Week 1 Anesthetic Pharm

Front 1

Meyer-Overton Rule
(Unitary Hypothesis)

Back 1

- Potency of inhaled anesthetics is directly correlated with lipid solubility
- Implies that anesthesia results form dissolved anesthetic molec. at hydrophobic sites
- 2 limitations: only applies to gases and volatile liquids b/c the olive oil:gas partition coefficients can't be determined for liquids. And olive oil is poorly characterized mixture of oils

Front 2

Agent-specific theory

Back 2

inhalation agents don't have a predominant structure-fxn relationship

Front 3

Unitary Hypothesis

Back 3

all inhalation agents share a common mechanism of action at the molecular level (Meyer-Overton)

Front 4

Critical volume hypothesis

Back 4

anesthetics bind to hydrophobic sites in lipid bilayer and expand the membrane beyond a critical volume

Front 5

Disruption of membrane form

Back 5

disrupts ion channels, etc
- Fluidization theory
- Lateral phase separation theory

Front 6

5-Antsrom theory (Eger)

Back 6

- Anesthetics produce anesthesia by an action of 2 sites separated by a distance of 5 angstroms
- Max potency achieved with a molecule that is 5 carbons long (5 angstroms); having 2 active sites at each end

Front 7

Neurotransmitters associated with anesthesia

Back 7

1. Acetylcholine
2. Epi/Norepi
3. Serotonin
4. Glutamate
5. GABA
6. Glycine
7. Endorphins

Front 8

surgical stress

Back 8

1. psychological
2. tissue injury
3. IV volume changes
4. Anesthetic agent chosen
5. Pain (SNS stimuli)
6. Organ manipulation

Front 9

What is the Stress Response?

Back 9

Activation of the Hypothalamic-pituitary-adrenal axis and SNS
- Increased cortisol, catecholamines, and cytokins
- Resulting in:
1. Tachycardia
2. HTN
3. increased metabolism
4. hypercoagulability
5. decreased immune fxn

Front 10

According to Eger: How do inhaled anesthetics work?

Back 10

Anesthesia is a reversible state mediated by the central nervous system that produces:
1. Immobility with noxious stimuli
2. Amnesia/unawareness
3. unconsciousness
4. Analgesia
5. Suppression of autonomic reflexes
6. relaxation of muscles

Front 11

What 5 things do you want in an ideal anesthetic?

Back 11

1. induce anesthesia smoothly and rapidly
2. permit rapid recovery
3. wide margin of safety
4. no adverse effects
5. low cost

Front 12

4 sites of action for anesthetics

Back 12

Central Nervous System:
1. Spinal cord
2. Reticular Activating System
3. Cerebral cortex
4. Synaptic Transmission

Front 13

Describe how the Spinal cord works with anesthetics

Back 13

- immobility
- actions here underlie the determination of MAC
- specific location me by the motor neuron

Front 14

Describe how the Reticular Activating System works with anesthetics

Back 14

- inhibit information transfer through the brain stem
(normal fxn: involved in arousal)

Front 15

Describe how the Cerebral Cortex works with anesthetics

Back 15

- memory and awareness
- alteration of cortical electrical activity
(major site for storage and retrieval of info)

Front 16

Describe the PREsynaptic Action with regards to anesthetics

Back 16

- alter neurotransmitter release
- alter reuptake of neurotransmitter following release

Front 17

Describe the POSTsynaptic Action with regards to anesthesia

Back 17

- alter the binding of the neurotransmitter to receptor sites

Front 18

Neurotransmitters Release

Back 18

1. action potential depolarizes the presynaptic membrane and causes vesicles containing neurotransmitter to empty into the cleft
2. released neurotransmitter causes immediate change in permeability characteristics of the post-synaptic membrane causing either excitation or inhibition of the post-synaptic neuron based on effect of ion channels

Front 19

Resting membrane action potential

Back 19

-70 to -90mA

Front 20

When is the action potential triggered

Back 20

when the threshold reaches -50mA

Front 21

Effects of Stimulation on the action potential

Back 21

- first excitatory stimulus causes transient depolarization
- then increasing the stimulus strength increases the depolarization to reach threshold

Front 22

Efftects of Inhibition on the action potential

Back 22

- similar suprathreshold stimulus causes depolarization beyond threshold
- inhibition then prevents the second excitatory stimulus from reaching threshold

Front 23

voltage-gated ion channels include:

Back 23

1. sodium
2. Potassium
3. Calcium
4. Chloride

Front 24

Ligand-gated ion channels include:

Back 24

1. Nicotinic cholinergic receptors
2. Amino acid receptors
3. GABA
4. NMDA

Front 25

Transmembrane receptors include

Back 25

1. Adrenoreceptors (alpha, beta)
2. Muscarinic cholinergic receptors
3. Opiods
4. Serotonin
5. Dopamine

Front 26

Describe how GABA works

Back 26

- major inhibitory neurotransmitter in the CNS
- estimated that 1/3 of the synapse in the brain are GABAergic
- When GABA binds to the receptor the chloride channel opens allowing chloride ions to flow into the neuron causing it to become hyperpolarized (more negative)
- GABA receptor is a prime anesthetic target
-But it can't cross the BBB

Front 27

9 Surgical considerations when developing an anesthetic plan

Back 27

1. length of surgery
2. position
3. muscle relaxation requirement
4. blood/fluid loss
5. pain scale
6. pt co-mobidities
7. meds
8. family/pt hx
9. height and wt