Pharmacology Flashcards
Treatment for methemoglobinemia in G6PD deficient patient?
Ascorbic acid because methylene blue uses the hexose phosphate pathway which is dysfunctional and will cause red blood cell lysis
Drug of choice in WPW?
stable rhythm: procainamide
unstable rhythm: cardioversion
Sugammadex dose for 2 twitches observed with TOF stimulation?
2 mg/kg
Sugammadex dose for 1-2 post titanic counts and NO twitches with TOF stimulation?
4 mg/kg
Sugammadex dose for immediate reversal after 1.2 mg/kg of rocuronium?
16 mg/kg
Side effects of Gabapentin?
nausea, sedation, dizziness, ataxia, nystagmus, peripheral EDEMA, and weight gain.
Mechanism of action of gabapentin
Binds alpha2-delta subunit of L-type voltage gated CALCIUM channels –> decreased NMDA release of excitatory GLUTAMATE from dorsal root ganglia
Triptan drugs are effective in migraine pain relief via agonism of which receptors? Contraindicated in which population?
5-hydroxytryptamine serotonin (5HT 1B/1D) agonism —> vasoconstriction of cerebral vessels > coronary vessels
Contraindicated in cardiac disease
Triptan drugs also target the trigeminal ganglion.
where does aprepitant antagonize substance P neurokinin 1 receptors?
in the brain stem - in the nucleus tractus solitarius that is ventral to the area postrema; works best in combination with 5HT3 antagonist dolasetron or a corticosteroid dexamethasone.
Effects of an acute dose of cannabis in a NAIVE user?
Tachycardia*
Systolic hypertension*
Malignant arrhythmias (afib, vfib, v-tach, brugada pattern)
Coronary spasm if previous CAD
Cerebral vasodilation and increased cerebral blood flow*
Airway hyperreactivity or upper airway obstruction (uvulitis)
Effects of acute dose of cannabis in a CHRONIC user (THC > or = 10 mg)?
Bradycardia –> tachycardia
postural/orthostatic hypotension
sinus arrest
airway hyperreactivity
Altered thermoregulation = intraoperative hypothermia –> postop shivering
coronary vasospasm/MI
cerebral vasospasm –> ischemic stroke (posterior circulation affected in 50%)
Primary pharmacological effect of magnesium on the neuromuscular junction?
Inhibition of CALCIUM-mediated RELEASE of acetylcholine from the PRESYNAPTIC membrane
Other minor effects: reduced muscle membrane excitability and inhibition of postjunctional potentials
Opioids to use in a CYP2D6 poor metabolizer?
hydromorphone, morphine, and oxymorphone are NOT metabolized through CYP2D6
How is PR interval affected by hypocalcemia, hypokalemia or hypomagnesium?
Shortened PR interval
**Hypokalemia and hypomagnesium are risk factors for atrial fibrillation
How is PR interval affected by hypercalcemia, hyperkalemia and hypermagnesium?
Prolonged PR
“HyPeR”
QRS complex change with hypokalemia or hypomagnesiumia?
Narrowed QRS
QRS complex change with hyperkalemia or hypermagnesiumia?
Widened QRS
QT interval changes with DECREASED calcium, potassium, or magnesium?
Long QT
QT interval changes with hypercalcemia?
Short QT
T-wave changes with hypocalcemia?
T-wave inversion
T-wave changes with hypercalcemia or hyperkalemia?
Peaked T-waves
Things that enhance the response to non depolarizing NMBDs versus things that diminish the response?
Enhanced (4 As): Volatile anesthetics, local anesthetics, anti-arrhythmics, and aminoglycosides.
Diminished response: steroids, calcium, and phenytoin
Drugs to avoid in assisted reproductive therapy?
Droperidol and metoclopramide due to increased prolactin levels which impairs follicle maturation and corpus luteum function.
Commercially prepared local anesthetic solutions with epinephrine differ from local anesthetic with freshly added epinephrine in what way?
“Pre-mixed” solutions have a lower pH –> more ionized so does not cross lipid membrane easily –> increased onset time
mode of delivery for calcium chloride versus calcium gluconate?
calcium chloride: give centrally
calcium gluconate: give peripherally
Amount of bicarb required to correct metabolic acidosis
sodium bicarb = 0.2 * kg * base deficit
Which type of toxicity is associated with cyclosporine and tacrolimus?
nephrotoxicity
Which type of toxicity is associated with methotrexate?
myelosuppression; also “LFTs” liver toxicity, pulmonary fibrosis, and thyroid
Which type of toxicity is associated with doxorubicin/daunorubicin?
Cardiac toxicicity
A type I protamine reaction is mediated by?
mast cell degranulation and histamine release caused by the polycationic structure of protamine during rapid administration –> systemic hypotension
A type II protamine reaction is mediated by?
IgE mediated anaphylaxis – prior exposure to protamine or similar protein necessary
A type III protamine reaction is mediated by?
thromboxane A2 released by platelets - pulmonary hypertensive crisis leading to right heart failure
first line treatment for neuropathy? second line?
1st line: TCAs, SNRIs, gabapentin, and pregabalin
2nd line: tramadol, capsaicin patches, and lidocaine patches
Which non-depolarizer to avoid in renal failure?
Vecuronium because of the active metabolite, 3-desaceryl-vecuronium – has 80% of the potency of vecuronium and can significantly prolong DOA in renal failure
Recent study with ketamine vs. saline placebo did not show a difference in the rate of ________?
Delirium
However patients were more likely to experience nightmares and hallucinations than the placebo group, especially with higher doses of ketamine.
Presumed mechanism of myoclonus with etomidate?
DISINHBITION of extrapyramidal motor activity in the SUBCORTEX: likely cortical activity is suppressed faster than subcortical activity. Patient becomes unconscious from loss of cortical activity but then has myoclonus due to LOSS of cortical inhibition of the SUBCORTEX (until that too is suppressed).
Mechanism of primary cardiac toxicity of bupivicaine?
A decrease in the rate of repolarization in the fast-conducting tissues of the Purkinje fibers and ventricular muscle (mediated by fast sodium channels)
indication and mechanism of action for intrathecal ziconotide?
indication: chronic neuropathic pain, common in poorly controlled cancer pain
mechanism: inhibit calcium channels and decrease nociceptive neurotransmitter release to afferents that TERMINATE in the dorsal horn (so action is more superficial than the dorsal root ganglion)
new drug approved for the treatment of opioid-induced constipation in adults with chronic NONcancer pain?
methylnaltrexone: selective PERIPHERAL acting mu-receptor ANtagonist -AND- kappa-opioid receptor PARTIAL agonist
**bc it acts peripherally and does not cross the BBB, there is no effect on opioid-mediated analgesia.
Drug used for neuropathic pain that is contraindicated in closed-angle glaucoma?
topiramate
Indication and mechanism of action of calcitriol?
Indication: hypocalcemia associated with hypOparathyroidism
Mechanism: calcitriol is the active form of vitamin D which increases GI uptake of calcium and decreases renal excretion
drugs that greatly reduce IOP versus drugs that mildly reduce IOP?
significant reduction: Benzes, barbs and volatiles
mild reduction: opioids, non-depolarizers and nitrous oxide
The three antibiotics with the broadest spectrum of activity against gram positives (including MRSA!) and gram negatives?
ceftaroline
tigecycline
TMP-SMX
Pseudocholinesterase deficiency affects the metabolism of which anesthetic drugs?
sux
mivacurium
ester LAs (chlorprocaine, tetracaine, cocaine)
heroin
metabolism of remifentanil and esmolol are by which enzyme?
nonspecific blood and tissue esterases
acetazolaminde causes what acid-base disturbance?
hyperchloremic metabolic acidosis
Which is a better option to treat ACEi/ARB induced hypotension in the perioperative setting and why? (Norepinephrine or vasopressin)
Both will treat hypotension but NE is better because it preserves cardiac output and gastric perfusion
Drugs used in the treatment of myotonic dystrophy EPISODES?
phenytoin, quinine, procainamide, direct infiltration of the affected muscle with LA, or a high concentration of volatile anesthetic
Neuromuscular blocking agents do NOT effectively treat myotonic reactions
Propofol effects on CMRO2 and CBF?
Decreases both
Volatile anesthetic effects on CMRO2 and CBF?
Uncoupling! CMRO2 decreased but CBF increased in dose-dependent fashion
How to convert percent volatile anesthetic delivered to partial pressure delivered?
barometric pressure * percent delivery
for example: 760 mmHg (sea level) * 0.01 = 7.6 mmHg volatile delivered
Variable bypass vaporizers are designed to deliver a fixed ______ of volatile anesthetic. (isoflurane and sevoflurane)
partial pressure
(So at higher altitudes, the partial pressure of volatile anesthetics remain the same as sea level because vaporizer automatically increases the PERCENT delivered to compensate for a lower barometric pressure)
Desflurane vaporizers are designed to deliver a fixed ______ of volatile anesthetic.
percentage
(So at higher altitudes, the dialed concentration needs to be increased to compensate for a lower barometric pressure. Remember barometric pressure * percent = mmHg concentration delivered)
Most appropriate initial treatment for MRSA ventilator-associated pneumonia?
Vancomycin
No mortality benefit with combination therapy
Best initial treatment for neuroleptic malignant treatment? And in more severe cases?
Diphenhydramine with benztropine
Dantrolene, bromocriptine and amantadine in severe cases
Supportive measures such as sedation, IV fluids, cooling blankets, etc
Key facts to remember about tramadol?
it is a prodrug that is converted to amore potent opioid active metabolite therefore genetics play a big role
it is multimodal: opioid receptor agonist -PLUS- central monoaminergic reuptake inhibitor (serotonin, epinephrine and norepinephrine)
side effect profile is no longer considered lower risk than classic opioids
decreased efficacy (of both drugs) when administered with serotonin antagonists like ondansetron
decreases seizure threshold
watch out for serotonin syndrome
Sister drug: tapentadol (Nucynta) is a mu opioid agonist and NE reuptake inhbitor (but not SSRI)
mechanism of action of methylnaltrexone?
PERIPHERAL mu-opioid receptor antagonist
Used for opioid induced constipation in adults with chronic noncancer pain or advanced illness receiving palliative care
Subunit difference between junctional versus extra-junctional acetylcholine receptors
mature junctional: alpha, beta, delta, and epsilon
immature extra-junctional: alpha, beta, gamma and delta
Autoantibodies to what in GBS?
Schwann cells
Analgesic medication to avoid in Grave’s thyrotoxicosis?
Aspirin because it increases serum free T4 and T3 by interfering with protein binding
Why is oxycodone a particularly useful opioid in pediatrics?
because it is NOT a PRO-drug
Pain meds that lower the seizure threshold?
TCAs and tramadol
Meperidine may lead to seizures because of active metabolite normeperidine, not because it lowers seizure threshold.
MOA of metyrosine?
competitively inhibits tyrosine hydroxylase, the rate-limiting step of catecholamine production.
Helpful in reducing tumor stores of catecholamines in pheochromocytoma.
preoperative drug of choice in pheochromocytoma?
phenoxybenzamine: non-competitive alpha blockade
drug to avoid in thyroid storm?
aspirin bc leads to unbinding of thyroid hormone from thyroid binding glubulin
How does tapentadol differ from tramadol?
it is mostly norepinephrine reuptake inhibition (minimal SSRI)
it is not a prodrug so does not require CYP450 activation
Drugs contraindicated with reuptake inhbitors?
MAO-I inhibitors x 14 days
MAO-I-Pride In Shanghai: phenelzine, isocarboxazid, selegiline
Prolongation of ROCURONIUM-induced neuromuscluar blockade is influenced by?
advanced age female sex volatiles hypothermia acidosis
other factors: lap cholecystectomy chronic satins obstructive jaundice chronic renal failure
Effect of methyl prednisone and prednisone on rocuronium-induced neuromuscluar blockade?
Shortened blockade
Serotonin syndrome can be precipitated by fentanyl….why?
There is decreased reuptake of serotonin with many things including TCAs, SSRIs, SNRI’s (venlafaxine, duloxetine, milnacipran), other antidepressants (like trazodone, nefazodone), phenyl piperidine opioids (fentanyl, alfentanil, sufentanil, methadone, meperidine and tramadol, dextromethorphan), and other miscellaneous items (ondansetron, granisetron, and St. John’s Wort)
Common treatment for serotonin syndrome?
cyproheptadine or IV chlorpromazine
only antibiotic reported to reduce effectiveness of hormone-based contraceptives
rifampin
preop management of garlic?
discontinue 7 days prior to surgery
does not interfere with neuroaxial blocks
Perioperative lithium effects?
increases duration of neuromuscular blockade (both depolarizing and nondepolarizing)
high incidence of hypOthyroidism
decreased MAC
NSAIDs may increase lithium by up to 40%
metabolized solely by kidneys so levels can rise quickly with renal failure
How much SUX reaches the neuromuscular junction in a healthy individual? how is blockade reversed?
only 10%
diffusion away from the junction into bloodstream
principle TOXIC metabolite of acetaminophen?
n-acetyl-p-benzoquinone imine (NAPQI)
Dose of hydrocortisone during minor or moderate risk procedures when cortisol supplementation is needed?
50 mg IV before incision and
25 mg every 8 hours x 24 hours
then usual daily dose
Dose of hydrocortisone during superficial procedures like dental surgery or biopsies when cortisol supplementation is needed?
usual daily dose
Dose of hydrocortisone during major procedures when cortisol supplementation is needed?
100 mg IV before incision followed by
50 mg IV every 8 h x 24 hours
plus taper until usual daily dose is reached
3 main effects mediated by dexmedetomidine?
(1) increase in GABA release –> sedation
(2) decreased substance P & decreased glutamate via alpha2C and alpha2A receptors in the dorsal horn –> hyperpolarization of interneurons –> analgesia
(3) stimulation of presynaptic alpha2 receptors in the brain and spinal cord –> sympatholysis leading to decr HR and blood pressure
Why are topical opioid analgesics not used for acute pain from surgical incisions?
topical opioids impair wound healing
Main effects of aging on pharmacodynamics and pharmacokinetics of FAT-soluble drugs?
Volume of distribution of fat soluble drugs is INCREASED –> Longer elimination half-life
Decreased total body water –> INCREASED blood concentrations after bolus doses
Overall –> increased sensitivity to anesthetic drugs
Relationship of local anesthetic molecular weight with potency?
higher molecular weights also have higher potency (possibly due to a greater affinity for voltage gated sodium channels)
order of elimination half-life for common benzos including midazolam, alprazolam, lorazepam, and diazepam
shortest to longest: midazolam < alprazolam < lorazepam < diazepam
how does liver failure affect NMBDs?
increased volume of distribution dilutes drug –> delayed onset of action therefore need to wait longer for prior to intubation or increase initial dose
altered hepatic clearance of rocuronium will prolong duration of action
What pharmacokinetic parameter is delayed with transdermal fentanyl?
onset delayed because takes 12-24 hours to form depot in skin tissue
offset delayed because long half life of 17 hours
dosing for transdermal fentanyl?
Calculate total breakthrough opioid dose: give 25 mcg/hr patch per 90 mg morphine equivalent in 24 hours
Drugs that follow zero-order kinetics?
THE PAW theophylline heparin ethanol phenytoin aspirin warfarin
ED95 for most drugs versus ED95 for neuromuscular blocking drugs?
ED95 for most drugs = median effective dose in 95% of the population
ED95 for NMB drugs = 95% twitch suppression in 50% of the population
DOC for ventricular arrhythmias in LAST?
Amiodarone
