General and local anesthetics Flashcards
1
Q
Mechanism of action for inhaled general anesthetics 1
A
- Cause loss of consciousness, immobility, amnestic and analgesic effects (highly lipid soluble)
- The sites of action for general anesthetics include brainstem-hypothalamus/thalamus (control of sleep and attention) and the cerebral cortex (loss of consciousness)
- Suppressing the thalamus alters sensory and motor information going to/from the brain
2
Q
Mechanism of action for inhaled general anesthetics 2
A
- Molecular targets: potentiation of GABAA and Gly receptor activity (causing hyperpolarization) as well as inhibition of glutamate and NMDA receptors (prevents glutamate binding to NMDA-> no depolarization)
- Also will inhibit Ca, Na, and K channels (causes hyperpolarization of neurons)
- Overall the increased inhibitory transmission and decreased excitatory transmission provide the general effects of anesthesia (multiple site hypothesis)
3
Q
Pharmacokinetics/dynamics of inhaled general anesthetics 1
A
- Uptake: vaporized drug passes thru alveolar-arterial membrane into the blood stream
- Partition coefficient: the ratio of amount of drug in blood: amount of drug in gas (blood/gas)
- The partial pressure of the gas will equilibrate w/ the partial pressure in the brain, the objective is to achieve a constant brain partial pressure of the inhaled anesthetic (distribution)
- At equilibrium the CNS partial pressure equals the blood partial pressure which equals the gas partial pressure
4
Q
Pharmacokinetics/dynamics of inhaled general anesthetics 2
A
- Solubility of a gas will affect the partition coefficient (how fast a drug will become equilibrated in the blood)
- A lower solubility means a lower partition coefficient (more drug in the gas form), and this means faster induction of the drug
- A low partition coefficient means less anesthetic needs to be dissolved in blood before Palveoli equilibrates w/ Parterial
- Thus, a higher partition coefficient means slower induction
5
Q
Pharmacokinetics/dynamics of inhaled general anesthetics 3
A
- Potency: minimum alveolar concentration (MAC) means the concentration required to suppress movement in 50% of pts
- Want lowest MAC possible
- Metabolic profile of drugs is negligible, b/c elimination thru the pulmonary system is responsible for recovery from anesthetized state (as Pcns begins to fall)
6
Q
Side effects of inhaled general anesthetics
A
- All cause CNS obtundation, decrease cerebral metabolic rate, increase cerebral blood flow via vasodilation
- The drugs w/ MAC greater than 1 will increase ICP
- All are myocardial depressants, they decrease mean arterial pressure due to drop in vascular resistance
- They all increase respiratory rate and decrease tidal volume
- However at higher concentrations ventilation slows
- Decrease in respiratory systemic resistance causes decreased pulmonary tone and bronchodilation
7
Q
Intravenous general anesthetics
A
- These have a rapid onset and short duration of action
- All of them except for one (ketamine) affect the GABA receptor in some way (decrease rate of GABA dissociation or enhance affinity)
- Ketamine works by blocking the NMDA receptor
- Overall these also cause generalized hyperpolarization of neurons
- They are also highly lipophilic and easily cross the BBB
8
Q
Pharmacokinetics and dynamics of IV general anesthetics
A
- They have a very short T1/2, mostly due to a combination of redistribution and metabolism
- The agents move from sites that are highly perfused (like brain) to areas less perfused in peripheral compartments, followed by normal metabolism/elimination
- They are metabolized by hepatic nzs followed by renal elimination
9
Q
Actions of IV general anesthetics on different parts of the body
A
- The ones that act on GABA receptors affect the body in the same ways as the volatile general anesthetics
- This includes CNS depression (decrease metabolic rate but increase vasoconstriction instead of vasodilaiton), cardiac depression, eventual respiratory depression, analgesia
- The NMDA-acting drug (ketamine) is different, it causes vasodilation in brain, increases metabolic rate and increases ICP, it stimulates the CV system (hypertension and tachycardia), and it decreases RR
10
Q
Inhaled general anesthetics
A
- Sevoflurane
- Desflurane
- Isoflurane
- Nitric oxide
11
Q
IV general anesthetics
A
- Isopropylphenols (propofol)
- Barbiturates
- BZDs
- Phencyclidine (ketamine)
12
Q
Local anesthetics mechanism of action 1
A
- Local anesthetics inhibit voltage-gates Na channels to block Na conductance (either esters or amides: esters have 1 “i” in name, amides have 2)
- The agents must be inside the cell to achieve their effect, they also must be protonated (charged)
- How lipid soluble the agents are and their pKa directly affect how well they act
- The ideal drug is one w/ a pKa close to 7.4 (physiologic pH) so that 1/2 the drug is protonated and 1/2 isn’t
- Most local anesthetics have pKa higher than 7.4 and thus most of the drug is protonated (pH lower than pKa-> majority of compound is protonated)
- Therefore the drug is active but cannot get into the cell
13
Q
Local anesthetics mechanism of action 2
A
- Diffusion into the cell requires the non-protonated form, but activity requires the protonated form
- The lower the pKa the faster the onset of action b/c more of the drug will be not protonated and thus can pass thru the membrane
- To solve this inject bicarbonate in w/ the drug to increase the pH closer the the pKa so more of the drug is deprotonated and can pass into the cell
- But once in the cell the drug needs to be protonated so that it can be active
- Potency is not related to pKa (only time of onset is)
14
Q
Manifestation of inhibiting Na channels
A
- Interruption of transmission of motor, autonomic, and sensory impulses
- Results in paralysis, autonomic blockade, and sensory anesthesia
- Local anesthetics affect nerve fibers differently, according to their size, function, and presence or absence of myelin
- Large neurons have faster nerve conduction, and generally are myelinated
15
Q
Classification of nerve fibers
A
- Type A: myelinated, large, fast, many functions
- Type B: myelinated, small, medium speed, preganglionic (autonomic)
- Type C: unmyelinated, small, slow, dull pain, temp, touch
- Order of being affected by local anesthetics: C->B->A
- Small fibers get anesthetized first
