Induction + Pain Management - Quiz 3 Flashcards
Etomidate
Causes Hypnosis
No Pain Properties
Minimal CV Effects
Etomidate’s Chemical Structure
Carboxylated Imidazole
2 Isomers: R+ is active
PG Solvent
pH: 8.1
Only induction med that is NOT racemic mixture
Etomidate MOA
Potentiates GABAA mediated Chloride Shift
Act like Barbs at Higher Doses
Etomidate Pharmacokinetics
- Rapid half-life, Rapid Total Clearance
- Single Dose - extremely short duration (3-5 min)
- Peak: 1 min
- Protein Bound
- 3 Compartment Model
- Hepatic extraction
- Minimal Buildup - can redose
What limits use of Etomidate
Transient Depression of Adrenocortical Function
- Lasts 4-8 hrs.
- Reversible
- increased mortality in Septic/Hemorrhaging Pts.
- Advantage: stress free anesthetic
Etomidate CNS Effects
Decreased CBF
Decreased CMRO2
Decreased ICP while maintaining CPP
Maintains cerebral vessel response to CO2
Decrease IOP
Etomidate CV Effects
CV stability - minimal changes
except
Pts. w/ aortic stenosis or mitral valve disease - significant drop in BP, PAP, PCWP
Etomidate Respiratory Effects
Decrease Minute Volume
Compensatory increase RR
Decrease ventilatory response to CO2
Apnea followed by Hyperventilation
Etomidate’s other effects
PONV
Does NOT effect duration of seizure
Myoclonic Jerks (decreased w/ prior opioid med)
No Histamine Release
Low Allergy Risk
Precedex
Highly Selective Alpha 2 Agonist
1600 : 1 - alpha2 : alpha 1
(220 : 1 for Clonidine)
Water Soluble
D-isomer is the Active Part
Precedex MOA
Negative Feedback on a2 receptors and makes a2 agonist effects
Sleep mimics Normal sleep
Pain Properties
Tolerance happens
Why is Clonidine sometimes used on kids?
Adjunct therapy for ADHD
Precedex Pharmacokinetics
Protein Bound
Rapid Hepatic Metabolization
Excreted in Urine & Bile
Rapidly Cleared
Precedex CNS Effects
Decrease CBF
No ICP Change
No CMRO2 Change
Decrease Plasma Catecholamine
Decrease MAC Requirement
Decrease need for Opioid
Precedex CV Effects
Moderate ↓HR & ↓SVR
Bolus may cause brief increase in BP & Bradycardia
Precedex Respiratory Effects
Small ↓Tidal Volume
No signifcant change in RR
No change to CO2 Response
Mild Airway Obstruction
Synergistic w/ other Sedatives
What is the max infusion time for Precedex per the package insert?
24 Hours
Still safe after 24hrs, but you might see lack of effect and changes in blood pressure.
Precedex Withdrawal
Upregulation of Receptors
An abrupt stop = accelerated HTN
Higher risk of HTN for pts who are already at risk.
General Anesthetics and Preggos
- Black Box Warning: causes poor cognitive and school performance for the kid
General Anesthetics and Preggos:
American College of Ob/Gyn
Disagrees w/ Black Box Warning - Can’t generalize based on animal testing
General Anesthetics and Preggos
JAMA
Sibling Study: No adverse effects in child development
General Anesthetics and Preggos
MASK Trial
Single Exposure: No deficits
Secondary Exposure: Possible deficits in processing speeds and fine motor skills
Nociceptive Pain
Has obvious site of pain
Nociceptive Stimulation
Noxious Stimuli release neural chemicals that stimulate other nociceptors
- Bradykinin, Substance P, Potassium, Histamine, Prostaglandin, Luekotriens
- Transmits signal to Spinal Cord
Nociceptive Transmission
Action potential moves from stimuli site to dorsal horn of spinal cord, then CNS
- Many pathways
- A Fibers: large diameter, myelinated - sharp pain
- C Fibers; small diameter, unmyelinated - dull, aching pain
What are released from the dorsal horn during nociceptive transmission?
Glutamate
Substance P
Calcitonin Peptide
Nociceptive Perceception
Conscious Pain Experience
Impulse relayed thru thalamus
Nociceptive Modulation
Impulse Inhibition via Brain Stem
- Body’s opioid
- Serotonin
- Norepi
- GABA
Neuropathic Pain
Does NOT follow pain cascade
Nerve Misfire
Never damage, Persistance Stimulation, Autonomic Dysfunction
Burning, tingling, shocks, hyperalgesia, headache
What is Chronic Pain
> 3 months or past the time of normal healing
20% of non cancer pts. receive opiods
Pain Monitoring
- Provocative factors
- Quality
- Radiation
- Severity
- Temporal relations
Opiate Addiction
> 5 days = addiction risk
6% s/p minor surgery kept using opiates for at least 90 days
Increased addiction risk for middle age (45-64 yo)
Who are at risk for Inadequate Pain Control
Minorities
Women
Elderly
Cognitively Impaired
Cancer/EOL
Optimal Length of Opioid Scripts
- General Surgery: 4-9 days
- Women’s Health Procedures: 4-13 days
- Musculoskeletal Procedures: 6-15 days
How does Esmolol work for pain?
Blunts cardiovascular effects of massive sympathetic outflow
Short half-life
Location of Opioid Receptors
Brain
Spinal Cord
GI Tract
What are the subtypes of Opioid Receptors
Delta
Kappa
Mu - primary
Nociceptive
Delta Opioid Receptors
Brain & Peripheral Nerves
Analgesia, Antidepressant, Dependence
Kappa Opioid Receptors
Brain, Spinal Cord, Periphery
Analgesia, Sedation, Miosis, Dysphoria, ADH Inhibition
Urinary Hesitance
Mu Opioid Receptors
Brain, Spinal Cord, Periphery, Intestine
- Mu1: Analgesia, Dependence
- Mu2: Resp. depression, euphoria, reduced GI motility, dependence
- Mu3: Unknown
Nociceptive Opioid Receptors
Brain, Spinal Cord
Anxiety, Depression, Appetite, Tolerance to Mu Agonist
How do Opiates Work
Presynaptic:
Binds to G-Coupled Proteins (2nd msgr) - Amplifies signal –> Inhibits Adenylate Cyclase –> lowers cAMP –> less Ca++ –> stops neurotransmitter release (stopping some pain signal)
Postsynaptic:
Glutamate can still bind, but opiate also binds here –> opens K+ channel for K+ release –> creates negative field –> glutmate unable to cause action d/t hyperpolarization
NMDA Receptors & Opioids
Can reduce opioid effectiveness
Glutamate overstimulation = neuropathic pain
Methadone blocks NMDA
Which structure form of Opioids have agonist action?
Levo Rotary Forms
Are Opioids Ionized?
Yea, they gotta be to form a strong bond with the opioid receptor
(Lipophilic with an Ionized branch)
How does codeine work?
Its a prodrug needing to be metabolized to turn into morphine.
Morphine and Pain
- Increases pain threshold and modifies pain perception
- Works better for continuous dull pain vs sharp pain
- Effective for visceral, skeletal, and skin pain
- Most effective if given before surgical stimulus
- Cause dysphoria if there is not pain
Does morphine need to enter CNS to work?
No
Morphine Metabolism
85%: M3G (Inactive)
10%: M6G (Active) & 100x more potent
Renal failure can cause M6G buildup
Morphine CV Effects
Bradycardia
Reduced SNS Response
Histamine Release - itching, vasodilation
Orthostatic Hypotension
Morphine Respiratory Effects
Dose dependent ventilatory depression
via
Mu2 Receptors
↓CO2 Response
↑Resting PaCO2
Asynchronous breathing + Cough Suppression
Morphine CNS Effects
Careful with Head Injuries
Effects Wakefulness
Pupil Constriction
↑ICP
Broken Blood Brain Barrier increases morphine sensitivity
How does pt’s EEG look on Morphine?
Looks like sleep w/ no seizure activity
With Morphine, sedation happens ________ pain relief and is not equivalent.
BEFORE
How does morphine effect the biliary tract?
Cause biliary spasms and increased pressure
What can be used to treat opioid induced biliary spasms?
Glucagon 2mg IV
(normally used for bradycardia from beta blocker overdose)
Morphine and GI Tract
Constipation
Biliary Colic
Delayed Emptying
NV from Chemoreceptor Trigger Zone Stimlulation
How to treat Opioid Induced Constipation
- Senna, NOT Docusate
- Add 2-3 OTC laxatives
- Consider New Mu Antagonist
Morphine GU Effects
Have to pee but cant
Morphine Other Effects
No affect on NMB drugs
Rapid injection = chest rigidity
Exaggerated CNS depression w/ MAO inhibitors
Dilaudid Vs Morphine
Synthetic and has no active metabolites
More Stable for Renal Dysfunction
No significant Histamine Release
Fentanyl vs Morphine
More Potent
Faster Onset (Not Instant)
Shorter Duration
Protein Bound
More Lipophilic
Fentanyl Pharmacokinetics
Redistributes to Inactive Tissues
Lungs store 75% of single dose
Stay in blood for a while d/t reuptake from inactive tissues
Fentanyl Metabolism
Liver Enzymes
Norfentanyl Metabolite (limited activity)
Excreted in urine
Can be detected in urine for 72 hrs.
Fentanyl CNS Effects
Modest ↑ICP
No Seizure
Low-Mod doses don’t effect evoked potentials
Fentanyl CV Effects
Bradycardia
↓BP
↓CO
No Histamines
Fentanyl Respiratory Effects
Persistent Ventilation Depression
Recurrent ventilation depression from second Peak
What kind of drug interactions do Opioids have with Benzos?
Synergism
1+1 = 3
Why is there less opioid plasma concentration in cardiopulmonary bypass?
Fentanyl sticks to the machine
Intrathecal Fentanyl
Rapid
Profound Labor Pain Relief
Oral Fentanyl (Actiq)
Used to reduce Pre-op Anxiety
and
Help with Induction
Fentanyl Patch
Last 3 Days
Takes much longer for it to work
Sufentanil vs Fentanyl
5-10x more Potent
Shorter Half Life than Fentanyl
Sufentanil Metabolism
Liver Enzymes
Renal Dysnfunction = prolonged ventilation depression
Sufentanil CNS Effects
↓CMRO2
↓CBF
Sufentanil CV Effects
Bradycardia
↓CO
Sufentanil Respiratory Effects
Ventilation Depression
Chest rigidity
Alfentanil
1/5 - 1/10 as potent as Fentanyl
Short half-life
Fast effect-site equilibrium
Useful for ICU intubation, cardioversion, retrobulbar block
Afentanil Metabolism
Highly Dependent on Liver
Remifentanil
Selective Mu Agonist
Similar Potency to Fentanyl
Fast site equilibrium similiar to Alfentanil
Moderatly Lipophilic
Structurally Unique - Ester Link
Remifentanil Pharmacokinetics
Very rapid Clearance - 3L/min
Works the same in all shapes and sizes of people
Remifentanil Metabolism
Excreted by kidneys
6 minute half life
No buildup
Precisely Titratable
Remifentanyl CNS Effects
No ICP/IOP Change
High Dose = ↓CMRO2 & ↓CBF
Remifentanil CV Effects
Mild ↓HR
Mild ↓BP
No Histamine release
Remifentanil Respiratory Effects
Ventilation Depression
Nausea and Vomiting
Remifentamnil Tolerance
High Post-Op Analgesia requirement
