Exam 2: Basic Pharmacology of Anesthetics Flashcards
What functions are impaired in minimal sedation/anxiolysis?
Cognitive
Coordination
What additional functions are impaired in moderate/conscious sedation?
Level of awareness; pts respond purposefully to verbal command
What additional functions are impaired in deep sedation?
Level of awareness; pts respond purposefully to pain stimulus
Airway/ventilatory function (may need assistance)
What additional functions are impaired in general anesthesia?
Level of awareness (nonresponsive)
Airway/ventilatory function (will need airway assistance)
Cardiovascular function
Define general anesthesia:
Generalized, reversible central nervous system depression
Four characteristics of general anesthesia:
No sensory perception
Loss of consciousness
No recall of events
Immobility
Seven types of drugs used in general anesthesia:
Pre-op/sedation Induction NMB Inhalational Opioids/LA Antiemetic Reversal
Prototype benzodiazepine:
Diazepam
5 effects of all benzos:
Anxiolysis Sedation Anterograde amnesia Anticonvulsant Muscle relaxation
At what level do benzos cause muscle relaxation?
Spinal level
Benzo mechanism of action:
Potentiates binding of GABA to receptor
Increases GABA potency 3x
What changes do benzos cause in the neuronal membrane?
Increased Cl- influx
Hyperpolarization
Decreased excitability
During what perioperative stage(s) are benzos used? Why?
Pre-operative; very long half-life
Adverse effects of benzos:
Ventilatory decrease, especially with opioids; potential hypoxemia
Decreased SVR (high dose) and resulting hypotension
Contraindication(s) for benzos:
Pregnancy
At what level(s) do opioids suppress pain?
Spinal and supraspinal
What system do opioids activate?
Endogenous pain suppression system
Opioid mechanism of action:
Agonist at stereospecific opioid receptors
Increased K+ outflow - hyperpolarization
Ca++ channel inactivation
Where are the receptors that opioids affect?
Pre- and post-synaptic sites in the brainstem, spinal cord, and peripheral tissues
During which perioperative stage(s) are opioids used?
All of them
Pre-medication
Intra-op pain management
General anesthesia
Post-op pain management
Adverse effects of opiates:
Bradycardia Respiratory depression Miosis Urinary retention Constipation Dependence Sedation
Characteristics of opioid-induced respiratory depression:
Rate decreases TV increases (but not enough to overcome)
Barbiturate mechanism of action:
Decreases rate at which GABA dissociates from receptors (prolongs Cl- channel opening)
Mimics GABA (activates Cl- channels)
What system do barbiturates depress?
Reticular activating system (thus inducing sleep)
Prototype barbiturate drug:
Thiopental
Anesthetic uses of barbiturates:
Sedation/hypnosis
Cerebral protection
Anticonvulsive
Induction of GA
In which patients is a barbiturate induction beneficial?
Pts with increased ICP or focal brain ischemia
Are benzos or barbiturates more effective anticonvulsants?
Benzos
Adverse cardiopulmonary effects of barbiturates:
SNS depressant (peripheral vasodilation, BP/CO decrease) Ventilatory depression
Under what circumstances will barbiturates cause significant cardiac depression?
SNS not intact
Hypovolemia
Large doses
What occurs if barbiturates are injected intra-arterially?
Very high pH (10-11) - drug precipitates quickly if injected arterially, causes vasoconstriction, gangrene, nerve damage
Adverse metabolic effects of barbiturates:
Potent hepatic enzyme inducers
Accelerates production of heme
Drugs that barbiturates increase the metabolism of:
Muscle relaxers Oral anticoagulants Phenytoin TCAs Corticosteroids Vitamin K
What condition is a strong contraindication to use of barbiturates?
Porphyria
Barbiturate allergies:
1 in 30,000
High mortality
Barbiturates and pregnancy:
Readily crosses the placenta
Propofol is supplied as:
1% solution in egg, soy, glycerol base
Preservatives used in propofol and related caution:
EDTA
Sodium metabisulfite - can cause rxn in asthmatics
Special care in drawing up propofol:
Highly susceptible to contamination
All vials are single-use; do not spike a bottle twice
Propofol mechanism of action:
Potentiates binding of GABA to B1 subunit of receptor
Decreases rate of GABA dissociation from receptor
Effects (5) of propofol:
Sedation/hypnosis Antiemetic Antipruritic Anticonvulsant Reduction in bronchoconstriction
Anesthetic uses of propofol:
IV sedation Induction Maintenance (TIVA) Part of maintenance (combined technique) Antiemetic
Consideration with injection of propofol:
Very painful - use lidocaine + opioid before propofol
Cardiopulmonary effects of propofol:
Ventilatory depression
Myocardial depression
Vasodilation
No reflex tachycardia (baroreceptor inhibition)
Muscular/tissue/hematologic effects of propofol:
Myoclonus (esp. with large induction doses)
Painful injection
Lipidemia with long-term infusion
Pre-synaptic events at the neuromuscular junction:
- Action potential depolarizes nerve terminal
- Ca++ channels open
- Ca++ diffuses down gradient to nerve terminal
- ACh spills into synaptic cleft
Post-synaptic events at the neuromuscular junction:
- ACh combines with nicotinic receptors (both must be occupied)
- Na+, Ca++ diffuse into cell, K+ diffuses out
- Motor end plate depolarizes
- Action potential
- Contraction
Structure of ACh receptor:
5 protein subunits
Central cation channel
Which subunits on the ACh receptor must be bound to ACh to activate it?
Both alpha subunits
Succinylcholine class:
Depolarizing neuromuscular blockade
Succinylcholine mechanism of action:
Binds to nicotinic receptors
Causes a single contraction then muscles stay relaxed until drug diffuses back into circulation
Metabolism of succinylcholine:
Plasma esterases - NOT acetylcholine esterases in the synapse
Anesthetic uses of succinylcholine:
Optimize intubating conditions
RSI
Treatment of laryngospasm
Adverse effects of succinylcholine:
Cardiac dysrhythmias Hyperkalemia Muscle pain Increased ICP, IOP MH triggering agent
Conditions that predispose pts to hyperkalemia with succs:
Burns Trauma Nerve damage Neuromuscular disease Renal failure
Pts that should not receive succinylcholine:
Atypical acetylcholinesterase
Head injury patients
Vecuronium class of drugs:
Non-depolarizing muscle relaxant
Monoquaternary aminosteroid
Vecuronium mechanism of action:
Competitive antagonist at pre- and post-synaptic ACh receptors (occupies alpha subunit without conformational change)
Anesthetic uses for vecuronium:
Facilitate intubation
Optimize surgical conditions (abdominal surgeries)
Condition(s) that make effects of vecuronium prolonged/unpredictable:
Liver/kidney disease Neuromuscular disease Hypothermia Electrolyte imbalances Aminoglycoside antibiotics
Condition(s) that make patients resistant to vecuronium:
Burns
Signs of residual neuromuscular blockage:
“Floppy fish” appearance
TOF twitches not equally strong
Isoflurane class of drug:
Inhalational anesthetic
Halogenated methyl ethyl ester
What characteristic of isoflurane determines onset, duration, etc?
Lipid solubility
Isoflurane eliminated almost entirely via:
Lungs
Contemporary inhaled anesthetics eliminated via:
Minimal hepatic metabolism and renal excretion
Anesthetic uses of isoflurane:
Bronchodilation General anesthesia (maintenance - Sevo best for induction)
Adverse effects of isoflurane:
Respiratory depression
Cardiac depression/vasodilation
Malignant hyperthermia
Physiology of malignant hyperthermia:
Ca++ channel interference
Muscle rigidity
Increased temperature
Increased CO2
Characteristics of isoflurane respiratory depression:
Increased rate
Decreased volume
Define MAC:
Mean alveolar concentration
Concentration at which 50% of patients do not move to noxious stimulus
MAC of isoflurane:
1.2%
MAC of nitrous oxide:
104%
Local anesthetic mechanism of action:
Inhibits Na+ channels during inactivated closed state and blocks impulse conduction during depolarizing phase
Prototype local anesthetic:
Lidocaine
Pharmacologic effects of local anesthetics:
Block afferent nerve transmission; analgesic/anesthesia without effect on consciousness
Three modalities that local anesthetics block:
Autonomic
Somatic sensory
Somatic motor
Classification of lidocaine:
Amide local anesthetic
Structure of local anesthetic molecule:
Lipophilic head (aromatic ring) Intermediate chain (amide NH or ester COO-) Hydrophilic tail (tertiary amine)
CNS s/s of local anesthetic toxicity:
Circumoral/tongue numbness, tinnitus, vision changes Dizziness, slurred speech Restlessness Seizure CNS depression Apnea Hypotension
Cardiac s/s of local anesthetic toxicity:
Hypotension
Myocardial depression
Reduced SVR/CO
Cardiac s/s of bupivicaine toxicity:
Arrythmias
AV heart block
Hypotension
Arrest
Cardiac s/s of cocaine toxicity:
Massive SNS outflow
Coronary vasospasm
MI
Dysrhythmias (v-fib)
