Pharm Unit 2 Flashcards
What can be given for pre-eclampsia?
Magnesium sulfate
What are the 5 components of anesthesia?
Hypnosis, analgesia, muscle relaxation, sympatholysis and amnesia
How do barbiturates exert their effect?
Potentiating GABA-a channels, also act on glutamate/adenosine/neuronal nicotinic ACh receptors
What do barbiturates do the CBF/CRMO?
Act as a cerebral vasoconstrictor, reduce CBF and CRMO by about 55%
Why do you want to avoid infusions of barbiturates?
Prolonged context-sensitive half time. They also rapidly redistribute into other tissues.
Dose of Thiopental?
4 mg/kg IV
Dose of methohexital?
1.5 mg/kg IV
How does methohexital affect seizures?
Lowers seizure threshold = easier to have one, making it an ideal drug for ECTs
Basic effects of barbiturate’s on ventilation?
Dose dependent depression with slower frequency and lower tidal volume, similar to narcotics
What happens during intra-arterial injection of a barbiturate?
Immediate intense vasoconstriction and pain. Treat with vasodilators: lidocaine or papaverine
List the induction, conscious sedation and maintenance doses of propofol
Induction = 1.5 - 2.5 mg/kg IV
CS = 25 - 100 mcg/kg/min
Main = 100 - 300 mcg/kg/min
Describe Ampofol and Aquavan relative to Propofol
Ampofol = low-lipid emulsion with no preservative, higher incidence of pain on injection (good d/t less effect on triglycerides)
Aquavan = prodrug that converts into active form, no pain on injection, by has unpleasant sensation related side effects
Describe Propofol MOA
Selective modulator of GABA-a = increased Cl conductance and hyperpolarized cell
Describe the BP/HR changes with propofol, etomidate and ketamine
P = decreased BP and HR
E = no change to BP and HR
K = increased BP and HR
T/F: Propofol is safe for alcoholic patients?
T: awakening time does not change with healthy vs ETOH patients
How does the dose of Propofol change with children vs elderly?
Children = increased dose, elderly = decreased dose (by 25-50%)
Why is Propofol advantageous as a sedative?
Prompt recovery, low PONV, anti-convulsant, amnestic, anti-oxidant. Does not provide analgesia however
What is the sub-hypnotic dose of Propofol?
10-15 mg IV followed by 10 mcg/kg/min
Anti-pruritic dose of Propofol?
10 mg IV
What effect does Propofol have on the airway?
Bronchodilation
Anti-convulsant dose of Propofol?
1 mg/kg IV
Effects on CRMO with Propofol?
Decreases CRMO, CBF and ICP. D/t autoregulation, CBF and PaCO2 are maintained
Black box warning for Propofol?
Profound bradycardia leading to asystole in healthy patients
Describe Propofol infusion syndrome including dose
Greater than 75 mcg/kg/min longer than 24 hours. Can cause severe refractory bradycardia in children, lactic acidosis, brady-dysrhythmias and lactic acidosis. Green urine.
Etomidate MOA?
Selective modulator of GABA-a
Dose for Etomidate?
0.2-0.4 mg/kg/ IV
Best indication for etomidate?
In an unstable CV patient
What is the big side effect of etomidate?
Myoclonic movements, very common. Can be prevented with fentanyl 1-2 mcg/kg IV
Contraindication to etomidate?
Adrenal suppression - it makes it worse so you lose your stress response
Relationship of CRMO/CBF to etomidate?
Decrease CBF, CRMO and ICP by 35-45% via cerebral vasoconstriction
Etomidate effects on ventilation?
Is a depressant but less so than barbiturates. Vt decreases are offset by compensatory increases in RR
What is advantageous of ketamine over etomidate/Propofol? Cons?
No pain on injection and profound analgesia at subanesthetic doses. Dose have delirium concerns and abuse potential.
Compare isomers of ketamine
S (the left or -) = more intense analgesia, more rapid recovery, less salivation, lower incidence of emergence reactions
R = (right or +) = cocaine like effect, less fatigue, less cognitive impairment
Where does ketamine work?
NMDA receptors (prevents glutamate from activating them), all opioid receptors (mu, delta and kappa) and weak actions at GABA-a and sigma opioid receptors. Also affects calcium and neuronal nicotinic ACh channels (analgesic effect)
Induction doses IV and IM of ketamine?
IV = 0.5 - 1.5 mg/kg
IM = 4 - 8 mg/kg
Maintenance doses of IV/IM ketamine?
IV = 0.2 - 0.5 mg/kg
IM = 4 - 8 mg/kg
Subanesthetic/analgesic dose of ketamine?
0.2 - 0.5 mg/kg IV
Post op sedation/analgesia dose of ketamine?
1 - 2 mg/kg hour
What anti-sialagogue do you give with ketamine?
Glycopyrrolate
What is the coronary artery disease cocktail (include dosages)?
Valium = 0.5 mg/kg IV
Ketamine = 0.5 mg/kg IV
Ketamine infusion of 15-30 mcg/kg/min
How does ketamine affect ICP? At what dose does the ICP effect plateau?
Potent cerebral vasodilator = 60% increase in CBF, no further increase in ICP at 0.5 - 2 mg/kg IV
Effects of ketamine on the CV system?
Increase in pretty much everything; HR, BP, PAP, CO
Effects of ketamine on ventilation?
No depression of ventilation, airway reflexes are maintained, increase in salivary secretions, bronchodilator
What is the relationship of ketamine to volatiles, NMBDs and Sux?
NMBD = enhanced effect
Sux = prolonged
V = hypotension
Define hyperalgesia and allodynia
Hyper = increased pain sensations to normally painful stimuli
A = perception of pain in response to non-painful stimuli
Where does transduction, transmission, modulation and perception occur in nervous system?
Transduction = signals starting at the nerve endings
Transmission = travel of the electrical impulses to the nerve body connecting to the dorsal horn
Modulation = altering of the signal at the dorsal horn
Perception = discrimination of stimuli in the somatosensory cortex
What is the function of the hypothalamus?
To act as a relay station for incoming pain signals
What medication classes act at peripheral nociceptors or rather affect transduction?
LAs and NSAIDS
What medication classes act on transmission of nerve signals? Where?
LAs and on the a-delta and c-fibers
What medication classes act on modulation and where does this occur?
LAs, opioids, ketamine a2-agonists and in the spinal cord, primarily in the dorsal horn
What medication classes act on perception and where does this occur?
Opioids, a2-agonists, GAs. In the brain -> somatosensory cortex
Describe the process a stimulus would take to travel throughout the CNS
Stimulus -> nociceptor -> exceed resting threshold -> transmission -> modulation -> interpretation/perception
Describe the physiology of c-fibers and type 1 (a-beta) and type 2 (a-delta) fibers including speed
C-fiber = burning pain and sustained pressure pain (2 meters/second)
AB = heat, mechanical and chemical pain
AD = heat
Both alpha = much faster
What are some chemical mediators of pain?
Peptides (substance P, calcitonin, bradykinin, CGRP), eicosanoids, Lipids (PGAs, thromboxane, leukotrienes and endocannabinoids), neutrophins, cytokines, chemokines and extracellular proteases/protons
What are peptide mediators of pain?
Substance P, calcitonin, bradykinin, CGRP
What are lipid mediators of pain?
PGAs, thromboxane, leukotrienes and endocannabinoids
Define primary vs secondary hyperalgesia
P = at the original site of injury, decreased pain threshold, increased response to stimuli, spontaneous pain and expansion of receptive field
SH = uninjured skin surrounding the injury that has been sensitized by central neuronal circuits
Basic function of the dorsal horn
Relay center for nociceptive and other sensory activity
What do the ascending pathways do?
Transmit sensations such as pain to the brainstem and forebrain
What fibers would you find in lamina I?
Afferent C-fibers
What would you find in Lamina II?
The substantia gelatinosa, afferent c-fibers, also where opioids can exert their effect
Where does substance P work?
Lamina III and IV
Where would you find myelinated fibers in the cord? What do they innvervate?
Lamina I, IV, VII and the ventral horn, and they innervate muscles and viscera
Describe the gate theory of pain
If the gate is open, the pain is projected to supraspinal brain regions, if the gate is closed, pain is not felt with simultaneous inhibitory impulses
What happens if you rub an injured area?
The a-beta fibers deliver information about the rubbing/touching which override the slower information from a-delta and c-fibers regarding pain
What does the limbic cortex and thalamus do with pain information?
They are involved with perception of motivational-effective pain components
What does the PAG and RVM (rostro-ventral medulla) do with pain information?
Depress or facilitate the integration of pain information in the spinal dorsal horn
What does tissue injury release?
Substance P and glutamate
What are things damaged cells can release that cause pain?
Bradykinin, histamine, PGAs, serotonin, hydrogen ions and lactic acid
What are some excitatory impulses? Inhibitory?
E = glutamate, calcitonin, neuropeptide Y, aspartate, substance P
I = GABA, glycine, enkephalins, norepi, dopamine
What information travels the spinothalamic tract? Lamina?
Pain, temperature and itch, I VII and VIII
What information travels the spinobulbar tract? Lamina?
Behavior towards pain, I V and VII
What information travels the spinohypothalamic tract? Lamina?
Autonomic, neuroendocrine and emotional aspects of pain, I V VII and X
Describe the descending inhibitory pain pathway
Brain -> PAG/ RVM -> synapse in dorsal horn
What are the neurotransmitters used in the descending inhibitory tracts?
Endorphins, enkephalins, serotonin
What happens when you hyperpolarize a-delta and c-fibers?
Decreased release of substance P via opening of K channels and closing of Ca channels
What are the receptors for the PAG-RVM system?
Mu, Kappa and Delta receptors
Treatment for neuropathic pain?
Common to have allodynia and hyperalgesia, opioids, gabapentin, anti-depressants and cannabis
Describe visceral pain
Diffuse and poorly localized, if it is referred to the muscle/skin it become somatic pain
When does pain become perceivable in an neonate?
23 weeks
What are some endocrine responses to pain?
Increase catabolic hormones (catecholamines, cortisol, glucagon) and decrease anabolic hormones (insulin, testosterone) combined = negative nitrogen balance, carb intolerance and increased RAAS
What are some examples of phenanthrenes?
Morphine, codeine and thebaine
What are some examples of benzylisoquinolines?
Papaverine and noscapine
How do opioid agonists work?
Inhibit ACh, dopamine, norepi and substance P, they increase K conductance (hyperpolarize), inactivate Ca channels and decrease neurotransmission
Where would you find opioid receptors in the Brain, spinal cord and outside the CNS?
B = PAG, locus ceruleus, RVM and hypothalamus
SC = dorsal horn at the substantia gelatinosa (lamina II)
Out = sensory neurons and immune cells
What is the only opioid receptor that is not supraspinal?
Mu2
What effects would you expect from Mu1 vs Mu2 receptors?
1 = analgesia, euphoria, low abuse, miosis, bradycardia, hypothermia and urinary retention
2 = analgesia, ventilatory depression, physical dependence, constipation
Is there any difference in the agonists/antagonists of Mu1/Mu2?
No, they are all the same. Ago = endorphins, morphine and synthetics. Antag = naloxone, naltrexone and nalmefene
What effects occur at Kappa?
Analgesia, dysphoria/sedation, low abuse potential, miosis, diuresis
What effects occur at delta?
Analgesia, depression of ventilation, physical dependence, constipation, urinary retention
What are the body’s endogenous agonists of kappa and delta?
K = dynorphins, D = enkephalins
What opioid receptors depress ventilation?
Mu2 and delta
What opioid receptors have dependence issue?
Mu2 and delta
What opioid receptors have low abuse potential?
Mu1 and kappa
What opioid receptors cause miosis?
Mu1 and kappa
What opioid receptors cause urinary retention?
Mu1 and delta
What opioid receptor has the most effects?
Mu1
What opioid receptors cause euphoria? Dysphoria/sedation?
Eu = Mu1
Sedation = kappa
What drug could you give to help reverse the opioid ventilation s/e but keep the analgesia going?
Physostigmine
What skeletal issues do opioids have?
Can make the muscles rigid, treat with a muscle relaxer or naloxone
What is spasm of biliary smooth muscle called?
Sphincter of oddi spasms
What is the primary concern with Oddi spasms?
delayed gastric emptying and constipation, N/V
Treatment for sphincter of Oddi spasm?
Glucagon 2 mg, naloxone 40 mcg, atropine 0.2 mg, Nalbuphine 10 mg, NTG (nitroglycerin) 50 mcg
How long does tolerance generally take to occur?
2-3 weeks
What opioids have the shortest onset, peak intensity and duration?
Demerol and fentanyl
What opioid(s) have the longest onset, peak intensity and duration?
Methadone
Intraop and postop doses for morphine
I = 1 - 10 mg
P = 5 - 20 mg
Intraop dose of fentanyl?
1.5 - 3 mcg/kg
Intraop dose of sufentanil?
0.3 - 1 mcg/kg
Intraop dose of remifentanil?
load 0.5-1 mcg/kg over 1 min
Intraop and postop dose of dilaudid
I = 1-4 mg
P = 1.5 - 5 mg
Infusion rate for sufentanil?
0.5 - 1 mcg/kg/hr
Infusion rate for remifentanil?
0.125 - 0.375 mcg/kg/min
What type of pain does morphine relieve?
Visceral/skeletal, dull more than sharp
IV peak of morphine?
15 - 30 minutes
How is morphine metabolized?
Via glucuronidation into 2 metabolites: Morphine-3 (75-95% but inactive) and morphine-6 (active)
Compare demerol to morphine
1/10th the potency, 12.5 mg for post-op shivering, lasts 2-4 hours, faster withdrawal s/sx relative to morphine
What receptors does demerol hit?
kappa and A2 receptors
Compare fentanyl to morphine
75 - 125x potency, does have a lung first pass effect, large VD
List the context sensitive half times of all fentanyl’s from least to greatest
Remifentanil -> sufentanil -> alfentanil -> fentanyl
List the analgesia, induction and inhaled anesthetic doses of fentanyl
A = 1 - 2 mcg/kg IV
Ind = 1.5 - 3 mcg/kg IV
Inh = 2 - 20 mcg/kg IV
What is the surgical anesthesia dose of fentanyl?
50 - 150 mcg/kg IV
Transdermal dose of fentanyl?
75 - 100 mcg over 18 hours
Advantage of fentanyl vs morphine in terms of s/e?
No histamine release, no significant bradycardia though can decrease BP and CO
What was morphine originally derived from?
Poppy (Papaver Somniferum)
Why is fentanyl discouraged in cardiopulmonary bypass?
You can lose some to the circuit
How much does fentanyl increase ICP?
6-9 mmHg
What is fentanyl synergistic with?
Benzo’s and Propofol (this can be a good thing, combined you could lower the dose of the propofol)
List the fentanyl in order of least to most potent
Alfentanil < Remifentanil and Fentanyl (both the same) < Sufentanil
Which is more potent, fentanyl or sufentanil?
Su: 5 - 12x
What does sufentanil bind to (not receptors)?
A1-acid glycoprotein
Give the analgesia, induction, intra-op and infusion doses of sufentanil
A = 0.1 - 0.4 mcg/kg IV
Ind = 18.9 mcg/kg IV
Intraop = 0.3 - 1 mcg/kg IV
Inf = 0.5 - 1 mcg/kg/hr IV
Compare and contrast potency and onset of fentanyl and alfentanil
Alfentail is 1/5 less potent, but has a faster onset of 1.4 minutes
Which 2 fentanyl’s have the same protein binding?
Alfentanil and sufentanil
What is the induction, induction alone and maintenance dose of alfentanil?
Ind = 15 - 30 mcg/kg IV
Ind A = 150 - 300 mcg/kg IV
M = 25 - 150 mcg/kg/hour IV
What is a contraindication to alfentanil?
Parkinsons and other neuromuscular disorders (MG, muscular dystrophy etc)
What fentanyl is dosed in IBW?
Remifentanil
Which fentanyl rapidly reaches steady state?
Remifentanil
Give the induction and maintenance dose of remifentanil
I = 0.5 - 1 mcg/kg IV
M = 0.25 - 1 mcg/kg IV or 0.005 - 2 mcg/kg/min IV
Which fentanyl is not recommended for spinal/epidural use?
Remifentanil
Compare hydromorphone and morphine
Hydromorphone is 5x more potent, less hydrophilic, no histamine release and does have an active metabolite
Dose range for dilaudid?
0.5 - 4 mgs IV
Cough suppressant and analgesia dose range for codeine?
CS = 15 mg
A = 60 - 120 mg
Dose of tramadol? Primary drug interaction?
3mg/kg and interacts with coumadin
Which opioids have the greatest and least context sensitive half times?
Greatest = fentanyl
Least = remifentanil
Which opioids have the highest protein binding? Least?
High = Su, al and remifentanil
Low = morphine
Which opioids have the highest and lowest clearance?
High = fentanyl
Low = alfentanil
Which opioids have the highest/lowest VD?
High = fentanyl
Low = alfentanil
Which opioids have the highest/lowest partition coefficient?
High = sufentanil
Low = morphine
Which opioids have the highest/lowest E1/2?
High = fentanyl
Low = remifentanil
Which opioids have the highest/lowest blood/brain equilibration times?
High or longest = fentanyl
Low or shortest = remifentanil
Which opioid requires you give a longer acting one before dc’ing it?
Remifentanil
What are the advantages of opioid agonist-antagonists?
Provide analgesia, limited depression of ventilation, low chance of dependence and ceiling effect prevents additional responses
What receptors does pentazocine work on?
Delta and kappa
Describe pharmacokinetics of pentazocine
1/5th as potent as nalorphine, antagonized by naloxone, may have withdrawal s/sx
What OAA crosses the placental barrier?
Pentazocine
Dosage of PO and IV pentazocine?
IV = 10 - 30 mg
PO = 50 mg
General CV effects of pentazocine?
Increased HR, BP, PA and LV-EDP
Compare butorphanol and pentazocine potency
Butorphanol is 20x more potent agonist and 10 - 30x more potent antagonist relative to pentazocine
Describe receptor affinity for pentazocine
low affinity for Mu and sigma, moderate for kappa
so low antagonism and dysphoria, but can produce analgesia and anti-shivering effects
What is the caution for use of Butorphanol?
Do not use with other opioid agonists
What is the only OAA that does not increase CV effects?
Nalbuphine
What OAA would you use in cardiac cath lab?
Nalbuphine
List the OAA from least to most potent
Nalbuphine < Pentazocine < Nalorphine < Butorphanol
Which OAA has 50x more affinity for mu receptors relative to morphine?
Buprenorphine
Why isn’t Nalorphine used?
High incidence of dysphoria (sigma receptor)
Which OAA is more potent than morphine?
Buprenorphine
Which antagonist can increase myocardial contractility?
Naloxone
Dose of Naloxone?
1 - 4 mcg/kg IV
Duration of Naloxone?
30 - 45 minutes
Dose of Naloxone in continuous infusion, shock and epidural
CI = 5 mcg/kg IV
S = greater than 1 mg/kg IV
E = 0.25 mcg/kg/hour IV
Use of naltrexone?
ETOH, lasts for 24 hours
Dose of Nalmefene? potency relative to naloxone?
15 - 25 mcg q 2-5 min, same potency
What is methylnaltrexone used for?
Gastric emptying and antagonizing N/V
What is Alvimopan used for?
Post-op ilieus
What is the only drug listedin lecture here to be metabolized by the gut flora?
Alvimopan
What are some of the tamper or abuse resistant opioids?
Suboxone (buprenorphine and naloxone), Embeda (ER morphine and naltrexone) and Oxynal (oxycodone and naltrexone)
How much does fentanyl reduce MAC of Iso or des?
50%
How much does su, al and remifentanyl reduce mac?
Su = 70 - 90%
Al = up to 70%
Remi = 50 - 91%
With neuraxial opioids, what are you targeting?
The opioid receptors in the substantia gelatinosa
How much more drug do you give with an epidural relative to a spinal?
5 - 10x more
What can you do to prevent systemic absorption of an epidural?
Add epinephrine
List in order of increasing lipid solubility: sufentanil, fentanyl, morphine
Morphine < fentanyl < sufentanil
If you had a left hip replacement with the hip up, right hip down, would you want a high or low baracity (hypobaracity) epidural?
Low so that it would float
If you had a left hip replacement with the hip down and right hip up, would you want a high or low baracity epidural?
High so that it would sink down to the hip
Which opioid would experience the most cephalad movement in the CSF?
Morphine
Common s/e of neuraxial opioids?
Pruritis, N/V, urinary retention (more so in males)
What is the most reliable sign of decreased ventilation with neuraxial opioids? Treatment?
Decreased LOC secondary to hypercarbia. 0.25 mcg/kg/hour IV of naloxone
What do you base barbiturate dosing on?
Lean body weight due to its propensity to go into other tissues
Why are barbiturates no longer used as a pre-medication in pre-op?
They are notorious for having a bad hangover effect
Which isomer of barbiturates are more potent?
S-isomers, though they are only marketed as a racemic mixture
How much do barbiturates generally decrease HR/BP?
10 - 20 mmHg drop in BP, 15 - 20 reduction in HR
For what drug class is SSEP monitoring required?
Barbiturates
What are the plasma levels of unconscious vs awake of propofol?
Unconscious = 2-6 mcg/ml
Awake = 1 - 1.5 mcg/ml
Where would you find nociceptors?
Skin, muscles, joints, viscera and vasculature
Where would you find the NKI receptor where substance P would act?
Lamina III and IV
Which opioids have the highest incidence rates of spasm of the oddi sphincter?
Fentanyl > Demerol > Morphine
Why do you never give codeine IV?
Histamine related hypotension
All the fentanyl’s are derivatives of what opioid?
Demerol
Which of the fentanyl’s have an ester structure?
Remifentanil
Which fentanyl is dosed based on IBW?
Remifentanil
Which fentanyl’s bind to A1-Acid glycoprotein?
Al and Sufentanil
Which fentanyl has a very rapid onset/offset with minimal tissue accumulation?
Remifentanil
What is the common reason to use an OAA?
If the patient cannot tolerate a pure opioid agonist
What OAA is resistant to narcan?
Buprenorphine
