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Clinical Pharmacology, Therapeutics & Intro to Prescribing > Lecture 25- Anaesthetics > Flashcards

Lecture 25- Anaesthetics Flashcards

1
Q

For patients undergoing surgical or medical procedures, different levels of sedation can provide important benefits to facilitate procedural interventions. These levels of sedation range from anxiolysis to general anesthesia and can create:

A
  • Sedation and reduced anxiety
  • Lack of awareness and amnesia
  • Skeletal muscle relaxation
  • Suppression of undesirable reflexes
  • Analgesia
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2
Q

Because no single agent provides all desired objectives….

A

Anaesthetic techniques can be combines

several categories of drugs are combined to produce the optimum level of sedation required

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3
Q

Preoperative medications provide

A

anxiolysis and analgesia and mitigate unwanted side effects of the anesthetic or the procedure itself

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4
Q

name 4 preoperative medications

A
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5
Q

neuromuscular junction blockers enable

A

endotracheal intubation and muscle relaxation to facilitate surgery.

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6
Q

name 5 analgesics

A
  • acetaminophen
  • celexocib
  • gabapentin
  • ketamine
  • opioids
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7
Q

Potent general anesthetic medications are delivered via

A

inhalation and/or intravenously.

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8
Q

Except for nitrous oxide, inhaled anesthetics are…

A

inhaled anesthetics are volatile, halogenated hydrocarbons

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9
Q

while intravenous (IV) anesthetics consist of

A

consist of several chemically unrelated drug classes commonly used to rapidly induce and/or maintain a state of general anesthesia.

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10
Q

name 4 inhaled (volatile) general anaesthetics

A
  • desflurane
  • isoflurane
  • NO
  • sevoflurane
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11
Q

name 4 IV general anaesthetics

A
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12
Q

local anaesthetics can be

A

amides or esters

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13
Q

Overall considerations when delivering an anesthetic.

A
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14
Q

levels of sedation

A

evels of sedation start with light sedation (anxiolysis) and continue to moderate sedation, then deep sedation, and finally a state of general anesthesia. The hallmarks of escalation from one level to the next are recognized by changes in mentation, hemodynamic stability, and respiratory competency

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15
Q

what is general anaesthesisa

A

a reversible state of central nervous system (CNS) depression, causing loss of response to and perception of stimuli. The state of general anesthesia can be divided into three stages:

  1. induction
  2. maintenance
  3. recovery.
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16
Q
A
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17
Q

Induction of general anaesthetics is…..

A

the time from administration of a potent anesthetic to development of unconsciousness,

  • General anesthesia in adults is normally induced with an IV agent like propofol, producing unconsciousness in 30 to 40 seconds.
  • Often, an IV neuromuscular blocker such as rocuronium, vecuronium, or succinylcholine is administered to facilitate endotracheal intubation by eliciting muscle relaxation.
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18
Q

maintenance of anaesthesia is…

A

the sustained period of general anesthesia.

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19
Q

recovery of anaesthesia starts…

A

After cessation of the maintenance anesthetic drug, the patient is evaluated for return of consciousness.

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20
Q

Inhaled gases are used primarily for

A

maintenance of anesthesia after administration of an IV drug

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21
Q

inhalation anaesthetics include

A

nitrous oxide and volatile, halogenated hydrocarbons.

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22
Q

potency in anaestheticsw

A
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23
Q

MAC is the

A

median effective dose (ED50) of the anesthetic, expressed as the percentage of gas in a mixture required to achieve that effect.

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24
Q

The more lipid soluble an anesthetic, the

A

lower the concentration needed to produce anesthesia and, therefore, the higher the potency

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25
Q

Factors that can increase MAC

A

(make the patient more resistant) include hyperthermia, drugs that increase CNS catecholamines, and chronic ethanol abuse.

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26
Q

Factors that can decrease MAC

A

(make the patient more sensitive) include increased age, hypothermia, pregnancy, sepsis, acute intoxication, concurrent IV anesthetics, and α2-adrenergic receptor agonists (clonidine and dexmedetomidine).

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27
Q

use of NO and volaltile anaesthetics

A

Side effect profile of volatile= reduced because MAC is reduced due to addition of NO

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28
Q

Solubility in blood

A

This is determined by a physical property of the anesthetic called the blood:gas partition coefficient

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29
Q

blood:gas partition coefficient

A

the ratio of the concentration of anesthetic in the liquid [blood] phase to the concentration of anesthetic in the gas phase when the anesthetic is in equilibrium between the two phases

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30
Q

blood: gas partition coefficient examples

A

For inhaled anesthetics, think of the blood as a pharmacologically inactive reservoir.

Drugs with low versus high blood solubility differ in their rate of induction of anesthesia. When an anesthetic gas with low blood solubility such as nitrous oxide diffuses from the alveoli into the circulation, little anesthetic dissolves in the blood. Therefore, equilibrium between the inspired anesthetic and arterial blood occurs rapidly with relatively few additional molecules of anesthetic required to raise the arterial anesthetic partial pressure.

By contrast, anesthetic gases with high blood solubility, such as isoflurane, dissolve more fully in the blood; therefore, greater amounts of gas and longer periods of time are required to raise blood partial pressure. This results in longer periods for induction, recovery, and time to change in depth of anesthesia in response to changes in the drug concentration. The solubility in blood is ranked as follows: isoflurane > sevoflurane > nitrous oxide > desflurane.

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31
Q

Nitrous oxide

A

unable to create a state of general anesthesia.

Nitrous oxide does not depress respiration, and maintains cardiovascular hemodynamics as well as muscular strength. Nitrous oxide can be combined with other inhalational agents to establish general anesthesia, which lowers the required concentration of the combined volatile agent. This gas admixture further reduces many unwanted side effects of the other volatile agent that impact cardiovascular output and cerebral blood flow.

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32
Q

IV anesthetics

A
  • cause rapid induction of anesthesia often occurring in 1 minute or less.
  • It is the most common way to induce anesthesia before maintenance of anesthesia with an inhalation agent.
  • IV anesthetics may be used as single agents for short procedures or administered as infusions (TIVA) to help maintain anesthesia during longer surgeries.
  • In lower doses, they may be used solely for sedation.
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33
Q

name 3 Intravenous general anaesthetics

A

Propofol (rapid), Barbiturates (rapid), Ketamine (slower).

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34
Q

Propofol

A

Propofol [PRO-puh-fol] is an IV sedative/hypnotic used for induction and/or maintenance of anesthesia. It is widely used and has replaced thiopental as the first choice for induction of general anesthesia and sedation. Because propofol is poorly water soluble, it is supplied as an emulsion containing soybean oil and egg phospholipid, giving it a milklike appearance.

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35
Q

Barbiturates

A

Thiopental [THYE-oh-PEN-tahl] is an ultra–short-acting barbiturate with high lipid solubility. It is a potent anesthetic but a weak analgesic. Barbiturates require supplementary analgesic administration during anesthesia.

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36
Q

Benzodiazepines

A

The benzodiazepines are used in conjunction with anesthetics for sedation and amnesia. The most commonly used is midazolam [meh-DAZ-o-lam]. Diazepam [dye-AZ-uh-pam] and lorazepam [lore-AZ-uh-pam] are alternatives. All three facilitate amnesia while causing sedation, enhancing the inhibitory effects of various neurotransmitters, particularly GABA.

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37
Q

Opioids

A

a short-acting anti-NMDA receptor anesthetic and analgesic, induces a dissociated state in which the patient is unconscious (but may appear to be awake) with profound analgesia.

38
Q

Ketamine

A

a short-acting anti-NMDA receptor anesthetic and analgesic, induces a dissociated state in which the patient is unconscious (but may appear to be awake) with profound analgesia.

39
Q

local anaesthetics

A

block nerve conduction of sneosry impulses from the peripherp-y to the CNS

  • sodium ion channels are blocked to prevent AP conduction
40
Q

delivery techniques of local anaesthetics

A

elivery techniques include topical administration, infiltration, and perineural and neuraxial (spinal, epidural, or caudal) blocks.

41
Q

The most widely used local anesthetics are

A

bupivacaine [byoo-PIV-uh-cane], lidocaine [LYE-doe-cane], mepivacaine [muh-PIV-uh-cane], ropivacaine [roe-PIV-uh-cane], and tetracaine [TET-truh-cane].

42
Q

why are local anaesthetics delivered with adrenaline (epinephrine)

A

Local anesthetics cause vasodilation, which leads to a rapid diffusion away from the site of action and short duration when these drugs are administered alone. By adding the vasoconstrictor epinephrine, the rate of local anesthetic absorption and diffusion is decreased. This minimizes systemic toxicity and increases the duration of action.

43
Q

Anesthetic Adjuncts

A

Adjuncts are a critical part of the practice of anesthesia and include drugs that affect

  • gastrointestinal (GI) motility
  • Post operative nasea and vomiting (PONV)
  • anxiety
  • analgesia.

Adjuncts are used in collaboration to help make the anesthetic experience safe and pleasant.

44
Q
A
45
Q

GI medication adjuncts

A

aim to reduce gastricic acidity in the event of aspiration

  • H2 receptor antagonists e.g. ranitine
  • PPI e.g. omeprazole
46
Q

risk factors for PONV

A

Risk factors for PONV include

  • female gender, nonsmoker
  • use of volatile and nitrous anesthetics
  • duration of surgery
  • postoperative narcotic use
47
Q

drugs used to prevent PONV

A
  • 5-HT3 receptor antagonists e.g. ondastron
  • glucocorticoid dexamethasone
48
Q

Anxiety medications

A

Anxiety is a common part of the surgical experience.

Benzodiazepines also elicit anterograde amnesia, which can help promote a more pleasant surgical experience.

49
Q

Regarding levels of sedation, which one applies to loss of perception and sensation to painful stimuli?

A. Anxiolysis

B. General anesthesia

C. Moderate sedation

D. Deep sedation

A

Correct answer = B. Anxiolysis is a state of relaxation, but consciousness remains. General anesthesia is a total loss of perception and sensation to stimuli. Moderate sedation maintains mentation with adequate airway and respiratory competency. Deep sedation has some response to stimuli, but respirations may be inadequate.

50
Q

13.2. Which of the following decreases minimum alveolar concentration (MAC)?

A. Hyperthermia

B. Cocaine intoxication

C. Pregnancy

D. Chronic ethanol abuse

A

Correct answer = C. Pregnancy is the only choice that decreases minimum alveolar concentration. All the other options increase MAC.

51
Q

Which one of the following is a potent intravenous anesthetic and analgesic?

A. Propofol

B. Midazolam

C. Ketamine

D. Fentanyl

A

Correct answer = C. Ketamine is unique in its blockage of NMDA receptors, yielding both potent anesthetic and analgesic properties. Propofol is a potent anesthetic but a weak analgesic. Benzodiazepines such as midazolam have little analgesic effect, but can be a potent anesthetic at high doses. Fentanyl is a potent analgesic.

52
Q

A 23-year-old patient with a history of severe postoperative nausea and vomiting is coming in for plastic surgery. Which anesthetic drug would be best to use for maintenance in this situation?

A. Isoflurane

B. Sevoflurane

C. Nitrous oxide

D. Propofo

A

Correct answer = D. A propofol infusion (TIVA) anesthetic would be best for this patient with a history of postoperative nausea and vomiting. Propofol is the only anesthetic listed with antiemetic properties. Both fluorinated hydrocarbons (isoflurane and sevoflurane) and nitrous oxide are linked to nausea and vomiting during surgery.

53
Q

Anaesthetic technique can be combined

A
54
Q

Conscious sedation

A

use of small amounts of anaesthetic or benzodiazepines to produce a ‘sleepy-like’ state (maintain verbal contact but feel comfortable

55
Q

general anaesthetics either

A
56
Q

Inhalational or ‘Volatile’ General Anaesthesia.

A

Via the lungs via a vaporiser

57
Q

Guedels signs illustrate the

A

stages of anaethesia

58
Q

stage 1

A

analgesia and consciouness

59
Q

stage 2

A

unconscious, breathing erratic but delirium could occur, leading to an excitement phase

60
Q

stage 3

A

surgical anaesthesia, with four levels descriving increasing depth until breathing weak

61
Q

stage 4

A

respiratorey paralysis and death

62
Q

Anaesthetic potency is measured by MAC or minimum alveolar concentration

A
  • [Alveolar] (at 1atm) at which 50% of subjects fail to move to surgical stimulus (unpremedicated breathing O2/air)
  • At equilibrium [alveolar] = [spinal cord]
  • Anatomical substrate for MAC is spinal cord
    • In animal models if section cord (i.e., remove connection to the brain) MAC is unchanged.
63
Q

Total intravenous anaesthesia (TIVA)

A

can be defined as a technique of general anaesthesia using a combination of agents given solely by the intravenous route and in the absence of all inhalational agents including nitrous oxide.

64
Q

How Do We Describe Intravenous Anaesthetic Potency ?

A
65
Q

main molecular targets of interest

A
66
Q

general anaesthetic molecular target

A

Common ‘Anaesthetic’ theme : GABAA receptors

  • GABAA receptors critical target for anaesthetics
  • Major inhibitory transmitter
  • Ligand Gated Ion Channel (Cl- conductance)- reduce likelihood of AP
  • Potentiate GABA activity
    • Anxiolysis
    • Sedation
    • Anaesthesia
67
Q

With the exception of ……,….. and …… all anaesthetics potentiate GABAA mediated Cl- conductance to depress CNS activity.

A

Xe,N2O and ketamine

NMDA receptors probable other site

68
Q

In the brain consciousness is (simplistically) a balance between

A

excitation (Glutamate) and inhibition (GABA).

Anaesthetics modulate this balance.

69
Q

Parts of the brain involved with anaesthetic action

A
  • Reticular formation (hindbrain, midbrain and thalamus) depressed. Connectivity lost.
    • Reticular system often called “activating system” due to ability to increase arousal.
  • Thalamus transmits and modifies sensory information.
  • Hippocampus depressed (memory).
  • Brainstem depressed (respiratory and some CVS).
  • Spinal cord-depress dorsal horn (analgesia) and motor neuronal activity (MAC).
70
Q

Local and regional anaesthetics

A
71
Q

Local Anaesthetics e.g.

A

Lidocaine, Bupivacaine, Ropivacaine and Procaine.

72
Q

Characteristics of local anaesthetics

A
  • Higher lipid solubility higher greater potency
  • Dissociation constant (pKa) – time of onset.
    • Lower pKa faster onset
  • Chemical link – metabolism
    • Ester (short acting) or amide (longer acting) link
  • Protein binding = longer duration (higher for longer duration)
73
Q

Local anaesthetic mode of action.

A
  • Block voltage gated sodium channels (molecular drivers of AP)–>therefore reduced AP, reduced neuronal activity
  • Uncharged anaesthetic passes plasma membrane, becomes charged and then blocks sodium channel –>prevents sodium transmissionUse dependent block
  • The greater the degree to which ion channels are firing, the greater the block
  • Adding adrenaline increases duration of action by causing vasoconstriction preventing the local anaesthetic from moving away from the site
74
Q

Regional anaesthesia

A

As the name suggests selectively anaesthetising a part of the body.

  • Often described as a ‘block’ of a nerve and hence the patient remains awake.
  • Uses local anaesthetic and or an opioid.
  • Upper extremity (e.g.,); interscalene, supraclavicular, infraclavicular, axillary.
  • Lower extremity (e.g.,) ; femoral, sciatic, popliteal, saphenous.
  • Extradural (epidural) / Intrathecal / Combined (labour).
75
Q

Main Anaesthetic Side Effects. (from the very common 1:10 category for GA)

A

Too many agent specific effects to list and remember polypharmacology !

General anaesthesia

  • PONV (opioids)–> post operative nausea and vomiting
  • CVS – hypotension
  • POCD- post operative cognitive dysfunction (increases with increasing age)
  • Chest infection

Local and regional

  • Depends on the agent used and usually result from systemic spread (Locals are Na+ channel blockers so cardiovascular toxicity)

Increased general concern re: allergic reactions/anaphylaxis

76
Q

The more lipid soluble an anesthetic, the

A

lower the concentration needed to produce anesthesia and, therefore, the higher the potency

77
Q

what is MAC

A

median alveolar concentration–> the lower the MAC the higher the potency

concentration of inhaled anesthetic within the alveoli at which 50% of people do not move in response to a surgical stimulus

78
Q

what can increase MAC

A

(make the patient more resistant) include hyperthermia and chronic ethanol abuse.

79
Q

Factors that can decrease MAC

A

(make the patient more sensitive) include increased age, hypothermia, pregnancy, sepsis, acute intoxication

80
Q

blood: gas partition coefficient examples: anesthetic gases with high blood solubility

A

By contrast, anesthetic gases with high blood solubility, such as isoflurane, dissolve more fully in the blood; therefore, greater amounts of gas and longer periods of time are required to raise blood partial pressure. This results in longer periods for induction, recovery, and time to change in depth of anesthesia in response to changes in the drug concentration. The solubility in blood is ranked as follows: isoflurane > sevoflurane > nitrous oxide > desflurane.

81
Q

IV anesthetics

A

cause rapid induction of anesthesia often occurring in 1 minute or less.

IV anesthetics may be used as single agents for short procedures or administered as infusions (TIVA) to help maintain anesthesia during longer surgeries.

82
Q

benzodiazepines e.g. midazolam induce

A

amnesia and also reduce anxiety

83
Q

ketamine is both

A

anaesthetic and analgesic

84
Q

Propofol is the only anesthetic listed with

A

antiemetic properties

85
Q

guedels signs represent

A

stages of anaethesia

4 stages-> 4th stage need intubation

86
Q

Total intravenous anaesthesia (TIVA)

A

A

can be defined as a technique of general anaesthesia using a combination of agents given solely by the intravenous route and in the absence of all inhalational agents including nitrous oxide.

87
Q

Common ‘Anaesthetic’ theme :

A
  • GABAA receptors
    • GABAA receptors critical target for anaesthetics
    • Major inhibitory transmitter
    • Ligand Gated Ion Channel (Cl- conductance)- reduce likelihood of AP
    • Potentiate GABA activity
      • Anxiolysis
      • Sedation
      • Anaesthesia
88
Q

with sodium channel blockers…

A

The greater the degree to which ion channels are firing, the greater the block

Adding adrenaline increases duration of action by causing vasoconstriction preventing the local anaesthetic from moving away from the site

89
Q

main side effects of anaesthetics

A

PONV (opioids)–> post operative nausea and vomiting

CVS – hypotension

POCD- post operative cognitive dysfunction (increases with increasing age)

Chest infection

90
Q

Use of Mesna alongside cyclophosphamide

A

Mesna – thiol group for cytoprotection and polar group – high renal excretion and protection at bladder epithelium – p.o. 2 hours before or i.v. with cyclophosphamide

91
Q

examples of gram positive bacteria

A

streptococcus

staphyloccus

92
Q

examples of gram negative

A

neisseria gonorrhea

chlamydia trachomatis

Clinical Pharmacology, Therapeutics & Intro to Prescribing (39 decks)

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