NCE part 2 Flashcards
Type A nerve fibers - describe their myelination
heavy
Type B nerve fiber describe their myelination
light myelination
type c nerve fibers- describe their myelination
no myelination
what is type A alpha nerve fiber responsible for
proprioception
motor
what is type a gamma nerve fiber responsible for
muscle spindles
gaMMa - “M’s for Muscles”
type a delta nerve fiber is responsible for
pain
temperature
“DELToid Pain”
type a beta nerve fibers is responsible for
touch
pressure
“make a BET!” –>and slam your hand down!!
A- gamma nerve is responsible for
Muscle Spindles - think muscle tone
A-delta nerve fibers are responsible for :
Pain and Temperature
Which nerve fibers are preganglionic autonomic ?
Type B nerve fibers
C fibers are responsible for 1) _____via the dorsal root and are _______
Pain via dorsal root
and are
Postganglionic Sympathetic fibers
Which fiber is responsible for pain via the dorsal root ?
C fibers
Those are Postganglionic sympathetic nerve fibers .
C fibers
1 cause of methemoglobinemia
Benzocaine
Describe Zero Order kinetics . What are drug examples ?
1)Constant AMOUNT of drug eliminated per unit of time
2) Metabolic pathways are saturated
Drug ex: Salicylate, theophylline , phenytoin , and ethanol .
What is First Order kinetics? Which examples of drugs ?
1) Constant FRACTION of drug eliminated per unit of time
2) Elimination proportionate to amount of drug in the body
Drug ex: Most drugs are first order kinetics – SUX
Volume distribution
Amount of drug in body divided by amount in the in the blood
drug in body/drug in blood
Large Vd= lipid solubility
Small Vd= lipid insolubility
What is clearance ?
Complete drug removal from a volume of plasma per unit of time.
Elimination half time is : Time to eliminate 100% of drug from the plasma . True or False
False !
50% ( half)
4 half lives =
94% complete
Context - Sensitive Half-time :
Time needed for the plasma drug concentration to decrease by 50% (or any other percentage ) AFTER DISCONTINUING a continuous infusion with a specific duration .
Context = infusion duration
It considers combined effect of : distribution + metabolism+ duration of a continuous IV administration on the drug’s pharmacokinetics
A drug that is eliminated by first order kinetics has a half-life of elimination of 6 hours. How much drug remains after 18 hours if 10mg is administered
1.25mg
160 mg of drug is administered and 20 mg remains 30 hours later. How much drug is lost in the next 20 hours if the drug is eliminated by first order kinetics:
15 mg
at third 1/2Life = 20mg
4th = 20/2 = 10mg
5th = 10/2 = 5mg
in the next 20 hours you add the 4th and 5th 1/2 lives b/c they’re each 10 hours = this gives you 15mg of drug lost in the “next 20 hours”
mu2
Analgesia (Spinal)
Respiratory depression(decrease sensitivity of resp. center to CO2)
Addiction
Constipation (marked) decrease motility and tone of GI muscles
increase CSF pressure (cerebral edema) C/I in head injury
kappa
Analgesia (Spinal & Supraspinal)
Dysphoria
Low abuse
Potential
Miosis
Diuresis
delta
Analgesia (Spinal & Supraspinal)
Respiratory depression
Physical dependence
Constipation (mild)
what type of compound is neuromuscular blocker
quaternary ammonium compound
all neuromuscular blockers are structurally related to
acetylcholine
T?F
majority of NMBD are synthetic alkaloids
true
NMBD classified by chemical class:
Steroidal
Benzylisoquinoinium
Other
H-2 Blockers: name 3 of them
Cimetidine
Ranitidine
Famotidine
H-2 Blockers moa
H-2 Blockers: Blocks acid stimulating effects of histamine and ACh
Anti-Muscarinic Effect:
Scopolamine is a high affinity muscarinic antagonist
Substance P
Neurokinin 1 Antagonists:
substance p
Aprepitant: Only PO
Fosprepitant: IV is available
** fun fact: Fosaprepitant is an antiemetic drug, administered intravenously. It is a prodrug of aprepitant
name Serotonin Antagonists:
we use
ondanestron
Anti-Histaminergic:
Diphenhydramine: Both antihistamine and anticholinergic effects:
Anti-Cholinergic:
what may be useful in neuraxial induced n/v
Glycopyrrolate may be useful in neuraxial induced N/V
Antidopaminergics:
Butyrophenones: Droperidol
Phenothiazines: Prochlorperazine
Benzamines: Metoclopramide
Chemotactic Trigger Zone (CTZ)- where is this found
4th ventricle of the brain (located on the floor)
name the 5 receptors found in the CTZ that cause n/v
Dopaminergic Serotonergic Histaminic Muscarinic Substance P
what MAC is an HPV inhibitor
1mac of sevo, iso, des
what is nitrous affects on HPV
inhibits HPV
what is the effect of thoracic epidural on HPV
little or no effect
when does thoracic epidural anesthesia have an indirect effect on 02
if hypotension is allowed and a fall in co
what is the IV anesthetic effect on HPV
little or no effect
volatile anesthetics inhibit HPV in dose dependent fashion. what is the greatest to least for volatile anesthetics
halothane>enflurane>isoflurane/desflurane/sevoflurane
older volatiles were potent HPV inhibitors contributing to high incidence of hypoxemia during OLV in the 60’s and 70’s
just an FYI- nagelhout says its because they were using 2 mac of halothane
explain HPV
increase in pulmonary vascular resistance in atelectatic lung area. HPV optimizes overall gas exchange by shifting blood flow to better ventilated areas of the lung
what drug has been demonstrated to enhance effects of NO and may blunt rebound pulmonary pressure that occur during weaning off of inhaled NO
sildenafil
sildenafil and tadalafil have shown benefits in what chronic condition but not approved for these settings
chronic pulmonary arterial HTN
phosphodiesterase 5- (PDE5)- do they have higher expression in pulmonary circulation or systemic circulation
pulmonary circulation
due to phosphodiesterase 5 higher expression in pulmonary circulation do they have higher selective effect on PVR or SVR
PVR
phosphodiesterase inhibitors prevent the degradation of what two things
cGMP and cAMP
when phosphodiesterase inhibitors inhibit the degradation of cGMP and cAMP what activates this two things
NO
so when NO activates cGMP and cAMP what does that lead to
vasodilation
the vasodilation that results when cGMP and cAMP is activated by NO is through activation of
protein kinases and reduction of cytosolic calcium
what type of of phosphodiesterase enzyme inhibitor is milrinone
adenosine 3,5-cAMP selective phosphodiesterase
nebulized milrinone leads to a reduction in
relative reduction in PVR compared to SVR
Calcium Channel Blockers are particularly successful in treating hypertension in the what three groups
elderly
african american
salt sensitive patients
Median Nerve Injury
Ape Hand (unable to oppose Thumb)
Ulnar Nerve Injury
claw hand
Radial Nerve Injury
wrist drop
Axillary Nerve Injury
Inability to abduct arm
Musculocutaneous Nerve Injury
Inability to Flex Forearm
Intravascular infusion of which of the following substances would be most effective in promoting the osmotic movement of water into the circulation from the extracellular space A.) NaCl B.) Mannitol C.) Dextrose D.) Albumin
albumin
The most potent inhalational anesthetics have A.) low blood solubility B.) High blood solubility C.) Low lipid solubility D.) High lipid solubility
High lipid solubility
Build up of inhalational anesthetic in the brain is fastest for an agent that has: A.) low blood solubility B.) High blood solubility C.) Low lipid solubility D.) High lipid solubility
A.) low blood solubility
How many mg are there in 10 mL of a 4% solution of cocaine
400 mg
4% = 40 mg x 10 cc = 400
K+ Sparing: works where in the kidney tubes
Distal part of distal convoluted tubule
Collecting ducts/tubules
Carbonic Anhydrase inhibitors: work where in the kidneys
Brush border of proximal tubule
Loop: where do they work
loop of henle
thiazide: work where
Proximal Part of distal convoluted tubule
Osmotic: work where in the kidney
Proximal convoluted tubule
descending limb of loop of henle
distal part of distal convoluted tubule
collecting ducts/tubules
plasma cholinesterase production is the work of how many genes?
2 genes
what does Dibucaine number of 80 represent
DN = 80 = present on both genes = homozygous (plasma cholinesterase)= Normal
dibucaine number of 40-60 represent
DN = 40-60 = only present on one gene = heterozygous (1 in 480) produce 50% of enzyme
dibucaine number of 20
DN = 20 = missing on both genes = homozygous (atypical plasma cholinesterase) (1in 3200).
Succinylcholine Disadvantages (6)
Myalgia
Hyperkalemia
Cardiac dysrhythmias
MH
Phase II Block: Resembles NMDR (>4 mg/kg)
Second Dose Effect: Brady after close second dose secondary to succinylmonocholine
Drugs that interfere with Plasma Cholinesterase:
5
- Organophosphate exposure
- Anticholinesterase meds
- Metoclopramide
- MAOI
- Oral contraceptives used long-term
why is succinylcholine dose 2x ed95
because of its rapid hydrolysis by plasma cholinesterase
is succs competitive with Ach
no.
are NMDR competitive with ACH
Yes
name 5 conditions that interfere with plasma cholinesterase
Liver disease (severe) Chronic renal failure Starvation Dialysis (soon after) Infants (50%) by age 6 (70%), puberty (100%)
in context of neuromuscular blockers- what is ED50 and ED 95
Measured by the amount of drug necessary to decrease the height of the baseline twitch by 50% and 95%
How do we compare the potency of NMDR?
Potency and onset have an inverse relation
low potency = Higher rate of onset
high potency = lower rate of onset
low potency NMBD
rapid onset
high potency NMBD
slow onset
the onset of action of NMBD is inversely proportional to what
potency
Molar potency is highly predictive of a dugs time to onset of effect. what drug is the exception to this rule
atracurium
molar potency is expressed in what units?
Why?
micromoles/kg
molecules of drug are VARIABLE
number of nicotinic receptors are FIXED
therefore, the fewer the number of molecules it takes (per kg of body wt) to saturate the receptor, the greater the affinity the drug has (the greater the potency) .
L - does that work for you? or want more? :D
The rationale for expressing potency in moles per kilogram is…[because] ultimately, we have a variable number of molecules chasing a fixed number of nicotinic receptors. The fewer molecules it takes (per kilogram of body weight) to achieve a given degree of receptor occupancy, the greater the affinity the drug has for the receptor. This is best expressed in micromoles per kilogram rather than in milligrams per kilogram.
what is the issues with hyperparathyroidism and NMBD
hypercalcemia is associated with decreased sensitivity to atracurium and thus a short duration of neuromuscular blockade
Muscle-nerve models have shown hypercalcemia to decrease sensitivity to tubocurarine and pancuronium
why does chronic use of anticonvulsant therapy need an increase dose to NMBD to achieve blockage.
can be attributed to
- increased clearance.
- increased binding of the nueuormuscular blockers to alpha 1 acid glycoproteins
- and/or up regulation of neuromuscular acetylcholine receptors.
hypothermia or magnesium sulfate do what to NMBD
potentiates blockade
antidysrhythmics such as quinidine do what to NMBD
potentiate NMBD
LA given in large doses do what do NMBD
potentiate it
high magnesium concentrations do what to calcium channel at the presynaptic nerve terminals
inhibit release of acetylcholine
antibiotics can potentiate neuromuscular blockers name 5 of them
aminoglycosides polymyxin lincomycin clindamycin tetracycline
what is the moa of how antibiotics potentiate neuromuscular blockers
inhibit the prejunctional release of acetylcholine and
depresses post junctional nicotinic acetylcholine receptor sensitivity to acetylcholine.
Inhalation anesthetics potentiate the neuromuscular blocking effect of NMBD
what is the order
DES > SEVO > ISO > Halothane > Nitrous Oxide, barbiturate, or propofol
3 Mechanisms for inhalation potentiation of NMBD:
Central effect on alpha motoneurons and interneruonal synapses
Inhibition of postsynaptic nicotinic acetylcholine receptors
Augmentation of antagonist’s affinity at the receptor site
roc is how many times less potent than vec
6times
roc eliminated by and excreted in
eliminated by liver excreted in bile
roc remains stable for how many days at room temperature
60
vecuronium is metabolized to
3-OH, 17-OH, 3,17-di-OH
why does vecuronium have prolonged neuromuscular blockade with prolonged admnistration
3-oh has 80% the neuromuscular blocking potency and this metabolite will build up and increase the blocking potency of vec
duration of vecuronium relies on liver or renal function more
liver function more than renal function
pancuronium is it long or short acting. potent or not
potent long acting
pancuronium has what two special properties
Vagolytic and butyrylcholinesterase inhibiting properties
how long is pancuronium stable for at room temps
6mo
accumulation of 3-oh metabolite is responsible for pancuroniums what
prolongation of the duration of action
what percent of pancuronium is eliminated by kidneys
40-60%
what is the only currently available short acting NMBD
Mivacurium
mivacurium is metabolized by
Metabolized by butylcholinesterase at about 70-88% the rate of Sch to a monoester
what can be considered problematic if we push mivacurium too fast
May produce histamine release especially if given rapidly
name the isomer of astracurium
cisatracurium
how is cisatracurium eliminated
hoffman elimination to laudanosine and a mono quaternary alcohol metabolite
what percent is hoffman elimination
other ogans
renal
77%
23%
16%
how much more potent is cisatracurium than atracurium
4-5x
what is the relationship to aludanosine
5 times less laudanosine is produced and is thought one of no clinical consequence
does cisatracurium produce histamine release
no
Tubocurarine
Tubocurarine: Monoquarternary, long acting No active metabolism Excreted unchanged in urine; liver is secondary Not suitable for renal or liver failure patients Onset slow Duration is long Recovery slow Intubating dose 0.5 – 0.6 mg/kg Maintenance dose are 0.1 – 0.2 mg/kg
Atracurium
Atracurium
Racemic mixture of 10 stereoisomers
Isomers are separated into 3 geometrical isomer groups that are designated cis-cis, cis-trans, and trans-trans
Designed to undergo spontaneous degradation at physiologic temp and pH by Hofmann elimination yielding a laudanosine (tertiary amine) and a monoquaternary acrylate metabolite
Can undergo ester hydrolysis
Hoffmann elimination fragments atricurium to laudanosine and a monoquaternary acrylate
Laudanosine depends on the liver for clearance with ~70% excreted in bile with remainder in the urine
slide 15&
16
tetracycline potentiates NMBD by exhibiting ONLY what activity
by depressing POST junctional nicotinic acetylcholine receptor sensitivity to acetylcholine ONLY
no inhibition of prejunctional release
