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The state of "general anesthesia" includes: (5)

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1. analgesia 2. amnesia 3. loss of consciousness 4. suppression of reflexes 5. skeletal muscle relaxation

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Which single drug can achieve *balanced anesthesia*?

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NO SINGLE DRUG. Combination is used to produce anesthetic state.

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The onset of inhalational anesthetics is

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slow (usually anesthetized with IV agent)

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Halogenated hydrocarbons are __________ analgesics and a ___________ is ____________.

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1. not good 2. supplemental 3. required

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These drugs are used to provide adequate paralysis for surgical access

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Neuromuscular blockers

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2 types of general anesthetics

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1. Inhaled anesthetics 2. IV anesthetics

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2 types of inhaled anesthetics

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1. Gases (i.e. N2O) 2. Volatile Halogenated Hydrocarbons (i.e. halothane)

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The example of a Gas used as an Inhaled Anesthetic

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N2O

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6 examples of volatile halogenated hydrocarbons used as inhaled anesthetics

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1. Haloth*ane* 2. En*flurane* 3. Iso*flurane* 4. Des*flurane* 5. Sevo*flurane* 6. Methyoxy*flurane*

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4 Examples of IV anesthetics

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1. Barbiturates 2. Propofol 3. Ketamine 4. Etomidate

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These general anesthetics are used alone, or in combination with other drugs to: 1. achieve anesthesia; 2. as components of balanced anesthesia; 3. sedate patients in ICU who must be mechanically ventilated for long periods

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IV anesthetics: 1. Barbiturates 2. Propofol 3. Ketamine 4. Etomidate

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These anesthetics are used for maintenance of anesthesia

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Inhaled Anesthetics 1. Gases: N2O 2. Volatile Halogenated Hydrocarbons: xxx*furane*

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6 *Common Features* of Inhaled Anesthetics

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1. increased perfusion of brain (i.e. increased ICP) 2. bronchodilation 3. decrease minute ventilation (hypoventilation) 4. potency ? liposolubility 5. rate of onset 1/? blood solubility 6. recovery due to redistribution from brain

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The actions of inhaled anesthetics are the consequence of direct interactions with

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*ligand-gated ion channels*: 1. positive modulation of *GABA-A and glycine* (*G*o on *G*aba and *G*lycine) 2. inhibition of *nicotinic* receptors (*N*o on *n*icotine)

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Inhaled anesthetics _______________ GABA-A and glycine receptors, while ______________ nicotinic receptors

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1. positively modulating 2. inhibiting

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This is the standard for comparison of potency of general anesthetics

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*Minimum Alveolar Concentration (MAC)*

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The *MAC* refers to

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*concentration that results in immobility of 50% of patients when exposed to a noxious stimulus (i.e. surgical incision)* (MAC is expressed as % of alveolar gas mixture)

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MAC relationship to potency

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1. LOW = potent 2. HIGH = weak (Big MAC is weak compared to the Whopper)

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The dose-reponse curves (DRC) for inhalational anesthetics are generally ____________ and the MAC tells us ____________ about the DRC

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1. steep 2. nothing (note very small window between 50% anesthetized and 97% anesthetized)

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The values of various MAC values are

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*additive*: 0.7 MAC isofurane + 0.3 MAC N2O = 1 MAC (thus Nitrous Oxide gas can be used as a "carrier gas", decreasing the anesthetic requirement of other inhaled anesthetics)

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Compare MAC Values

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NB: Big MAC = weak; so Methoxyfurane = most potent

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The Meyer-Overton Correlation

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*potency* of anesthetic *predicted by* its *liposolubility*

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A good measure of the *lipo*solubility of an inhaled general anesthetic

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?(oil:gas) (oil:gas partition coefficient)

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The potency of an anesthetic can be predicted from its

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liposolubility (Meyer-Overton Correlation)

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The relationship between ?(oil:gas) and MAC

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*inverse*: the more liposoluble, the more potent, but the smaller the MAC the less needed to take effect (i.e. not solubilized, rather mobilized)

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The partition coefficient of an anesthetic is the ratio of

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the concentrations of a compound in one solvent to the concentration in another solvent (ex. a ?(oil:gas) of 19 means that the anesthetic is 19x the concentration in oil than it is in alveolar gas when the partial pressure of the anesthetic is identical at both sites)

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The induction of anesthesia requires transfer of anesthetic from (3)

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1. alveolar air -> 2. blood -> 3. brain

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The rate at which a given concentration of anesthetic in the brain is reached depends on: (5)

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1. *solubility of anesthetic* 2. *concentration in inspired air* 3. *pulmonary ventilation rate* 4. *pulmonary blood flow* 5. *arterio-venous concentration gradient*

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This is a useful index of an anesthetics solubility in blood

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?(blood:gas)/blood:gas partition coefficient (defines the relative solubility of an anesthetic in blood compared to air)

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An anesthetic with low solubility in blood diffuses from lung into the arterial blood and the arterial tension ___________.

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rises quickly

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An anesthetic with high solubility diffuses from lung into the arterial blood and the arterial tension ___________.

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rises slowly (more molecules of the anesthetic will dissolve in blood before the partial pressure changes significantly)

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The relationship between ?(blood:gas) and the rate of rise of its tension in arterial blood

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inverse

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*A low blood:gas partition coefficient determines a __________ onset of anesthesia*

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*a faster onset* (molecules less inclined to stay in blood, so they go to brain)

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Which anesthetics have the 1) *highest* and 2) *lowest* ?(blood:gas), or the slowest and fastest onsets.

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1. methoxyflurane 2. nitrous oxide

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The ?(blood:gas) of halothane

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*2.3; very soluble* in blood, but slow onset (Mnemonic: *H*alothane is *H*appy to be in blood)

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The ?(blood:gas) of Nitrous Oxide

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0.47; quick increase in arterial tension and quick onset

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The rate of rise of anesthetic gas tension in arterial blood is directly dependent on ______________ and ______________ of ventilation

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1. rate 2. depth

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The magnitude of the effect of ventilation rate on the rise of anesthetic gas tension in arterial blood depends on

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the blood:gas partition coefficient

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An anesthetic with low blood solubility will cause a ___________ in arterial tension with an increase in pulmonary ventilation

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only a slight increase

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An anesthetic with a moderate or high blood solubility will cause a _____________ in arterial tension with an increase in pulmonary ventilation

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a significant increase

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An increase in pulmonary blood flow (i.e. increased cardiac output) has this effect on rate of rise of arterial tension of anesthetic

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slows the rate of rise (because exposes larger volume of blood to the anesthetic and blood "capacity" increases)

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The arteriovenous concentration gradient is dependent mainly on the

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*uptake of the anesthetic by tissues*

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The uptake of anesthetics by tissues has this effect on onset

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*slows down the onset*

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This process is largely the reverse process of uptake of anesthetics

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elimination

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Agents with low blood and tissue solubility will have a recovery from anesthesia that

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mirrors induction regardless of duration of anesthetic administration

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Agents with high blood and tissue solubility will have recovery from anesthesia that is _______________. Why?

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1. a function of the duration of anesthetic administration 2. because the anesethetic accumulated in fat over time, this will prevent blood (and therefore alveolar) partial pressures from falling rapidly (molecule out of blood, another one from accumulation goes into blood)

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The general effects of inhaled anesthetics on the CVS (2)

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1. depress normal cardiac contractility 2. decrease MAP

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These 2 inhaled anesthetics reduce MAP *mainly by myocardial depression* with little effect on PVR

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1. *Halothane* 2. *Enflurane* (Mnemonic: *H*eart *E*ffected more than periphery, not good for people with impaired cardiac function, but could give *scopolamine* to prevent muscarinic effects))

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These 3 inhaled anesthetics produce vasodilation and have minimal effect on cardiac output

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1. *Isoflurane* 2. *Desflurane* 3. *Sevoflurane* (*better choices for patients with impaired myocardial function*)

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Nitrous Oxide's effect on blood pressure as compared to other inhaled anesthetics

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lowers blood pressure *less than* others

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This inhaled anesthetic *sensitizes the myocardium to circulating catecholamines*, which may lead to ventricular arrhythmias

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*Halothane*

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Volatile anesthetics have this effect on the lungs

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1. bronchodilation 2. respiratory depression

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These 2 anesthetics are "pungent" and therefore not suitable in patients with bronchospasm

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1. Isoflurane 2. Desflurane

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These 2 volatile anesthetics are the most respiratory depressant

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1. Isoflurane 2. Enflurane (Mnemonic: severe *E*ffects on *I*nspiration)

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This inhaled anesthetic is the least respiratory depressant

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N2O

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All inhaled anesthetics have this effect on the CNS and are therefore undesirable in these patients.

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1. *increase ICP* 2. patients with increased ICP: a. tumor, or b. head injury

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At high concentrations, this anesthetic may cause tonic-clonic movements

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Enflurane

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This anesthetic exchanges with other molecules in air-containing body cavities, entering faster than it escapes and therefore can increase the volume and/or pressure of the cavity

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*Nitro*us oxide *exchanges* with *nitro*gen in air of air-containing cavity

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Because of its gas-exchanging capabiltites, this anesthetic should be avoided in these 7 scenarios

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*nitrous oxide* 1. pneumothorax 2. obstructed middle ear 3. air embolus 4. obstructed loop of bowel 5. intraocular air bubble 6. pulmonary bulla 7. intracranial air

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This anesthetic can result in potentially severe, life-threatening and irreversible *h*epatotoxicity that may require transplant

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*H*alothane (*H*alothane = *H*epatotoxic (and *H*eart effected)

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Due to fluoride being released during its *m*etabolism, this anesthetic has nephrotoxic potential

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*M*ethoxyflurane

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This is potentially fatal genetic disorder of skeletal muscle that is triggered in susceptible individuals when they inhale volatile anesthetics (i.e. *halothane*) and depolarizing skeletal muscle relaxants (i.e. *succinylcholine*)

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Malignant Hyperthermia

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Malignant hyperthermia is genetically transmitted as ________________ trait

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*autosomal dominant* (incidence is 1:12,000)

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*This is one of the main causes of death due to anesthesia*

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Malignant hyperthermia

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A patient is begun on anesthesia and develops *tachycardia*, *hypertension*, *severe muscle rigidity*, *hyperthermia*, *hyperkalemia* and *acidosis*. They are experiencing

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malignant hyperthermia

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The genetic defect in malignant hyperthermia is in the ____________ *gene* and syndrome results from _____________. The treatment is with _____________.

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1. *ryanodine receptor gene (RYR1)* 2. *altered control of Ca++ release from SR* 3. *Dantrolene*: blocks Ca release from SR

question

The *ryanodine receptors (RYRs)* are located

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on the sarcoplasmic reticulum of muscle cells

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The ryanodine receptors associate with

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DHPRs: voltage-gated proteins in plasma membrane in T-tubule

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The defective ryanodine receptor leads to

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unregulated Ca release from the SR of muscle cells

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The increased Ca concentration in muscle cells after release by defective ryanodine receptors leads to (5)

answer

1. sustained muscle contraction that generates heat 2. accelerated aerobic metabolism produces CO2 and depletes O2 and ATP 3. anaerobic metabolism dominates and worsens acidosis 4. energy stores are depleted 5. muscle fibers die -; release K+ and myglobin

question

The most *reliable* test to establish malignant hyperthermia

answer

*Caffeine-Halothane Muscle Contraction Test* 1. muscle sample removed from thigh (with anesthesia not known to cause MH) 2. strips prepared 3. strips put in physiological bath 4. attached to simulator (twitches every 10 s) 5. strength measured 6. Halothane (3%) or 2 mM caffeine administered 7a. . Normal muscle will not change baseline by more than 0.5 gm 7b. abnormal indicated by ;0.2 gm evoked by caffeine

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Prolonged exposure to this anesthetic can decrease methionine synthase activity and cause megaloblastic anemia, which can present as this potential occupation hazard for staff working in poorly ventilated dental operating suites

answer

*Nitrous Oxide* and *hematotoxicity*

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4 Intravenous Anesthetics

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1. Barbiturates 2. Propofol 3. Ketamine 4. Etomidate

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2 "ultra-short acting* barbiturates

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1. *thiopental* 2. *methohexital*

question

These 2 ultra-short acting barbiturates are used for induction of anesthesia and for short surgical procedures

answer

1. thiopen*tal* 2. methohexi*tal*

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Ultra-short acting barbiturates have this effect on ICP

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*decrease* ICP (good combo with volatile inhaled anesthetics)

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With respect to pain, barbiturates may cause

answer

hyperalgesia

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Barbiturates are a concern for these patients because of their potential AEs

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1. asthmatic 2. apnea, coughing, chest wall spasm, laryngospasm, bronchospasm

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This is the most popular IV anesthetic that *does not often cause postoperative vomiting* and is used for induction and maintenance of anesthesia

answer

propofol

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Propofol produces no ___________, is rapidly metabolized by ____________, is a potent ______________ and reduces ______________.

answer

1. no analgesia 2. metabolized by the liver 3. potent respiratory depressant (MJ) 4. reduces ICP

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This IV anesthetic is primarily used for anesthetic *induction of patients at risk for hypotension*

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Etomidate

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This IV anesthetic is *associated with nausea and vomiting* and may *inhibit steroidogenesis* with decreased levels of hydrocortisone

answer

Etomidate (Mnemonic: *E*tomid*ate* is *E*metic and can make you aspir*ate* so give Odansetron)

question

This IV anesthetic produces anesthesia characterized by catatonia, amnesia, and analgesia with or without loss of consciousness

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*Ketamine* produces *dissociative anesthesia*

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This is the only IV anesthetic with analgesic properties and the ability to produce CV stimulation

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Ketamine (*K*etamine may change your E*K*G)

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This IV anesthetic increases ICP

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Ketamine (*K*etamine is not good for you *K*ranium)

question

This IV anesthetic can cause sensory and perceptual illusions and vivid dreams. This is called ______________ and can be reduced with ____________ (3)

answer

1. ketamine 2. *'emergence phenomena'* 3. diazepam, midazolam, or propofol

question

*Neurolept analgesia* can be established with the combination of (2)

answer

1. *fentanyl* (potent opioid) 2. *droperidol* (potent neurolept)

question

Neurolept analgesia may be converted to ____________ by the concurrent administration of ____________.

answer

1. *neurolept anesthesia* 2. 65% N2O in O2

question

5 Adjuvants to Anesthetics

answer

1. *Benzodiazepines* 2. *Opioids* 3. *Neuromuscular blockers* 4. *Antiemetics* 5. *Antimuscarinics*

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BZDs are used as anesthetic adjuvants for

answer

anxiolytic and anterograde amnestic properties

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Opioids are used as adjuvants for anesthesia for

answer

analgesia

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NM-blockers are used as adjuvants to anesthesia in order to

answer

achieve muscle relaxation

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Antiemetics, such as ___________, are used to

answer

1. *ondansetron* 2. prevent possible aspiration of stomach contents (possibly from Etomid*ate*, which may make you aspir*ate*)

question

Antimuscarinics such as ____________ are used for (3)

answer

*scopolamine* 1. amnestic effects 2. prevent salivation and bronchial secretions 3. protect the heart from bradycardia caused by inhalational agents (i.e. H&E) and NM blockers

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