benzo MOA
GABAa Agonist at the benzodiazapine receptor site
Midaz effects compared to other benzos
More Amnesia than sedation
Midaz Pregnancy
Crosses the placenta
Midaz Metabolism
And metabolite, Acitve or inactive
Mostly in the liver by Microsomal oxidation and glucuronide conjugation
Metabolite–> l-hydroxymedazolam
Active 1/2 potency of midaz, but is rapidly conjugated. Renal imparement prolongs the effects
What effects microsomal oxidation?
Midaz (5)
Age
liver disease
Obesity
Gender
Renal status
Half life of Midazolam
Diazepam
Lorazepam
Midaz- 1.9 hours
Diaz- 43 hours
Loraz- 14 hours
1-Hydroxmedazolan
Metabolite of midaz 1/2 the potency is rapidly conjugated, but can have longer lasting effects in renal impairment
Cardiovascular effects of benzos
Sedation-> minimal unless paired with opioids or geriatrics
Induction dose decreasees SBP and SVR
Resp Effects of Benzos
Dose dependant respiratory depression (Midaz the most)
Synergistic Resp depression with opioids
When are Benzos Contraindicated
Acute Porphyria
Midaz Dosing Onset Duration
Sedation- IV / Oral
Induction
Sedation Oral- 0.25-1mg/kg PO MAX 20 mg–> 20-30 min before surgery
IV- 0.25-2.5 mg onset 20-60 seconds
Duration- 15-80 minutes
Induction 0.1-0.2 mg/kg IV over 30-60 seconds
Remimazolam offset
and half life
11-14 minutes Following last dose
half life of 37-53 minutes
Remimazolam metabolism
No active metabolites,
Remimazolam Doseing initial and maintanance
Adult
ASA III-IV
Adult- 5 mg IV over 1 minute
Maintenance- 2.5 mg over 15 seconds
ASA III-IV- 5 mg IV over 1 minute
Maintenance- 1.25 mg-2.5 IV over 15 seconds
Flumenizil dosing
0.2 mg IV
Additional 0.1 mg to total of 1 mg may be given in 60 second intervals
Flumenizil Onset
2 minutes
MOA flumenizil
Competative antagonist of benzodiazepines receptor
Flumenizil duration
30-60 minutes
Flumenizil contraindications
Antiepileptic Drug use
Neuro patients (head bleed)
Ketamine effects
Amnesia, dissociative, Analgesia
Nystagmus
Ketamine MOA
Antagonism of NMDA receptors (Kappa and Mu)
Dissociates the Thamlmus (sensory) from the limbic system (awareness)
Other effects on the Monoamine (MAO), Cholinergic, Opiate, Muscarinc, and adenosin receptors
Direct inhibition of cytokines in blood
inhibits TNF Alpha and IL-6 gene expression leading to anti-inflammatory and antihyperalgesia
NMDA receptor
Subtype of glutamate receptor involved in transfer of signal from brain and spinal cord
Channel must be open to work
Metabolism of ketamine
and metabolites
Extensive hepatic metabolism
Demethylation of ketamine by P450 to form Norketamine
Norketamine is 1/5-1/3 the potency
Chronic admin increases enzyme activity
Ketamine dosing
IV Induction
IM
Sedation
Infusion chronic pain
depression
Inductions- 1.0-=4.5 mg/kg for 5-10 minutes surgical time
IM- 4-8 mg/kg for 12-25 min
sedation- 0.1-0.5 mg/kg IV
Infusion for chronic pain- 0.1-0.3 mg/kg/hr
Depression- 0.5mg/kg over 30-40 min
Ketamine Protein bound
12 % protein
Ketamine Onset
2-5 minutes
Ketamine elimnation
2-3 hours
Ketamine Hepatic extraction
High so elimination is depednatnt on flow to the liver
CNS effects of ketamine
Increase CBF ICP CMRO2
Nystagmus
Increase EEG activity (seizure risk)
Drunk effects (decrease coordination slur speech)
Long term analgesia
Increases Blood flow by 60%
CV effects of ketamine
Circulatory Stim
Increase Myocardial O2 consumption
DONT GIVE WITH MI or HEART DISEASE
Increase BP HR Cardiac contractility and CVP
Respiratory effects of ketamine
Short duration bronchodilation
Reflexes (vomit) and respiratory tone intact
Does NOT release histamine
Increase pulmonary compliance
Increase in secretions!
Dexmedetomidine Class
Imidazolines
Dex MOA
Alpha 2 agonist (in CV and CNS)
Stimulation decreases catacholamine relsease
activates sleep
Analgesia d/t receptors in the anterior horn
Dex Metabolism
Metabolites and elimination
Rapid hepatic metabolism involving conjugation of N-methylation and hydroxylation
NO ACTIVE METABOLITES
Secerted in urine and bile
Dex half life
6 minutes
Onset of Dex
10-20 minutes
protein binding of dex
94 %
Loading dose for Dex
and Maintanence dose
1mcg/kg over 10 minutes
0.2-0.7 mcg/kg/hr
CNS effects of dex
dose dependatnt sedation that resemblees sleep
Good Wake up test
Dose not interfere with Electrophys monitoring
NO change in CMRO2 ICP
Decreased CBF
CV effects of Dex
Hypotension and bradycardia
due to alpha stim and systemic vasodilation
Dex Resp effects
small decrease in reflex
Normal CO2 response
Refelexes maintained
Decrease airway reactivity in COPD
