Induction Agents - Quiz 2 Flashcards
What helps moves neurotransmitters to the endplate to release itself to the synapse then to the receptor?
Calciuim
What is broken down to form GABA
Glutamate
What kind of an effect does the GABA Agonist have?
Inhibitory Neurotransmitter
How does Glutamate work?
Released by calcium –> binds with NMDA –> Influx of Positively charged ions
Excitatory Effect
How can the effects of Glutamate be blocked?
Ketamine - Noncompetitive Antagonist
(also rapid antidepressant)
How does the Alpha2 Receptor Negative Feedback Loop Work?
Excess Norepi binds to presynaptic alpha2 receptor and inhibits release of Norepi
How does Precedex work?
Binds to presynaptic alpha2 receptors, blocking release of Norepi = sedation
Location of Baroreceptors
Aortic Arch, Carotid Body - signals travel to medulla and regulate heart rate, arterial, and venous tone according MAP
What nerves do baroreceptor impules travel through?
Vagus, Glossopharyngeal, and Hering’s
Action: Inhibits/Stimulates sympathetic/parasympathetic system
Central Chemoreceptors
Respond to pH and CO2 changes
(Peripheral Chemoreceptors responds to O2)
Advantages of IV Anesthesia
Rapid onset of General Anesthesia (30 sec - 1 min)
Can be used for maintenance of General Anesthesia
Provides sedation for MAC
How long does it normally take for a patient to wake back up from induction meds?
9 Minutes
Disadvantages of IV Anesthesia
There is no ONE med that provides hypnosis, amnesia, analgesia, and immobility.
What is Balanced Anesthesia
Use of Multiple drugs
- Inhalation agents
- IV induction agents
- Sedative/Hypnotic
- Opioids
- Neuromuscular Blockade
Are IV Induction Agents hydrophilic or lipophilic?
All are Lipophilic - for rapid onset in brain and spinal cord
Body Mass % of Normal Adult
- Vessel Rich: 10%
- Vessel Poor: 20%
- Fat: 20%
- Muscle: 50%
Blood Flow % of Cardiac Output
- Vessel Rich: 75%
- Vessel Poor: <1%
- Fat: 6%
- Muscle: 19%
How is the effect of a Single Dose of IV Induction agent stopped?
Distribution, Not Metabolism
Drug redistributed to less perfused tissues: vessel rich & poor
When does metabolism of IV Induction medications come into play?
When multiple doses are given and when there’s a buildup of the drug
IV Bolus Three Compartment Model
Med goes to general circulation –> distributes to vessel rich organs –> rapid redistribution to vessel poor (shallow) –> slow distribution to peripheral compartments (deep) –> metabolism
What are the vessel rich organs?
Brain
Liver
Kidneys
Gut
What are the Vessel Poor Organs
Shallow Compartment
Muscles
What is part of the Deep Compartment?
Fat
In what phase does distrbution last for 2-4 minutes?
Rapid distribution phase to vessel poor group
List classes of IV Induction Agents
Barbiturates
Benzos
Propofol
Ketamine
Etomidate
Precedex
Barbiturates
1930’s - Oldest Class
Sedative, Hypnotic, Anticonvulsant
Chemical Structure of Barbiturates
Barbituric Acid - lacks CNS Activity
How do hypnotic, sedative, and anticonvulsive effects occur regarding barbituric acid?
Subbing on N1, C2, C5 sites
Why do myoclonic jerks occur when bolus dose of induction agent is given?
Body’s natural response to bolus of inhibition = Sympathetic outflow
Barbiturate MOA
Acts with GABA to enhance profound hyperpolarization
What are GABA-mimetic effects?
Barbiturates dont need GABA with higher doses as opposed to Benzos
How does plasma albumin effect barbiturate binding?
Decreased albumin causes higher unbound barbs
What causes higher unbound fraction of barbiturate?
Decreased plasma protein concentration
- Uremia
- Liver disease
- 3rd Trimester
What drugs compete with Barbiturates?
Aspirin
Naproxen
Indomethacin
Warfarin
Pharmacokinetics of Barbiturates
3 Compartment Model
Redistribution has major effect on duration
Metabolism
Inactive metabolites excreted in urine
CNS Effects of Barbiturates
- Rapid Loss of Consciousness
- Significant post anesthesia drowsiness
- No pain management properties
- Decrease in O2 Consumption (CMRO2)
- Decrease Cerebral Blood FLow
- Decrease ICP & IOP
- Anticonsulvant Properties
Barbiturates CV Effects
- Decrease Medullary vasomotor center
- Decrease Sympathetic system
- Decrease BP d/t vasodilation (transient)
- Compensatory Increase in HR
- Decreased venous return
When are exaggerated hypotensive responses seen with Barbiturates?
Hypovolemia
Cardiac Tamponade
Cardiomyopathy
CAD
Valvular Disease
Large Induction Dose
Rapid Drug Injection
Barbiturate Respiratory Effects
- Dose related respiratory depression
- Laryngo/Bronchospasm
- Transient apnea
- Decrease stimulation by CO2 to breath
- Laryngeal reflex/cough reflex suppression
Barbiturate Anaphylaxis
- Cause histamine release -> vasodilation
- 1 in 30,000
- Tissue necrosis if injected not in vein
- Immunosuppression
What happens if you inject barbiturates in the artery?
Immediate Vasospasm and Constriction
Intense Pain
Entire Extremity Blanching
Ischemic Gangrene
How to treat arterial injection of Barbiturates
- Dilute with injection of NS through same site
- Treat vasospam with Papaverine 40-80mcg
- Stellate or Brachial Plexus block to increase flow to extremity
- Systemic Heparin
Absolute Contraindications to Barbiturates
- History of Allergic Reaction
- History of Porphyria - Less than 20,000/yr
- Autonomic System Disturbance
- Abd Pain
- Skin Lesions
- HTN
- Tachycardia
- Seizures
Benzo Drugs
Librium
Diazepam
Serax
Ativan
Versed
Benzo MOA
Activates GABA Receptor
Big Influx of Chloride Ions - Hyperpolarizes
Versed has greater potency & affinity for GABA
2-3x more than diazepam
Why are Benzos used more in clinical Situations
Broad scope of properties with low side effect profile
- Anxiolitic - amygdala, hippocampus, limbic
- Sedation - brainstem & cortical receptors
- Muscle relaxation - spine
- Amnesia - Forebrain & hippocampus
Benzo Vs. Bariburates
Less abuse potential
Bigger margin of safety
Less significant drug interactions
Dont induce liver enzymes
Imidazole Ring of Versed
- Open at pH:4
- Closed > pH 4 = lipophilic = rapid onset
Versed Pharmacokinetics
Highly protein bound
Rapid onset, but slow effect site equilibrium
CYP substrate
Urinary excretion
Benzo CNS Effects
Decreased CMRO2
Decreased CBF
CANNOT make isoelectric EEG
No ICP change
Anticonvulsant
Paradoxical excitement in < 1%
Benzo CV Effects
Decreased BP (Versed > Diazepam)
Cardiac Output unchanged
Does NOT prevent sympathetic response to intubation
Benzo Respiratory Effects
Same as Barbiturates
Benzo Side Effects
- Allergic rxns rare
- Pain on injection - ativan, diazepam
- NonRestorative sleep
- Anterograde Amnesia
Benzo and Barb Withdrawal
Lasts weeks to months
Anxiety, insomnia, seizures, coma, agitation, psychosis, mania, suicide
HTN, Tachycardia, Postural Hypotension
Benzo & Barb Overdose
Resp. depression, hypotension, coma, confusion
Use supportive therapy first before reversing
What is the reversal for only Benzo Overdose
Flumazenil - competitive antagonist
200 mcg q1-2 min, max 3mg/hr
May cause immediate withdrawal
Remimazolam
Metabolism via Esterases
Rapid Clearance - may only stay in 1st or 2nd compartment
Less Buildup
Propofol
Most frequently used for induction
Needs lipid vehicle so it doesnt separate out
Supports bacterial growth
Propofol Reformulations
Swtched from EDTA to Sodium Metabisulfite
Anaphylaxis and Asthmatic Episodes
Propofol MOA
Acts on GABA receptors
Propofol Pharmacokinetics
Rapid Onset
Rapid Return of Consciousness (3-10 Min)
Rapid Clearance - less hangover
3 Compartments
CYP Substrate & Inhibitor
Propofol CNS Effects
Same as Benzos and Barbz
Propofol CV Effects
Profound dereased BP - afterload & preload
Dramatic Inhibition of Baroreceptor Reflex
Profound Bradycardia
How does Propofol supress apoptosis and inflammation
Structurally looks like Vitamin E
Propofol Respiratory Effects
- Potent respiratory depressant
- Apnea after induction dose
- Decreased response to CO2 and O2
- Big reduction in airway reflexes
- Less risk of laryngo and bronchospasms than barbs
Other Propofol Effects
- Anti-emetic (10mcg/kg/min)
- Does not potentiate muscle relaxants
- Injection Pain - stay way from hand
- Elevated triglycerides
- Risk for PE
- Antipyretic
- Antioxidant
Propofol Infusion Syndrome
Lactic Acidosis for use > 48 hrs or 67mcg/kg/min
Unexpected Tachycardia
Hepatomegaly
How do you treat Propofol Infusion Syndrome
Stop infusion
Treat acidosis
Support multi-system failure
How does propofol infusion syndrome present in kids?
Anion Gap Acidosis
Bradyarrhythmia
Rhabdo
Liver Dysfunction
MODS
Hyperkalemia
AKI
How does Propofol work in kids’ bodies
- Enters mitochondria easily, stops ATP production, and stops fatty acid metabolism = fatty acid buildup
- Carb deficiency makes kids more prone to these problems
Fospropofol (Lusedra)
Water Soluble Produg of Propofol
no need for lipid vehicle
Fospropofol vs. Propofol
Slower Onset
Stronger & Longer Duration
More Itching & Paresthesia
Less Pain on Injection
Doesnt enter CNS until metabolized
Ketamine
Dissociative Anesthesia
EEG Dissociation b/t thalamocortical & limbic
Pt. Non Communcative
Blank stare
Limited skeletal movement
What does ketamine do well and dont do well?
Great pain control
but
No complete amnesia, needs a benzo
Emergence Delerium - reduced by benzo
Ketamin’s chemical structure is similiar to what?
PCP
Partially water soluble
S-enantiomer (Ketanest) is more potent, but cost $$$$$$$
Ketamine MOA
NMDA Noncompetitive Receptor Antagonist
Inhibits C++ Influx
Weak action on GABA
May effect opioid, muscuranic, and monoaminergic receptors
How does Ketamine produce its analgesic effects?
Inhibits Nitric Oxide Synthase
How does Ketamine stimulate Sympathetic system?
Inhibits Catecholamine Reuptake
How does Ketamine produce Beta-2 agonism and respiratory relaxation?
Induces Catecholamine Release
Ketamine Pharmcokinetics
Not really bound to plasma proteins
Leaves blood fast to be distributed to tissues
Extremely lipophilic
3 Compartment Model
Metabolism of Ketamine
Really metabolized by liver enzymes
Demethylation of ketamine to norketamine
What is Norketamine
Active Metabolite of Ketamine
- 1/3 - 1/5 as potent
- contributes to prolonged effects of ketamine
- Hydroxylated then conjugated into water soluble inactive metabolites
Ketamine CNS Effects
Increases CBF
Increases CMRO2
Used for seizures if other meds fail
May cause myoclonic jerks
Ketamine CV Effects
Direct Myocardia Depressant
Produces significant transient Increases in BP, HR, CO
Increased Cardiac Metabolic Requirment for Oxygen
Ketamine Respiratory Effects
No Respiratory Depression
Respiratory response to CO2 present
Transient hypoventilation
Relaxes bronchial smooth muscle
Increased Salivation
Ketamine Side Effects
Emergence Reactions: 10-30%
Vivid Dreams, Out of Body Experience, Hallucinations
Can last hours
Nystagmus
What is the half-life of Flumazenil
1 Hour
Where do barbs bind on the GABA receptor?
Between GABAB and GABAY
Where do Benzos Bind on the GABA Receptor
Between GABAa and GABAY
Where do GABA Neurotransmitters bind on the GABA Receptor
Between GABAa and GABAB
