Intro to Anesthetics

Question 1

Characteristics of general anesthesia?

Answer 1

No sensory perception, loss of consciousness, no recall of events, immobility, muscle relaxation, suppression of autonomic reflexes, analgesia, anxiolysis.

Question 2

5 pharmacologic effects of benzodiazepines

Answer 2

Anxiolysis, Sedation, anterograde amnesia, anticonvulsant actions, muscle relaxation (spinal level)
Prototype: Diazepam

Question 3

Mechanism of action: Benzodiazepines

Answer 3

Potentiates binding of GABA to GABA receptor
Increases GABA potency 3x
1. Increases chloride influx
2. Hyperpolarization
3. Decreased neuronal excitability

Question 4

What ion channel do GABA receptors affect?

Answer 4

Chloride channels (opens it)

Question 5

What are the uses for Benzos in anesthesia?

Answer 5

Premedication (main), IV sedation, GA induction (rare), GA maintenance (rare), Post-op anxiolysis (rare)

Question 6

Benzodiazepine adverse effects

Answer 6

Hypoxemia and hypoventilation enhanced with opioid. Decreases SVR at induction dosages, BP drops with hypovolemia, contraindicated in pregnancy, dose dependent decrease in ventilation.

Question 7

Mechanism of action: Opioids

Answer 7

Causes supra spinal and spinal analgesia: activates endogenous pain suppression system; agonist at stereospecific opioid receptors. 1. Acts at pre and post synaptic sites 2. Acts at brainstem, spinal cord, peripheral tissues. 3. Decreased neurotransmission
Increased K conductance (hyper polarization); Ca channel inactivation; decrease in neurotransmitter release

Question 8

What do we use opioids for in anesthesia practice?

Answer 8

Premedication; intraoperative pain management (IV, epidural, spinal); general anesthesia at high doses, post-op pain management; Prototype: Morphine

Question 9

Adverse effects of opioids

Answer 9

Bradycardia, respiratory depression (decreased RR and increased TV); miosis; urinary retention; constipation; physical dependence; sedation

Question 10

Mechanism of action: Barbituates

Answer 10

Decreases the rate at which GABA dissociates from its receptor, increases duration of activated GABA (Cl channel opening); inhibits post-synaptic neuron; depresses RAS; Prototype drug: Thiopental

Question 11

What are Barbituates used for?

Answer 11

Sedation and hypnosis, cerebral protection, anti seizure (benzos are more effective), induction of general anesthesia (useful in patients with increased intracrainial pressure or brain ischemia)

Question 12

Barbs (thiopental) adverse effects

Answer 12

“hang over effect”; depression of medullary vasomotor center decreases SNS outflow; peripheral vasodilation; preload decreases; SBP decreases; compensatory HR increase. Intraarterial injection (wet gangrene) Ventilatory depression. If SNS not intact, hypovolemia, large dose, will see decreases in BP and myocardial depression. Hepatic enzyme induction; D-aminolevulinic acid synthetase- porphyria; crosses placenta

Question 13

What is the class of Propofol?

Answer 13

Nonbarbituarate intravenous anesthetic; supplied as a 1% solution in egg, soy, glycerol base. EDTA vs. sodium metabisulfite

Question 14

Mechanism of action: Propofol

Answer 14

Potentiates binding of GABA to GABA receptor (B1 subunit); decreases rate of disassociation of GABA from receptor. 1. increases chloride influx 2. hyper polarization 3. decreased neuronal excitability

Question 15

5 pharmacological effects of propofol

Answer 15

1. Dose dependent sedation and hypnosis
2. antiemetic
3. antipruritic
4. anticonvulsant
5. attenuation of bronchoconstriction

Question 16

Anesthetic uses for Propofol

Answer 16

IV sedation; induction of general anesthesia; TIVA; balanced technique; antiemetic (small doses)

Question 17

Propofol: adverse effects

Answer 17

Dose dependent ventilatory depression and myocardial depression/vasodilation (HR unchanged due to baroreceptor inhibition) bradycardia related deaths; myoclonus, painful injection; lipidemia, infection and bronchospam from preservative (but helps with bronchoconstriction)

Question 18

Acetylcholine receptor number of sites and where does ACH bind (subunit)

Answer 18

5 protein subunits; Ach must bind to BOTH “a” subunits. “a” subunits are the site of agonism and antagonism

Question 19

Succinylcholine classification

Answer 19

DEPOLARIZING neuromuscular blockade

Question 20

Mechanism of action: Succinylcholine

Answer 20

Binds to NICOTINIC receptors:

1. channel opens, motor endplate depolarizes
2. Single contraction occurs
3. Sch not metabolized by true acetylcholinesterases
4. channel stays open until sch diffuses back into circulation
5. further action potentials CANNOT be initiated

Question 21

Anesthetic uses for succinylcholine

Answer 21

Neuromuscular blockade, optimizing intubation conditions, RSI, laryngospasm

Question 22

Adverse effects and precautions: succinylcholine

Answer 22

Cardiac dysrhythmias, hyperkalemia, muscle pain, ICP, IOP, potent malignant hyperthermia trigger, atypical acetylcholinesterase patients

Question 23

Vecuronium classification

Answer 23

Non-depolarizing muscle relaxant; monoquaternary aminosteroid

Question 24

Mechanism of action: Vecuronium

Answer 24

Competitive antagonist at pre and post neuromuscular junction nACH receptors:

• occupies alpha subunits of ACH receptor without induction a conformational change
• no action potential can be initiated

Question 25

Anesthetic uses for vecuronium

Answer 25

Muscle relaxation, paralysis for intubation, optimizing surgical conditions (for abdominal cases for example)

Question 26

Adverse effects for Vecuronium

Answer 26

Prolong, unpredictable effects with: liver/kidney dx; neuromuscular disease; hypothermia; electrolyte imbalances, abx, amino glycosides; resistance in burn patients, residual neuromuscular blockade (weakness)

Question 27

Isoflurane class

Answer 27

Inhalational anesthetic; halogenated methyl ethyl ether
Mechanism of action: too deep
elimiated via the lungs! Minimally eliminated by liver or kidney

Question 28

Anesthetic uses for Isoflurane

Answer 28

Bronchodilator, general anesthetic (sedation, hypnosis, partial muscle relaxation)

• induction (usually SEVO only)
• maintenance

Question 29

Adverse effects of Isoflurane

Answer 29

Respiratory depression (higher rate, lower volume); Cardiac depression, decreased CO, BP, vasodilation; malignant hyperthermia (Ca channel interference); aspiration; OR pollution

Question 30

Local anesthetic mechanism of action

Answer 30

Block impulse conduction during the DEPOLARIZATION phase of action potential.
Blockade is caused by the inhibition of the influx of sodium ions (sodium channel blockade)
Blockade only occurs when the Na channels are in the INACTIVATED CLOSED STATE. Prototype drug: Lidocain
Blocks afferent nerve transmission to produce analgesia and anesthesia without LOC: autonomic, sensory, motor blockade

Question 31

Classification of lidocaine

Answer 31

Amide local anesthetic

Lipophilic head, intermediate chain containing an amide (NH) or ester (COO-) and hydrophilic tail (tertiary amine)

Question 32

Local anesthetic adverse effects and precautions

Answer 32

CNS toxicity, circumoral numbness/tingling, tinnitus, vision changes, dizziness, slurred speech, restlessness; seizure followed by CNS depression, apnea, hypotension. CNS effects before cardiac. Myocardial depression, decreased SVR and CO. Bupivacaine- arrhythmias, AV heart block, hypotension and arrest. Cocaine overdose is increased SNS outflow.

Question 33

Where does GABA vs. Benzos bind?

Answer 33

GABA binds to 2 beta sites and Benzos bind to gamma site; on the GABA-A receptor (propofol potentiates binding of GABA to Beta1)

Question 34

Can you use Barbituates for induction?

Answer 34

Yes.
Induction of general anesthesia (useful in patients with increased intracranial pressure and/or focal brain ischemia)
Note barbiturates used for IV induction do cross the placenta but levels tend to be much lower in the fetal circulation compared with the maternal circulation.
Dose dependent depression of medullary and pontine ventilatory centers
Decreased ventilatory response to hypoxia and hypercapnia

Question 35

What is the most potent inducer of hepatic enzyme induction?

Answer 35

Phenobarbitol

Question 36

How is propofol eliminated?

Answer 36

Conjugated in liver to water soluble compounds
Renal Excretion-CRF doesn’t affect clearance.
Clearance exceeds hepatic blood flow
T ½ Elimination 0.5-1.5 hours

Question 37

What is Malignant Hyperthermia?

Answer 37

autosomal dominant mutation in the sarcoplasmic reticulum calcium channel. Also known as the ryanodine receptor. If the patient has inherited this genetic mutation exposure to succinylcholine or the inhaled agents causes uncontrolled calcium efflux from the SR with tetany and excessive heat generation. TX = dantrolene that blocks Ca release from the SR.