Pharmacology Flashcards
Which one of the following best describes
the main mechanism of propofol sedation?
a. Cyclo-oxygenase inhibition
b. Depolarizing neuromuscular blockade
c. Endocannabinoid activation
d. Non-depolarizing neuromuscular blockade
e. Potentiates GABA-A receptor activity
e. Potentiates GABA-A receptor activity
GABA(A) receptor activation. While pro- pofol may have multiple effects, the main mechanism of action is thought to result from activation of GABA(A) receptors, causing increased transmembrane chloride conduc- tance and hyperpolarization of the neuron preventing generation of an action potential.
Which one of the following combinations of
clotting factors are affected by warfarin?
a. II, IX, X, Protein C
b. II, VII, IX, X
c. II, VII, IX, X, Protein C, Protein S
d. II, VII, X, Protein C
e. II, VII, X, XII
c. II, VII, IX, X, Protein C, Protein S
II, VII, IX, X, Protein C, Protein S. Pro- tein C has a short half-life (8 h) compared with other vitamin K-dependent factors and therefore is rapidly depleted with warfarin initiation, resulting in a transient hypercoagulable state.
Which one of the following blood tests would you perform to monitor the effect of low molecular weight heparin?
a. Factor VII
b. Factor VIII
c. Factor Xa activity
d. Prothrombin time
e. Von Willebran Factor
c. Factor Xa activity
A 75-year-old patient presents with GCS E3V4M5 and due to ICH. INR is 5.0 on warfarin for atrial fibrillation. Assuming you have access to all of the following therapies, which one of the following is the most appropriate next treatment?
a. Fresh frozen plasma
b. Protamine
c. Prothrombin complex concentrate
d. Recombinant factor VIIa
e. Vitamin K
c. Prothrombin complex concentrate
A patient with a right extradural hematoma
fixes and dilates his right pupil on the way to
theater. The anesthetist administers 100 ml
of 20% mannitol and his pupil normalizes
after 2 min. Which one of the following best
explains the immediate effect of mannitol?
a. Autoregulatory vasoconstriction
b. Diuretic effect
c. Increased cerebral blood volume
d. Osmotic effect reducing interstitial
brain fluid
e. Local effect on pupillary constrictors
a. Autoregulatory vasoconstriction
Mannitol has hemodynamic, osmotic, and diuretic effects. Following a bolus of hyperosmolar manni- tol, body water is drawn (including from RBC) in to plasma causing expansion and reduction in blood viscosity (reduction in volume, rigidity, and cohesiveness of RBC). Altered blood rheology reduces cerebral vascular resistance, increases cerebral blood flow and CPP. Autoregulatory vasoconstriction then reduces CBV (to restore normal CPP) and reduces ICP. These immediate rheological effects may also explain why ICP reduction with mannitol occurs in situations where the BBB is not intact. The osmotic effect of mannitol in causing brain shrinkage by drawing water out requires an intact BBB (across which an osmotic gradient can be set up) and can take up to 30 min to develop. Adverse effects of mannitol include hypotension, renal failure (especially if serum osmolality >320) and rebound rise in ICP (penetration of osmotically active solutes into edematous brain reversing osmotic gradient).
Which one of the following best describes the mechanism of dexamethasone action in reducing cerebral edema?
a. Reduces cytotoxic edema through nitric oxide inhibition
b. Reduces cytotoxic edema through VEGF inhibition
c. Reduces vasogenic edema through VEGF inhibition
d. Reduces vasogenic edema through upregulation of aquaporins
e. Reduces vasogenic edema through nitric oxide signaling
c. Reduces vasogenic edema through VEGF inhibition
Tumor-related disruption in the blood-brain bar- rier resulting in vasogenic edema is caused by local factors increasing the permeability of vessels (VEGF, glutamate, leukotrienes) and absence of normal tight endothelial junctions in tumor vessels as they grow in response to VEGF and bFGF. In large part, VEGF is responsible for the loss of integrity of the blood-brain barrier in brain tumors. Gliomas, meningiomas, and metastatic tumors all have upregulation of VEGF. VEGF is secreted by tumor cells as well as host stromal cells and binds to its receptors VEGFR1 and VEGFR2, which are located pri- marily on the surface of endothelial cells. VEGF stimulates the formation of gaps in the endothe- lium, a process that leads to fluid leakage into the brain parenchyma, thereby resulting in vasogenic edema. Most patients with brain tumors and peri- tumoral edema can be adequately managed with glucocorticoids. Reduction of intracranial pres- sure and improvement in neurologic symptoms usually begins within hours. A decrease in capil- lary permeability (i.e. improvement in blood- brain barrier function) can be identified within 6 h and changes of diffusion-weighted MRI indi- cating decreased edema are identifiable within 48-72 h. However, adequate reduction in ele- vated ICP resulting from peritumoral edema may take several days with glucocorticoid therapy alone. Dexamethasone is the standard agent, because its relative lack of mineralocorticoid activity reduces the potential for fluid retention. In addition, dexamethasone may be associated with a lower risk of infection and cognitive impairment compared to other glucocorticoids. The mechanism of action of glucocorticoids for control of vasogenic edema is not fully understood. Dexamethasone has recently been shown to upre- gulate Ang-1, a strong BBB-stabilizing factor, whereas it downregulates VEGF, a strong permea- bilizing factor, in astrocytes and pericytes. Gluco- corticoids may also increase the clearance of peritumoral edema by facilitating the transport of fluid into the ventricular system, from which it is cleared by cerebrospinal fluid (CSF) bulk flow.
Propofol-related infusion syndrome is
usually characterized by which one of the
following?
a. Acute refractory bradycardia with metabolic alkalosis
b. Acute refractory bradycardia with metabolic acidosis
c. Acute refractory bradycardia with respiratory alkalosis
d. Acute refractory bradycardia with respiratory acidosis
e. Acute refractory bradycardia with normal
acid-base balance
b. Acute refractory bradycardia with metabolic acidosis
Propofol infusion syndrome (PRIS): acute refrac- tory bradycardia leading to asystole, in the
presence of one or more of the following: meta- bolic acidosis, rhabdomyolysis, hyperlipidemia, and enlarged or fatty liver. There is an association between PRIS and propofol infusions at doses higher than 4 mg/kg/h for greater than 48 h duration. It is proposed that the syndrome may be caused by either a direct mitochondrial respi- ratory chain inhibition or impaired mitochondrial fatty acid metabolism mediated by propofol. ECG shows new right bundle branch block with convex-curved (“coved type”) ST elevation in the right precordial leads (V1 to V3). Risk factors include young age, severe critical illness of central nervous system or respiratory origin, exogenous catecholamine or glucocorticoid administration, inadequate carbohydrate intake and subclinical mitochondrial disease. Hemodialysis or hemoper- fusion with cardiorespiratory support has been the most successful treatment.
Red man syndrome is seen with which one of
the following medications?
a. Levodopa
b. Procyclidine
c. Propofol
d. Rifampicin
e. Vancomycin
e. Vancomycin
Red man syndrome is characterized by a complex of symptoms including: pruritis, urticaria, erythema, angioedema, tachycardia, hypotension, occasional muscle aches, and a maculopapular rash that usually appears on the face, neck, and upper torso. The eti- ology is thought to be due to a non-immune related release of histamine.
Which one of the following is the initial
treatment for a dystonic reaction to
levodopa?
a. Adenosine
b. Bromocriptine
c. Cyclizine
d. Procyclidine
e. Topiramate
d. Procyclidine
Which one of the following would you monitor during infusion of an intravenous loading dose of phenytoin?
a. Capillary blood glucose
b. Cardiac monitoring
c. Nystagmus
d. Peak flow rate
e. Urine output
b. Cardiac monitoring
Cardiac monitoring. During intravenous loading of phenytoin for control of seizures cardiac monitoring is essential due to the risk of bradycardia and heart-block. Elderly patients requiring multiple intravenous doses of phenytoin should also be monitored for purple glove syndrome.
