Fundamental Flashcards
The pharmacologic effects of clopidogrel bisulfate (Plavix) are caused by which of the following?
Answers:
A. Irreversible inhibition of P2Y12 receptor on platelets
B. Reversible inhibition of P2Y12 receptor on platelets
C. Inhibition of glycoprotein IIb/IIIa on platelets
D. Reversible inhibition of thromboxane A2 formation in platelets
E. Irreversible inhibition of thromboxane A2 formation in platelets
Irreversible inhibition of P2Y12 receptor on platelets
Discussion:
Clopidogrel is a P2Y12 receptor inhibitor. Along with prasugrel and ticlopidine it irreversibly inhibits
this platelet receptor to block platelet activation. Ticagrelor reversibly inhibits P2Y12. Aspirin
irreversibly inhibits thromboxane A2. Abciximab, Eptifibatide, and Tirofiban all inhibit glycoprotein
IIb/IIIa to block platelet aggregation.
References:
Reference (1)
Savi P, Nurden P, Nurden AT, Levy-Toledano S, Herbert JM. Clopidogrel: a review of its
mechanism of action. Platelets. 1998;9(3-4):251-5. doi: 10.1080/09537109876799. PMID:
16793712.
Pubmed Web link
https://pubmed.ncbi.nlm.nih.gov/16793712/
Reference (2)
Beavers CJ, Naqvi IA. Clopidogrel. 2020 Jul 10. In: StatPearls [Internet]. Treasure Island (FL):
StatPearls Publishing; 2021 Jan–. PMID: 29261873.
Pubmed Web link
https://pubmed.ncbi.nlm.nih.gov/29261873/
A 70-year-old man with Alzheimer disease is admitted to the emergency department because of
increased agitation; he is treated with haloperidol. CT scan shows a left-sided chronic subdural
hematoma that is moderate-sized and hypodense; there is no midline shift. He undergoes bur hole
drainage of the hematoma under local anesthesia. A postoperative CT scan shows satisfactory
evacuation of the subdural blood. Twelve hours postoperatively, he continues to be agitated;
temperature is 40.5°C (104.9°F), pulse is 110/min, respirations are 18/min, and blood pressure is
160/70 mmHg. He is disoriented to place and time but can be aroused. Examination shows
diffusely rigid extremities but otherwise normal neurological status. Laboratory studies show a
serum creatine kinase level of 5000 IU/L (N 22–198). Which of the following is the most likely
diagnosis?
Answers:
A. Status epilepticus
B. Malignant hyperthermia
C. Propofol infusion syndrome
D. Neuroleptic malignant syndrome
E. Non-convulsive status epilepticus
Neuroleptic malignant syndrome
Discussion:
Haloperidol is a butyrophenone antipsychotic that can cause neuroleptic malignant syndrome due
to its dopamine receptor antagonist activity. Malignant hyperthermia occurs after anesthesia,
particularly inhaled halogens and succinylcholine. Neuroleptic malignant syndrome takes days to
develop whereas malignant hyperthermia occurs very soon after surgery so the former is more
likely in this patient. Status epilepticus and non-convulsive status epilepticus can cause alterations
in mental status but hyperthermia and elevated creatine kinase are unlikely. Propofol infusion
syndrome can cause elevations in creatine kinase but it occurs after being on high doses of
propofol for an extended period of time, which this patient was not.
References:
Chan TC, Evans SD, Clark RF. Drug-induced hyperthermia. Crit Care Clin. 1997
Oct;13(4):785-808. doi: 10.1016/s0749-0704(05)70369-9. PMID: 9330841.
Pubmed Web link
https://pubmed.ncbi.nlm.nih.gov/9330841/
Three weeks after sustaining a spinal cord injury that resulted in paraplegia, a 29-year-old patient
has increasing respiratory distress. Succinylcholine is administered prior to intubation. One minute
later, the patient’s ECG shows high-peaked T waves without prolongation of the Q-T interval.
Which of the following is the most likely diagnosis?
Answers:
A. Hypocalcemia
B. Hypercalcemia
C. Hypokalemia
D. Hyperkalemia
E. Hypomagnesemia
Hyperkalemia
Discussion:
The classic findings of hyperkalemia on ECG are peaked T waves, bradyarrhythmia, PR
prolongation and eventually ventricular fibrillation and asystole. This patient was at risk for
hyperkalemia due to administration of the depolarizing neuromuscular blocker, succinylcholine in
the setting of prior spinal cord injury. Hypokalemia can cause PR prolongation, QT prolongation, T
wave inversion, and prominent U waves. Hypercalcemia is associated with QT shortening and J
waves. Hypocalcemia is associated with QT prolongation and torsades de pointes.
Hypomagensemia is associated with PR prolongation, QT prolongation and torsades de pointes.
References:
Reference (1)
Littmann L, Gibbs MA. Electrocardiographic manifestations of severe hyperkalemia. J
Electrocardiol. 2018 Sep-Oct;51(5):814-817. doi: 10.1016/j.jelectrocard.2018.06.018. Epub 2018
Jul 4. PMID: 30177318.
Pubmed Web link
https://pubmed.ncbi.nlm.nih.gov/30177318/
Reference (2)
Stone WA, Beach TP, Hamelberg W. Succinylcholine–danger in the spinal-cord-injured patient.
Anesthesiology. 1970 Feb;32(2):168-9. doi: 10.1097/00000542-197002000-00019. PMID:
5414296.
Pubmed Web link
https://pubmed.ncbi.nlm.nih.gov/5414296
Which of the following is a common adverse reaction to bisphosphonates?
Answers:
A. cardiac arrythmia
B. Fatigue
C. Bronchospasm
D. Gastritis
E. Renal failure
Gastritis
Discussion:
Bisphosphonates are a commonly used class of drugs used for the treatment of osteoporosis.
They inhibit osteoclast-mediated bone resorption. Side effects for all drugs in this class include
nausea, heartburn, gastritis, esophagitis, gastric ulcer formation, and bone, joint or muscle pains.
Bisphosphonates act as topical irritants to the GI lining. This is hypothesized to result from the
drug compromising the protective, hydrophobic mucosal barrier allowing gastric acid to come in
contact with the epithelial lining.
References:
Kennel KA, Drake MT. Adverse effects of bisphosphonates: implications for osteoporosis
management. Mayo Clin Proc. 2009;84:632-7.
Diel IJ, Bergner R, Grötz KA. Adverse effects of bisphosphonates: current issues. J Support Oncol.
2007 Nov-Dec;5(10):475-82. PMID: 18240669
For each description, select the most closely associated drug (A-E).
GABA agonist
Answers:
A. Ketamine
B. Flumazenil
C. Strychnine
D. Baclofen
E. Fluoxetine
Baclofen
Discussion:
Baclofen is a GABA agonist. Other GABA agonists include barbiturates, benzodiazepines,
zolpidem, propofol, alcohol, volatile anesthetics, and etomidate. Flumazenil is a GABA antagonist.
Fluoxetine is a selective serotonin reuptake inhibitor. Ketamine is an NMDA receptor antagonist.
Strychnine is a toxic pesticide that acts as a glycine and acetylcholine receptor antagonist.
References:
Ghanavatian S, Derian A. Baclofen. 2021 May 15. In: StatPearls [Internet]. Treasure Island (FL):
StatPearls Publishing; 2021 Jan–. PMID: 30252293.
Pubmed Web link
https://pubmed.ncbi.nlm.nih.gov/30252293/
For each description, select the most closely associated drug (A-E).
Alpha-adrenergic blocking agent
Answers:
A. Dobutamine
B. Propranolol
C. Phenoxybenzamine
D. Albuterol
E. Clonidine
Phenoxybenzamine
Discussion:
Phenoxybenzamine is an alpha-adrenergic blocker. Propranolol is a beta-adrenergic blocker.
Clonidine is an alpha agonist. Albuterol is a beta agonist. Dobutamine is a beta and alpha agonist.
References:
Yoham AL, Casadesus D. Phenoxybenzamine. 2020 Nov 30. In: StatPearls [Internet]. Treasure
Island (FL): StatPearls Publishing; 2021 Jan–. PMID: 32809502.
Pubmed Web link
https://pubmed.ncbi.nlm.nih.gov/32809502
Which of the following is an early marker of propofol infusion syndrome?
Answers:
A. Hyperlipidemia
B. Hypokalemia
C. Hypercalcemia
D. Metabolic alkalosis
E. Tachycardia
Hyperlipidemia
Discussion:
Propofol infusion syndrome (PIS) has been reported in pediatric and adult patients undergoing
prolonged high-dose propofol therapy (4-5 mg/kg/hr for 48 hours). The clinical features of this
syndrome include rhabdomyolysis, resulting in high creatine kinase, urine myoglobin, or both. The
rhabdomyolysis results in renal failure, which is characterized by oligo- or anuria, elevated
creatinine, and hyperkalemia. Other important features of the syndrome include cardiac
bradyarrhythmias and ventricular arrhythmias with possible cardiac failure and death; lipemia,
manifested by high serum triglycerides; hepatomegaly and elevated transaminases, with evidence
of fatty liver. Metabolic acidosis is a primary feature and may be the first laboratory evidence of the
syndrome.
Treatment is to promptly stop the propofol infusion, especially if metabolic acidosis is noted.
Dialysis may be required. However, once the full syndrome develops the prognosis for survival is
poor. According to the available case reports and series, propofol infusion syndrome has not been
seen at dosages below 4 mg/kg/hr. Care should be taken to assure that such dosages are not
exceeded. As the safety of propofol for ICU sedation has not been formally studied in the pediatric
age group, propofol is not approved for this purpose in patients under the age of 16. High-dose
propofol has been used to treat patients with conditions such as severe head injury and refractory
seizures. Seizures, per se, have not been reported as part of this syndrome. There is some
evidence that patients receiving catecholamines or steroids concomitantly may harbor an
increased risk of developing PIS.
References:
Kam PC, Cardone D. Propofol infusion syndrome. Anaesthesia. 2007 Jul;62(7):690-701.
Smith H, Sinson G, Varelas P. Vasopressors and propofol infusion syndrome in severe head
trauma. Neurocrit Care. 2009;10(2):166-72. doi: 10.1007/s12028-008-9163-y. Epub 2008 Dec
3.PMID: 19051063
Clearance of which of the following anticoagulants is most affected by renal dysfunction (i.e., the
highest percentage of renal excretion)?
Answers:
A. Edoxaban
B. Rivaroxaban
C. Apixaban
D. Warfarin
E. Dabigatran
Dabigatran
Discussion:
Warfarin is one of the most commonly prescribed anticoagulants. However, over the past several
years, newer oral anticoagulants have been introduced and are being used (dabigatran, apixaban,
edoxaban, and rivaroxaban). These newer anticoagulants are thought to reduce the risk of stroke
or embolism and bleeding, as compared to warfarin. Dabigatran is a direct thrombin inhibitor and
approximately 80-85% of the drug is excreted by the kidneys. This makes it the most affected by
renal dysfunction. Apixaban, edoxaban and rivaroxaban are all factor Xa inhibitors and are not as
sensitive to renal dysfunction.
References:
Mueck W, Schwers S, Stampfuss J. Rivaroxaban and other novel oral anticoagulants:
pharmacokinetics in healthy subjects, specific patient populations and relevance of coagulation
monitoring. Thromb J. 2013 Jun 28;11(1):10.2.
Ogata K, Mendell-Harary J, Tachibana M, et al. Clinical Safety, Tolerability, Pharmacokinetics, and
Pharmacodynamics of the Novel Factor Xa Inhibitor Edoxaban in Healthy Volunteers. J Clin
Pharmacol. 2010 Jul;50(7):743-53
A 70-kg (154-lb), 60-year-old man has a persistent postoperative generalized tonic-clonic seizure.
Administration of which of the following medications and doses is the most appropriate first step in
management of the seizure?
Answers:
A. Administer intravenous diazepam
B. Obtain CT scan
C. Obtain MRI
D. Administer intravenous lorazepam
E. Determine serum glucose level
Administer intravenous lorazepam
Discussion:
The answer is administer intravenous Lorazepam. The recommended initial pharmacologic
treatment of a seizure consists of lorazepam (Ativan), 0.1 mg/kg up to 4 mg, given over two
minutes. Benzodiazepines are preferred as initial treatment because of their high efficacy and
rapidity of action. Lorazepam is preferred over diazepam (Valium) because of the greater duration
of its antiseizure effect (12-24 hours vs. 15-30 mins). Anticonvulsants such as phenytoin or
phenobarbital can be started in addition to this first-line treatment for prevention of subsequent
seizures. Hypoglycemia is a cause of seizures and checking a serum glucose level is appropriate,
after the patient is no longer actively seizing. Imaging is not appropriate when a patient is actively
seizing.
References:
Lowenstein DH, Alldredge BK. Status epilepticus. N Engl J Med. 1998;338:970-976.
Marik PE, Varon J. The management of status epilepticus. Chest. 2004;126:582-591
