General Anesthetics Flashcards

1
Q

Signs and stages in the development of general anesthesia

A

Stage I – analgesia

Stage II – excitement, delirium

Stage III – surgical anesthesia
Plane 1 regular, metronomic respirations
Plane 2 onset of muscular relaxation, fixed pupils
Plane 3 good muscular relaxation, depressed excursion of intercostal muscles during respiration
Plane 4 diaphragmatic breathing only, dilated pupils

Stage IV – medullary paralysis
Respiratory failure, vasomotor collapse and resulting circulatory failure lead to death within minutes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Differences between tissue groups that are important in determining uptake of general anesthetics

A

Vessel-rich group: highly vascularized tissues (brain, heart, kidney, liver and endocrine glands)

Uptake rate into these tissues is very high (minutes) because these tissues are very well perfused. Thus uptake into body tissue as a whole is dominated initially by the rate of uptake into this vessel-rich group.

Muscle group: (muscle and skin) Uptake into these tissues occurs over 2-4 hours. Uptake is slower into this tissue group because perfusion is lower than in the vessel-rich group.

Fat group: Inhaled anesthetic uptake occurs very slowly in fatty tissue owing to (i) the enormous amount of anesthetic that can be dissolved in fatty tissue, and (ii) the low perfusion. High lipid solubility of volatile anesthetics accounts for the huge anesthetic storage capacity of fatty tissue. Ultimately, the fat group comes to dominate the rate of uptake of gaseous anesthetic into total body tissue.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Characteristics of more potent GAs

A

More soluble in oil

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

MAC and its relationship to potency

A

Minimum Alveolar Concentration of a GA that produces insensibility to pain in 50% of subjects

Potency is proportional to 1/MAC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Actions of GAs in the therapeutic range

A

Duration of GABAa-recptor mediated inhibitory synaptic current is prolonged

Potentiation of glycine receptors (increased inhibitory transmission)

Inhibition of brain nicotinic ACh receptors (decreased excitatory transmission)

Potentiation of TASK-1 K+ channels that set resting potential (decrease excitability)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Actions of GAs that ONLY occur in higher doses than therapeutic ranges

A

Impaired conduction of action potentials: conduction block DOES NOT underlie anesthesia (in therapeutic doses). Conduction in peripheral nervous system is normal in anesthetized patients.

Inhalational anesthetics act on voltage-gated Na+, Ca2+ and K+ channels , but only at anesthetic levels substantially higher than that needed to induce surgical anesthesia.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What areas of the brain are suspected to be especially affected by GAs?

A

hypothalamic nuclei involved in sleep

reticular formation of the brainstem- involved in control of pain sensation, alertness and sleep and because damage to this region can cause unconsciousness

hippocampus- The amnesia of postoperative patients probably involves this because short-term memory

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Protein theory of GA action

A

Volatile GAs (i) partition into the membrane, and (ii) enter hydrophobic pockets in various membrane proteins such as GABAA receptors, other ion channels and perhaps proteins involved in neurotransmitter release.

Volatile GA occupancy of hydrophobic pockets in membrane proteins alters the function of these proteins, depressing central nervous system function and producing general anesthesia.

Volatile anesthetics and intravenous anesthetics potentiate GABAergic IPSPs in the CNS, and this effect seems to be key in anesthesia.

The hydrophobic protein pockets within which volatile anesthetics bind are not specific binding sites, but pocket size does account for the size cut-off for volatile anesthetics.

Because these pockets are not specific binding sites, volatile anesthetics exert clinically-relevant effects only at concentrations much higher (∼1-100 mM) than those needed for drugs with specific binding sites.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What factors determine the rate at which an effective concentration of anesthetic is reached in the brain?

A

(1) concentration of the anesthetic in inspired air,
(2) alveolar ventilation rate,
(3) pulmonary blood flow (cardiac output),
(4) blood:gas partition coefficient, and
(5) potency (oil:gas partition coefficient)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

4 phases in the uptake of volatile anesthetic

A

(I) lung factors
(II) uptake of anesthetic by blood from alveoli
(III) uptake from blood to body tissues
(IV) tissue distribution

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Lung factors affecting uptake of volatile anesthetic

A

Rate of increase in the partial pressure of anesthetic gas in the alveoli and pulmonary capillary blood is proportional to the rate of ventilation

The depth of anesthesia is not affected by ventilation rate

Rate of ventilation also affects recovery from GA, so respiratory depression can prolong recovery time

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Uptake of anesthetic by blood from alveoli

A

Uptake rate is determined by:

i. the solubility in blood of anesthetic gas: The blood:gas partition coefficient (λ) is a measure of the solubility of anesthetic gas in blood. The blood:gas partition coefficient is defined as the concentration of anesthetic in blood divided by anesthetic concentration in the inspired gas mixture
ii. pulmonary blood flow = cardiac output

Initial rise in arterial anesthetic gas concentration is slowed by increased pulmonary flow (cardiac output) – the faster that blood passes through the lungs, the less time there is for anesthetic to diffuse into the blood, and hence the lower the concentration of anesthetic in blood at early times after onset of administration of anesthetic.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Is the induction of anesthesia is slower or faster for a more soluble anesthetic gas?

A

SLOWER!!!

Higher GA solubility in blood, means that more anesthetic must be dissolved in blood in order to reach stage III, surgical anesthesia

The compartment size into which the anesthetic dissolves is larger for a more soluble anesthetic gas than it is for a less soluble one.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How is the rt of transfer of volatile anesthetic from alveoli to blood related to solubitily and pulmonary blood flow?

A

Inversely related to both!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Uptake from arterial blood to body tissues, particularly brain

A

The rate of uptake into tissues depends upon:

(1) anesthetic gas solubility in body tissues: tissue:blood (brain:blood) partition coefficient. Tissue:blood partition coefficients are ∼1 for lean tissues (brain, heart, muscle, skin), and&raquo_space;1 for fatty tissues.
(2) tissue blood flow: higher the blood flow, the faster the delivery of anesthetic
(3) partial pressures of anesthetic in blood and in tissues: faster rate when the difference in partial pressures is higher

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Pharmacokinetics of elimination of inhalational general anesthetics

A

Clearance by lungs is major route of removal for the volatile anesthetics

Elimination is not under the control of the physician, but is instead determined by cardiac output and respiration of the patient

In general, metabolism (in the liver) of volatile anesthetics is not important in terminating volatile anesthetic action

Products of hepatic metabolism of volatile anesthetics are often important as instigators of adverse reaction to volatile anesthetics

17
Q

Characteristics of an idea GA?

A

Rapid and smooth onset of action, a rapid recovery from anesthesia upon termination of drug administration, and the drug would have a wide margin for safe use as well

18
Q

Rationale for combination use of GA?

A

No single GA possesses all desirable properties, so a combination of drugs is used in modern anesthesiological practice to achieve optimal behavior.

Specific drug combinations are designed to take advantage of the desirable properties of individual drugs while attenuating undesirable side effects

19
Q

Nitrous oxide

A

Gaseous anesthetic

Low potency anesthetic, but excellent analgesic

MAC for N2O is 105%: N2O cannot be used as a sole anesthetic agent

Rapid onset (3-5 minutes), rapid recovery

20
Q

Desflurane (on drug list but not in ppt)

A

Volatile anesthetic

Relatively recently developed volatile anesthetic

Drawback: desflurane has a pungent odor, causing airway irritation and coughing

Contraindicated in patients with a predisposition to malignant hyperthermia

21
Q

Enflurane (on drug list but not in ppt)

A

Volatile anesthetic

Excellent analgesic

Induction and recovery are moderately fast

Good muscle relaxant

Most common use is as general anesthetic for maintenance of anesthesia in adults

Main drawback is that it can trigger seizures, either during induction or recovery

22
Q

Halothane

A

Volatile anesthetic

Until recently, most widely used inhalational anesthetic Moderately to highly potent; poor analgesic

Untoward effects:

(i) Respiratory and cardiovascular failure (arrhythmias)
(ii) Hepatotoxic
(iii) Malignant hyperthermia and central core disease

23
Q

Isoflurane

A

Volatile anesthetic

Has become most widely used inhalational anesthetic

Advantages: Somewhat more potent, less incidence of hepatotoxicity, renal toxicity ,little seizure propensity

More pungent odor than halothane, triggers coughing – use IV agents to overcome

24
Q

Sevoflurane

A

Volatile anesthetic

Pleasant odor – no coughing – so can be used for induction

Drawback: chemically unstable, releases fluoride ions, which are toxic to kidneys

25
Q

Propofol

A

Intravenous anesthetic

Potentiates GABAA receptor activity

Rapid onset anesthetic, similar in speed to thiopental

Faster recovery than for thiopental

Rapid metabolism

Seems to produce less nausea in the post-operative patient

26
Q

Etomidate (on drug list but not in ppt)

A

Intravenous anesthetic

Nonbarbiturate hypnotic lacking analgesic properties

Potentiates GABAA receptor activity

Used primarily for induction of general anesthesia and in “balanced anesthesia”

Minimal depression of cardiovascular and respiratory function

Can cause involuntary patient movements during induction

High incidence of nausea with vomiting, and pain, on injection

27
Q

Thiopental (on drug list but not in ppt)

A

Intravenous anesthetic

Very commonly used to induce general anesthesia

Ultra-short acting barbiturate

Potentiates GABAA receptor activity, prolonging IPSP duration at GABAergic synapses

Rapid deep anesthesia (20 sec), avoiding excitation/delirium

28
Q

Diazepam

A

Intravenous adjunct

Anti-anxiety agent (benzodiazepine)

29
Q

Ondansetron

A

Intravenous adjunct

Anti-emetic: reduce post-operative nausea and vomiting (common problem)

5-HT3–type serotonin receptor antagonist

30
Q

Fentanyl

A

Intravenous adjunct

Analgesic

Opioid

Advantageously short duration of action

31
Q

Glycopyrrolate

A

Intravenous adjunct

Anticholinergic drug

Reduce GA-induced hypotension, bradycardia, and excess
salivary secretions that can choke patient during anesthesia

32
Q

Ketamine (on drug list but not in ppt)

A

Intravenous GA

Produces dissociative anesthesia characterized by catatonia, amnesia, and analgesia

Problems with “emergence phenomena” of disorientation and hallucination

Antagonist of the NMDA-subtype of glutamate receptor

Effect is to inhibit excitatory, glutamatergic synaptic transmission in the central nervous system

No action on GABAA receptor

33
Q

Morphine

A

Intravenous adjunct

Analgesic

Opioid

34
Q

Neuromuscular Blocking Agents

A

Intravenous adjunct

Relax skeletal muscle, particularly for abdominal surgeries

35
Q

Dantrolene sodium

A

For malignant hyperthermia

Block RyR and relax muscle

36
Q

Pharmacokinetics of N2O

A

(i) Concentration effect: Big anesthetic vol. taken out of lung into blood, sucks more N2O gas into lung. Uptake rate is faster than predicted
(ii) Diffusion hypoxia: when anesthetic administration is terminated Large N2O volume leaving blood expands lung and dilutes alveolar O2 - hypoxia
(iii) Second gas effect: Like concentration effect, but with 2 gaseous GAs (75% N2O, 1% halothane) Huge volume uptake rate of N2O sucks more of both gases into lungs Thus, uptake of halothane is increased over expected value alone

37
Q

Therapeutic index of GA

A

Very narrow

Doses that are 2-4x amount needed for surgical anesthesia can cause circulatory failure