Anaesthetics

Question 1

Chemistry

-3 building blocks

Answer 1

1. Commercial preparations - salt solutions is acidified to pH of 4.4-6.4 to exist in water- soluble ionized form. Antioxidants are used to retard their breakdown, epinephrine containing solutions, antimicrobial preservatives.
2. Ionized (charged hydrophilic quaternary amines) and nonionized (uncharged lipophilic tertiary amines) - ionized interact with sodium channels and unionized gain access to receptors.
3. Lipophilic head and hydrophilic tail with an ester or amide linkage

Question 2

1. Amino-esters

2. Amino-amides

Answer 2

1. Procaine - they are metabolized quicker (by plasma cholinesterase)
2. Lidocaine (short acting, penetrate tissues quickly), Bupivacaine (long acting), Articaine - metabolized in the liver

• **imp. to know about the structure because of allergies
• **plasma 1/2 lives are short (1-2h)

Question 3

How do local anesthetics penetrate into the cell?

Answer 3

They penetrate (nerve sheath and axonal membrane) in unionised form and then bind intracellularly in ionized form –> they are weak bases

Question 4

Mechanism of action of local anesthetics (7)

Answer 4

• block action potential generation by blocking sodium channels
• they are amphiphilic molecules
• show use dependence –> depth of the block increase with action potential frequency
• they have higher affinity for the inactive state
• gain access to the channels more readily when the channel is open
• conduction block order –> small myelinated, non-myelinated and large myelinated axons
• nociceptive and sympathetic transmission is blocked first

Question 5

Unwanted effects of local anesthetics (4)

Answer 5

• main one: escape into the systemic circulation (it can block sodium channels in heart and brain)
• CNS: agitation, confusion, tremors progressing to convulsions and respiratory depression
• Cardiovascular: myocardial depression and vasodilation, leading to fall in blood pressure
• occasional hypersensitivity reactions

Question 6

How can local anesthetics be prevented from reaching systemic circulation?

Answer 6

1. drug is inject
2. vasodilation
3. increases the probability of being absorbed in the blood
4. give adrenaline at the same time
5. adrenaline causes vasoconstriction
6. prevents it from reaching the blood and prolong it’s effects

Question 7

General anesthetics

-Mechanism of action (4)

Answer 7

• affects synaptic transmission rather than axonal conduction
• inhibit release of excitatory transmitters and postsynaptic response
• inhibit excitatory channels (glutamate)
• facilitate inhibitory channels (GABAA, potassium, glycine)

Question 8

Inhalation anesthetics

- MAC (minimal alveolar concentration)

Answer 8

Minimal alveolar concentration of anesthetic preventing movement to surgical stimulation in 50% of the subjects

Question 9

Inhalation anesthetics

• characteristics (3)
• pharmacokinetics (3)

Answer 9

• goal is to achieve a certain alveoli concentration
• rapid induction and recovery
• affect NMDA receptors
• lungs are the only important route through which they enter and leave the body
• some halogenated anesthetics are metabolized
• contributes to toxicity (renal toxicity associated with fluoride production)

Question 10

1. Blood:gas partition coefficient

2. Oil:gas partition coefficient

Answer 10

1. solubility in blood - determines the speed rate of induction and recovery
   - the lower the coefficient = the faster is induction and recovery (ex: nitrous oxide, desflurane)
   - the higher the coefficient = the slower is induction and recovery (ex: halothane) (it is very soluble in blood)
2. solubility in fat - determines potency
   - high lipid solubility = accumulate in fat (ex: halothane) and may produce a prolonged “hangover” (delayed recovery from anesthesia, if used for a long period of time)

Question 11

Inhalation anesthetics

• names (3)
• unwanted effects (5)

Answer 11

• halothane, nitrous oxide, sevoflurane
• respiratory depression, cardiac depression, malignant hyperthermia, halothane hepatitis, halogenated anesthetics may cause cardiac arrhythmias

Question 12

Halothane

-characteristics (6)

Answer 12

• potent
• non-explosive and non-irritant
• may cause cardiac arrhythmia
• hypotensive
• hepatotoxicity
• high lipid solubility

Question 13

Nitrous oxide

-characeristics (6)

Answer 13

• low potency, so usually combined with other agents
• rapid induction and recovery
• accumulates in gaseous cavities
• good analgesic properties
• risk of bone marrow depression, if prolonged administration
• it can increase heart rate and blood pressure if used alone, because it increases sympathetic discharge and plasma noradrenaline concentration

Question 14

Sevoflurane

-characteristics (4)

Answer 14

• rapid onset of action
• more potent than desflurane
• produce levels of fluoride, but not enough to cause toxicity
• usually combined with nitrous oxide

Question 15

Intravenous anesthetics

-characteristics (3)

Answer 15

• usually used for induction of anesthesia, followed by inhalation anesthetics
• Propofol is usually used to maintain anesthesia
• Most of them act within 20-30s if given intravenously

Question 16

Intravenous anesthetics

-names

Answer 16

Thiopental
Propofol
Ketamine

Question 17

Thiopental

-characteristics (8)

Answer 17

• barbiturate with high lipid solubility
• rapid action due to rapid transfer across blood-brain barrier
• short duration due to redistribution, mainly to muscles
• low therapeutic window - could cause cardiac depression
• could accumulate in fat, so it is not given for a long period of time
• risk of vasospasms if injected into the artery
• no analgesic effect
• affects GABAA receptors

Question 18

Propofol

-characteristics (7)

Answer 18

• induction and maintenance of anesthesia
• rapid recovery
• rapidly metabolized
• no cumulative effect
• useful for day case surgery
• could cause respiratory depression and hypo-tension
• affects GABAA receptors

Question 19

Ketamine

-characteristics (7)

Answer 19

• slow onset of action (2-5min)
• affects NMDA receptors
• promotes “dissociative anesthesia”, patients remains conscious but amnesic and unresponsive to pain
• high incidence of hallucinations and dysphoria during recovery; usually used for minor procedures in children
• raises intracranial pressure, nausea, vomiting, oral/airways secretion
• do not cause respiratory and cardiac depression, it increases BP
• avoid in patients with brain injury!!!

Question 20

Intravenous sedation

-drug names

Answer 20

Dexmedetomidine

Benzodiazepines

Question 21

Dexmedetomidine

-characteristics (6)

Answer 21

• alpha-2 selective agonist
• onset of action is 15min, peak sedation 1h
• sedation –> patient more awake and interactive with less incidence of delirium
• does not cause respiratory depression
• discontinuation after prolonged infusion can cause withdrawal syndrome characterized by agitation, tachycardia and hypotension
• bradycardia, hypotension, sore throat

1. binds to alpha 2 receptors in pre-synaptic neurons
2. inhibit the release of norepinephrine
3. terminating the propagation of pain signals and sedation

Question 22

Benzodiazepines

• names (3)
• indications (4)
• pharmacokinetics

Answer 22

• midazolam, diazepam, lorazepam
• relief of anxiety, sedation, anti-convulsion effects, sleep
• short acting ones (lorazepam) are metabolized to inactive compounds. Long acting ones (diazepam) are converted to a long lasting active compound
• flumanezil can be used as an antidote

Question 23

Stages of anesthesia

Answer 23

1. Stage of analgesia –> patient is unconscious
2. Stage of excitement –> increase HR, BP and RR
3. Stage of surgical anesthesia –> normal respiration, loss of muscle tone and reflexes
4. Stage of medullary depression –> cardiac and respiratory depression