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
While propofol may have multiple effects, the main
mechanism of action is thought to result from
activation of GABA(A) receptors, causing
increased transmembrane chloride conductance 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
c—II, VII, IX, X, Protein C, Protein S. Protein 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 mannitol, 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 barrier 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 primarily on the surface of endothelial cells. VEGF
stimulates the formation of gaps in the endothelium, a process that leads to fluid leakage into the
brain parenchyma, thereby resulting in vasogenic
edema. Most patients with brain tumors and peritumoral edema can be adequately managed with
glucocorticoids. Reduction of intracranial pressure and improvement in neurologic symptoms
usually begins within hours. A decrease in capillary permeability (i.e. improvement in bloodbrain barrier function) can be identified within
6 h and changes of diffusion-weighted MRI indicating decreased edema are identifiable within
48-72 h. However, adequate reduction in elevated 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 upregulate Ang-1, a strong BBB-stabilizing factor,
whereas it downregulates VEGF, a strong permeabilizing factor, in astrocytes and pericytes. Glucocorticoids 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.
A 75-year-old patient presents with GCS E3V4M5 and due to ICH. INR is 5.0 on war- farin 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
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 refractory bradycardia leading to asystole, in the presence of one or more of the following: metabolic 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 respiratory 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 hemoperfusion with cardiorespiratory support has been
the most successful treatment.
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).
Red man syndrome is seen with which one of
the following medications?
a. Levodopa
b. Procyclidine
c. Propofol
d. Rifampicin
e. Vancomycin
e—Vancomycin
Redman 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 etiology 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 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 upre- gulation 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
3. c—Factor Xa activity.
4. c—Prothrombin complex concentrate
5. 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
124 PART I BASIC SCIENCE
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.
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
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.
Anticonvulsants:
a. Acetazolamide
b. Carbamazepine
c. Ethosuxamide
d. Gabapentin
e. Lacosamide
f. Lamotrigine
g. Levetiracetam
h. Perampanel
i. Phenytoin
j. Pregabalin
k. Sodium Valproate
l. Topiramate
m. Vigabatrin
n. Zonisamide
For each of the following descriptions, select the
most appropriate answers from the list above.
Each answer may be used once, more than once
or not at all.
1. Risk of thrombocytopenia and increased
warfarin effect
2. Affect T-type calcium current and used in
absence seizures
3. Associated with weight loss
1—k, Valproate;
2—c, Ethosuxamide;
3—l, Topiramate
- Chemotherapy:
a. Bevacizumab
b. Carmustine (BNCU)
c. Cisplatin
d. Erlotinib
e. Everolimus
f. Lomustine (CCNI)
g. Methotrexate
h. Procarbazine
i. Tamoxifen
j. Temozolomide
k. Vincristine
For each of the descriptions, select the
most appropriate answers from the list above.
Each answer may be used once, more than once
or not at all.
1. Microtubule inhibitor
2. VEGF inhibitor
3. SEGA treatment
4. Chemotherapy wafer for GBM
1—k, Vincristine;
2—a, Bevacizumab;
3—e, Everolimus;
4—b, Carmustine
