Anesthetics I and II Flashcards
(40 cards)
Glutamate is the; GABA is
what can volatile anesthetics do to either?
major excitatory NT in the brain;
an inhibitory NT in the brain;
they can inhibit glutamate release; they can increase and decrease GABA release
Glutamate receptor is a; GABA A receptor is
tetrameric protein with structurally related subunits; going to have 5 non-identical subunits
NMDA receptors and some facts on it
- glutamate-activated ion channels
- They conduct Na, K, Ca, and modulate long term synaptic responses
- Volatile anesthetics might INHIBIT NMDA receptors
- Ketamine is a potent and SELECTIVE inhibitor of NMDA receptors
- N2O can selectively inhibit NMDA receptors
GABA-activated ion channels and facts
- Most important inhibitory NT in CNS
- GABA A receptor mediates postsyn response by selectively allowing Cl ions to enter, hyperpolarizing neurons
- Modulated by barbs, anesthetic steroids, benzos; propofol, etomidate; volatile anesthetics
- Barbs, propofol, volatile anesthetics increase freq/length of time Cl channels are open (CONFORMATIONAL change in GABA A receptor); they likely bind to different sites on receptor
Glycine-activated ion channels:
glycine most important inhibitory NT in the spinal cord and brainstem
- Cl selective ion channel
- volatile anesthetics potentiate glycine acttivated currents and increase receptor affinity for glycine (could contribute to ANESTHETIC action)
- Propofol, alphaxalone, pentobarb can do same as 2
Meyer-Overton rule; unitary theory of anesthesia:
potency of anesthetic gases directly related to their solubility in OLIVE OIL;
variety of structurally unrelated drugs obey rule, they MUST bind at same hydrophobic site
Potency of inhibition correlates with; what is luciferase?
potency of anesthetic;
water soluble protein inhibited by anesthetics, and likely the anesthetics bind to the HYDROPHOBIC pockets on proteins like luciferase
SE’s of halothane? methoxyflurane?
Dysrhythmogenic, liver toxicity, hypotension;
hepatic metabolism increases Fl and then nephrotoxicity
What is the boiling point of desflurane?
22.8 degrees C
Inhaled anesthetics and course of uptake and distribution?
- absorbed from alveoli into pulmonary capillary blood (uptake)
- DISTRIBUTED to site of action (brain) and RESERVOIRS (vessels, muscle, fat)
- Variably metabolized
- eliminated principally via lungs
Henry’s Law? Also a partition coefficient is
concentration of gas dissolved in solution is DIRECTLY PROPORTIONAL to partial pressure of gas above solution;
ratio of solubilities of a gas between two compartments, e.g. blood:gas, brain:blood, at EQULIBRIUM
THINK: insoluble agents need FEW mc’s present in blood to raise the agent’s partial pressure
Equilibration between two phases for an anesthetic gas means
same PARTIAL PRESSURE of gas exists in both phases; however, does NOT mean same concentration exists in both phases
______ propel anesthetic to brain
Partial pressure gradients (e.g. equlibration between alveolar, pulmonary capillary blood, and brain partial pressures!!)
What determines PA? Factors to increase it?
Delivery of anesthetic to alveoli minus uptake of anesthetic into the blood:
increase delivery to alveoli:
1. increase inhaled partial pressure of agent (concentration effect, 2nd gas effect)
2. Increased alveolar ventilation
3. Decreased FRC (the RESERVOIR)
decrease uptake by blood
- decrease blood solubility of agent
- Decrease CO
- Decrease gradient between PA and Pa
What happens with inhaled partial pressure by the time it reaches the alveoli? How do you deal with this?
It’s been diluted b/c it mixes with gas in anesthesia circuit and gas in patient’s lungs;
INCREASE PI above what you need to induce anesthesia
2nd gas effect is what
- ability of high volume uptake of one gas (N2O) to accelerate rate of increase in PA of a second gas (your potent anesthetic agent)
- the large volume uptake of N2O increases concentration of remaining gases (O2 and anesthetic) in resulting SMALLER lung volume
Speed of anesthetic induction is determined by; poorly soluble agents
rate of rise of alveolar concentration of the anesthetic agent (FA/FI);
rapidly achieve a high alveolar concentration and induction occurs really quick (FA/FI = 1)
MAC is; other facts?; site of action
concentration of inhaled anesthetic agent at which 50% of patients WON’T move in response to surgical incision (ED 50);
related to SOLUBILITY in olive oil;
MACs are additive;
to produce immobility is the spinal cord (depression of excitation, enhancement of inhibition) and LOSS OF AWARENESS and recall occurs at .4-.5
What increases MAC? What decresaes it?
- Hyperthermia 2. Pheomelanin (red hair) 3. Increased CNS catecholamines 4. Cyclosporine 5. Hypernatremia 6. Increased central NT’s (MAOIs, cocaine, ephedrine, L-DOPA)
- Hypothermia 2. Increased age 3. Opposite of 3 above 4. Opioids, anxiolytics, alpha-2 agonists, lidocaine 5. hyponatremia 6. Pregnancy/post partum period
N2O: class, mechs, thera, SE’s, other SE’s, misc
Class: -
Mech: NMDA receptor antagonist
Thera: Mask induction in children
Important SE’s: Post-operative nausea and vomiting; inactivates vitamin B (leading to abnormal embryonic development, abortion); accumulates in closed, air-containing spaces (bowel, middle ear, pneumothoraces, air emboli) because N2O insoluble in blood; adverse effects on EMBRYONIC development
Misc: No muscle relaxation; used with volatile agents for MAINTENANCE
Isoflurane (Forane)
Class: Volatile anesthetic
Mech: Most potent
Thera: Gold standard for maintenance of anesthesia
Important SE’s: Pungent; dose dependent CNS depression (EEG, sensory evoked potentials, motor evoked potentials, cerebral metabolic rate), increase in cerebral blood flow and intracranial pressure; dose dependent decrease in systemic BP, decrease in respiratory function like TV and response to hypoxia or hypercarbia; relaxes skeletal muscle and airway smooth muscles; malignant hyperthermia in susceptible patients; more blood flow to brain, muscle skin, less to liver, kidneys, gut
Misc: Difficult for mask induction
Desflurane:
Class: Volatile anesthetic
Mech: Least soluble, least potent (allows for rapid emergence from anesthesia)
Important SE’s: Most pungent (airway irritation symptoms: coughing, salivation, breath holding, laryngospasm); dose dependent CNS depression (EEG, sensory evoked potentials, motor evoked potentials, cerebral metabolic rate), increase in cerebral blood flow and intracranial pressure; dose dependent decrease in systemic BP, decrease in respiratory function like TV and response to hypoxia or hypercarbia; relaxes skeletal muscle and airway smooth muscles; malignant hyperthermia in susceptible patients;
can get reflex tachy sometimes; more blood flow to brain, muscle skin, less to liver, kidneys, gut;
increase in HR due to reflex tachy
Sevoflurane (Ultane)
Class: Volatile anesthetic
Mech: Less soluble, less potent (but not irritating)
Thera: Mask induction in children and adults
Important SE’s: Can form CO if not combined with CO2 correctly by exposure to strong bases; dose dependent CNS depression (EEG, sensory evoked potentials, motor evoked potentials, cerebral metabolic rate), increase in cerebral blood flow and intracranial pressure; dose dependent decrease in systemic BP, decrease in respiratory function like TV and response to hypoxia or hypercarbia; relaxes skeletal muscle and airway smooth muscles; malignant hyperthermia in susceptible patients; more blood flow to brain, muscle skin, less to liver, kidneys, gut; also metabolized into inorganic Fl and compound A (latter a nephrotoxin in rats)
Barbituates qualities:
- prepared as aqueous solutions of Na salt
- Rapid onset, short duration of action
- ONLY hypnosis/sedation
- Hypnotic effect terminateed by drug redistribution from brain to muscle and fat
- Metabolized by liver
- Dosing based on lean body mass
- Used to induce ANESTHESIA
- Hyponosis by enhancing inhibitory NT’s (bind GABA A receptors to enhance Cl conductance; direct agonist at higher concentrations) and inhibiting actions of excitatory NT’s (target NMDA receptors)
- Barbs and propofol produce dose dependent decreases in BP due to vasodilation and also dose dependent respiratory depression; also NEGATIVE inotropes
