INTRAVENOUSANESTHESIA
Intravenous Anesthetics
widely used to facilitate rapid induction of anesthesia or to provide sedation during monitored anesthesia care (MAC)
NON-OPIOID IV ANESTHETICS
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Induction of anesthesiaMaintenance of anesthesia Sedation Antiemetic
PROPOFOL
PROPOFOL
Acts through potentiation of the chloride current through the -aminobutryric acid Type A (GABA-A) receptor complex
2,6 diisopropylphenol Alkyl phenol with HYPNOTIC properties Usually contains:
10% soybean oil 2.25% glycerol 1.2% lecithin
Milky-white Slightly viscous pH ~ 7 Rapidly metabolized in the liver Excreted through the kidneys
PROPOFOL
Cardiovascular EffectsVasodilation systemic blood pressure (SBP) is more
pronouncedExacerbates hypotensive effectProfound bradycardia and asystole
PROPOFOL
Respiratory EffectsPotent respiratory depressant >>
produces apnea post-inductionReduction in tidal volume and respiratory
rateReduces upper airway reflexes >>
Hence, the use of laryngeal mask airwayDecreases incidence of wheezing and
tracheal intubation among healthy and asthmatic patients
PROPOFOL
BARBITURATES
ThiopentalMethohexital
Barbituric acid
BARBITURATES Induction of Anesthesia
NMBDs are often administered shortly after the barbiturate to produce skeletal muscle relaxation
Thiopental + Succinylcholine: Classic drug regimen for rapid sequence induction of anesthesia
Neuroprotection
BARBITURATES
Lacks hypnotic effect
Formulated as sodium salts mixed with anhydrous sodium carbonate
After reconstitution with water and NSS, the solution is alkaline with pH >10 prevents bacterial growth and helps increase the shelf-life
BARBITURATES Central Nervous System Effects
Sedation to general anesthesia in induction doses
No analgesic effect (reduces the pain threshold)
Potent cerebral vasoconstrictor
Decrease CBF, CBV, ICP
Useful in management of patient with space-occupying intracranial lesions
BARBITURATESCardiovascular System EffectsDecreases BP VasodilationBarbiturate-induced depression of the medullary vasomotor center and decreased sympathetic nervous system outflow from the CNS
BARBITURATESRespiratory System Effects Depresses the respiration >> leads
to decreased minute ventilationthrough reduced tidal volume and RR.
Induction doses induces transient apnea
Decreases ventilatory response to hypercapnia and hypoxia
BENZODIAZEPINES
Midazolam
Lorazepam
Diazepam
Flumazenil
Preoperative medication Intravenous sedation Intravenous induction of anesthesia
Suppression of seizure activity
BENZODIAZEPINES
BENZODIAZEPINES
Activation of GABAA receptor complex and enhancement of GABA-mediated chloride currents leads to hyperpolarization of neurons and reduced excitability
Spectrum of EFFECTS: Sedative-hypnotic Amnestic Used to treat seizure Anxiolysis Mediated through the
-subunit of the GABA receptors
Mediated through the
1-subunit of the GABA receptors
BENZODIAZEPINES
BENZODIAZEPINES
Highly lipid soluble Rapid onset of action Metabolism in the liver through microsomal oxidation, N-dealkylation and aliphatic hydroxylation or glucuronide conjugation
Midazolam has the shortest context-sensitive half-time, which makes it the only one that is suitable for continuous infusion
KETAMINE
KETAMINE
Induction and Maintenance of Anesthesia
Analgesia (CS and neuraxial anesthesia)
KETAMINE
- Phencyclidine derivative
- Produces significant analgesia
- Known as dissociative anesthesia -patients eyes remain open with a slow nystagmus gaze (cataleptic gaze)
- Partially water-soluble, but highly lipophilic
KETAMINE Lacrimation and salivation are increased and
premedication with an anticholinergic is indicated to limit the effect
EMERGENCE reactions:
Vivid colorful dreams
Hallucinations
Out-of body experience
Increased and distorted visual, tactile, and auditory sensation
Associated with fear and confusion
ETOMIDATE
Carboxylated imidazole derivative
IV anesthetic with hypnotic but notanalgesic properties and with minimal hemodynamic effects
Alternative to Propofol and Barbiturates
ETOMIDATE
EFFECT on ENDOCRINE SYSTEM
Causes adrenocortical suppression by producing a dose-dependent 11 -hydroxylase, an enzyme necessary for the conversion of cholesterol to cortisol
Suppression last 4 to 8 hours
DEXMEDETOMIDATE
Short-term sedation
Adjunct to general anesthesia to provide sedation
DEXMEDETOMIDATE
Active S-enantiomer of medetomidine
Used in veterinary medicine
Highly selective 2-adrenergic agonist
DEXMEDETOMIDATE
Hypnosis results from structure of 2receptor in the locus ceruleus and the analgesic effect at the level of spinal cord
OPIOID IV ANESTHETICS
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OPIOIDS
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Receptor Clinical Effect Agonists
Mu
Supraspinal analgesia (-1)Respiratory depression (-2)Physical dependenceMuscle rigidity
MorphineMet-enkephalinBeta-endorphinFentanyl
KappaSedationSpinal analgesia
MorphineNalbuphineButorphanolDynorphinOxycodone
DeltaAnalgesiaBehavioralEpiletogenic
Leu-enkephalinBeta-endorphin
SigmaDysphoriaHallucinationsRespiratory stimulation
PentazocineNalorphineKetamine
Inhibits the presynaptic release and postsynaptic response to excitatory neurotransmitters (acetylchloine, substance P) from neurons.
Transmission of pain impulses can be interrupted at the dorsal horn of the spinal cord
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OPIOIDS
OPIOIDS
AbsorptionFentanyl - low molecular weight
and high lipid solubility (rapid onset = 10 min, but short duration of action)
Morphine - low lipid solubility (slows passage across the blood brain barrier)
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OPIOIDS
Excretion
Eliminated via kidneys (10% via biliary excretion)
Morphine 3-glucuronide & morphine 6-glucuronide (morphine metabolites) that could lead to narcosis and ventilatory depression in renal failure
Normeperidine (meperidine end product) has an excitatory effect on the CNS (myoclonic activity and seizures)
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OPIOIDS
Cardiovascular effects
Meperidine - increases heart rate
Morphine, fentanyl, sufentanil, remifentanil, alfentanil - bradycardia (vagus-mediated)
Meperidine & morphine - decrease BP and systemic vascular resistance (histamine release)
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OPIOIDS
Respiratory effects
depress ventilation and respiratory rate
Morphine and meperidine -histamine induced bronchospasm
Fentanyl, sufentanil and alfentanil -chest wall rigidity 36
OPIOIDS Cerebral effects
reduce cerebral oxygen consumption, cerebral blood flow and intracranial pressure
nausea and vomiting are due to stimulation of the medullary chemoreceptor trigger zone
Meperidine - decreases shivering 37
OPIOIDS Gastrointestinal
reduces peristalsis by slowing the gastric emptying time
Biliary colic is due to opioid-induced contraction of the sphincter of Oddi
Constipation due to decrease GI motility
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OPIOIDS
Endocrine
blocks the release of hormones (catecholamines, antidiuretic hormone and cortisol) during surgical stimulation
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"Anesthetics have been used for 160 years, and how they work is one of the greatest mysteries of neuroscience,"
-James Sonner,
M.D. (UCSF)
Thank You &Good Morning!