L18- General Anesthetics Flashcards
define the state of ‘General Anesthesia’
- loss of consciousness
- analgesia (no pain)
- amnesia (no memory)
- suppression of reflexes
- relaxation of skeletal muscle
______ is when several drugs used in combination create a state of general anesthesia
balanced anesthesia
what are the types of general anesthetics, include functions and lack of functions
IV agents- to initiate anesthetic state, rapid action
Inhaled agents- to maintain anesthetic state, slower action
- lacks analgesic effects – give opioid
- lacks skeletal muscle relaxation effects – give neuromuscular blocker
list the inhaled anesthetics
Gases: N2O
Volatile halogenated hydrocarbons:
- halothane
- euflurane
- isoflurane
- desflurane
- sevoflurane
- methoxyflurane
list the uses for IV anesthetics
Alone or in combination:
- achieve anesthesia
- component of balanced anesthesia
- sedation of ICU patients who will be mechanically ventilated for long periods
list the uses for inhaled anesthetics
maintain anesthetic state after administration of IV agent
list the IV anesthetics
- barbiturates
- propofol
- ketamine
- etomidate
Inhaled Anesthetics:
- potency correlates with (1)
- rate of onset inversely correlates with (2)
- all will have a (3) effect on cerebral blood flow
- recovery from anesthetics results from (4)
- (5) are the common respiratory effects
1- liposolubility (more lipophilic => crosses BBB easier)
2- blood solubility (less lipophilic => less soluble => rapid onset of action)
3- inc cerebral perfusion
4- redistribution of anesthetics from brain
5- bronchodilation, dec minute ventilation (respiratory depression)
describe the main MOA of inhaled anesthetics
- positive modulation of GABA and Glycine activity in brain and spinal cord (inc inhibitory mechanisms of CNS)
- direct interactions with ligand-gated ion channels
- inhibition of nAChR
define MAC (inhaled anesthetics)
Minimum Alveolar Concentration
- concentration of inhaled anesthetic that results in anesthetic state / immobility in 50% of population
- expressed as % of alveolar gas in mixture
-therefore the lower the percentage, the less amount needed to achieve anesthetic state –> more potent agents (large % for low potent agents)
describe the effect on MAC when inhaled anesthetics are used in combination
(minimum alveolar concentration)
-MAC values are additive when used together, but also lower the individual MACs of each other
-N2O is commonly used as a carrier gas to dec amount needed of other inhaled agents
list the inhaled anesthetics in order of potency / MAC
(highest MAC / lowest potency / lowest liposolubility / highest blood solubility —–> low MAC / high potency / high liposolubility / low blood solubility)
- N2O
- desflurane
- sevoflurane
- enflurane
- isoflurane
- halothane
- methoxyflurane
describe the Meyer-Overton correlation in relation to inhaled anesthetics
- potency can predicted by liposolubility
- λ(oil:gas) = partition coefficient measuring liposolubility; the higher λ => inc liposolubility => inc potency / dec MAC
define λ(oil:gas)
partition coefficient- ratio of concentrations of compound in oil compared to concentration in alveolar gas
ex: λ = 19 –> anesthetic agent 19x more abundant in oil than in alveolar gas at equal partial pressures / equilibrium
list the factors that effect induction of anesthetic agents
- solubility of anesthetic
- [agent] in inspired air
- pulmonary ventilation rate
- pulmonary blood flow
- arteriovenous concentration gradient
describe how solubility in blood of inhaled anesthetics is measured and its relationship with speed of onset
-λ(blood:gas) correlates with blood solubility of agents — same order as λ(oil:gas)
- the higher λ => higher solubility => slower equilibrium at BBB –> slower onset of action
- the lower λ => lower blood solubility => rapid equilibrium at BBB –> rapid onset of action
describe the relationship of potency and speed of onset of inhaled anesthetics
high potency —–> slower onset of action (higher liposolubility, higher blood solubility)
low potency —–> rapid onset of action (lower liposolubility, lower blood solubility)
how does i) [anesthesia] in inspired air, ii) ventillation rate, and iii) pulmonary blood flow –> correlate with speed of onset
SIMPLE:
i) inc [anesthetic] in inspired air => inc rate of induction
ii) inc ventilation rate => inc rate of induction
iii) inc pulmonary blood flow (inc CO) => dec rate of induction [inc blood volume exposed to anesthetic –> inc blood capacity –> tension rises slowly (equilibrium takes longer)]
how does arteriovenous concentration gradient correlate with speed of onset for inhaled anesthetic agents
Definition: gradient = [anesthetic]arteries - [anesthetic]veins
- gradient is reflection of solubility in tissues
- inc gradient = inc uptake of drug in tissues => slower rate of onset of drug and slower recovery
Elimination of Inhaled Anesthetics:
- most anesthetic is eliminated via (1)
- recovery from agents with low blood and tissue solubility mirrors (2) process (low potency, rapid action)
- recovery from agents with high blood and tissue solubility depends on (3) (high potency, slow action)
1- reverse process of uptake –> exhalation
2- anesthetic induction, regardless of duration of anesthetic administration (time in = time out, ex. N2O)
3- duration of anesthetic administration - anesthetic accumulates in fat (time in «< time out, ex. methoxyflurane)
Most inhaled anesthetics have a (1) effect on the heart with a (2) effect to CVS overall.
(3) agents reduce MAP via (4) process and have little effect on (5).
1- depress cardiac contractility
2- dec MAP
3- halothane, enflurane
4- myocardial depression
5- PVR
(1) anesthetic agents are preferred in patients with impaired myocardial function because they only produce (2) CVS effects.
1- isoflurane, desflurane. sevoflurane
2- vasodilation, minimal effects on CO
______ lowers BP less than all the other inhaled anesthetics
N2O (nitrous oxide)
Use of (1) inhaled anesthetic may lead to ventricular arrhythmias due to (2) process. This effect is minimal with use of (3) agents.
1- halothane
2- inc myocardial sensitization to cathecholamines
3- isoflurane, desflurane, sevoflurane
- (1) general respiratory effects of inhaled anesthetics
- (2) have the largest effects
- (3) have the least effects
1- respiratory depression: bronchodilator, dec minute ventilation
2- isoflurane, enflurane
3- nitrous oxide
(1) is the main CNS effect seen by use of inhaled anesthetics, therefore it is contraindicated in (2) cases. (3) has the smallest (1) effect.
1- inc ICP via inc cerebral perfusion
2- Pts w/ raised ICP via brain tumor or head injury
3- nitrous oxide
______ inhaled anesthetic at high enough concentrations may cause tonic-clonic movements
enflurane
describe the additional effect nitrous oxide has compared to other inhaled agents + the contraindications due to this effect
-N2O exchanges with N2 in air-containing cavities in body –> N20 escapes faster than N2 –> inc volume and or pressure of body cavities
Contraindications: pneumothorax, obstructed middle ear, air embolus, obstructed bowel lop, intraocular air bubble, pulmonary bulla, intracranial air
Use of (1) anesthetic may lead to hepatotoxicity where (2) is the treatment
1- halothane
2- possibly severe and life threatening –> no specific Tx –> possibly liver transplant
Use of (1) anesthetic may lead to nephrotoxicity due to (2) action / effects.
1- methoxyflurane
2- via fluoride release during metabolism
(1) is a potentially fatal genetic skeletal muscle disorder if the patient is exposed to (2) or (3) which apart of balanced anesthesia.
1- malignant hyperthermia - one the main causes of death due to anesthesia
2- halothane
3- succinylcholine (skeletal muscle relaxant)
The trait for predisposition for malignant hyperthermia is inherited in (1) fashion. It usually consists of a defect in (2) which normally has (3) function, but now has (4) function.
1- AD
2- RYR1 (ryanodine receptor gene)
3- regulates RYR release of Ca in response to depolarization of sarcomere
4- unregulated release of Ca from SR in skeletal muscle
list the signs and symptoms of malignant hyperthermia
- tachycardia, hypertension
- severe muscle rigidity
- hyperthermia
- hyperkalemia, acidosis
______ is used to treat and reverse malignant hyperthermia, include mechanism
dantrolene: blocks Ca release from SR
- reduces body T
- restores electrolyte and acid-balance
describe the pathogenesis of malignant hyperthermia
- genetic predisposition + agent inc skeletal depolarization administered
i) inc Ca release from SR
ii) inc muscle contraction –> *generates heat
iii) inc aerobic metabolism => inc CO2 + O2, ATP depletion
iv) anerobic metabolism => worsens acidosis via lactate production
v) energy stores depleted
vi) muscle fibers die => hyperkalemia + myoglobinuria
(1) is the most reliable test to establish risk / susceptibility to malignant hyperthermia. A sample of (2) is taken and a positive is indicated by (3).
1- Caffeine-Halothane muscle contracture test
2- muscle via thigh
3- contracture in response to halothane and caffeine
Prolonged exposure to (1) agent decreases the activity of (2) to cause (3), a hematotoxicity.
1- N2O
2- methionine synthase
3- megaloblastic anemia
Note- occupational hazard in poorly ventilated dental suits
(1) are the ultra-short acting barbiturates used for (2) purpose. Recovery from (1)/(2) can occur do to (3- explain), although elimination of (1) requires (4).
1- thiopental, methohexital (IV anesthetics)
2- induction of anesthesia for short surgical procedures
3- redistribution from brain –> other tissues: 1st- brain, liver, kidneys; 2nd- muscle; 3rd- skin
4- hepatic metabolism
Barbiturates other effects:
- (1) effect on brain/skull
- (2) effect on sensory system
- (3) effect on lungs, therefore contraindicated with (4) patients
1- dec ICP
2- hyperalgesia (no analgesia effects)
3- apnea, cough, chest wall spasm, laryngospasm, bronchospasm
4- asthma
Propofol:
- (1) main use
- (2) additional useful effect
- lacks (3) effect
1- induction and maintenance of anesthesia (IV anesthetic)
2- anti-emetic, postoperative vomiting is very uncommon
3- no analgesia
(1) is the prodrug of propofol. Propofol is normally (rapidly/slowly) metabolized by the liver.
1- fospropofol
2- rapid metabolism in liver
list the main AEs of propofol
- potent respiratory depression
- dec ICP
- hypotension via dec PVR (contraindication in susceptible patients)
(1) is used for anesthetic induction of patients at risk for hypotension. (1) lacks (2) effects. In compared to other anesthetics it has minimal effects on (3). (1) will also reduce (4) and is associated with (5) as other adverse effects.
1- etomidate 2- analgesic 3- CVS, respiratory (depression) 4- ICP 5- n/v
(1) produces dissociative anesthesia, characterized by (2). (1) has (3) as its MOA. (1) is the only IV anesthetic that has (4) properties and stimulates (5).
1- ketamine
2- catatonia (disturbed movements and behavior as seen in schizophrenia), amnesia, analgesia +/- LOC
3- NMDA receptor (glutamate) blockade
4- analgesic
5- CVS –> therefore good for people in shock
Ketamine AEs:
- raises (1)
- causes ‘emergence phenomenon’, define as (2) and can be prevented or reduced by using (3)
1- ICP
2- sensory and perceptual illusions, vivid dreams
3- sedatives: diazepam, midazolam, propofol
describe the classic Neuroleptic-Opiod combination and how it might cause neurolept analgesia and then neurolept anesthesia
(neurolept –> sedation, opioid –> analgesia)
-*fentanyl + droperidol –> neurolept analgesia
-fentanyl + droperidol + 65% N2O in O2 –> neurolept anesthesia = balanced anesthesia
Adjuncts to anesthesia:
- (1) are for anxiolytic and anterograde amnesic effects, typically given pre-surgery
- (2) are for analgesia
- (3) are to achieve muscle relaxation
1- benzodiazepines
2- opioids
3- neuromuscular blockers (succinylcholine)
Adjuncts for anesthesia:
- (1) is the typical anti-emetic given in order to avoid (2) as complications
- (3) is the typical anti-muscarinic given for its (4) effects, to prevent (5), and protect (6)
1- odansetron
2- prevent aspiration of stomach contents (–> choking, obstructions, ect)
3- scopolamine
4- amnesic effects
5- prevent salivation / bronchial secretions
6- protect heart from bradycardia (via inhalation anesthetics and neuromuscular blockers)
