AC: PDA 3 Exam 1 (Neuromuscular Blocking Agents, Anesthetics, Benzodiazepines)

How is the mechanism of transmission within a neuron?

electrical - action potential

How is the mechanism of transmission between neurons?

chemical - synaptic transmission

Which part of the neuron works by receiving input from other neurons by way of NTs?

dendrites

Which part of the neuron works by also receiving input and determining whether an action potential will occur based on all of the +/- inputs?

cell body

Which part of the neuron works by carrying the action potential and is all or none?

axon

Which part of the neuron works by action potential being translated into NT release?

nerve terminal

What does electrical transmission depend on based on structure?

protein molecules called ion channels

What are the 3 different types of membrane channels?

ligand binding, voltage, phosphorylation

What are the stages of electrical transmission within a neuron?

resting membrane potential, local potentials, threshold, AP

What are small, transient changes in membrane potential produced by some stimulus?

local potentials

What is it when a stimulus makes the membrane potential more positive and what does this result from and what is this described as when produced by a neurotransmitter at a synapse?

depolarization; opening of Na+ channels/influx of Na+; excitatory postsynaptic potential

What is it when a stimulus makes the membrane potential more negative, what does this result from, and what is it described as when produced by a neurotransmitter at a synapse?

hyperpolarization; opening of Cl- channels and influx of Cl- or opening of gated K+ channels and efflux of K+; inhibitory postsynaptic potential

What does the summation of local potentials at the axon hillock need to reach to meet threshold and for an action potential to be generated?

-50 mV

What happens at -50 mv or when threshold is reached and what phase of the AP is this?

large numbers of voltage-gated Na+ channels open causing the membrane potential to quickly rise to +4- mV; rising phase

What happens during AP when +40 mV is reached and what is this called?

Na+ channels close and can't reopen for a period of time; absolute refractory period

When absolute refractory period is occurring, what does the change in potential that occur in the rising phase do and what is this called?

opens voltage-gated K+ channels resulting in return of membrane potential to a level slightly more negative than RP - 70 mV; relative refractory period

What does Ca2+ do and cause at the synaptic terminal?

interacts with proteins on surface of synaptic vesicles and proteins inside the presynaptic neuron; causes exocytosis of neurotransmitters through fusion of synaptic vesicles to membrane

What are ionotropic receptors?

receptors that are ion channels

What are metabotropic receptors and what type of activity do they have?

receptors that are biochemically coupled to effectors and second messengers; enzymatic activity

What type of action do Gs coupled receptors have for the G-protein alpha subunit, what is the effector, what is the second messenger and what does this activate?

stimulatory; adenyl cyclase; increase cAMP; activate PKA

What do Gi coupled receptors do for the G-protein alpha subunit, what is the effector, what is the second messenger, and what altered activity occurs?

inhibits; adenylyl cylase; decrease cAMP; decreased PKA activity

What do Gq coupled receptors do for G-protein alpha subunit, what are the second messengers, and what is activated?

activated phospholipase C; DAG, IP3; Ca2+ release from ER

What is the second messenger and altered activity that occurs for Gi beta-gamma subunit signaling when K+ channels are the effector molecule?

none; opens channel - hyperpolarization

What is the second messenger and altered activity that occurs for Gi beta-gamma subunit signaling when voltage-sensitive Ca2+ channels are the effector molecule?

none; inhibits opening - decreases transmitter release

What is the second messenger and altered activity that occurs for G? beta-gamma subunit signaling when phosphoinositide 3 kinase is the effector molecule?

none; activates activity

What neurotransmitter do motor neurons release?

ACh

What type of channel are nicotinic receptors and what happens when ACh binds them?

ionotrophic ligand gated; Na+ channels open

What is AChEsterase and where is it found?

when ACh unbinds from NMJ it breaks it down right away

What are the two types of NMJ blockers?

non-depolarizing/competitive antagonists, depolarizing agents

What is the MOA of non-depolarizing NMJ blockers?

competes with ACh for binding of the nicotinic receptor on skeletal muscle

How can the action of non-depolarizing NMJ blockers be overcome?

increasing ACh with a cholinesterase inhibitor

How are non-depolarizing NMJ blockers classified?

DOA, chemical class

What are the two chemical classes of non-depolarizing NMJ blockers and what are the name endings for these two classes?

benzylisoquinolones - curiums, ammonio steroids - curoniums

What is a cholinesterase inhibitor and what type of drug will this reverse the effects of?

neostigmine; non-depolarizing NMJ

What is a Suggammadex?

drug that will reverse action of rocuronium and vecuronium

What do low doses of non-depolarizing NMJ blockers effect, what do moderate doses effect, and what do high doses effect? How is recovery from these doses?

small muscles of the fingers/eyes; arms, legs, neck, trunk; intercostal muscles and diaphragm; in reverse order

What are the isoquinoline derivative non-depolarizing agents?

atracurium, cistatracurium

Where are the longer acting non-depolarizing NMJ blockers eliminated by?

liver and/or kidney

What are the adverse effects of non-depolarizing NMJ blockers?

histamine release, ganglionic block, vagolytic

What are the results of histamine release from non-depolarizers?

bronchospasm, hypotension, bronchial, salivary, and GI secretions

What does the ganglionic block caused by non-depolarizers cause?

decreased BP due to decreased SNS

What does the vagolytic effect of non-depolarizers cause?

increased HR due to loss of vagal input to heart

What is the only non-depolarizer that can be vagolytic and cause tachycardia?

pancuronium

What is the depolarizing agent for NMJ blockers?

succinylcholine

What is the MOA of succinylcholine?

bind and stimulate nicotinic receptors at the NMJ similar to ACh

What is the relationship between succinylcholine and AChE?

the drug is resistant to the enzyme

What does the longer-lasting depolarization of succinylcholine cause?

flaccid paralysis

What is phase I paralysis caused by succinylcholine due to?

prolonged depolarization

What is phase 2 of paralysis caused by succinylcholine due to?

due to desensitization

What do sustained or repeated contractions of the muscle require?

series of APs and calcium pulses

When SCh is given, how does it produce a paralysis effect?

holds nicotinic receptors open, allowing Na+ to continue to flow into cell, but cell can't repolarize

Because of the repeated binding of SCh to receptors, what does this cause for muscle cells?

muscle cells don't repolarize because SCh is keeping receptor channel open and fast Na+ channels don't reset

What does prolonged depolarization of nicotinic receptors prevent during use of succinylcholine?

fast Na+ channels from resetting, keeping them in refractory conformation

What happens to Ca2+ when succinylcholine is used?

no AP, so Ca2+ stays stuck in SR

How long is the onset of action of SCh and how long is the duration?

30-60 secs; 5-10 mins

What eventually breaks SCh down and how?

plasma butyrylcholinesterase hydrolzes to succinic acid and choline

What are the uses of SCh?

brief procedures, long procedures if followed by longer acting agent

Before SCh causes paralysis, what does it cause? What type of side effect does this lead to for 1-2 days?

muscle fasciculation; soreness

Are the effects of SCh reversible?

no

What type of patients will see a long duration of action for SCh?

pts with defective plasma cholinesterase

What does prolonged use of SCh cause?

K+ release from muscle

What is a side effect of SCh due to muscle contraction and rigidity?

malignant hyperthermia

How are the structures of NMJ blockers?

highly polar with 1 or 2 quaternary amines

Are NMJ blockers orally active and are they water soluble? Do they penetrate the BBB? How are they usually admined?

no; yes; no; IV

Why might a muscarinic antagonist also be needed after use of NMJ blockers?

effects on muscarinic receptors

What does the use of an AChEI do to succinylcholine and why?

prolongs the actions of SCh; block SCh breakdown and by increasing the depolarization block will increase agonist

If using inhaled anesthetics to produce muscle relaxation, what do we do to the dose of NMJ blockers?

reduce dose

Why is there a drug interaction between aminoglycosides and tetracyclines with NMJ blockers and what may we need to do to the dose of NMJ blockers if given with these ABX?

produce neuromusclar blockade by inhibiting release of ACh or chelating Ca2+; reduce

What is the MOA of Botox?

inhibits vesicular release of ACh

What are the ideal characteristics of general anesthetics?

unconsciousness, analgesia, amnesia, skeletal muscle relaxation, suppression of reflexes

What are some examples of inhaled anesthetics and what are these used for?

ether, nitrous oxide, halthane, etc.; major surgery

What are some examples of IV anesthetics and what are these used for?

barbiturates, BZD, opioids; outpatient procedures/induction

Which stage of anesthesia is the patient conscious but drowsy and their response to pain is reduced?

Stage 1 - analgesia

Which stage of anesthesia is loss of consciousness, does not respond to non-painful stimuli, coughing/gagging reflexes are intact/exaggerated, the patient may move, talk, vomit, and breath irregularly?

stage II - excitement

Which stage of anesthesia is respiration becoming regular and then shallow at deeper levels and autonomic reflexes to incision are reduced and skeletal muscles relax?

Stage III - surgical anesthesia

Which stage of anesthesia is vasomotor tone and control stopped along with respiration where death can occur within minutes?

Stage IV - medullary depression

Which stage of anesthesia do we want to minimize and which do we want to avoid?

II; IV

The higher the partition coefficient or the more lipophilic an inhaled anesthetic is, the more what it is?

potent

What is the GABA-A receptor and what is it opened by?

ligand gated ion channel; GABA

When the GABA-A receptor opens, what occurs and what type of membrane potential does this cause?

Cl- influx; hyperpolarized

When an anesthetic is present, to gain a level of membrane current takes less of what at the GABA-A receptor and what does this mean?

takes less GABA; GA potentiate the affects of GABA at that receptor

What does the depth of anesthesia vary with for inhaled anesthetics?

concentration in the brain

What is the step by step process of where inhaled anesthetic goes in the body once breathed in?

alveoli --> blood --> brain

What type of gradient does inhaled anesthetic travel down?

partial pressure gradient

What are the 4 important factors to consider for administration of inhaled anesthetics?

conc. of inspired gas, pulmonary ventilation, solubility in blood, loss of anesthetic to tissues

The faster a person breaths in inhaled anesthetic, what occurs? Does this affect the depth of anesthesia?

faster induction; no

What must happen in the blood to general anesthetics before they can distribute to the brain?

blood must be saturated

How do well-perfused tissues like the brain reach equilibrium as compared to less well-perfused tissues like the fat?

faster

How are inhaled anesthetics primarily removed from the body and what is the minor way this occurs?

ventilation of anesthetic-free air; metabolism/urinary excretion

Which inhaled anesthetic has 20% of its elimination through metabolism?

halothane

What describes the ability of the anesthetic to dissolve in the blood and is a ratio of concentration when partial pressures are equal between alveoli and blood?

blood: gas partition coefficient

What is the main determinant of induction time for inhaled anesthetics?

blood: gas partition coefficient

As the blood: gas coefficient goes up, what happens to induction time and why?

increases; implies the drug is more soluble in the blood and takes longer to reach PP

If a drug has a low blood:gas coefficient, what does this mean about it?

low solubility in blood

What is the concentration at which 50% of pts don't move in response to noxious stimulation?

minimum alveolar concentration - MAC

What is the main determinant of recovery from inhaled anesthetics?

brain: blood partition coefficient

What describes anesthetics ability to dissolve in the brain and is a ratio of concentrations when PP are equal between blood and brain?

brain: blood PC

Drugs that are poorly soluble in the brain or have a low brain:blood have what type of recovery?

fast

Which inhale anesthetic is potent with a good margin of safety but is flammable, explosive, unplesant induction, produces secretions due to irritation, and causes N/V during recovery?

ethyl ether

Which inhaled anesthetic is potent, relaxes skeletal muscle, is non-flammable, non-irritating, has narrow safety margin, liver/kidney toxicity, and causes cardiac arrest and arrhythmias?

chloroform