Week 7 Local and general anesthesia Flashcards
What are the two major types of local anesthetics?
- Ester: procaine, cocaine, chloroprocaine, tetracaine
2. Amides: lidocaine, bupivacaine (have “i” in 2nd syllable of name)
Where do local anesthetics work?
- at binding site on voltage gated Na+ channels in neuronal cell membranes, on nerve axons
- on inner side of membrane channel
- blockade of transmission of action potentials
How do local anesthetics work?
- uncharged (lipophilic) molecules have greater solubility across the plasma membrane
- charged molecule is active component to bind to sodium channel
- charged:uncharged ratio of drug is important
- pka>7.4, greater proportion of molecule in cationic/protonated form
- bicarbonate can be given to local anesthetic sln to change pH and pKa ratio. Increases amount of neutral form to enable local anesthetic molecule to cross the membrane.
- when pKa is high, there is delay in onset
How is local anesthetic nerve conduction blockage determined by fiber diameter, myelin, and function?
- nerve conduction is faster with greater nerve diameter and myelin
- need higher dose Cm (min concentration of local anesthetic) for greater nerve diameter
- sequence of clinical effects (which nerves affected first): Type C nerve fibers (dull pain, temp, touch), Type B (pre gang autonomic), Type C (proprioception, large and small motor, touch, pressure, muscle tone, pain, temp
What is the sequence of clinical effects following local anesthetic administration?
- Autonomic nervous system blockade: vasodilation
- sensory anesthesia: pain, temp, touch, pressure
- Skeletal muscle paralysis: motor blockade
What factors impact the systemic absorption during local infiltration and nerve plexus block when administrating local anesthesia?
- Dose
- physicochemical properties of drug
- use of epinephrine-cause vasoconstriction to localize and prevent migration of anesthetic molecules
- Site of injection and local tissue blood flow
- protein binding, the more lipid soluble the drug, the great the degree of protein binding
How are local anesthetics metabolized and eliminated?
- esters: hydrolysis in the plasma
- amide: hepatic metabolism by Cyt P450
What are some adverse effects of local anesthetics?
- CNS: circumoral numbness, facial tingling, restlessness, vertigo, tinnitis, slurred speech, seizures
- Cardiovascular system: hypotension, myocardial depression (from blockade of cardiac sodium ion channels)
- ECG changes-PR interval prolongation and widened QRS complex
How can CNS or CV toxicity due to local anesthetics be treated?
Lipid rescue=lipid emulsion administered which enables a “lipid sink” extraction of these lipophilic local anesthetic molecules to reduce the effective plasma concentration
What is the state of anesthesia?
The following occurs: -loss of consciousness -Amnesia -Analgesia -Immobility MAC=minium alveolar concentration, used to measure immobility
What are the anatomic sites of action of general anesthetics?
- brainstem-hypothalamic/thalamic network
- cerebral cortex
What are the molecular targets general anesthetics?
- inhibitory neurotransmitters: glycine, GABA–>potentiation of GABA A and glycine activity (Cl- conduction leading to hyper polarization)
- Excitatory neurotransmitters: NMDA–>inhibition of excitatory glutamate and NMDA receptors
- Inhibition of Na, Ca, and K+ channels in cell membranes
How do volatile anesthetics get to the brain?
- volatile anesthetics are liquid at room temp, vaporized in machine and carried by oxygen
- they diffuse through alveolar-arterial membrane (uptake)
- transported to brain in circulation
- brain, heart, lung, kidneys are vessel rich group due to high volume of blood to these organs
Describe the uptake of volatile anesthetics.
- uptake=movement of anesthetic molecules into the lung and will move into the lungs until the partial pressure in alveoli=that in blood
- insoluble agents-alveolar concentrations rise faster and induction faster since taken up by blood less readily
- Blood/gas coefficient: the lower the greater the anesthetic’s insolubility, the faster the onset
How is the potency of a general anesthetic measured?
by MAC=minimum alveolar concentration
-indicates the relative value/amount of anesthetic given
How are general anesthetics metabolized/eliminated?
Elimination though the lungs. reversal of Pbrain–>Parterial–>Palveoli. Metabolism is negligible.
What are the CNS effects of general anesthetics? general CV and pulmonary effects?
-CNS obtundation
-decreased cerebral metabolic rate (CMRO2)
-increase cerebral blood flow through vasodilation
-increased intracranial pressure with MAC>1
Also:
-decreased activity in the CV and pulmonary system
What is the mechanism of intravenous general anesthetics?
- alteration of synaptic function of GABA or NMDA neurotransmitters
e. g. - propofol decreases rate of GABA dissociation
- ketamine is a NMDA receptor antagonist
- etomidate has enhanced GABA binding to receptors
Describe the pharmacokinetics of intravenous anesthetics.
- Distribution:
- highly lipid soluble distribute to VRG (vessel rich group)
- degree of protein binding can decrease distribution - Redistribution:
- termination of clinical effect, movement of IV agent from site of action to less perfused peripheral compartments, followed by metabolism and elimination - Metabolism and Elimination
- Metabolized by liver enzymes and eliminated by kidneys
- measured by half lives
What are the effects of intravenous anesthetics on CNS, CV, and pulmonary systems?
- propofol, etomidate, barbiturates, and benzodiazepines are CNS, CV, and pulmonary depressants
- ketamine on CNS and CV organs are stimulatory
