Pharmacology 4 Flashcards
In a patient receiving chronic methadone treatment, an electrocardiogram (ECG) should be obtained prior to administering which of the following medications?
Patients taking methadone, especially at doses greater than 120 mg/day, are at risk of developing a prolonged QT interval. This places these patients at risk for developing lethal arrhythmias, such as torsades de pointes. Cytochrome p450 inhibiting medications should be used with caution in patients taking methadone to prevent unintentional elevations in serum methadone levels.
TrueLearn Insight : Methadone has N-methyl-D-aspartate (NMDA) antagonistic properties in addition to opioid receptor agonism. This promotes pain control and reduces tolerance in patients with chronic pain. Methadone may also be used in the intensive care unit (ICU) to reduce tolerance to opioids and maintain adequate pain control.
A 64-year-old woman is undergoing total hip arthroplasty under spinal anesthesia. You are using isobaric bupivacaine 15 mg for your spinal anesthetic. Which of the following factors will have the MOST significant impact on the spread of block height?
Site of injection and total dose are the most important factors in determining block spread in isobaric solutions. CSF volume is inversely correlated with block spread, but the clinical utility of this is limited as factors such as age, weight, height, and BMI have been found to be poorly correlated with CSF volume.
TrueLearn Insight : In hyperbaric and hypobaric solutions, patient positioning plays the most important role in block spread of spinal anesthetic.
Which of the following respiratory effects is expected of midazolam?
Midazolam and all benzodiazepines cause a dose dependent decrease in minute ventilation. The decreased minute ventilation is mainly a result of decreased tidal volume. Benzodiazepines decrease the respiratory sensitivity to CO2 and act synergistically with opioids.
Which of the following produces the largest concentration of fluoride ions upon metabolism?
Methoxyflurane created the largest concentrations of inorganic fluoride ions and fluoride-induced nephrotoxicity. Enflurane was related to renal concentration effects of fluoride ions causing nephrotoxicity. Sevoflurane produces more fluoride ions than enflurane while being administered, but the concentration of fluoride rapidly declines with cessation of administration, owing to its low blood and tissue solubility. Fluoride ion production: methoxyflurane > sevoflurane > enflurane > isoflurane > desflurane.
TrueLearn Insight : Nephrotoxicity occurs when fluoride levels are >50 µmol/L. Moderate renal injury occurs between 50-80 µmol/L and severe injury occurs at >80 µmol/L.
Which of the following vasodilators will most likely cause an increase in renal perfusion?
Fenoldopam is a selective dopamine-1 agonist that increases renal blood flow despite decreased systemic arterial blood pressure. Fenoldopam has little to no alpha, beta, or dopamine-2 receptor agonist activity.
Which of the following induction agents is the LEAST associated with myoclonus?
Etomidate, ketamine, and methohexital are associated with myoclonus. Propofol, although less common, is also associated with myoclonic movements. Midazolam has Remifentanil and esmolol are metabolized by nonspecific blood and tissue esterases and would not be affected by a pseudocholinesterase deficiency. Succinylcholine, mivacurium, ester local anesthetics (2-chloroprocaine, tetracaine, procaine), cocaine, and heroin are metabolized via hydrolysis by pseudocholinesterase, also known as plasma cholinesterase and butyrylcholinesterase. A deficiency or defect in this enzyme would result in decreased metabolism and prolonged effects of the substance.
TrueLearn Insight : Patients who have been receiving echothiophate eye drops are at risk for significant prolongation of succinylcholine’s effects for up to 2 weeks after therapy is discontinued.
been associated with myoclonus.
A 28-year-old female is 39 weeks pregnant with her first child. She states she has pseudocholinesterase deficiency but is otherwise healthy. Which of the following medications can be used as usual, without significant change in pharmacokinetics?
Remifentanil and esmolol are metabolized by nonspecific blood and tissue esterases and would not be affected by a pseudocholinesterase deficiency. Succinylcholine, mivacurium, ester local anesthetics (2-chloroprocaine, tetracaine, procaine), cocaine, and heroin are metabolized via hydrolysis by pseudocholinesterase, also known as plasma cholinesterase and butyrylcholinesterase. A deficiency or defect in this enzyme would result in decreased metabolism and prolonged effects of the substance.
TrueLearn Insight : Patients who have been receiving echothiophate eye drops are at risk for significant prolongation of succinylcholine’s effects for up to 2 weeks after therapy is discontinued.
Which of the following groups of patients is LEAST likely to have an exaggerated increase in serum potassium following succinylcholine administration?
Succinylcholine administration transiently raises serum potassium approximately 0.5 mEq/L in healthy patients. Succinylcholine is contraindicated in patients with neuromuscular disorders, prolonged immobility, and those >24 hours status post burns, trauma, or denervation injuries. This is due to an upregulation of extrajunctional nicotinic acetylcholine receptors, leading to an increase in serum potassium up to 3.5 mEq/L following succinylcholine administration. In children, there is a risk of cardiac arrest from hyperkalemia rhabdomyolysis.
Which of the following inhalational anesthetics is associated with megaloblastic hematologic changes?
Nitrous oxide inhibits the vitamin B12-dependent enzymes, methionine synthetase and thymidylate synthetase. This may lead to subclinical problems in relatively healthy patients, but may cause neurologic and hematologic sequelae in critically ill and vitamin B12-deficient patients.
Which of the following MOST correctly describes the advantage of low molecular weight heparin over unfractionated heparin?
LMWH, such as enoxaparin and dalteparin, work similarly to UFH by binding the serine protease inhibitor ATIII. Binding of ATIII by UFH or LMWH induces a conformational change that increases ATIII’s activity by 1000-fold to inhibit activated factor X and thrombin.
Inhibition of thrombin requires simultaneous binding of heparin to both ATIII and thrombin, but inhibition of factor Xa only requires heparin binding to ATIII. A longer polysaccharide chain (higher molecular weight) is required for the increased binding sites leading to thrombin inhibition. The shorter polysaccharide chains (lower molecular weight) of LMWH is more restricted in binding solely to ATIII, therefore more selectively inhibits Xa.
Selective Xa inhibition can be desirable as factor Xa has limited function outside the coagulation system, unlike thrombin which also plays a role in the immune system and inflammatory pathways.
A 50-year-old man is scheduled to undergo a right total knee arthroplasty under general anesthesia. He has a history of grand mal seizures for which he takes phenobarbital for many years. Which of the following is MOST likely true regarding the anesthetic management of this patient?
Barbiturates are known to induce the cytochrome P450 enzyme system. Drugs that require the cytochrome system for degradation will have enhanced metabolism in patients taking barbiturates and therefore will require a dose increase. Other drugs known to induce P450 enzymes include phenytoin, rifampin, carbamazepine, and ethanol. Drugs known to inhibit P450 enzymes include fluconazole, metronidazole, valproic acid, and ciprofloxacin.
Which of the following medications is LEAST likely to cause hyperkalemia?
Administration of mannitol can cause a translocational hyperkalemia (B). Since mannitol is significantly hypertonic, intravascular administration causes water efflux from cells. Solvent drag then occurs by which intracellular potassium follows the water efflux and becomes intravascular.
Terbutaline and other β2-agonists can cause hypokalemia. Multiple medications and medication classes, seen in the above table, can cause hyperkalemia.
A 48-year-old diabetic male is scheduled to undergo renal transplantation for dialysis-dependent end stage renal disease secondary to diabetic nephropathy. The patient also has a history of depression for which he takes St. Johns Wort daily. Which of following is MOST likely true?
St. John’s Wort is an herbal antidepressant that induces the CYP enzymes and can alter drug responses with anti-rejection medications, warfarin, and intraoperative anesthetics. It should be stopped at least 5 days prior to any surgical operation.
Primary surgical and anesthetic concerns include induction of CYP 3A4 resulting in enhanced metabolism of drugs such as lidocaine, alfentanil, and midazolam as well as CYP 2C9, which is involved in the breakdown of warfarin. Warfarin therapy is therefore unreliable in patients taking St. John’s Wort and puts them at risk for DVT and thromboembolism.
Which of the following changes would most likely DECREASE the time constant when attempting to reach a state of equilibrium in an anesthetic circuit?
The time constant (t) is calculated by dividing the volume or capacity of the circuit (Vc) by the fresh gas flow (FGF). Therefore, in order to decrease the time constant, we can either decrease the capacity of circuit or increase the fresh gas flow.
Intraoperative administration of a calcium channel blocker to a naïve patient will MOST likely cause which of the following interactions with neuromuscular blocking drugs?
Calcium channel blockers can augment depolarizing and nondepolarizing muscle relaxants, particularly when the two drugs are administered concurrently to CCB-naïve patients. Consider the careful titration of NBDs in this setting. In patients taking chronic CCBs, the augmentation effect is clinically insignificant.
TrueLearn Insight : During treatment of malignant hyperthermia, CCBs should not be given in combination with dantrolene because it can lead to life-threatening hyperkalemia and myocardial depression. However, if a patient on a chronic CCB develops malignant hyperthermia, dantrolene should always be given as withholding dantrolene can significantly worsen mortality.
