Intro to Anesthetics Flashcards
Characteristics of general anesthesia?
No sensory perception, loss of consciousness, no recall of events, immobility, muscle relaxation, suppression of autonomic reflexes, analgesia, anxiolysis.
5 pharmacologic effects of benzodiazepines
Anxiolysis, Sedation, anterograde amnesia, anticonvulsant actions, muscle relaxation (spinal level)
Prototype: Diazepam
Mechanism of action: Benzodiazepines
Potentiates binding of GABA to GABA receptor Increases GABA potency 3x 1. Increases chloride influx 2. Hyperpolarization 3. Decreased neuronal excitability
What ion channel do GABA receptors affect?
Chloride channels (opens it)
What are the uses for Benzos in anesthesia?
Premedication (main), IV sedation, GA induction (rare), GA maintenance (rare), Post-op anxiolysis (rare)
Benzodiazepine adverse effects
Hypoxemia and hypoventilation enhanced with opioid. Decreases SVR at induction dosages, BP drops with hypovolemia, contraindicated in pregnancy, dose dependent decrease in ventilation.
Mechanism of action: Opioids
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
What do we use opioids for in anesthesia practice?
Premedication; intraoperative pain management (IV, epidural, spinal); general anesthesia at high doses, post-op pain management; Prototype: Morphine
Adverse effects of opioids
Bradycardia, respiratory depression (decreased RR and increased TV); miosis; urinary retention; constipation; physical dependence; sedation
Mechanism of action: Barbituates
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
What are Barbituates used for?
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)
Barbs (thiopental) adverse effects
“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
What is the class of Propofol?
Nonbarbituarate intravenous anesthetic; supplied as a 1% solution in egg, soy, glycerol base. EDTA vs. sodium metabisulfite
Mechanism of action: Propofol
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
5 pharmacological effects of propofol
- Dose dependent sedation and hypnosis
- antiemetic
- antipruritic
- anticonvulsant
- attenuation of bronchoconstriction
Anesthetic uses for Propofol
IV sedation; induction of general anesthesia; TIVA; balanced technique; antiemetic (small doses)
Propofol: adverse effects
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)
Acetylcholine receptor number of sites and where does ACH bind (subunit)
5 protein subunits; Ach must bind to BOTH “a” subunits. “a” subunits are the site of agonism and antagonism
Succinylcholine classification
DEPOLARIZING neuromuscular blockade
Mechanism of action: Succinylcholine
Binds to NICOTINIC receptors:
- channel opens, motor endplate depolarizes
- Single contraction occurs
- Sch not metabolized by true acetylcholinesterases
- channel stays open until sch diffuses back into circulation
- further action potentials CANNOT be initiated
Anesthetic uses for succinylcholine
Neuromuscular blockade, optimizing intubation conditions, RSI, laryngospasm
Adverse effects and precautions: succinylcholine
Cardiac dysrhythmias, hyperkalemia, muscle pain, ICP, IOP, potent malignant hyperthermia trigger, atypical acetylcholinesterase patients
Vecuronium classification
Non-depolarizing muscle relaxant; monoquaternary aminosteroid
Mechanism of action: Vecuronium
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
Anesthetic uses for vecuronium
Muscle relaxation, paralysis for intubation, optimizing surgical conditions (for abdominal cases for example)
Adverse effects for Vecuronium
Prolong, unpredictable effects with: liver/kidney dx; neuromuscular disease; hypothermia; electrolyte imbalances, abx, amino glycosides; resistance in burn patients, residual neuromuscular blockade (weakness)
Isoflurane class
Inhalational anesthetic; halogenated methyl ethyl ether
Mechanism of action: too deep
elimiated via the lungs! Minimally eliminated by liver or kidney
Anesthetic uses for Isoflurane
Bronchodilator, general anesthetic (sedation, hypnosis, partial muscle relaxation)
- induction (usually SEVO only)
- maintenance
Adverse effects of Isoflurane
Respiratory depression (higher rate, lower volume); Cardiac depression, decreased CO, BP, vasodilation; malignant hyperthermia (Ca channel interference); aspiration; OR pollution
Local anesthetic mechanism of action
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
Classification of lidocaine
Amide local anesthetic
Lipophilic head, intermediate chain containing an amide (NH) or ester (COO-) and hydrophilic tail (tertiary amine)
Local anesthetic adverse effects and precautions
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.
Where does GABA vs. Benzos bind?
GABA binds to 2 beta sites and Benzos bind to gamma site; on the GABA-A receptor (propofol potentiates binding of GABA to Beta1)
Can you use Barbituates for induction?
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
What is the most potent inducer of hepatic enzyme induction?
Phenobarbitol
How is propofol eliminated?
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
What is Malignant Hyperthermia?
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.
