Midazolam Class
Benzodiazepine
Midazolam Glucuronidation leads to
active metabolite 1- hydroxymidazolam
Efficacy measures intrinsic ability of a drug to produce clinical effects. What is the intrinsic ability of Midazolam ?
Full effect
In selected patient ____or opioid maybe added to propofol for continuous IV sedation .
Midazolam
Cerebral blood flow velocity changes in______direction with changes in PCO2 in the presence of propofol and _______
Parallel ; Midazolam
At equal sedation level _____produces same degree of memory impairment as ______ , while ______produces less and fentanyl produces none.
Propofol ; Midazolam; Thiopental
Cerebral vasomotor response is preserved during propofol and Midazolam Anesthesia in humans . True or False.
True
Imidazole nucleus renders etomidate and Midazolam water soluble at ___pH and Lipid soluble at ___pH
Acidic; physiologic
Most commonly used benzo in the perioperative period is…because …
Midazolam ; because diazepam and Lorazepam have a prolonged context 1/2 life
Which is the only benzo used for prolonged administration when rapid recovery is desired ?
Midazolam
___in contrast with barbituates and propofol is unable to produce isoelectric EEG.
Midazolam
Although clinical significance is unclear, This drug’s inhibition of platelet aggregation reflects conformational changes in platelet membranes
Midazolam significantly inhibits platelet aggregation
Midazolam is a —-soluble drug with a ——ring that contribute to its stability in ——solution and rapid metabolism
Water soluble; imidazole ; aqueous
Which benzo has replaced diazepam in the periop ?
Midazolam
with Midazolam and other benzo the amenesic effect is _____than the sedation effect .
More
Midazolam is unlike other benzo because it has a
Subtituted imidazole ring
What happens to Midazolam at physiological pH in the bloodstream
90% of midazolam is unprotonated and lipid soluble
Does Midazolam cause IV discomfort ? And compatible with what ?
No IV or IM discomfort , ok with LR, can be mixed with acidic drugs i.e: opioids and anticholinergic
Midazolam PO has substantive first pass effect : meaning
Only 50% of PO dose of Midazolam reaches the systemic circulation
Midazolam absorption
Rapid absorption in GI tract
Midazolam BBB
Crosses BBB but has a slow effect site equilibrium compared to thiopental and propofol
Midazolam and plasma protein binding
Extensive ; 98%; its protein binding is independent to its plasma concentration
Midazolam has an extensive protein binding yet a short DOA( like diazepam ) why ?
98% protein binding , but high lipid solubility = fast high redistribution from the brain to inactive tissue
Metabolism of Midazolam is done by the
Hepatic and small intestine cytochrome P450 CYP3A4 to active and inactive metabolites
1 hyrdoxymidazolam is rapidly glucorunated to 1 hydroxymidazolam glucuronide and is then excreted by the kidneys .
4- hydroxymidazolam is the other active metabolite ..but so little
1 hydroxymidazolam has ____ the activity of the parent drug
1/2
Midazolam metabolism is slowed in the presence of which other drugs ?
Cimetidine Erythromycin CCB Antifungal meds * they inhibit P-450 enzymes = unexpected CNS depression !!
What medication inhibits the hepatic clearance of Midazolam
Fentanyl
Hepatic clearance of Midazolam is ____greater than Lorazepam and ____greater than diazepam
5; 10.
What is the elimination halt time of Midazolam and what can prolong it .
2 hours (1.9) May be doubled in elderly= bc of decreased hepatic blood flow
What happens to Volume distribution of elderly and obese ?
It’s increased
Elderly and Obese have increased Vd of Midazolam . True or False ?
True
Midazolam has extensive hepatic metabolism . Therefore renal failure will not alter Midazolam’sm
1) Vd
2) t1/2
3) clearance
Paradoxical excitement of versed . Give
Flumazenil . Benzo antagonist .
CRMO2 and CBF effects of Midazolam
Decreased
the same as propofol and barbituates .
Acceptable induction alternative to barbiturates in patients with increased ICP
Midazolam and anticonvulsion
Potent anticonvulsant; good status epilecticus
Can outcome in incomplete ischemia but no neuroprotective properties .
We know Midazolam is ok to use in increased ICP but it can increased ICP when
Severe head trauma + ICP is less than 18 ( open circles )
Benzodiazepines and swallowing reflex and upper airway activity
Decreased
What benzo can you give for paradoxical vocal cord motion ?
0.5mg- 1 mg of Midazolam
Midazolam induction dose
- 0.1 - 0.2 mg/Kg IV
Does CO increase or decrease with Midazolam
Neither. BP drops because Midazolam causes decreased SVR.
Actually improved CO in CHF
Does Midazolam prevent BP and HR changes due to Intubation ?
No.
Oral Midazolam syrup concentration , and effects
2mg/ml.syrup
Max 20 mg PO( 1mg/kg)
Sedation + anxiolysis at dose 0.25mg/kg plus minimal ventilatory and O2 sat effects
0.5mg/kg to children 30 minutes before induction= sedation + anxyiolysis w/ no delayed awakening .
How long before surgery recommended to give PO Midazolam
20 minutes before induction
But 10 minutes produces best antregrade amnesia
Midazolam Sedation dose ( regional or therapeutic procedures )
1 - 2.5 mg IV
Onset : within 1 minute ( 30s-60s)
DOA: 15 - 80 minutes
Peak 1/2t : 6 minutes(5.6)
Midazolam + opioids or other CNS depressant =
Exaggerated ( synergistic ) Midazolam -induced ventilation depression ( decreased Hypoxic drive ) esp COPD
Hypnotic effect of midazolam on the elderly .
Increased sensitivity to the hypnotic effects in the elderly .
Also increased pharm variability
Midazolam seldom for induction but you would give how much
0.1- 0.2mg/kg over 1 minute
1-3 minutes before giving it , give 50 - 100 mcg of Fentanyl to facilitate onset of unconsciousness
When Versed caused increased CV responses it’s because of
Peripheral vasodilation
Yes! You can supplement use ____to supplement opioids, Inhaled anesthetics, and propofol
Midazolam
Emergence time from Midazolam infusion is increased in the presence of
Elderly
Obese
Liver disease
Butorphenol given with Fentanyl =
Will partly reverse the fentanyl analgesia in pts taking chronic opioids
Redistribution of drugs from Highly perfused tissue to fat =
Offset of drug effect following a bolus or IV infusion of lipid soluble drugs like fentanyl
Which drugs have pulmonary 1st pass effects that exceed 65% of the dose
1) Fentanyl
2) Sufentanil
3) Alfentanil
4) Meperidine
5) Lidocaine
6) Propranolol
Most abundantly expressed P450 isoform is
CYP3A4
Opioids( Fentanyl, alfentanil, Sufentanil) , LA, Anti-histamines( terfenadine), Benzodiazepines, Immunosupressant(Cyclosporin)
Fentanyl peak effect after injection is
- 5 minutes
* Morphine is 90 minutes .
Opioids decrease MAC of inhaled anesthetic required to suppress noxious stimuli . 1/5 ng/ml of fentanyl plasma concentration decreases MAC by
50%
After the initial reduction in MAC there is limited benefit from additional fentanyl
Clearance of high extraction drugs fentanyl and sufentanil is minimally influenced by
Changes in the rate of metabolism
In elderly , decreased co= decreased hepatic blood flow + decrease hepatic enzyme =
Prolonged DOA in lidocaine and Fentanyl
Fentanyl and morphine____effect on somatosensory sensory evoked potential
Decreases SSEP . Less than volatiles though !
On a neuro aspect ECG changes support a ____% dose reduction of opioid for the elderly
50
Droperidol + fentanyl =
Neuroleptalnagesia .
Droperidol does what to Fentanyl ?
Does not enhance it’s analgesia but prolongs it’s DOA
Derivatives of Meperidine
Fentanyl , Sufentanil, alfentanil
When pt get Meperidine and derivatives with MAOI = adverse reactions (toxicity )
Fentanyl first pass uptake is
Variable, up to 90%
BB + nifedipine and high dose fentanyl.
Patients tolerate high dose fentanyl , and do not show cardiac depressive effects when using verapamil added
BB blocker and high dose fentanyl
No alteration in CV response even in presence of pre existing BB
Which drugs prevent tachycardia vs increase SBP in tracheal intubation
Fentanyl, Lidocaine and Esmolol ( Attenuates the HR )
Pulmonary First pass uptake is decreased in patients taking
Propranolol chronically .
= 2 to 4 times as much fentanyl enters the systemic circulation
What drugs protect against digitalis- enchance automaticity
Fentanyl , Enflurance , to a lesser extent Isoflurane
PONV is much less than inthratecal midazolam than with inthratecal …
Fentanyl
After administration of Fentanyl epidural in parturient , the opioid in breast milk is
Negligible
Early depression of ventilation in Fentanyl happens in _____
2 hours
After epidural fentanyl , it peaks in the CSF in ____minutes
20 minutes
Sufentanil- 6 minutes
Lidocaine dose
1 - 1.5 mg/kg IV for indication
Class 1b antidysrrhythnmic
Lidocaine 0.5% + Epinephrine Submucosally =
Doubles the dose of epinephrine necessary to provoke ventricular dysrhythmia.
Mixing propofol with lidocaine can lead to
Coalescence of oil droplet= risk of PE
Accidental intraarterial injection of barbituates . What do you do?
1) Immediately try to dilute the drug
2) prevent arterial spasm with vasodilator such a s lidocaine or papaverine
3) general measures to sustain adequate blood flow
Adding 0.5 mcg/kg of dexamedetomidine to lidocaine =
Improves quality of anesthesia and post op analgesia without side effects
Lidocaine produces analgesia by
Suppressing activity of sodium channels in neurons that respond to noxious stimuli . Preventing nerve conduction and pain transmission . VGSC play a role in neuronal excitability . Abolish pain temporarily
Lidocaine was synthesized as an ____local anesthetic in 1943. Produces more____than procaine.
Amine , rapid , intense , longer lasting conduction blockade than procaine. Cardiac antidysrhythmic , effective topically = that’s why all LA are compared to Lidocaine
Lidocaine Potency, onset, duration , max dose , pka, protein binding , toxic plasm concentration
Potency : 1 Onset : rapid DOA : 60- 120 minutes Max single dose for infiltration: 300mg Pka: 7.9 Protein Binding : 70%
Intrisic vasodilation of lidocaine influences potentcy. Lidocaine more vasodilation than mepivicaine =
Greater systemic absorption and shorter DOA of lidocaine .
Lidocaine has high uptake into the lung =
Rapid decreased in plasma concentration initially.
* the concentration also decreases bc of rapid distribution to heart , brain , kidneys( high perfused tissues )
What drug decreased plasma clearance of lidocaine
Propranolol
Anesthesia which may decrease the hepatic blood flow and hepatic disease can affect lidocaine metabolism how?
Decrease the rate of metabolism . Especially when volatiles are used
Liver disease and Lidocaine …
Elimination half time increase 5 folds
Lidocaine can cause depressed myocardial contractility without arrhythmia. True or False
True
The seizure threshold for lidocaine in related to
Serotonin. Accumulation of serotonin lowers the threshold for seizures for lidocaine, and prolongs the DOA of seizures
Lidocaine to pt with mexelitine ( antidysrhythmic) =
Lowers threshold for neurotoxicity
EMLA
2.5% lidocaine combined with 2.5% prilocaine cream
Onset of action of Lidocaine
1- 3 minutes
For spinal anesthesia using lidocaine , limit dose to
60 mg
Lidocaine and requirement for volatile drugs
Decreased volatile requirement
Dose of lidocaine to decreased cough reflex during tracheal intubation
> 2 mcg/ml
Stump pain but not phantom pain is temp diminished buy IV lidocaine
True
Lidocaine may _____defibrillation threshold
Increase
LA significant antibiotic effect
Tetracaine>Bupivicaine>Lidocaine
Tumescence
5L of subQ infiltration of 0.05 - 0.10% of Lidocaine with epinephrine 1: 100,000
Slow and sustained release of Lidocaine < 1.5mcg/ml peak at 12- 14 hours then decline gradually over the next 6- 14 hrs
Dose 35-55mcg/kg of highly diluted Lidocaine aka mega dose
Inhaled Lidocaine attenuates
Histamine related Bronchospasm
Mild bronchodilation but constriction in asthma patients
Treatment of PVC
Lidocaine BB CCB Amiodarone Radioactive ablation
How much Lidocaine to suppress Ventricular dysthymia by digitalis
1-2mg/kg
Lidocaince, Diazepam and propanol can do what to Verapamil
Can increase the pharmacologically active unbound portion of verapamil
Lidocaine class IB. MOA
Less SCB than IA, shortens the duration of action potential and refractory period in normal heart
Lidocaine terminates Vtach
Yes
Lidocaine can decrease conduction in the
AV node and His- Purkinje
Etomidate is good for __(3 things)but terrible for(7things)______
Good for
1) hemodynamically unstable. Minimal CV effects
2) Lowers ICP and CBF and CRMO2
3) Status epilepticus : bc has anticonvulsant properties
Not good for
1) not a very good analgesic or anesthesic ( only 15 minutes )
2) Painful on injection
3) Suppression of adrenal function and immune system : inhibits cortisol
4) acute intermittent porphyria
5) high risk of PONV
6) do not give to patient with sepsis
7) Not for patient with hx of seizures . Activity of seizure Foci
MOA of etomidate
Interacts with specific GABAa , appears to decrease the rate of dissociation of inhibitory NT = increased DOA of GABA activated opening of Cl- channels= Hyperpolarization ( propofol and barbiturates do the same )
Etomidate change in BP and HR how ?
No change!!!
How is Etomidate unique among injected and inhaled anesthetics ?
It’s administered as a single isomer
Anesthetic effect is R + isomer which is 5 times more potent than the S - isomer
Etomidate effects on GABAa
Binds to a specific site on the protein and increases the affinity of the inhibitory NT GABA for these receptor
Increases GABA affinity to GABAa receptor
Steroid-induced psychosis is inhibited by which drug
Etomidate ( it enhances GABA receptor function)
Etomidate has a ____Vd, a _____Lipid solubility , and is a weak base
Large, moderate and is a weak base
What has abolished pain on IV injection of etomidate
It was changed to a fat emulsion from it’s previous preparation with 35% propylene glycol with pH 6.9
* but myoclonus still not changed
Is Etomidate a potent cerebral vasodilator?
No . it’s a direct cerebral vasoconstrictor.
Etomidate decreases Intraocular pressure same as which drug?
Thiopental , propofol
Etomidate is used when maintenance of spontaneous ventilatory response because
It stimulates ventilation independently of the medullary center
Spontaneous movement particularly myoclonus occurs in 50- 80 % of patients receiving
Etomidate . But this happens in the absence of premedication.
Albumin level effect on Etomidate
Low plasma albumin level= dramatic increased in unbound, active etomidate
Etomidate distribution
99% unionized at physiological ph ( pka 4.9, ph 8) = crosses lipid membranes easily, and rapidly peaks in brain within 1 minute.
Etomidate metabolism
Rapidly metabolized by ester hydrolysis( to carboxylic acid ester = now water soluble = now inactive ).
Hydrolysis by 1) hepatic P450 microsomal enzymes 2) plasma esterase
Etomidate elimination
Urine (86%) and small amount in bile (10-13% bile )
Half time 2- 5 hours. 5 times more clearance than Thiopental.
Etomidate is a high hepatic extraction drug
How to attenuate etomidate myoclonic activity
With premedication using an opioid
Ex: Fentanyl 1-2 mcg/kg IV or a Benzo
Etomidate produces analgesia. True or False?
False
Alternative drug to propofol and thiopental ( they decrease seizure duration) in patients undergoing Electroconvulsive therapy is…
Etomidate
Etomidate and PONV
Increased risk when used for anesthesia induction.
Thats just a view but doesn’t actually show increased PONV when compared to propofol
What is the main limiting factor of etomidate in it’s use for induction of anethesia ?
It has the ability to transiently suppress adrenocortical function= inhibits conversion of cholesterol to cortisol( inhibits 11 b-hydroxylase) = low cortisol . ( stress-free anesthesia )
So sepsis and hemorrhage patients need cortisol = do not give the etomidate !
Etomidate vs propofol in 30 day mortality
Etomidate has increased 30 day mortality in non cardiac surgery pts
Etomidate and allergy
It does not release histamine from mast cells
Low allergy risk .
Patient with history of seizure , can you give them Etomidate. Why?
Try not to . Because etomidate disinhibits subcortical structures that normally suppresses extrapyramidal motor activity .
What can explain myoclonus upon awakening with etomidate administration?
The extrapyramidal system emerge before the cortex that normally inhibits it .
What can rapid injection fo Etomidate do to your ventilation
Apnea
Etomidate = low tidal volume ( vent depressant < barbiturates) but etomidate = increased frequency of breathing : the decreased tV is then offset
Etomidate ventilation effect is transient and only lasts 3- 5 minutes
Depression of vent by etomidate may be more frequent and more intense when combined with inhaled anesthetic or opioid
Patient with no cardiac reserve , what to give for induction :
Etomidate
Dose adjustment in elderly for etomidate
Decrease by 20%
Total Volume distribution of propofol ( vast
5,000L
Propofol IV maintenance
100- 300mcg/kg/min
Propofol anti pruritic dose
Anti emetic Dose
Maintenance dose
10mg
10- 15 mg
100- 300mcg/kg/min
How long can open bottle of propofol be used for. Why
6 hours
E. coli and Pseudomanas aeruginosas and Candice albican
Patient movement , deepen the anesthesia with bolus of____ and that will do what to their recall
Bolus of propofol , the recall from short term memory will not go to the long term memory and patient will be amnestic
Propofol infusion syndrome is
>75mcg/kg/min 1) lactic acidocis 2) Bradydysrhythmias 3) Rhabdo Metabolic acidosis, severe refractory bradycardia(in children ), unexpected tachycardia on infusion ( adults )= look for metabolic lactic acidosis
Propofol and BIS numbers for rapid recovers
Titrate propofol to 45 to 60 BIS then allow it to increase 60-75 in the last 15 minutes of surgery.
Two drugs that increase SSEVP
Ketamine and etomidate
Propofol and opioids lower the SSEVP , yes or no
Yes !
Lowers threshold of vasoconstriction and Sweating
Propofol and Alfentanil.
Propofol and platelet aggregation
1) Propofol is pro inflammatory
2) inhibits aggregation of platelets by inducing pro inflammatory lipid mediated thromboxane A2 and PAF
3) * does not affect the platelet function only the aggregation
Propofol is antioxidant and resembles which vitamin?
E
Prolonged profolol turn urine___ color because
Green;
Because of phenols in the urine
Name of propofol chemical name
2, 6 diisopropylphenol
Propofol onset duration and Clearance
Onset: 30- 60 minutes DOA : 30- 60 seconds Duration 5- 10 minutes Clearance : Extrahepatic clearance in the lungs ( Apex) Liver P-450 , Clearance exceeds liver blood Flow
Propofol anticonvulsant dose
> 1mg/kg
Propofol more Myocardial Injury in Cardiac surgery patient than SEVO
True
Does Propofol cause drug-induced spinal cord depression ?
No, volatile anesthetics do
Propofol increases uterine contractility at anesthetic concentrations by how much ?
Only slightly
Propofol airway protection .
Decrease pharyngeal contraction force . Thats we give it in laryngospasm
Propofol and Parkinson’s
abolition of their tremors short term
Ketamine decreases activity of what receptor
NMDA. It’s an NMDA antagonist
Other receptors it acts on : Mu Delta Kappa ( directly )
Anti Nociceptive because it acts on the descending inhibitory monoaminergic pain pathways
Ketamine produces Delirium, Brondilation and emergence delirium because ….
Because its an ANTAGONIST at Muscurinic receptors
Ketamine is administered as a racemic mixture …elaborate
The S+ enantiomer is more potent than the R-enantiomer and is less like to cause emergence delirium
Doses of Ketamine
Analgesia: 0.20- 0.50 mg/kg Induction : 1-2 mg/kg IV IM Induction : 4-8mg/kg 0.3/mg/kg/hr = improves analgesia reduces opioid tolerance Post-Op infusion for pain : 1-2mgkg/hr Concentration : 50mg : 1 ml *
Ketamine can cause funky s/e :
Nystagmus
Sialhorrea
Ketamine inhibits platelet aggregation along with
Propofol and Midazolam
But Ketamine : contributes to Known bleeding undergoing surgery
Ketamine plus Nitrous =
Neurotoxicity .
Intermittent treatment of ketamine for OCD
Decreases OCD
Thiopental, Diazepam , or Midazolam blunt _____increased in Cerebral blood flow
Ketamine
What type of anesthesia does Ketamine produce. Describe
Dissociation between of Thalamocortical and Limbic system.
Dissociative Anesthesia of Ketamine resemble
Cataleptic state : eyes remain open with slow nystagmus gaze.
Various degree of hypertonus & skeletal movement independent of surgical stimulation
Ketamine properties
Amnesic
Intense analgesic
Anticholinergic
Ketamine + Heart that is Beta Blocked=
Heart Failure . Activate SNS = increase SVR = high afterload + BB reduced Myocontractility = HF
BB will decrease Ketamine induced increase in SBP and HR*
Ketamine is a myocardial depressant, that myocardial depressant is unmasked with Patient with depleted catecholamine source .
That is true
Ketamine + volatile or + Verapamil
Decreased BP
Ketamine alone ( effects on BP )
Increased BP
Ketamine Anesthesia is partially antagonized by
Anticholinesterase drugs
Think of Ketamine effects anticholinergic symptoms : emergency delirium , Bronchodilation, and the sympathomimetic
Ketamine mine inhibits Plasma cholinesterase =
Prolong duration of Sux
Atropine what type of muscurinic agonist
Broad spectrum
Isoflurane induced decrease in Heart rate is attenuated by
Atropine and Pancuronium( because they are vagolytic )
Propofol causes profound ______and _____ even in healthy patient treated with prophylactic IV anticholinergic
Bradycardia and asystole.
Propofol attenuates the the heart rate response to IV _______ . What to give instead in case of proprofol induced bradycardia. Why?
Atropine . Even giving larger dose of atropine with not help
Give epinephrine instead bc it is a direct beta agonist
Propofol suppresses SNS activity thats why you have to give direct acting
Atropine can ____spike of EEG
Decrease
Atropine and Ketamine
Ketamine cause salivation + increase risk laryngospasm
Give antisialogogue but Glyco preferred over Scopolamine and atropine because the cross the BBB and may increase incidence of Ketamine emergence delirium
Scopolamine is ____times more potent than atropine at decreasing the activity at the reticular activating system
100.
And 3 times more potent antisioliguoge
IM atropine antisiologuoge dose
.4-.6 mg IM
Less effect than Scopolamine 0.3 - 0.5 mg IM
Atropine Fever happens more in
Small children
Opioid induced ureter tone and peristalsis increase can be reversed with anticholinergic
Atropine
What is atropine effect on analgesia
Antagonizes analgesia
Meperidine structurally resembles atropine . That is why
It has anti spasmodic effect and increased HR unlike other opiods
Causes Mydriasis ( not miosis like the others )
And caused dry mouth
Atropine is effective at ____and ____ bradycardia
Treating and preventing
Atropine should be paired with ? What dose ? And why ?
Anticholinesterase + anticholinergic agent in reversal of NMB
7-10 mcg/kg of atropine matches the onset of edrophonium 0.5-1mg/kg
Administer anticholisterases over 2- 5 minutes
Glyco + Neostigmine
Glyco : 7-15 mcg/kg
Neo 40 - 70 mcg/kg
NEO max dose per Flood : 60-80mcg/kg
Patient with pre existing cardiac disease, do you use atropine or glyco ?
Glyco preferred over atropine
Drugs to treat dig toxicity
Phenytoin
Lidocaine
Atropine ( 35 - 70 mcg/kg IV)
Timolol bradycardia and hypotension is refractory to
Atropine
BB induced excessive bradycardia and hypotension should initially be treated with
7mcg/kg atropine
Amiodarone prolongs QTc and causes Bradycardia that does not respond to
Atropine
For 40 minutes Atropine can ____LES pressure and _____barrier pressure and ____resistance to reflux
Decreases, decreases , decreases .
* Glyco does it too for 1 hour
Atropine opposes Reglan increased LES time . What dose
0.6mg/kg IV
Pg 839
X
Atropine bronchodilation is by inhibiting
Muscurinic 3 (M3) like atrovent
Atropine has sedative and amnesic action : true or false
True
Atropine has the least antisiologuoge than
Glyco and scopolamine
You should avoid _____in patients with Cystic Fibrosis
Atropine
Avoid ____in beta blocked patients
Ketamine
Propofol is a weak acid or weak base ?
Weak acid
Propofol t 1/2
0.5 to 1.5 hrs . 30- 90 minutes
11.6 hours for thiopental
More rapid and complete awakening
Cv effects of propofol m
Both BP and SVR are decreased
More ventilatory effect than Thiopental
Antiemetic via CTZ and the vomiting center : 10- 15 mg
Anticonvulsant : 0.5- 1 mg/kg
Antipruritic Dose : 10mg
Decreased cerebral blood flow and cerebral metabolism
Propofol induction vs infusion which to use : LBW to TBW ?
Induction : Lean
Infusion : Total
Which anesthetic is by TBW?(4)
Versed (except 50% dose reduced in elderly)
Fentanyl
Maintenance propofol
Sux
Tylenol
NMDA antagonist Substance P nitric oxide NMDA Cox 3 PG Descending seratonergic pathways pain by ...
Propofol receptor activation
GABAa and little glycine
Low lipid emulsion version of propofol is
Ampofol 5% soybean and 0.6% egg lethicin
Alternative lipid emulsion propofol preperation
Aquavan . Propofol sulfate progrug that results in propofol = no pain on injection but burning in genitalia
Unconsciousness reached in how long with propofol
30 seconds
What is the conscious dose of propofol?
25mcg- 100mcg/kg/min
Or
0.7mg/kg with 3 minute lockout using a pump = continuous IV sedation *
Maintenance propofol
100- 300mcg/kg/min
Antiemetic dose of propofol
10- 15 mg *** in the PACU
1- 1.5ml
Or
10 mg IV followed by 10mcg/kg/min to achieve antiemetic propofol plasma concentration
Greater than 1 mg/kg of propofol has ____property
Anticonvulsant
Metabisulfite is a preservative of generic propofol and cause
Bronchoconstriction in asthamatic and healthy patient .
Propofol augments pressor response of
Ephedrine
Norketamine
Demethylated by P450 enzyme of Ketamine
Ketamine doses
Intrathecal : 5 - 50mg in 3 ml saline
Ketamine dose in coronary artery Disease ?
Diazepam .5 /mg + ketamine .5mg/kg then 15 -30 mcg/kg/min
TIVA Ketamine + proprofol better than
Prop and Fent .
Reversal of opioid tolerance dose of Ketamine
0.3mg/kg/hr
Ketamine blocks NMDA and mentally leads to
Less depression and OCD.
And less restless leg syndrome by the way !
Mechanically vented neonate and ketamine
2mg/kg of ketamine = dexcreased ant. Fontanelle pressure (ICP)
Ketamine + inhaled anesthetics
Depression of hemodynamics bc CNS no longer intact by inhaled anesthetic
Ketamine plus NMB
Enhance of NMB
Ketamine + BB
Reduce ketamine induced HR and BP= lower BP and low HR
Ketamine + verapamil
Low BP High HR
Ketamine + Sux
Prolongs Sux apnea bc ketamine decreased pseudocholinesterase
Ketamine + volatile anesthetic
Hypotension because : volatile stops CNS fromworking = no sympathetic outflow = ketamine myocardial depression is unmasked = low BP
ROCURONIUM DOA , onset
36 minutes
What is structure of Sux ?
two molecules of acetylcholine linked through the acetate methyl groups
Sux 1/2 life
Succinylcholine has an elimination half-life of 47 seconds
What is dose of succinylcholine causing on average 95% suppression of twitch height
(the ED95) is approximately 0.3 mg/kg
time to recovery to 90% muscle strength following administration of 1 mg/kg succinylcholine ranges from
9 to 13 minutes.
Why sux short DOA?
rapid hydrolysis by butyrylcholinesterase (plasma cholinesterase) to succinylmonocholine and choline, such that only 10% of the administered drug reaches the neuromuscular junction.
Factors that have been described as lowering butyrylcholinesterase activity are
advanced liver disease, advanced age, malnutrition, pregnancy, burns, oral contraceptives, monoamine oxidase inhibitors, echothiophate, cytotoxic drugs, neoplastic disease, anticholinesterase drugs, metoclopramide, and bambuterol.
Esmolol inhibits, effects on sux
esmolol inhibits butyrylcholinesterase but causes only a minor prolongation of succinylcholine block.
Explain pregnancy decrease of butyrylcholinesterase
High estrogen levels, as observed in parturients at term, are associated with up to 40% decreases in butyrylcholinesterase activity
CV effects of SUX
Sinus bradycardia, junctional rhythm, and even sinus arrest may follow administration of succinylcholine.
Cardiac dysrhythmias are most likely to occur when a second dose of succinylcholine is administered approximately
Cardiac dysrhythmias are most likely to occur when a second dose of succinylcholine is administered approximately 5 minutes after the first dose. Sinus bradycardia (resulting from stimulation of cardiac muscarinic receptors) is frequently seen in children49 and in adults after a repeated dose of succinylcholine.50
The administration of succinylcholine is associated with approximately_____increase in plasma potassium
0.5 mEq/dL increase in the plasma potassium concentration in healthy individuals, which is well tolerated and generally does not cause dysrhythmias.
Why not give SUX to children
Because of the risk of massive rhabdomyolysis, hyperkalemia, and death in children with undiagnosed muscle disease, succinylcholine is not recommended for use in children except for emergency tracheal intubation.
Sux IOP increase , describe
The intraocular pressure peaks at 2 to 4 minutes after administration and returns to normal by 6 minutes.
Atracurium metabolism : 2 mechanisms
Hofmann elimination, yielding laudanosine (a tertiary amine) and a monoquaternary acrylate as metabolites.
Furthermore, atracurium can undergo ester hydrolysis.
Cistratricurium elimination
Hoffman elimination
No ester hydrolysis
Yield Laudosine too. But 5 times less than atricurium bc cistratricurium is 4-5 times more potent
Which has Histamine release. Atricurium vs Cistratricurium
Atricurium ,
Also : Mivacurium,
Cistratricurium Induction dose ?
- 1mg/kg *
0. 03mg/kg/min
Pancuronium is potent long acting NMB with ______and ______properties .
a p otent long-acting neuromuscular blocking drug with both vagolytic and butyrylcholinesterase-inhibiting properties
Why is Pancuronium DOA long ?
Accumulation of the 3-OH metabolite is responsible for prolongation of the duration of block induced by pancuronium
Pancuronium in renal failure …
40 - 60 % elimination in kidneys…so , avoid
Vecuronium elimination
T he liver is the principal organ of elimination for vecuronium, and renal excretion accounts for excretion of approximately 30% of the administered dose
Vecuronium Duration of NMB depend on
Hepatic function , to lesser extent renal
Vecuronium structure is
Vecuronium is simply pancuronium without the quaternizing methyl group in the 2-piperidino substitution
What is The rank order of potentiation of NMB by anesthetic drugs
The rank order of potentiation is desflurane >sevoflurane > isoflurane > halothane> nitrous oxide–barbiturate–opioid or propofol anesthesia.
Antibiotic that potentiate NMB
Aminoglycosides ( both) Tetracycline ( post Junction ) Lincomycin (both) Clindamycin (both ) Polymyxin ( both )
Most local anesthetics when given in large doses do not potentiate neuromuscular block. True or False ?
False ! They do :)
what type of patient is phenylephinre useful for
coronary artery disease and in patients with aortic stenosis because it increases coronary perfusion pressure without chronotropic side effects, unlike most other sympathomimetics.
what strange heart rate might occur when giving phenylephinre
reflex bradycardia
phenylephinre overdose results in blood pooling in the pulmonary vasculatore- what medication must be avoided
beta blockers- they will go into heart failure as the heart is unable to pump out the backed up fluid
infusion of phenylephrine + potassium- what occurs
potassium doesn’t shift intracellulary
phenylephrine continuous infusion dose
20-100mcg/min
phenylephrine push dose
50-100mcg
ephedrine push dose
5-10mg
ephedrine antiemetic dose
Ephedrine, 0.5 mg/kg intramuscularly, has an antiemetic effect
ephedrine dose can result
tachyphylaxis after 1st dose form inhibition of alpha receptor.
ephedrine
Ephedrine is an indirect-acting synthetic sympathomi- metic that stimulates a- and b-adrenergic receptors. The pharmacologic effects of ephedrine are partly due to di- rect stimulation of adrenergic receptors (direct-acting)64 and partly due to stimulation of release of endogenous norepinephrine (indirect-acting)
oral ephedrine
bronchodilation
norepinephrine infusion dose
A continuous infusion of norepinephrine, 2 to 16 mcg per minute
norepinephrine is poorly tolerated by
Both of these may be poorly tolerated by patients with right heart failure
ephedrine has what with the eye
mydriasis
ephedrine is resistant to metabolism by
Ephedrine is resistant to metabolism by monoamine oxidase (MAO) in the gas- trointestinal tract, thus permitting unchanged drug to be absorbed into the circulation after oral administration
where is NE stored
postganglionic sympathetic fibers
Epinephrine is the prototype
sympathomimetic
neostigmine works by
nhibiting acetylcholinesterase
binding to muscarinic (but not nico- tinic) cholinergic receptors
Ketamine is unique because
it produces intense analgesia at low dose and produces prompt induction of anesthesia at higher doses
Preservative in ketamine
is benzethonium chloride
Esmolol Typical INITIAL Dose is
0.5mg/kg over seconds
full effect within 5 minutes
out of your system in 10 - 30minutes
Esmolol 150 mg IV over 2 minutes before DL and ET provides
reliable protection against both increase in SBP and increase HR which predictably accompanies tracheal intubation .
Lidocaine and Fentanyl blunts increased SBP accompanied by DL but not the HR. True or False
True
What other dose of esmolol give prevent tachycardia and HTN by DL ?
you give 100-200 mcg over 15 seconds .
When you 500 mcg/kg/minute of Ketamine ( aka 0.5mg/kg over 60 seconds) during electroconvulsive therapy with anesthesia by methohexital + SUX will result in
1) attenuation of heart
2) decreased legth of electrically induced seizure !!!
What other conditions can you use Esmolol for ?
1) Pheochromocytoma
2) Thyrotoxicosis
3) Pregnancy induced HTN
4) epinephrine or cocaine induced cardio toxicity ( but you can have fulfillment pulmonary edema + coronary vasospasm and irreversible CV collapse = NTG and SNP and Phentolamine would better )
5) TOF when having hypercyonotic spells
6) HOCM
Esmolol 1mg/kg followed by 250 mcg/kg/min effect on propofol
you need less propofol to prevent movement . but no one knows how this happens
Pain on injection with esmolol ?
yes , because its buffered to a ph 4.5 to 5.5 ( one factor that causes the pain )
Esmolol metabolism is independant of
renal or hepatic
Esmolol metabolism is in done where and by what ?
in the BLOOD by plasma esterases. ( a little methanol can also occur from it’s metabolism )
Return of predrug HR within____minutes after stopping Esmolol
15 minutes . can’t find the drug in the plasma after 15 minutes
What is the 1/2 life of esmolol?
9 minutes
For intraoperative myocardial ischemia what is the dose of esmolol?
1 - 1.5 mg/kg IV followed by continuous infusion
50- 300mcg/kg/min
Esmolol continuous infusion dose
50-300 mcg/kg/min - onset is 1-2 minutes full effect in 5 minutes half life 9 minutes DOA: 10 30 minutes but it's gone from your system by 15 min
What is the beta to alpha ratio of labetalol
B:a is 3:1
Esmolol acts in what phase Action Potential
Decrease Phase 4 rate of depolarization
Suggamedex structure ….elaborate
1) modified Y-cyclodextrin - 4 gylcosyl bond.
2) produced from starch
3) its 3 dimensional structure = hollow /truncated cone or doughnut.
4) Hydrophobic cavity + Hydrophillic exterior
How Suggamedex trap the drug it is reversing
the hydrophic cavity traps the drug into the doughnut hole = now you have a guest-hole complex that is water souble.
now you have a guest in the hole :)
1:1 ratio of encapsulation
For 30 million complex of suggameddex only ___ dissociates
1
Does Suggamedex binds to plasma protein ?
NO
Rocuronium mainly eliminated in the
biles >75 %
only 10- 25%
Suggamedex -rocuronium complex is water soluble and therefore major route of elimination is
kidney : 65- 97% is recovered in the urine .
* predominantly unchanged in urine bc metabolism is so limited
Renal impairment and Suggademex
1) clearance is decreased.
2) elimination half life increased
3) dialyzing won’t work , its not constistant
Suggamedex should be avoided in patient with creatinine clearance of ?
<30ml/min
TOF 1-2 give ___Suggamedex
TOF 2 give
TOF 0 give
4mg/kg for 1-2 twtiches
2mg/kg - 2 twitches
8- 16 mg/kg- 0 twitches
Neostigmine in inthratecal
analgesia
Neostigmine can cause Bronchospasm because
it stimulates muscarinic receptors in brinchial smooth muscles
Neostigmine is unpopular choice for neuraxial adjuvent therapy because
Adverse GI effect . but epidural neostigmine does not cause nausea .
Neostigmine to a lesser degree edrophonium causes profound ( decrease or increase) in butyrylcholinesterase activity
decrease !!
Neostigmine effect on acetylcholinesterase
it has a ceiling effect.
Maximum depth of block that can be antagonized by neostigime is a TOF of
TOF of 4 twitches
Neostigmine and _____prolongs duration of SUX
pyridostigmine