general anesthetics Flashcards
Nitrous oxide, N2O
Inhaled General Anesthetic (GA)
MAC = 105 %, by itself cannot achieve the desired depth of anesthesia
-analgesia at 20% conc. of inhaled air, sedation 30%-80%
-used in dentist’s offices
-Blood : gas partition coefficient = 0.47–rapid induction and recovery or emergence
Isoflurane (Forane®)
Inhaled General Anesthetic (GA)
MAC = 1.2%, pungent
Blood:gas partition coefficient = 1.4
>99% eliminated unchanged via the lungs
Enflurane (Ethrane®)
Inhaled General Anesthetic (GA)
MAC = 1.6%, sweet
Blood:gas partition coefficient =1.8
2–8 % metabolized in liver
Desflurane (Suprane®)
Inhaled General Anesthetic (GA)
MAC = 6%
*Irritating gas – coughing, respiratory, secretions, must use IV GA to induce anesthesia
Blood : gas partition coefficient = 0.45
>99% eliminated unchanged via lungs
SEs: dec. in BP, CO is well preserved, dec. in vent. rate
Sevoflurane (Ultane®)
Inhaled General Anesthetic (GA) MAC 2% alone is non-irritating to airways and may be used to induce anesthesia Blood : Gas partition coefficient = 0.65 *>99% eliminated unchanged via lungs
Propofol (Diprivan®)
IV General Anesthetic
Induction dose 1.5-2.5 mg/kg, duration of action 4-8 min
Not water soluble (may be dissolved in vegetable oil) – very fatty, caution in pts with high TG levels
*Most common induction agent of anesthesia in US
-Enhance effects of GABA at GABAA inhibitory receptors
Etomidate (Amidate®)
IV General Anesthetic
Induction dose 0.2-0.4 mg/kg, duration of action 4-8 min
-Not water soluble (35% propylene glycol), Used for pts at risk for hypotension
-Used for induction and maintenance of anesthesia
-Enhance effects of GABA at GABAa inhibitory receptor, Activate receptor without GABA present
-Metabolized in liver, metabolites eliminated in urine
Ketamine (Ketalar®)
IV General Anesthetic
Induction dose 0.5-1.5 mg/kg duration of action 10-15 min
-Water soluble (100 mg/ml preparation)
-Given IV also oral, rectal, IM
-Produces profound analgesia – no need for opioid co-administration
-Competitive antagonist of NMDA receptor
-Inhibition of voltage sensitive Na, K channels
-Metabolized in liver to norketamine (has further action on CNS), rapid clearance
Midazolam (Versed®)
GA Adjunct, benzo
water soluble, no pain on injection, rapid onset (2 min, IV), rapid recovery
-benzos used for pre-op sedation (Midazolam» diazepam > lorazepam): dec. brain MR, BF, dec. BP, vent. rate
Fentanyl (Sublimaze®)
GA Adjunct, opioid
Minimize vascular reflex to noxious, painful stimuli, induction for later intubation
30 min duration of action; used in terrorist situations
-μ opioid receptor agonist
SEs: N/V, dec. vent rate, dec. HR, dec. BP
Dexmedetomidine (Precedex®)
GA Adjunct, α2 adrenergic agonist
dec. catecholamine release
-used for sedation in critically ill adults, off label use as GA
adjunct; IV use only, no amnesia
SEs: dec. BP, bradycardia, no change in vent rate, Useful in non-intubated patients
Dantrolene (Dantrium®)
Ryanodine receptor inhibitor
tx for malignant hyperthermia
Also used to treat spasms and spastic disorders
how are GAs dangerous
very narrow therapeutic index of 2 – 4 (LD50/ED50) and extremely fast acting
3 requirements for anesthetic state
Amnesia – occurs through depressing neuronal activity in the hippocampus -benzos
Immobility in response to noxious stimulation –NMJ blockers
Attenuation of autonomic response to noxious stimulus (^HR, ^BP); -analgesic opioids (fentanyl)
*inhaled and IV GAs enhance all three
-balanced implies use of multiple classes to get to desired depth of anesthesia
pre-op sx drugs
for sedation?
for slowing HR?
to prevent vomiting/acid reflux? regurgitation?
barbiturates, diazepam, midazolam for sedation
- Atropine to counteract bradyarrhythmia (blocks ACh)
- Serotonin receptor antagonist (Ondansetron) for vomiting
- Histamine R2 antagonist (Ranitidine) for acid reflux
- both these prevent regurgitation due to LES relaxes with musc. relaxers
?? are used to induce anesthesia because they faster acting (~1 min) than inhaled GAs
Intravenous GAs
-inhaled also tast bad
For maintenance of anesthesia, ?? are used.
inhaled GAs
-constantly monitored, can be fine tuned, N2O typically used, reduces amount GA used
other substances given during anesthesia
- fentanyl: reduce dose of GAs and blocks the noxious stimulus reflex in the ANS
- Succinylcholine or other NMJ blocking agents as needed (e.g. endotracheal intubation)
may have this effect post-op
“Emergence excitement” is a condition where the half conscious patient exhibits restlessness, crying, moaning, and in extreme cases thrashing
-may have rebound HTN and tachycardia
tx for post-op hypothermia/shivering
meperidine (12.5mg) to reduce the shivering threshold
tx for post-op pain
NSAIDS for pain, avoid narcotics until sx drugs wear off
real life example of balanced anesthesia
Oxygen + Desflurane Propofol (induce anesthesia) Fentanyl (narcotic pain) Midazolam (tranquilizer sedative) Rocuronium (muscle relaxer)
GA pharmacokinetics
- effect proportional to concentration in CNS
- GA diffusion from lung–>blood–>CNS determines rate of induction/recovery
- rate of induction for inhaled GAs not too important (IV GAs used for induction), rate of recovery is important (faster=better)
- High water (blood) solubility = slow induction
Blood/gas partition coefficient is a measure of ??
water solubility
[GA] in blood / [GA] in lung; when gas is in equilibrium
Compare speed of induction of N2O and halothane
N2O— poorly soluble in blood (blood/gas partition coefficient = 0.47) —
rapid induction
Halothane— very soluble in blood (blood/gas partition coefficient = 2.3)—-slow induction.
minimum alveolar concentration (MAC)
measure of potency;the concentration of inhaled GA needed for 50% of patients to NOT respond to pain.
-proportional to lipid solubility
GA mechanism: inhibit neuronal activity by causing ??
1) neuronal hyperpolarization
2) inhibition of excitatory synapses
3) enhancing inhibitory synapses
GA theories
Lipid theory: GAs swell lipid membranes causing a general alteration in ion channel conduction; Myer-Overton rule – potency correlates with its solubility in olive oil
Specific protein - GA interaction theory: GAs interact specifically with ion channels/receptors; isoflurane +/- sterioisomers (same lipid solubility) have diff. MAC values, but GABAa receptor point mutations abolish effects of isoflurane and enflurane (it’s a receptor not solubility thing)
GAs alter cell membranes and enhance inhibitory membrane- bound receptors (GABA) or inhibit excitatory membrane-bound receptors (e.g. NMDA)
how to determine DoA (depth of anesthesia)
EEG; analyzed by Bispectral (BIS) index
-scale of 100 (awake) to 0 (deep coma)
N2O SEs
Air pockets (e.g. middle ear) may expand
Can change blood pressure depending on what is co-administered
Depresses ventillary response to hypoxia
Does not trigger malignant hyperthermia
Enflurane SEs
- Dec. BP, cardiomyocyte contractility, peripheral vasodilation (cerebral vasculature), no change in HR
- *Produces electrical seizure activity, though no evidence, contraindicated for epileptics
- Muscle relaxation enhanced with NMJ blockers
- Decrease in vent. rate
Isoflurane SEs
-Dec. in BP, vasodilation only (cerebral vasculature),
CO maintained
-Mild tachycardia
-Decrease vent. response reflex to hypoxia/hypercapnia
-Modest vasodilation in cerebral vasculature, however metabolic rate of brain is decreased
-Preferred GA for neurosurgery
-Muscle relaxation enhanced with NMJ blockers
-Decreased renal blood flow
Sevoflurane SEs
- Decrease in blood pressure, systemic vasodilation
- No change in CO
- Preferred GA for patients prone to myocardial ischemia
- Renal effects
- Sevoflurane and soda lime combine to produce “Compound A” which may cause short term renal damage. Because of this, the FDA recommends sevoflurane administered with fresh gas at a rate of 2 L/min; semi closed or open gas administration.
Propofol SEs
Major decrease in BP, vasodilation and decrease myocardial contractility
- Pain of injection, reduced with local anesthetic or inject in large vessel
- Decrease in vent rate - (killed Michael Jackson)
- Anti-emetic properties – very useful property for people given opioids
- Does not cross placenta, safe for pregnant women
Etomidate SEs
- Pain of injection, reduced with local anesthetic or inject in large vessel
- Myoclonic movements, benzos co-admin to prevent
- N/V
- Inhibition of adrenal gland synthetic enzymes
- No decrease in BP or CO
Ketamine SEs
-No pain of injection – no need for local anesthetics
-^cerebral blood flow, no change in brain metabolism
-Emergence delirium (1 hour post emergence)
-Hallucinations, vivid dreams, illusions (drug of abuse) -Benzos lessen the hallucinations
-only modest decrease in vent. rate and is potent bronchodilator
CV: ^BP, ^CO, ^HR- useful for pts at risk for hypotension
-severe deterioration of the urinary bladder (after only 2-3 years of abuse (~5 grams injected per day))
hypothermia as a sx complication
body temp is below 36°C
- cold OR, room-temp IV fluids, many GAs cause vasodilation–>heat loss
- ^chance cardiac arrest, unstable angina, MI
malignant hyperthermia
-adverse reaction to inhaled GAs, high mort rate; core temp rapidly increases to over 42°C (108°F) due to uncontrolled muscle rigidity
-complication of most inhaled GAs; not N2O and not succinylcholine (NMJ blocker)
-ryanodine Ca2+ channels don’t close–>uncontrolled muscle contraction–>heat generation.
-Fatigued myocytes eventually lyse releasing K+–>fatal cardiac events.
(KCl is the 3rd and final drug given in conventional lethal injection protocols)
