general anesthetics Flashcards
what are the goals of general anesthesia?
Amnesia / Hypnosis - Hypnosis – impairment of perceptive awareness Analgesia - Lack of pain sensation Akinesia - Lack of motor movement Control of physiology - Block sympathetic responses to stimuli
what are the pharmacologic components of a general anesthetic?
Pharmacologic components of a general anesthetic
- Inhalational agents
- Induction and intravenous amnestic agents
Propofol, Thiopental, Ketamine, benzodiazepines
- Neuromuscular blocking agents
- Opioids
- Local anesthetics
- Reversal agents and antagonists
what’s the concentration gradient for general anesthetic? and what are the factors that change this?
Concentration gradient:
delivered > inspired > alveolar > arterial > brain
Factors inspired concentration alveolar ventilation solubility cardiac output
what are the systemic effects of inhalation anesthetics?
- Respiratory decrease tidal volume increase respiratory rate blunt response to CO2 bronchodilation - Cardiovascular vasodilation decrease contractility decrease blood pressure - Central nervous system decrease cerebral metabolic rate for oxygen cerebral vasodilation increase cerebral blood flow - Other organs: renal, hepatic, uterine - Malignant Hyperthermia Autosomal dominant hypermetabolic disorder
what is meant by the balanced technique?
No single agent can achieve all goals safely
Commonly, a combination of inhaled and intravenous agents is used
Many Variables:
- medical condition of the patient
- surgical procedure
- patient’s age, weight, etc
- intraoperative events
do we know the mechanism of action of inhaled anethetics?
no, we don’t know the complete picture
what are the theories behind the mechanism of action of inhaled agents?
Unitary Hypothesis (Claude Bernard) 1870’s
- All anesthetic act through a common mechanism
Meyer-Overton rule ~ early 1900’s
- Strong correlation between potency of anesthetics and their solubility in (olive) oil
Old theory: volatile anesthetics act nonspecifically on hydrophobic lipid components of cells
what is the mechanisms of action at excitatory nicotinic Ach receptors and inhibitory GABA receptors?
At Excitatory Nicotinic ACh receptors:
- anesthetic binding decreases excitatory cholinergic currents, making the generation of action potentials less likely
At Inhibitory GABA receptors:
- anesthetic binding increases chloride fluxes, hyperpolarizing neurons, and making the generation of action potentials less likely
Suppression of motor responses primarily in spinal cord
Hypnosis and amnesia occurs within the brain
Various sites includes reticular activating system, cerebral cortex, cuneate nucleus, hippocampus, etc.
Various receptors involved
Most studied so far: GABA, nicotinic acetylcholine, glycine, N-methyl D-aspartate
what is minimum alveolar concentration?
MAC is the concentration at 1 atmosphere that produces immobility in 50% of subjects exposed to a noxious stimulus - skin incision
MAC is a measure of potency
Similar to ED50
95% of subjects are immobile to noxious stimulus at 1.3 MAC
Similar to ED95
MAC values are additive for anesthetic gases
eg. nitrous oxide and sevoflurane)
Various factors affect MAC
Age, temperature, pregnancy, extreme physiologic states (hypotension, acidosis, etc.)
what are intravenous agents?
- Induction Agents
one “arm-brain” circulation
rapid redistribution terminates effect
eg. propofol, ketamine, thiopental, etomidate - Benzodiazepines
for premedication or co-indcution
eg. midazolam, diazepam, lorazepam
reversal: flumazenil - Opioids
used to blunt hemodynamic response to intubation and surgical incision
adequate intraoperative analgesia leads to comfortable patient upon emergence
eg. fentanyl, sufentanil, remifentanil, morphine, demerol
reversal: naloxone
for intravenous agents, what are neuromuscular blocking agents?
- Neuromuscular blocking agents aka “muscle relaxants” uses: facilitate intubation facilitate surgical access prevent movement in critical surgery/tests
for intravenous agents, neuromuscular blocking agents what are depolarizing?
Depolarizing only succinylcholine used clinically mechanism of action: binds to NMJ nicotinic cholinergic receptor causes depolarization and fasciculations offset by diffusion and hydrolysis
what are non-depolarizing neuromuscular blocking agents?
Non-depolarizing rocuronium, cisatracurium, pancuronium mechanism of action: competitive inhibition of acetylcholine at NMJ drug choice based on: onset/offset elimination profile side effects
what are neuromuscular reversal agents?
- Mechanism of action:
inhibit cholinesterase
increase [acetylcholine] at NMJ - Side effects:
bronchospasm and bradycardia (muscarinic cholinergic agonism)
prevented by anticholinergic agents: atropine or glycopyrrolate
