NCE Pharm review 1 and 2 power points Flashcards
The two volatile agents that decrease Systemic Vascular Resistance more than the others?
Iso
Des
Which VA causes hypothermia because it suppresses the hypothalamic temperature regulators?
Isoflurane
What four things do VA change in relation to blood flow and the brain?
Dilate cerebral vessels
Increase cerebral blood flow
Increase cerebral blood flow and ICP
Decreases neuronal function and cerebral metabolism
The increase in ICP by Iso can be negated by what?
hyperventilation
Which VA is the least likely to dangerously increase ICP if keep the patient moderately hypocapnic?
Iso
Which VA has a slightly higher incidence of causing a cough reflex during maintenance when used with a LMA?
Isoflurane
How much MAC of a VA will completely block the ventilatory response to hypoxemia. Therefore, hypoxemia will not stimulate ventilation when using a volatile agent?
0.1 MAC
Hypoxic Pulmonary Vasoconstriction HPV is inhibited by a high concentration of volatile, what is the concentration?
1-1.5 or higher MAC
What volatile is considered completely halogenated with fluorine?
Des
Volatile agents that suppress ventilation the most?
The least?
Most: Des, Enflurane
Least: Halothane
What volatile agents most depresses the baroreceptor reflex?
Which one does it the least?
Most depress : Halothane and Sevo: No increase in HR even with decreases in blood pressure
Least depress: Iso and Des: HR increases as a reflex to decrease in blood pressure
Acute ETOH intoxication effect on MAC ?
decreases
Rank opioids most lipid soluble to least lipid soluble
Meperidine Remifentanil Morphine Fentanyl Sufentanil alfentanil
Sufentanil »_space; fentanyl»_space;> alfentanil»_space;> meperidine > remifentanil > morphine
What receptors do spinal opioids work on?
Primarily Mu-2 but work on mu-1, kappa, and delta to produce supraspinal analgesia
Stimulation of mu-1 receptors cause what response?
Spinal and supraspinal analagesia Euphoria Miosis Bradycardia Hypothermia Urinary retention pruritus
Mu-1 have a high or low abuse potential?
Low abuse potential
Opioid can cause nausea and vomiting by?
Stimulation of CTZ of the forth ventricle (floor). The triggered CTZ activates vomiting center near the brain stem.
Which opioid is not metabolized by the liver?
Remifentanil and is metabolized by nonspecific esterases in the blood stream.
Agonist/antagonist opioids work on what receptor(s) for therapeutic effect?
Primarily Kappa and also on delta
Naloxone reverses what actions of opioids?
Pruritus
Urinary retention
N/V
Higher doses of naloxone are required to reverse what opioid issue?
Reverse profound sedation and respiratory depression
Does morphine produce arterial or venous dilation?
Both due to histamine release
What two opioids cause histamine release?
Morphine and Meperidine
There are 3 CV actions that may cause a decrease in BP in an anesthetized patient given a high dose of fentanyl?
Decrease SVR (dilate arterial vessels)
Decrease venous return (dilate venous capacitance vessels)
Decrease in HR
How are ester locals “metabolized”?
Hydrolyzed by plasma and tissue cholinesterase
PABA is excreted where?
PABA is excreted unchanged in the urine
True or False?
Cross reactions between esters and amides?
No cross reactions
How could an ester be prolonged?
Prolonged in plasma cholinesterase deficiency
What does the PKa of a LA mean?
when 50% is ionized and 50% is unionized
lipid solubility of a LA parallels what?
potency of the LA
Protein binding of a LA parallels what?
duration of action of the LA
What is the short acting LA and what is the long acting LA?
Short : procaine
Long: bupivacaine and tetracaine
What is the progression of LA blockade? (what do you lose first to last)
Autonomic Temperature Pain Touch Pressure Motor Vibrate/Proprioception
Treatment of LA toxicity?
20% Intralipid:
1.5 mL/kg over 1 minute
Continuous infusion of 0.25 mL/Kg until hemodynamically stable
Limit: 10 mL/Kg over 30 minutes
When administered alone does Nitrous cause hypotension?
No, but instead causes cutaneous vasoconstriction and increased SVR.
When administered alone what will Nitrous cause?
Nitrous will cause an increase in cardiac output when administered alone.
(also cutaneous vasoconstriction and increased SVR)
What is the dose limit of exogenous EPI if using Iso, Des, or Sevo?
5-6 mcg/kg
Fluid replacement for surgical trauma?
Minimal – 5 ml/kg/hour
Moderate - 6 ml/kg/hour
Extensive – 8 ml/kg/hour
Goal directed fluid therapy is guided by UOP, what is the amount of UOP you want per hour?
0.5ml/kg/hour
hemodynamically stable
Nerve fibers, tell me about type A, B, and C in relation to myelination?
Type A = Heavy myelination
Type B = Light myelination
Type C = No myelination
Type A nerve fibers have alpha, beta, gamma, and delta fiber subtypes, what are the reactions associated with each subtype?
Alpha: Proprioception, motor
Beta: Touch, pressure
Gamma: Muscles spindles
Delta: Pain, temperature
Type B nerve fibers, are they pre or post ganglionic autonomic?
preganglionic autonomic
Type C nerve fibers details?
Dorsal Root: Pain
Sympathetic: Postganglionic
Which ester local anesthetic is the #1 cause of methemoglobinemia?
Benzocaine
explain zero order pharmacokinetics?
What drugs follow this order?
Constant amount of drug is eliminated per unit of time
Metabolic pathways are considered saturated
Drug Examples: salicylates, theophylline, phenytoin, and ethanol
First order pharmacokinetics explain what you know?
Constant fraction of drug is eliminate per unit of time
Elimination rate is proportionated to the amount of drug in the body
Most drugs are eliminated in this manner
What is volume of distribution?
Amount of the drug in body divided by the amount in the blood
Small volume of distribution would tell you what about a drug?
lipid insolubility
Large Vd would tell you what about a drug?
lipid solubility (soluble)
Clearance is defined as?
Complete drug removal from a volume of plasma per unit of time
elimination half time is defined as?
Time to eliminate 50% of drug from the PLASMA
4 half lives = 94% complete
define context sensitive half time?
Describes the time necessary for the plasma drug concentration to decreases by 50% (or any other percentage) after discontinuing a continuous infusion of a specific duration (context refers to infusion duration). It considers the combined effect of distribution and metabolism as well as duration of continuous IV administration on drug pharmacokinetics
The relationship between Volume of Distribution, Clearance, and Half-Life?
T1/2 = 0.693 x Vd/CL
The relationship between Volume of Distribution, Clearance, and Half-Life?
T1/2 = 0.693 x Vd/CL
what is under the division sign is opposite to what is on the other side of the = sign
when half life is increased what else increases?
volume of distribution is increased
A drug follows first order kinetics and has a half life elimination of 6 hours. How much drug remains after 18 hours if 10mg was administered?
1.25mg after 18 hours.
(10mg to start, after 6 hours you have half which is 5mg, then after 6 more hours you have 2.5mg left, then after 6 more hours which = 18 total hours you have 1.25mg left)
most drugs are eliminated by what order of kinetics?
first order kinetics
major negative effects of mu-2 receptor?
Analgesia (Spinal)
Respiratory depression(decreased sensitivity of resp. center to CO2)
Addiction
Constipation (marked) decreased motility and tone of GI muscles
increased CSF pressure (cerebral edema) C/I in head injury
In the resting state is the acetylcholine receptor open or closed?
closed
In the resting state are the acetylcholine receptors open or closed?
closed
what will open the channel at the neuromuscular junction?
Simultaneous binding of 2 acetylcholine molecules to the alpha subunits initiates conformational changes that open the channel
if a single molecule of a non-depolarizing neuromuscular blocker (a competitive antagonist) binds to one alpha subunit at the neuromuscular channel what happens?
produces neuromuscular block
how does Sch work?
Sch produces a prolonged depolarization of the endplate region that results in desensitization of nicotinic acetylcholine receptors; inactivation of voltage gated sodium channels at the neuromuscular junction and increase in potassium permeability in the surrounding membrane. Thus producing the failure of the action potential generation due to membrane hyperpolarization and a block ensues.
what is true cholinesterase?
Acetylcholinesterase
what is responsible for the rapid hydrolysis of released acetylcholine to acetic acid and choline?
acetylcholinesterase
other names for plasma cholinesterase?
where is it synthesized?
what is it’s function?
Butyrylcholinesterase (plasma cholinesterase or pseudocholinesterase) is synthesized in the liver. It catalyzes (causes or accelerates) the hydrolysis of succinylcholine which occurs mainly in the plasma.
all NMB are what type of compounds and structurally related to what
All neuromuscular blockers are QUATERNARY AMMONIUM compounds and are structurally related to acetylcholine.
Majority of NMB are synthetic alkaloids, what is the exception?
Exception is tubocurarine which is extracted from and Amazonian vine. It is cheaper to isolate from this plant than to synthesized.
what are the two classes of NMBD?
Benzylisoquinolinium
Steroidals
list the benzyl lisoquinoliniums
Cisatracurium
atracurium
Tubocurarine
Mivacurium
Tell me everything you know about Nimbex? isomer of? what does it metabolize to? what % is cleared renally? potency compared to atricurium? does it cause histamine release?
Isomer of atracurium
Hoffman elimination to laudanosine and a monoquaternary alcohol metabolite
No ester hydrolysis of parent molecule
Hoffman is ~ 77% of clearance
23% is cleared by other organs with 16% being renal
4-5 times as potent as atricurium
5 times less laudanosine is produced than atricurium and is thought to be of no clinical consequence
Does not cause histamine release like atracurium if given in clinical dose range
The only currently available short acting NMBD that is not available in the US?
Mivacurium
Significant details about Pancuronium (steroidal compound)
potent long acting
at room temp. remains stable for 6 months.
Vagolytic and butyrylcholinesterase inhibiting properties
~40-60% eliminated by kidneys and 11% in bile
Vecuronium:
duration of action?
elimination?
liver or renal function more relied on?
metabolites and prolonged blockade?
intermediate duration of action
Principle elimination is liver with renal accounting for about 30%
30-40% cleared in bile
Duration relies on liver function more so than renal function
3-OH has 80% the neuromuscular blocking potency of Vecuronium and with prolonged administration this metabolite may contribute to prolonged neuromuscular blockade.
Rocuronium:
onset/ duration of action?
more or less potent than vecuronium?
eliminated by?
stable for how long at room temp?
onset is fast, duration is intermediate acting.
6 times less potent than Vec
Primarily eliminated by liver and excreted in bile
stable for 60 days at room temperature
what does ED50 or ED95 mean in relation to NMBD?
Expressed in terms of dose response relationship
50% depression of twitch height ED50 and 95% would be ED95
Inhalation anesthetics potentiate the neuromuscular blocking effect of NMBD, what is the order from most to least?
DES > SEVO > ISO > Halothane > Nitrous Oxide, barbiturate, or propofol
What is the mechanism for potentiation of NMBD by VA?
Central effect on alpha motoneurons and interneruonal synapses
Inhibition of postsynaptic nicotinic acetylcholine receptors
Augmentation of antagonist’s affinity at the receptor site
Certain antibiotics can potentiate NMB…. name some?
Aminoglycoside
Polymyxins
Lincomycine
Clindamycin
Which antibiotic exhibits post junctional activity only on the NMJ? (potentiates NMB)
Tetracycline
how do antibiotics that potentiate NMB do so?
All inhibit the prejunctional release of acetylcholine and also depress postjunctional nicotinic acetylcholine receptor sensitivity to acetylcholine.
what does hypothermia or magnesium sulfate do to NMBD?
Potentiates blockade
How does magnesium potentiate NMBD?
High magnesium concentrations inhibit calcium channels at the presynaptic nerve terminals that trigger the release of acetylcholine
Can LA potentiate NMBD?
ONLY in large doses, at clinical amounts it is not significant
Which antidysrhythmic potentiates NMBD?
quinidine
factors decreasing potency of NMBD?
hyperparathyroidism (atracurium)
Hypercalcemia for tubocuraine and pancuronium
potency of NMBD… is inversely proportional to what?
Onset of action is inversely proportional to potency of NMBD
Low potency = rapid onset
High potency = slow onset
Molar potency is highly predictive of a dugs time to onset of effect. Which NMB is the exception to the rule?
Atracurium
potency of NMBD is expressed in what unit?
(micro)moles per kilogram and NOT mg/kg
How do we compare the potency of NMBD?
ED50 and ED95
Measured by the amount of drug necessary to decrease the height of the baseline twitch by 50% and 95%
ALL NMBD are competitive with Ach except for?
Sch
why does Sch need 2 x the ED95 for dosing?
because of its rapid hydrolysis by plasma cholinesterase.
Conditions that interfere with Plasma Cholinesterase?
Liver disease (severe)
Chronic renal failure
Starvation
Dialysis (soon after)
Infants (50%) by age 6 (70%), puberty (100%)
Drugs that interfere with Plasma Cholinesterase?
Organophosphate exposure
Anticholinesterase meds
Metoclopramide
MAOI
Oral contraceptives used long-term
Succinylcholine Disadvantages?
Myalgia
Hyperkalemia
Cardiac dysrhythmias
MH
Phase II Block: Resembles NMDR (>4 mg/kg)
Second Dose Effect: Brady after a 2nd dose within 5 min. can also cause asystole
explain dibucaine number and what a dibucaine number of 80, 40-60, and 20 means?
Plasma cholinesterase production is the work of 2 genes
DN = 80 = present on both genes = homozygous (plasma cholinesterase)= Normal
DN = 40-60 = only present on one gene = heterozygous (1 in 480) produce 50% of enzyme
DN = 20 = missing on both genes = homozygous (atypical plasma cholinesterase) (1in 3200).
where do osmotic diuretics work? (4 locations)
Proximal convoluted tubule
Descending limb of loop of Henle
Distal part of distal convoluted tubule
Collecting ducts/tubules
where do loop diuretics work?
loop of henle
where do thiazide diuretics work?
Proximal Part of distal convoluted tubule
where do potassium sparing diuretics work?
Distal part of distal convoluted tubule
Collecting ducts/tubules
where do carbonic anhydrase inhibitors work?
Brush border of proximal tubule
How many mg are there in 10 mL of a 4% solution of cocaine?
400mg
4% is 40mg (0.4% would be 4mg) move the decimal place once to the right.
Thus 40mg per cc, and it is 10 cc so that would be 40mg x 10 = 400mg
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
The most potent inhalational anesthetics have A.) low blood solubility B.) High blood solubility C.) Low lipid solubility D.) High lipid solubility
D) high lipid solubility
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
D) Albumin
what type of nerve injury will cause wrist drop?
radial nerve injury
what type of nerve injury will cause ape hand?
median nerve injury
what type of nerve injury will cause claw hand?
ulnar nerve injury
what type of nerve injury will cause inability to flex the forearm?
musculocutaneous nerve injury
what type of nerve injury will cause an inability to ABDuct the arm?
axillary nerve injury
Calcium Channel Blockers are particularly successful in treating hypertension in what three populations?
elderly
African Americans
salt sensitive patients
what type of drug is milrinone?
an adenosine-3’, 5’- cAMP-selective phosphodiesterase enzyme (PDE) inhibitor
which drug is described: selectively dilates the pulmonary vasculature without systemic effects.
milrinone
what does nebulized milrinone reduce?
PVR compared to SVR
How do phosphodiesterase inhibitors work?
prevent the degradation of cGMP and cAMP which are activated by NO and are intermediaries in a pathway that leads to vasodilation.
the vasodilation caused by PDE inhibitors is via what?
via the activation of protein kinases, and reduction in cytosolic calcium.
where do PDE5 inhibitors work?
higher expression in pulmonary circulation versus the systemic circulation. Thus PDE5 inhibitors have a relative selective effect on PVR as opposed to SVR.
what two drugs have shown benefits in chronic Pulmonary Arterial Hptn (PAH) in prospective controlled trials (but most studies have been case studies and small cohort studies). These drugs have not been approved for these acute settings?
Sildenafil and Tadalafil
which drug has been demonstrated to enhance effects of NO and may blunt rebound pulmonary pressure that occur during weaning off of inhaled NO?
sildenafil
Explain Hypoxic Pulmonary Vasoconstriction (HPV)?
an increase in pulmonary vascular resistance in atelectatic lung areas. HPV optimizes overall gas exchange by shifting blood flow to better ventilated areas of the lung.
True or False:
IV anesthetic agents have significant effect on HPV?
False, they have little effect.
What drugs DO inhibit HPV in a dose dependent fashion?
and what would be the order from greatest to lest?
VA
halothane>enflurane>isoflurane/desflurane/sevoflurane
What is avoided during thoracic anesthesia bc it inhibits HPV?
Nitrous
what vasodilators decrease the action of HPV?
NTG and Nitroprusside
What are the the three VA that at 1 MAC are weak HPV inhibitors and pretty equal?
ISO, SEVO, DES
Receptors located in the 4th ventricle of the brain (floor) that cause N/V?
Dopaminergic Serotonergic Histaminic Muscarinic Substance P
Anti- dopaminergic drugs would be? (3)
Butyrophenones: Droperidol
Phenothiazines: Prochlorperazine
Benzamines: Metoclopramide
Serotonin antagonist is?
zofran (5HT3)
Anti-Histaminergic drug would be?
Diphenhydramine: Both antihistamine and anticholinergic effects (Benadryl)
Anti- cholinergic drug would be?
Glycopyrrolate may be useful in neuraxial induced N/V
name three H-2 Blockers
also tell me the function
Blocks acid stimulating effects of histamine and ACh
Cimetidine
Ranitidine
Famotidine
Anti - Muscarininc drug would be?
Scopolamine is a high affinity muscarinic antagonist
Substance P drug would be?
Neurokinin 1 Antagonists
Aprepitant: Only PO
Fosprepitant: IV is available
Comparable to ondansetron but lasts longer and is synergistic with other PONV medications
