Nervous System- Anesthetics By Schriefer

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Nervous System- Anesthetics by Schriefer

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Nervous System- Anesthetics by Schriefer

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Uptake, Distribution and Elimination of Anesthetic Gases

Partial Pressure

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the pressure exerted by a gas in a mixture of gases. For our purposes it is a measure of the CONCENTRATION of a gas.


Blood/Gas partition coefficient (λ) – a measure of the solubility of an anesthetic gas in the blood. lower the lambda, the faster the onset.

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Nitrous Oxide

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saturate the blood quickly, increasing the amount in the gaseous phase. goes from the blood into the body's tissues (esp. the brain)

this happens quickly because N2O doesn't saturate in the blood well.

faster onset. saturated and transfered more quickly.

lower the lambda, the faster the onset!

The speed of induction and emergent(recovery) is determined by the rate of change of the partial pressure (concentration) of the gas in the brain, which is determined by the partial pressure of the gas in arterial blood.
The best correlation with speed of induction is with blood/gas partition coefficient (inverse correlation).

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Uptake, Distribution and Elimination of Anesthetic Gases:
Summary

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During administration of an anesthetic, its concentration in blood rises toward that in the inspired gas.

Tissue concentrations rise also, approaching the concentration in the arterial blood. The concentration rises most rapidly in tissues with high blood flow, and lags in tissues with lower flow.

Eimination determined by the above factors operating in the reverse direction. lambda of 1 will go to sleep and wake up quicker than a lambda of 4

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What is the therapeutic indices for general anesthetics?

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Therapeutic indices for most general anesthetics is low (2-4); accurate control of dosage is necessary for safe use.

don't really kill because if you give too much, just turn it off, and the pt. will exhale the extra for you.

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what is MAC?

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Potency – for most drugs usually expressed as activity per unit weight administered. This expression not useful for anesthetic gases because no fixed dose is given

-Relative potency of anesthetic gases expressed as MAC
-MAC is defined as the Minimal Alveolar Concentration that will block movement of 50% of patients in response to incision
-MAC correlates with lipid/gas partition coefficient

sounds like the ED50 (effective dose)

if you're giving too much gas, you're not giving enough oxygen, so potency is a concern.

as MAC increases, the lipid solubility decreases. this means that if you give .76 halothane, half the patients will go to sleep. nitrous oxide isnt very potent because it's not very lipid soluble. halothane is very lipid soluble so it's more potent, so less you have to give, so the lower the MAC.

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lambda onset

MAC potency

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lambda onset

MAC potency

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Efficacy... nitrous oxide vs a complete anesthetic

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Efficacy – for anesthetic gases, efficacy is related to potency

Since most are extremely potent, they can produce all stages of anesthesia at low concentrations allowing sufficient O2 to the patient. These are known as complete anesthetics.

Nitrous oxide is an incomplete anesthetic because it can’t produce all stages of anesthesia without producing hypoxia (MAC = 105). Therefore N2O has less efficacy than a complete anesthetic.

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Characteristics of an ideal general anesthetic (what do we want from our anesthetics?)

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-Provide a smooth and rapid induction of unconsciousness
-Produce amnesia
-Block troublesome reflexes
-Produce skeletal muscle relaxation
-Produce analgesia
-Provide a smooth and rapid emergence and recovery without long lasting adverse effects


use combo of drugs to achieve these goals.

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Preanesthetic Medications

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Preanesthetic medications – drugs given generally prior to anesthesia (may be given during or after, as well) in order to:
-Decrease anxiety without producing excessive drowsiness
-Facilitate a rapid, smooth induction without prolonging emergence
-Provide amnesia for the perioperative period
-Relieve pre-and post-operative pain
-Minimize undesirable side effects of anesthetics

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Conscious sedation”

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used for colonoscopy. give a benzo. dont need an anesthesiologist.

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Theories of Anesthetic Action

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No single theory adequately explains how anesthetics exert their pharmacological effects.
Physical theories
Based on physico-chemical properties of anesthetics, e.g., lipid solubility. Are obsolete, but do explain how anesthetics reach site of action.
Receptor theories
State that anesthetics exert their effects by direct interactions with proteins (membrane receptors or in ion channels).
Most anesthetics directly and indirectly increase GABAA and glycine activity.
Anesthetics also generally inhibit the activity of excitatory transmitters acetylcholine (Nicotinic) and serotonin. Ketamine and nitrous oxide inhibit glutamate activity.
Thus neurons are hyperpolarized.

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General pharmacological effects

CNS, ANS, CV, Respiration, Hypothermia

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CNS – dose dependent depression of all portions of CNS. Order of sensitivity (most to least) is RAS and cortex → hippocampus → basal ganglia → cerebellum → spinal cord → medulla (irregularly descending anesthesia)

Autonomic nervous system: Inhibition of sympathetics; Stimulation of parasympathetics; Nausea and vomiting

Cardiovascular: Dose related negative inotropic effect; ↓ BP; Arrhythmias
Sensitization to circulating catecholamines (epinephrine); Increased cerebral blood flow and CSF pressure

Respiration: Dose dependent depression of medullary respiratory center

Hypothermia: Altered thermoregulatory control and reduced metabolic rate

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Miscellaneous effects

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Decrease lower esophageal sphincter tone
*Halothane hepatitis – free radical metabolites (immune phenomenon)
*Malignant hyperthermia – genetic susceptibility
Post-operative cognitive dysfunction
Anesthesia awareness (muscle relaxant w/o anesthetic)

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what is the only anesthetic gas?

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nitrous oxide

lambda 0.5
lipid solubility 1.4
MAC: 100 (incomplete anesthetic)

fast onset and recovery because of the low lambda

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Name 5 volatile liquids

(inhalation = "-ane")

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Halothane (Fluothane) ; MAC 0.8, lambda 2.4

Isoflurane (Forane) – commonly used anesthetic for adults; MAC 1.2 will put people to sleep

Enflurane (Ethrane) – like isoflurane, except increased risk of *seizures. Rarely used

Desflurane (Suprane) – similar to isoflurane except for more rapid emergence, and more irritating to airway. Commonly used.

Sevoflurane (Ultane) – similar to desflurane except not irritating to airway. Commonly used.

Methoxyflurane- renal nephrotoxicity

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Intravenous agents

Thiopental

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Thiopental- rapid acting barbiturate and used as an induction agent (put people to sleep); short duration of action not because it's metabolized quickly, but because of REDISTRIBUTION right to the brain, stored in the fat.

with repeated use, you get accumulation, giving slow recovery and a hangover.

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the most common induction agent nowadays is.... heeee heeeee heeeeeeeee oW!

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Propofol. replacing thiopental. you can continue to give propofol for a long duration of time and you don't get that slow recovery. you can use it as a sole anesthetic agent if you wish.

fast onset, fast recovery. some CV and resp. depression. pain at the injection site.

milk of amnesia!

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General pharmacological effects

CNS, ANS, CV, Respiration, Hypothermia

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CNS – dose dependent depression of all portions of CNS. Order of sensitivity (most to least) is RAS and cortex → hippocampus → basal ganglia → cerebellum → spinal cord → medulla (irregularly descending anesthesia)

Autonomic nervous system: Inhibition of sympathetics; Stimulation of parasympathetics; Nausea and vomiting

Cardiovascular: Dose related negative inotropic effect; ↓ BP; Arrhythmias
Sensitization to circulating catecholamines (epinephrine); Increased cerebral blood flow and CSF pressure

Respiration: Dose dependent depression of medullary respiratory center

Hypothermia: Altered thermoregulatory control and reduced metabolic rate

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ketamine

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Dissociative

causes psychomemeto effects.
doesnt put you to sleep, but to a dissociative state. if you throw nitrous oxide with it, you will go to sleep.

you get weird dreams, so you have to be quiet in the OR when the patient is waking up.

not used all that much.

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Miscellaneous effects

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Decrease lower esophageal sphincter tone
*Halothane hepatitis – free radical metabolites (immune phenomenon)
*Malignant hyperthermia – genetic susceptibility
Post-operative cognitive dysfunction
Anesthesia awareness (muscle relaxant w/o anesthetic)

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what is the only anesthetic gas?

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nitrous oxide

lambda 0.5
lipid solubility 1.4
MAC: 100 (incomplete anesthetic)

fast onset and recovery because of the low lambda

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Benzodiazepines:

diazepam, diazolam

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not used much, need to use a good amount.

advantage is little CV and resp. depression

slow onset, slow recovery.
diazapam- action terminated by redistribution.

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Name 5 volatile liquids

(inhalation = "-ane")

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Halothane (Fluothane) ; MAC 0.8, lambda 2.4

Isoflurane (Forane) – commonly used anesthetic for adults; MAC 1.2 will put people to sleep

Enflurane (Ethrane) – like isoflurane, except increased risk of *seizures. Rarely used

Desflurane (Suprane) – similar to isoflurane except for more rapid emergence, and more irritating to airway. Commonly used.

Sevoflurane (Ultane) – similar to desflurane except not irritating to airway. Commonly used.

Methoxyflurane- renal nephrotoxicity

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when do you use etomidate?

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used for short procedures (putting in chest tubes, etc) or intubation.

Fast onset, fairly fast recovery
Excitatory effects during induction and recovery, Adrenocortical suppression (when used for a long time)
Less cardiovascular and respiratory depression than with other iv drugs; Causes pain at injection site

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Intravenous agents

Thiopental

Back 26

Thiopental- rapid acting barbiturate and used as an induction agent (put people to sleep); short duration of action not because it's metabolized quickly, but because of REDISTRIBUTION right to the brain, stored in the fat.

with repeated use, you get accumulation, giving slow recovery and a hangover.

Front 27

Dexmedetomidine (Precedex) is what receptor type interaction?

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α2 agonist

used in the ICU to keep intubated patients sedated.

Front 28

the most common induction agent nowadays is.... heeee heeeee heeeeeeeee oW!

Back 28

Propofol. replacing thiopental. you can continue to give propofol for a long duration of time and you don't get that slow recovery. you can use it as a sole anesthetic agent if you wish.

fast onset, fast recovery. some CV and resp. depression. pain at the injection site.

milk of amnesia!

Front 29

ketamine

Back 29

Dissociative

causes psychomemeto effects.
doesnt put you to sleep, but to a dissociative state. if you throw nitrous oxide with it, you will go to sleep.

you get weird dreams, so you have to be quiet in the OR when the patient is waking up.

not used all that much.

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Benzodiazepines:

diazepam, diazolam

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not used much, need to use a good amount.

advantage is little CV and resp. depression

slow onset, slow recovery.
diazapam- action terminated by redistribution.

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when do you use etomidate?

Back 31

used for short procedures (putting in chest tubes, etc) or intubation.

Fast onset, fairly fast recovery
Excitatory effects during induction and recovery, Adrenocortical suppression (when used for a long time)
Less cardiovascular and respiratory depression than with other iv drugs; Causes pain at injection site

Front 32

Dexmedetomidine (Precedex) is what receptor type interaction?

Back 32

α2 agonist

used in the ICU to keep intubated patients sedated.

Front 33

General pharmacological effects

CNS, ANS, CV, Respiration, Hypothermia

Back 33

CNS – dose dependent depression of all portions of CNS. Order of sensitivity (most to least) is RAS and cortex → hippocampus → basal ganglia → cerebellum → spinal cord → medulla (irregularly descending anesthesia)

Autonomic nervous system: Inhibition of sympathetics; Stimulation of parasympathetics; Nausea and vomiting

Cardiovascular: Dose related negative inotropic effect; ↓ BP; Arrhythmias
Sensitization to circulating catecholamines (epinephrine); Increased cerebral blood flow and CSF pressure

Respiration: Dose dependent depression of medullary respiratory center

Hypothermia: Altered thermoregulatory control and reduced metabolic rate

Front 34

Miscellaneous effects

Back 34

Decrease lower esophageal sphincter tone
*Halothane hepatitis – free radical metabolites (immune phenomenon)
*Malignant hyperthermia – genetic susceptibility
Post-operative cognitive dysfunction
Anesthesia awareness (muscle relaxant w/o anesthetic)

Front 35

what is the only anesthetic gas?

Back 35

nitrous oxide

lambda 0.5
lipid solubility 1.4
MAC: 100 (incomplete anesthetic)

fast onset and recovery because of the low lambda

Front 36

Name 5 volatile liquids

(inhalation = "-ane")

Back 36

Halothane (Fluothane) ; MAC 0.8, lambda 2.4

Isoflurane (Forane) – commonly used anesthetic for adults; MAC 1.2 will put people to sleep

Enflurane (Ethrane) – like isoflurane, except increased risk of *seizures. Rarely used

Desflurane (Suprane) – similar to isoflurane except for more rapid emergence, and more irritating to airway. Commonly used.

Sevoflurane (Ultane) – similar to desflurane except not irritating to airway. Commonly used.

Methoxyflurane- renal nephrotoxicity

Front 37

Intravenous agents

Thiopental

Back 37

Thiopental- rapid acting barbiturate and used as an induction agent (put people to sleep); short duration of action not because it's metabolized quickly, but because of REDISTRIBUTION right to the brain, stored in the fat.

with repeated use, you get accumulation, giving slow recovery and a hangover.

Front 38

the most common induction agent nowadays is.... heeee heeeee heeeeeeeee oW!

Back 38

Propofol. replacing thiopental. you can continue to give propofol for a long duration of time and you don't get that slow recovery. you can use it as a sole anesthetic agent if you wish.

fast onset, fast recovery. some CV and resp. depression. pain at the injection site.

milk of amnesia!

Front 39

ketamine

Back 39

Dissociative

causes psychomemeto effects.
doesnt put you to sleep, but to a dissociative state. if you throw nitrous oxide with it, you will go to sleep.

you get weird dreams, so you have to be quiet in the OR when the patient is waking up.

not used all that much.

Front 40

Benzodiazepines:

diazepam, diazolam

Back 40

not used much, need to use a good amount.

advantage is little CV and resp. depression

slow onset, slow recovery.
diazapam- action terminated by redistribution.

Front 41

when do you use etomidate?

Back 41

used for short procedures (putting in chest tubes, etc) or intubation.

Fast onset, fairly fast recovery
Excitatory effects during induction and recovery, Adrenocortical suppression (when used for a long time)
Less cardiovascular and respiratory depression than with other iv drugs; Causes pain at injection site

Front 42

Dexmedetomidine (Precedex) is what receptor type interaction?

Back 42

α2 agonist

used in the ICU to keep intubated patients sedated.

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Anesthetic Antagonists:

Naloxone (Narcan) and nalmefene (Revex) reverses

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opioids

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Flumazenil (Romazicon) reverses

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benzodiazepines