Bb W4 Pharmacology Of General Anesthetics

Front 1

Morphine is derived from

Back 1

The opium poppy

Front 2

What was the use of chloroform as a general unaesthetic banned

Back 2

– Hepatotoxicity
– Cardiotoxicity

Front 3

Why is methoxyflurane not commonly used anymore as a GA drug

Back 3

Nephrotoxicity

Front 4

What is general anesthetic

Back 4

Altered physiological state characterized by:
- hypnosis
- analgesia,
- amnesia,
- immobility,
- inhibition of autonomic and somatic reflexes
- +/- muscle relaxation

Front 5

What are some examples of inhaled anesthetics

Back 5

– Hydrocarbons
– Ethers
– Nitrous oxide
– Xenon

Front 6

What are the most commonly used general anesthetics today

Back 6

Inhaled ethers:
- Sevoflurane
- Desflurae

Front 7

What determines the depth of anesthesia

Back 7

Critical concentration of agent that reaches the brain [partial pressure in brain, Pbr]

Front 8

What determines the rate of uptake of an inhaled anesthetic

Back 8

The ratio of the alveolar anesthetic concentration to the inspired unaesthetic concentration overtime which is determined by:
– Solubility in blood
– Partial pressure difference between alveoli and pulmonary venous blood
– Alveolar ventilation

Front 9

Partition coefficient

Back 9

The solubility of inhaled anesthetics is expressed as partition coefficient (i.e. how soluble is it in gas as opposed to blood)
– The more soluble an agent is in the blood, the faster it gets the brain and the faster it reachs equilibrium there

Front 10

Which of the comment and held anesthetics are most soluble in gas (low partition coefficient)

Back 10

Nitric oxide > desflurane > sevoflurance > isoflurane

Front 11

What is the significance of a high blood gas solubility/partition coefficient

Back 11

– Takes longer for the "blood pool "to fill
– Takes longer to reach equilibrium between alveoli and blood and eventually brain
==> the lower the rate of induction

NB high blood solubility of an unaesthetic is a waste, it is wanted in the brain

Front 12

Actions of the held anesthetics on excitable tissues

Back 12

– Facilitation of inhibition
– Inhibition of excitation

Front 13

Explain facilitation of inhibition by GA

Back 13

– Increase GABAa receptor mediated transmission
– Increased background "leak" Potassium conductance

Front 14

Explained inhibition of excitation in GA

Back 14

Reduced glutamate and acetylcholine receptor mediated transmission

Front 15

Importance of knowing the metabolism of inhaled anesthetics

Back 15

– Metabolite toxicity (esp kidneys and liver)
– Degree of metabolism influences rate of decrease in alveolar pressure at conclusion of an anesthetic

Front 16

What is an MAC

Back 16

Minimal alveolar concentration = the concentration of an inhaled aesthetic in the alveoli at 1atm that prevent movement in response to painful stimuli in 50% of patients (ie dose). Measured as EC50.

Front 17

Approximately __ MAC prevent movement and 95% of patients

Back 17

1.2

Front 18

Why are volatile anesthetics dangerous drugs to use clinically

Back 18

– Steep dose response curve
– Low therapeutic index

Front 19

What factors will decrease an agents and MAC?

Back 19

– Increased age
– Decreased temperature
– Pregnancy
– Opioids
– Other anesthetics and CNS drugs

Front 20

Meyer-Overton Rule

Back 20

States that an agents MAC is inversely correlated with its lipid solubility. I.e. the more lipid soluble and unaesthetic agent, the more potent it is.

Front 21

Inhaled anesthetics target which excitable tissues

Back 21

– CNS
– PNS
– Cardiac
– Skeletal
– Smooth muscle

Front 22

Effects of inhaled anesthetics on the CNS

Back 22

– Decrease in cerebral metabolic rate
– Cerebral vasodilation [increase in cerebral blood flow]

Front 23

Effects of inhaled aesthetics on the cardiovascular system

Back 23

– Decreasing bacterial blood supply as a result of: reduction and cardiac output and/or total peripheral vascular resistance
– Ventricular arrhythmias [halothane]
– Mild sympathetic stimulation [nitric oxide]

Front 24

Effects of inhaled anesthetics on the respiratory system

Back 24

– Respiratory depression: increase in rate and decrease in depth of breathing, reduction in alveolar ventilation and elevation of PaCO2, decrease in respiratory response elevation and PaCO2
– Decrease in airway resistance

Front 25

Effects of inhaled anesthetics on the kidney

Back 25

– Reduction in renal blood flow leading to decrease in GFR and urinary output

Front 26

Effects of inhaled anesthetics on skeletal muscle

Back 26

– Muscle relaxation
– potentiation of the effects of nondepolarizing muscle relaxants

Front 27

Effects of inhaled anesthetics on the uterus

Back 27

– Uterine relaxation
- +/- prolonger uterine atony & severe blood loss in parturients

Front 28

Clinical uses of inhaled anesthetics

Back 28

– Induction of anestesia
– Maintenance of anestesia
– Part of balance anestesia techniques

Front 29

Advantages to using inhaled anesthetics

Back 29

– Indication of depth of anesthesia
– Ability to increase or decrease depth
– Predictable pattern of recovery
– No need for adjuvants
– Knowledge of concentration of drug at site
– Broad range of oxygen concentrations possible

Front 30

What is the balance anesthesia approach

Back 30

Combination of agents and maximize advantages and minimize adverse effects.

Front 31

Dosing differences between IV and inhaled anesthetics

Back 31

In contrast to inhaled anesthetics, the dose of IV agents cannot be manipulated by the anesthesiologist once injected: thus, their specific pharmacokinetic properties must be known!

Front 32

Thiopental: clinical use

Back 32

– Rapid induction of hypnosis [no analgesic properties!]

Front 33

Thiopental: MOA

Back 33

Facilitation of inhibitory neurotransmission via GABAa receptor

Front 34

Thiopental: PK

Back 34

– Rapid induction in less than 20 seconds
– Patient normally wakes up approximate five minutes after single IV bolus injection due to redistribution
– Elimination and not redistribution determines the time of emergence [when tissues saturated]
- Half-life = 11 h

Front 35

Thiopental: adverse effects

Back 35

– Hypertension
– Respiratory depression
– Histamine release
– Arterial occlusion possible

Front 36

Propofol: clinical uses

Back 36

– Sedation, induction, and maintenance of anesthesia
– Smooth induction:
- Pleasant dreams
– Rapid
- Clear headed awakening
– Antiemetic properties

Front 37

Propofol: MOA

Back 37

Facilitation of inhibitory neurotransmission via GABAa receptors

Front 38

Propofol: PK

Back 38

– Rapid induction and even more rapid awakening compared to thiopental
– Rapid metabolism and liver [~ 1 hour]
– No significant redistribution so useful for infusion

Front 39

Propofol: adverse effects

Back 39

– Hypotension (more than thiopental)
– Respiratory distress and apnea
– Injection pain
– Potential for sepsis

Front 40

Ketamine: clinical uses

Back 40

- CONCIOUS SEDATION
– Induction of anesthesia in trauma shock
– Battlefield surgery
– Analgesia in burn patients
– i/m induction in children

Front 41

Ketamine: MOA

Back 41

Antagonist at NMDA receptors [type of glutamate receptor]

Front 42

Ketamine: PK

Back 42

– Rapid induction after IV bolus [but slower than other 2]
– Hepatic metabolism [~3hr 1/2 life]

Front 43

Ketamine: adverse effects

Back 43

– Bronchodilator
– Unpleasant dreams

Front 44

Etomidate: clinical uses

Back 44

– No analgesic properties
– **Minimal effect on hemodynamics [useful for induction of unstable patients]
– Produces adrenal suppression
– PK & MOA similar to propofol