Flashcards in Pharmacology Deck (100):
The route of administration associated with the lowest degree of bioavailability is:
By definition, intravenous administration is associated with 100% bioavailability. Intramuscular and sublingual administration is associated with 60 - 100% bioavailability. Intrathecal administration circumvents the blood-brain barrier, but is associated with very low overall bioavailability.
The oil/gas coefficient of an inhaled anesthetic agent best corresponds to the agent's:
-speed of induction
-speed of emergence
The oil/gas coefficient is an indicator of potency. The higher the solubility, the more potent the drug.
The antiemetic effects of ondansetron are the result of the drug's:
-antagonistic properties at serotonin type-3 receptors
-prokinetic properties on the GI tract
antagonistic properties at serotonin type-3 receptors
Drugs used in the preoperative preparation of the hyperthyroid patient, which inhibit organification of iodine and synthesis of thyroid hormone include:
The most important goal in managing the hyperthyroid patient is to make the patient euthyroid before any surgery, if possible. The drugs propylthiouracil and methimazole are thiourea derivatives that inhibit organification of iodide and the synthesis of thyroid hormone.
Respiratory insufficiency has been associated with the administration of:
-angiotensin-converting enzyme inhibitors
Pulmonary disease from amiodarone occurs with 5 - 15% prevalence and takes the form of chronic interstitial pneumonitis, organizing pneumonia, ARDS or a solitary mass of fibrosis.
Generalized pruritis associated with neuraxial fentanyl administration appears to be the result of:
-systemic histamine release
-local histamine release
-thalamic effects of the narcotic
-mu(u) receptor interaction
Opiates frequently produce a rash, itching and a feeling of warmth in the area of the face, upper chest, and arms. This occurs even with non-histamine-releasing drugs, such as fentanyl. Pruritis is especially common with neuraxial administration. The mechanism appears to be through central μ-receptor interaction.
Noncompetitive and nonselective α-blockade can be achieved with the administration of:
Phenoxybenzamine has both α1- and α2-blocking activity. The α-receptors are noncompetitively and irreversibly bound. Phenoxybenzamine is used in the preoperative preparation of patients with pheochromocytoma.
A graph depicting the rise and fall of an inhaled anesthetic agent in different body compartments is shown (Click here to display graph). By dragging & reordering the selections in yellow, match the component with the associated graph trace.
Tolvaptan is effective in the treatment of hyponatremic, hypervolemic congestive heart failure by:
-inhibiting arginine vasopressin receptors
-inhibiting the counter current multiplier
-increasing the hypertonicity of the renal medulla
-improving renal blood flow
inhibiting arginine vasopressin receptors
Recently, vasopressin receptor blocking agents, such as tolvaptan, have been developed that inhibit the action of AVP on the renal collecting ducts. These agents have proven to be safe and efficacious in hyponatremic patients, appearing to have particular value in patients with hypervolemic hyponatremia secondary to congestive heart failure.
The structures of several inhaled agents are shown (Click here to display structures). By dragging & reordering the selections in yellow, match the agent with the associated structure.
Desflurane - 1
Nitrous Oxide - 2
Sevoflurane - 3
Isoflurane - 4
The onset of action of a local anesthetic agent is closely correlated to its:
-degree of protein binding
-ester or amide linkage
Since local anesthetic agents need to first gain access to the interior of the neuron to have effect, local anesthetic agents with lower pKa, such as lidocaine, mepivacaine and prilocaine, tend to have a more rapid onset of action than drugs with a greater pKa, such as bupivacaine, tetracaine and procaine.
A patient is undergoing debridement of wounds under hyperbaric conditions. If the pressure in the hyperbaric chamber is 2 atmospheres, the minimum alveolar concentration of desflurane would be expected to be:
MAC as originally defined depends on atmospheric pressure. However, when agent concentration is expressed as a partial pressure, MAC becomes independent of ambient pressure. As a result, MAC, expressed as a percentage, decreases with increasing ambient pressure.
MAC of desflurane @ 1 ATM = 6% of 760 mm Hg = 45.6 mm Hg
MAC of desflurane @ 2 ATM = 45.6 mm Hg / 1520 mm Hg = 0.03 or 3%
The central nervous system effects of nitrous oxide include:
-a decrease in the cerebral metabolic rate of oxygen consumption(CMRO2)
-a decrease in cerebral blood flow(CBF)
-a decrease in cerebral blood flow(CBF)
-a decrease in cerebrovascular tone
-an ablation of the reduction in CBF from hyperventilation
-an uncoupling of CBF and (CMRO2)
-a decrease in intracranial pressure
a decrease in cerebrovascular tone, an uncoupling of CBF and (CMRO2)
Nitrous oxide decreases cerebral vascular tone significantly and increases CMRO2. Since the increase in CMRO2 exceeds the elevation in CBF there is an uncoupling of these parameters. Mild hyperventilation can attenuate the increase in CBF that accompanies the use of nitrous oxide.
Succinylcholine may cause bradycardia as a result of its action on cardiac:
-ganglionic nicotinic receptors
Succinlycholine has no action on ganglionic nicotinic receptors, but may cause bradycardia by an action on cardiac cholinergic muscarinic receptors.
In considering the two-compartment model of drug distribution, the central compartment:
-is composed of the intravascular and extracellular fluids
-is composed of the muscle, skin and abdominal contents
-represents approximately 10% of the body mass
-receives approximately 50% of the cardiac output
represents approximately 10% of the body mass
In the two-compartment model, the first compartment is termed the central compartment and is composed of intravascular fluid and the highly perfused tissues such as the heart, lungs, brain, liver and kidneys. The central compartment represents only about 10% of the body mass in the adult; however, it receives approximately 75% of the cardiac output and is sometimes referred to as the vessel-rich group.
Actions produced by opiate agonistic action on the kappa receptor include: (Select 3)
-inhibition of ADH release
analgesia, inhibition of ADH release, antishivering
An infusion of 1.5 μg/kg/min of epinephrine would be expected to produce:
-increased blood flow to the skeletal muscles
-renal vascular vasoconstriction
-vasoconstriction of the cerebral vasculature
increased blood flow to the skeletal muscles
With low doses of epinephrine (1.5 μg/kg/min), few alpha effects are seen and beta effects predominate. This results in increased perfusion of skeletal muscle.
The propofol infusion syndrome (PRIS):
-occurs in patients with a history of soy or egg allergy
-limits the use of propofol infusion to cases ogles than 8 hour duration
-is most commonly seen in elderly patients with critical illness
-results in cardiac and peripheral muscle necrosis
results in cardiac and peripheral muscle necrosis
PRIS is likely the result of the inhibition of oxidative phosphorylation by propofol. Symptoms include severe metabolic acidosis, bradycardia and refractory heart failure. Risk factors include young age, doses greater than 4 - 5 mg/kg/hr, critical illness and an infusion duration greater than 48 hours.
Relief of anginal pain by nitroglycerine is primarily the result of:
-a reduction in heart rate
-negative inotropic effects
-decreased preload and cardiac work
decreased preload and cardiac work
Nitroglycerine causes venodilation and a resultant decrease in preload. Its primary mechanism of action in the relief of angina is a decrease in preload and cardiac work.
The occupancy theory states that:
-expansion of lipid bilayer is responsible for the effects of inhaled anesthetic agents
-receptor signaling translates changes to G-protein
-receptors exist in either an activated or inactivated state
-the magnitude of a drug's effect is proportional to the number of receptors occupied
the magnitude of a drug's effect is proportional to the number of receptors occupied
Simply stated, the occupancy theory holds that the magnitude of a drug's effect is proportional to the number of receptors occupied.
The duration of action of a local anesthetic agent is closely correlated to its:
-ester or amide linkage
-degree of protein binding
degree of protein binding
The duration of action of local anesthetics demonstrates a relationship to protein binding and lipid solubility. In theory, drugs that have a high affinity for protein, attach more firmly to the sodium channel receptor and have a greater duration of action.
Diffusion hypoxia is a potential problem following the administration of:
During emergence, when high concentrations of nitrous oxide have been given, the drug exits the body quickly and can result in the dilution of normal respiratory gases such as oxygen and carbon dioxide. The administration of 100% oxygen for several minutes following the termination nitrous oxide entirely avoids this potential problem.
Ventilatory effects of the volatile anesthetic agents include increases in: (Select 3)
-the apneic threshold
-bronchial smooth muscle tone
ventilatory rate, PaCO2, the apneic threshold
Volatile anesthetic agents decrease responsiveness to CO2. The compensatory mechanism for the decreased tidal volume is an increase in rate; however, this is insufficient to prevent an increase in PaCO2. Depression of the hypoxic drive occurs with very low concentrations of volatile agents and bronchial tone is decreased with resultant bronchodilation.
Hydrolysis of succinylcholine by plasma cholinesterase results in the formation of: (Select 3)
succinic acid, choline, succinylmonocholine
Succinylcholine undergoes ester hydrolysis, catalyzed by pseudocholinesterase, to produce succinic acid, choline and succinylmonocholine.
Drug X is quickly distributed to the total body water of a 70 Kg patient. The estimated volume of distribution (Vd) is drug X is:
(Enter numerical answer in box below. Click 'Next' when completed.):
The typical Vd, normalized for the body weight of a 70 Kg adult, would be the quantity of total body water (42 L) divided by the body weight (70 kg). This results in a Vd of 0.6 L/Kg.
Stimulation of opioid receptors has been shown to:
-inhibit guanylate cyclase in the cell
-activate guanylate cyclase in the cell
-inhibit adenylate cyclase in the cell
-activate adenylate cyclase in the cell
inhibit adenylate cyclase in the cell
Opioid receptors are GPCRs and inhibit the activity of adenylate cyclase inside cells. This causes in a decrease in intracellular cAMP, which decreases conductance of the voltage-gated calcium channels and open potassium channels, resulting in decreased neuronal activity.
Positive chronotropic effects are generally absent with low-dose norepinephrine infusions as a result of the:
-absence of B1 activity with norepinephrine
-a-effects on the sinoatrial node
-increase in vascular resistance inducing reflex vagal activity
-coronary vasospasm that is induced by norepinephrine
increase in vascular resistance inducing reflex vagal activity
In low doses, norepinephrine show little β2 activity and the end result is largely unopposed α-receptor stimulation. In addition, the chronotropic effect seen with β1-receptor stimulation is generally absent with low-dose norepinephrine because of the increase in SVR, which induces reflex vagal activity.
Pharmacokinetic and pharmacodynamic properties of etomidate include: (Select 3)
-hydrolysis by plasma esterases
-patient awakening is the result of rapid metabolism
-increased cerebral blood flow and ICP with induction
-minimal hemodynamic changes with induction
-adrenocortical suppression with induction doses
-minimal ventilatory depression with induction
hydrolysis by plasma esterases, minimal hemodynamic changes with induction, adrenocortical suppression with induction doses
Etomidate is rapidly metabolized by hepatic microsomal enzymes and plasma esterases. However, rapid redistribution accounts for its extremely short duration of action. The primary clinical advantage of etomidate is the hemodynamic stability upon induction. Adrenal hormone levels decrease for up to 24 hours after etomidate administration, largely as a result of 11β-hydroxylase inhibition.
-has negative chronotropic effects
-has negative inotropic effects
-is highly selective for vascular smooth muscle
-is a dopamine-1 agonist
is highly selective for vascular smooth muscle
Clevidipine is a dihydropyridine L-type calcium channel blocker indicated as an IV antihypertensive. It is highly selective for vascular muscle and does not affect myocardial contractility or conduction.
The graded dose-response curve has a:
The graded dose-response curve, which is plotted in linear fashion, characterizes the changes in measured response as an administered dose is increased. The response curve has a hyperbolic shape. When plotted on a logarithmic scale, the curve takes on a sigmoid, or 'S', shape.
Vasoconstrictive properties are associate with use of: (Select 3)
cocaine, lidocaine, ropivacaine
Ropivacaine and lidocaine are the only parenterally administered local anesthetics with vasoconstrictive properties. Cocaine also has vasoconstrictive properties because of its ability to block the reuptake of norepinephrine.
A 23-year-old man is undergoing a thoracotomy for resection of blebs. He is currently has a 500 mL pneumothorax present. If the patient is anesthetized with an anesthetic of desflurane with nitrous oxide and oxygen in a 2:1 ratio, the resultant volume of the pneumothorax will approach:
A compliant airspace, such as a pneumothorax, will increase in volume during nitrous oxide administration. Theoretically, at 50% inspired nitrous oxide, the gas bubble would double in volume. Similarly, at 67% nitrous oxide could triple the volume.
The chemical interaction of sevoflurane with desiccated soda lime has been associated with:
-carbon monoxide poisoning
-anesthesia machine fires
-inactivation of the soda lime
-degradation of the chemical indicator in the soda lime
anesthesia machine fires
Sevoflurane can react chemically with desiccated soda lime and yield excessive temperatures that produce anesthesia machine fires and patient injuries. The proposed mechanism is a dehydrohalogenation of the sevoflurane with the release of hydrogen gas.
Causes of increased pseudocholinesterase activity include:
-patients receiving glucocorticoids
Thyroid disease, nephrotic syndrome and obesity have been associated with an increase in pseudocholinesterase activity. An increase has also been reported in cognitively impaired children.
Characteristically, drugs with large volumes of distribution are:
-lipid soluble with a high degree of protein binding
-lipid soluble with little protein binding
-water soluble with a high degree of protein binding
-water soluble with little protein binding
lipid soluble with little protein binding
Drugs that are free, unbound to plasma proteins and lipid soluble easily cross membranes to tissues and therefore have large calculated volumes of distribution with low plasma concentrations.
The production of a neurotoxic metabolite has been associated with the use of:
Meperidine is biotransformed by the liver to normeperidine, a neurotoxic metabolite, which has a 12 - 16-hour half-life. Repetitive dosing of meperidine can cause accumulation of normeperidine, which may precipitate tremulousness, myoclonus, and seizures.
Low-dose dopamine infusion causes increased urine output as a result of:
-an increase in renal blood flow
-the inhibition of the effects of aldosterone
-the inhibition of the release of ADH
-stimulation of renin release
an increase in renal blood flow
The stimulation of dopamine receptors in the renal artery promotes an increase in renal blood flow and a resultant increase in glomerular filtration rate and urine output.
Pharmacokinetic and pharmacodynamic properties of ketamine include: (Select 3)
-hydrolysis by plasma esterases
-antagonizes NMDA receptors in the brain
-increases in cerebral blood flow and ICP with induction
-has anti-inflammatory effects
-can cause histamine release and bronchospasm with induction
-reduces heart rate and blood pressure with induction
antagonizes NMDA receptors in the brain, increases in cerebral blood flow and ICP with induction, has anti-inflammatory effects
Ketamine noncompetitively inhibits the NMDA receptor in the brain producing amnesia and a profound analgesic state. It inhibits tumor necrosis factor-alpha and interleukin-6, accounting for its antiinflammatory action. Ketamine is metabolized by hepatic microsomal enzymes. It increases CMRO2, CBF and ICP. Ketamine causes a centrally-mediated increase in sympathetic tone with an increase in heart rate and blood pressure. It increases pulmonary compliance in patients with bronchospastic disease.
Vasoplegic syndrome has been seen with the induction of anesthesia in patients receiving:
Vasoplegic syndrome (VS) is defined as unexpected refractory hypotension resulting from low systemic vascular resistance. The incidence of VS in surgical patients may be as high as 50% in persons receiving renin-angiotensin system antagonists.
The therapeutic safety margin of a drug is defined as the:
-lethal dose in 1% divided by the effective dose in 99% of the population
-lethal dose in 50% divided by the effective dose in 50% of the population
-effective dose in 99% divided by the lethal dose in 1% of the population
-effective dose in 1% divided by the lethal dose in 99% of the population
lethal dose in 1% divided by the effective dose in 99% of the population
The effective dose 99% (ED99) and lethal dose 1% (LD1) identify the therapeutic safety margin of a drug. The lower the margin of safety of a drug, the more likely toxic effects will be seen.
Of the following, the rapidity of local anesthetic absorption is the greatest with:
-sciatic nerve block
-brachial plexus block
inter pleural block
Excluding blocks of the airway, the absorption of local anesthetics generally occurs in the following order of rapidity: interpleural block > intercostal block > caudal block > epidural block > brachial plexus block > sciatic-femoral block > subcutaneous blocks.
The greatest degree of anesthetic metabolism is seen with the use of:
Although approximately 5% of sevoflurane is metabolized, the release of free fluoride anion does not seem to cause any clinically significant toxicity.
Disruption of DNA synthesis through the inactivation of methionine synthetase has been associated with the prolonged administration of:
Prolonged or chronic exposure to nitrous oxide can lead to inactivation of the vitamin B12 component of methionine synthetase. This can disrupt DNA synthesis.
The primary means of rocuronium elimination is:
-hepatic and plasma hydrolysis
-hepatic oxidative metabolism
-biliary elimination of unchanged drug
-renal elimination of unchanged drug
biliary elimination of unchanged drug
Biliary elimination of rocuronium is the primary means of elimination. Approximately one-third undergoes renal excretion. As a result, prolonged neuromuscular blockade can be expected in patients with significant hepatic or renal disease
In the two-compartment drug distribution curve shown below, the α-phase is largely the result of:
-hepatic and renal elimination of the drug
-distribution of the drug throughout the intravascular fluid
-distribution of the drug throughout the extracellular fluid
-dispersal of the drug into the tissue compartments
dispersal of the drug into the tissue compartments
The first phase of the curve is the α-phase, or distribution phase, which represents the initial dispersal of drug into the tissue compartments from the central compartment.
Respiratory effects of opiate agonists include:
-a shift to the left of the CO2 curve
-a reduction in the responsiveness of the respiratory centers to increasing PaCO2
-a decrease in tidal volume
-an increase in minute ventilation
a reduction in the responsiveness of the respiratory centers to increasing PaCO2
All opiate agonists produce a dose-dependent depression of respirations via effects on mu and delta receptors. They reduce the responsiveness of the respiratory centers to both increasing carbon dioxide and decreasing oxygen levels. They also produce a shift to the right of the CO2-response curve and cause an increase in tidal volume with a decrease in ventilatory rate.
Pharmacodynamic properties of isoproterenol include: (Select 2):
-vasoconstriction of cutaneous blood vessels
-pulmonary artery vasoconstriction
-an increase in total systemic vascular resistance
-increased heart rate
-reflex bradycardia with higher doses
bronchodilation, increased heart rate
The profound β1 stimulation of isoproterenol results in both positive inotropic and chronotropic effects and causes a dramatic increase in myocardial oxygen consumption. Isoproterenol is also a potent bronchial dilator and pulmonary vasodilator.
The benzodiazepine with the longest elimination half-life is:
Diazepam has the longest elimination half-life of the available benzodiazepines, approximately 36 - 50 hours. Diazepam also exhibits a near-linear relationship between elimination half-life and patient age, which can result in prolonged effect in the elderly.
-blocks angiotensin receptors
-is a direct vasodilator
-is effective in the treatment of refractory congestive heart failure
Entacapone and tolcapone are used for the treatment of Parkinson's disease. They are selective and reversible inhibitors of COMT. Caution should be used when administering catecholamines as their half-life may be significantly prolonged and effects may be exaggerated.
Chemical antagonism is seen with the:
-reversal of rocuronium neuromuscular blockade by neostigmine
-reversal of isoproterenol-induced tachycardia by propranolol
-reversal of fentanyl narcosis by naloxone
-reversal of heparin-induced anticoagulation by protamine
reversal of heparin-induced anticoagulation by protamine
Chemical antagonism occurs when a drug's action is blocked by the antagonist's chemical binding of the drug. This occurs in the case of positively charged protamine forming an ionic bond with heparin or the chemical binding of rocuronium by γ-cyclodextrin.
The addition of epinephrine, in a concentration of 1:200,000, to lidocaine has been shown to:
-increase the absorption of lidocaine
-decrease the duration of the block
-result in a more profound block
-require a reduction in the total amount of lidocaine that can be given
result in a more profound block
The addition of a vasoconstrictor to local anesthetics has been shown to reduce the rate of absorption, allowing more of the drug to stay in the area where it was injected. This allows for increased neuronal uptake and a longer and more profound block. It also causes a reduction in the peak plasma concentration of the drug, thereby reducing systemic toxicity.
As compared to a 40-year-old adult, the required dose (MAC) of inhaled anesthetic agents in a 6-month-old infant is approximately:
-increased by 50-80%
-decreased by 50-80%
increased by 50 - 80%
The MAC or required dose of anesthetics is higher in infants and children and decreases with increasing age. Infants aged 6 months have a MAC 1.5 to 1.8 times higher than a 40-year-old adult. The MAC of inhalational agents is decreased by 4% per decade of age over 40 years.
Electroencephalographic evidence of seizure activity has been associated with the administration of:
Sevoflurane, unlike desflurane, isoflurane or nitrous oxide can predispose patients to epileptic activity.
Non-specific esterases are involved in the metabolism of:
Nonspecific esterases and Hofmann elimination are responsible for the metabolism of atracurium. Like ataracurium, cisatracurium undergoes Hofmann elimination; however, esterases are not involved in the metabolism of cisatracurium.
Drugs that undergo pseudocholinesterase catalyzed phase I hydrolysis include: (Select 2)
Succinlycholine, cocaine, procaine, chloroprocaine, tetracaine, neostigmine and pyridostigmine all undergo pseudocholinesterase catalyzed ester hydrolysis. Although remifentanil, atracurium, esmolol and clevidipine do undergo ester hydrolysis, the hydrolysis is accomplished by nonspecific esterases.
Endocrine effects of opiate administration during surgery include the increased release of:
Opiates reduce the stress response to surgery and have an immunosuppressant effect. Endocrinologic effects include the release of vasopressin and inhibition of the stress-induced release of corticotropin and gonadotropins. Release of thyrotropin is also inhibited.
Pharmacodynamic properties of milrinone include increased:
-influx of calcium into vascular smooth muscle
-preload and afterload
Milrinone is a phosphodiesterase type-3 inhibitor, which produces positive inotropic action and vasodilation without producing tachycardia. In smooth muscle, milrinone causes an efflux of calcium with resultant relaxation and vasodilation.
-is a non-competitive antagonist of the benzodiazepine receptor site
-has a short half-life as compared to most benzodiazepines
-is effective in reversing both ethanol and barbiturate sedation
-does not precipitate withdrawal reactions in patients chronically receiving benzodiazepines
has a short half-life as compared to most benzodiazepines
Flumazenil is a competitive benzodiazepine antagonist, which produces prompt reversal of benzodiazepine effects. Its relatively short half-life and duration of action make the possibility of resedation clinically relevant. Flumazenil can produce withdrawal reactions in patients who are benzodiazepine dependent. It does not reverse the actions of ethanol or barbiturates.
The primary antidysrhythmic effect of adenosine:
-is to interrupt re-entrant AV nodal tachycardia
-stimulate the release of acetylcholine from the vagus nerve
-decrease the slope of phase 4 in cardia myocytes
-increase the slope of phase 4 in the sinoatrial and atrioventricular nodes
is to interrupt reentrant AV nodal tachycardia
The primary antidysrhythmic effect of adenosine is to interrupt reentrant AV nodal tachycardia, which most likely relates to its K+ current rather than Ca2+ current effects.
A list of pharmacodynamic definitions is shown (Click here to display definitions). By dragging & reordering the selections in yellow, match the pharmacodynamic property with the associated definition.
1. A drug that binds to a receptor, resulting in the opposite action of the agonist.
2. A drug that binds to a specific receptor and triggers a response.
3. A drug that has affinity for the receptor, but no efficacy.
4. A drug that activates the receptor, but cannot produce a maximal response.
Inverse Agonist 1
Partial Agonist 4
Maximum dosage guidelines for the infiltrative injection of local anesthetic state that the maximum cumulative (per procedure) dose of lidocaine, without epinephrine, is:
-2.5 mg/kg; not to exceed 175 mg dose
-4.5 mg/kg; not to exceed 300 mg
-7.0 mg/kg; not to exceed 400 mg dose
-11 mg/kg; not to exceed 800 mg dose
4.5 mg/kg; not to exceed 300 mg dose
The maximum cumulative dose of lidocaine per procedure is: 4.5 mg/kg; not to exceed 300 mg dose. If epinephrine is added to the lidocaine, the dose can be increased to: 7 mg/kg; not to exceed 400 mg dose.
The anesthetic effect of volatile agents is greatly attenuated or lost if:
-the length of the agent's molecules exceeds 5 carbon atoms
-the length of the agent's molecules is less than 3 carbon atoms
-halogens replace hydrogen atoms in the anesthetic molecule
-an either-linkage is absent
the length of the agent's molecules exceeds 5 carbon atoms
The length of anesthetic molecules is significant in that immobility (anesthetic effect) is attenuated or lost if carbon atom chain length exceeds a distance of 5 - 6 carbon atoms.
Awakening after an induction dose of propofol is a result of:
-rapid hepatic metabolism
-rapid extra-hepatic metabolism
-redistribution of the drug to the peripheral compartment
-metabolism in the plasma by non-specific esterases
redistribution of the drug to the peripheral compartment
Rapid distribution following an induction dose of propofol into the brain results in fast onset of generally one circulation time. Rapid redistribution from the central compartment to the peripheral compartments produces a quick initial decline. Metabolism plays little role in the initial awakening of the patient.
Clinically significant histamine release has been associated with the use of:
Atracurium releases modest amounts of histamine.
The rates of rise of the inhalational agents are shown (Click here to display definitions). By dragging & reordering the selections in yellow, match the agent with the rate of rise.
-A(top of graph)
-D(bottom of graph)
Nitrous Oxide - A
Desflurane - B
Sevoflurane - C
Isoflurane - D
The opioid with the greatest degree of lipid solubility is:
Sufentanil has the greatest degree of lipid solubility, as measured by the octanol/water coefficient. Sufentanil is approximately 1750 times more lipid soluble than morphine.
When treating maternal hypotension, as compared to phenylephrine, ephedrine produces an increase in fetal acidosis as a result of causing:
-maternal metabolic acidosis
-an increase in fetal metabolic rate
an increase in fetal metabolic rate
Ephedrine produces increases in fetal metabolic rate leading to fetal acidosis due to beta stimulation, whereas phenylephrine does not.
Dexmedetomidine: (Select 2)
-is an a2-receptor antagonist
-produces sedation with central sympatholysis
-causes dose-dependent ventilatory depression
-increases cerebral blood flow
-interferes with electrophysilogic nervous system monitoring
-causes a decrease in blood pressure and heart rate
produces sedation with central sympatholysis, causes a decrease in blood pressure and heart rate
Dexmedetomidine is an α2-receptor agonist, which produces sedation with central sympatholysis. This results in a reduction in blood pressure and heart rate. dexmedetomidine does not interfere with neurologic monitoring or cause significant ventilatory depression.
-blocks the Gpllb-IIIa receptor on platelets
-blocks the binding the IgE to mast cells
-may increase the plasma half-life of fentanyl
-is a reverse transcriptase inhibitor
may increase the plasma half-life of fentanyl
Ritonavir is a protease inhibitor used in the treatment of HIV infection. Ritonavir can cause changes in the function of the cytochrome system and may reduce fentanyl clearance and increase its half-life.
Ion trapping can occur with the placental transfer of lidocaine to the fetus as a result of the:
-lower pH of fetal blood
-higher pH of fetal blood
-increased degree of protein binding of fetal blood
-increased degree of placental tissue binding of lidocaine
lower pH of fetal blood
The lipid-soluble fraction of basic agents such as lidocaine crosses the placenta easily. However, once there, because of the lower pH of the fetus, the drug becomes more ionized and cannot easily cross the lipid bilayer of the placenta, resulting in accumulation of drug in the fetus.
Local anesthetics that have been associated with the production of methemoglobin include: (Select 2):
Two local anesthetics, benzocaine and prilocaine, can cause methemoglobin formation. Prilocaine can produce methemoglobin as a result of the hemoglobin oxidizing effect one of its metabolites, o-toluidine.
Factors shown to increase the minimum alveolar concentration (MAC) of inhaled anesthetics include:
-chronic alcohol consumption
hyperthyroidism, chronic alcohol consumption
Factors that have been shown to increase the MAC include: youth, hyperthermia, hyperthyroidism, chronic alcohol consumption, acute amphetamine administration and red-headed females.
Propofol is prepared in a 1% lipid emulsion because of its:
-low degree of lipid solubility
-ability to support bacterial growth
Propofol is prepared in a lipid emulsion as a result of its lack of solubility in water, as reflected by its high pKa of 11.
Concerning the pharmacokinetics of neuromuscular blockers in elderly patients: (Select 2)
-onset of relaxation is delayed
-onset of relaxation is more rapid
-recovery is delayed
-recovery is more rapid
onset of relaxation is delayed, recovery is delayed
The onset times of the NMBAs are generally delayed in the elderly due to slower circulation times. Changes in hepatic and renal clearance and an increased volume of distribution account for the increased duration.
During drug metabolism, the products of phase II reactions:
-are more polar compounds than the parent drug
-have decreased solubility in water
-have increased lipid solubility
-have increased ability to the blood-brain barrier and placenta
are more polar compounds than the parent drug
Phase II reactions are also referred to as synthetic reactions in which the body actually synthesizes a new compound by donating a functional group. The products of Phase II reactions have little or no biologic activity and are more polar compounds that are more highly ionized and easily extractible by the kidneys.
Seizures, hyperthermia and death have been reported in patients receiving MAO inhibitors who also receive:
There is a significant drug interaction that can occur between meperidine and the first-generation monamine oxidase-inhibiting drugs. Hyperthermia, seizures and death have been reported.
Vasodilation in both arterioles and veins, through selective α1-receptor blockade is seen in patients receiving:
Prazocin, doxazosin and terazosin are selective α1-receptor antagonists used in the treatment of hypertension. Their lack of α2-blocking activity indicates that they have no effect on norepinephrine levels and are associated with less tachycardia than seen with the use of nonselective α-blocker
The anticoagulation effect of rivaroxaban is the result of:
-direct thrombin inhibition
-inhibition of factor Xa
-inhibition of the production of hepatic coagulation factors
inhibition of factor Xa
The “xaban” class of drugs, including rivaroxaban and apixaban, directly inhibit factor Xa. They prolong the PT and aPTT, but monitoring is not recommended and the INR should not be used.
Concerning the action of local anesthetics, a phasic block refers to:
-a faster onset of block in myelinated nerves
-a faster onset of block in unmyelinated nerves
-a faster onset of block in nerves repetitively depolarized
-blockade that occurs in successive nodes of Ranvier
a faster onset of block in nerves repetitively depolarized
Local anesthetics work faster as the sodium channels are repetitively depolarized. This is termed as use-dependent or phasic block.
If the absolute value of the pKa - pH of a drug is less than 1, then the drug will be:
-almost 100% nonionized
-almost 100% ionized
-partially ionized and partially nonionized
-hydrophilic, and not readily cross cell membranes
partially ionized and partially nonionized
If the absolute value of the pKa - pH is less than 1, regardless of whether the pH is lower or higher than the pKa, the drug will be partially ionized (hydrophilic) and partially nonionized (lipophilic).
Toxic effects to local anesthetics include:
-increased platelet aggregation
When injected directly into skeletal muscle, local anesthetics are mildly myotoxic. Local anesthetics depress normal blood coagulation by decreasing platelet aggregation and enhancing fibrinolysis.
When given as a sole inhaled agent, an increase in systemic vascular resistance, central venous pressure and arterial pressure can be seen with the administration of:
Nitrous oxide activates the sympathetic nervous system thereby increasing SVR, CVP and arterial pressure.
Fospropofol is converted to propofol through the action of:
-nonspecific plasma esterases
The prodrug, fospropofol, is converted to active propofol by alkaline phosphatase.
Cholinesterase inhibitors that lack an ester linkage and competitively inhibit the enzyme include:
Edrophonium is a simple alcohol that contains a quaternary ammonium group. Because a true chemical bond is not formed, acetylcholine competes with edrophonium for the binding site of cholinesterase.
For practical purposes, drugs undergoing first-order elimination are regarded as being fully eliminated after 5 half-lives have past. At this point, the amount of drug remaining is approximately:
The elimination half-life is the time necessary for the plasma content of a drug to drop to half of its prevailing concentration. Clinically a drug is regarded as being fully eliminated when approximately 95% or more has been eliminated. After 5 half-lives a the remaining amount of drug has been reduced to 3.125%.
Opioids that possess antagonistic effects at the μ-receptor site, while retaining agonistic effects at the κ-receptor site include:
Both nalbuphine and butorphanol are classified as agonist-antagonist opioids. These drugs act as antagonists at the μ-receptor site while providing agonistic effects at the κ-receptor site.
The rapid termination of effect after the discontinuation of an esmolol infusion is a result of rapid:
-hydrolysis by nonspecific plasma esterases
-redistribution from the central compartment
hydrolysis by nonspecific plasma esterases
Esmolol has an onset time of 2 minutes and an elimination half-life of approximately 9 minutes. Esmolol is metabolized by nonspecific esterases found in the cytosol of red blood cells.
The effects of local anesthetics appear to be the result of drug binding to receptors in:
-the outer gate of the sodium channels
-the outer gate of the potassium channels
-the inner gate of the potassium channels
-the inner gate of the sodium channels
the inner gate of the sodium channels
Local anesthetics must gain access to the interior of the neuron to reach their receptor. Once inside the neuron, the ionized fraction binds to the receptor on the inside of the sodium channel.
Bosentan reduces pulmonary artery pressure by:
-blocking calcium channels
-reducing hypoxic vasoconstriction
Bosentan is the best studied of the endothelin antagonists and through this action induces pulmonary vasodilation.
The protein binding of acidic drugs is largely with:
In the binding of drugs to plasma proteins, albumin is the most important. Plasma albumin binds, for the most part, acidic drugs, while basic drugs may be bound by β-globulin and α1-acid glycoprotein.
Treatment of systemic local anesthetic toxicity should include:
-the administration for calcium channel blockers for control of cardiac arrhythmias
-the administration of vasopressin for the treatment of pulseless electrical activity
-the administration of lipid emulsion
-increasing ionization of the local anesthetic, decreasing drug entry into the brain, with hypoventilation with 100% oxygen.
the administration of lipid emulsion
Prompt airway management is crucial to preventing hypoxia and acidosis which are known to potentiate local anesthetic systemic toxicity (LAST). If cardiac arrest occurs, vasopressin, calcium channel blockers and beta-blockers should be avoided. Lipid emulsion therapy should be administered at the first signs of LAST.
The most marked attenuation of hypoxic pulmonary vasoconstriction is seen with the administration of:
Hypoxic pulmonary vasoconstriction is attenuated to some extent by isoflurane administration, but is markedly attenuated or lost by the administration of nitrous oxide.
Pharmacodynamic characteristics of propofol include: (Select 3)
-a decrease in cerebral metabolic rate of oxygen consumption
-a decrease in cerebral blood flow
-an increase in intracranial pressure
-electroencephalographic evidence of epileptiform activity
-an increase in myoclonia
-mild histamine release
-an increase in vascular tone
a decrease in cerebral metabolic rate of oxygen consumption, a decrease in cerebral blood flow, an increase in myoclonic
Propofol administration is associated with a decrease in CMRO2,CBF and ICP. Propofol can produce myoclonia; however, it does not cause epileptiform activity on the EEG. Propofol causes a decrease in BP, heart rate and SVR. It does not cause histamine release and is a preferred agent for induction in asthmatic patients.
Pathologic states associated with resistance to depolarizing neuromuscular blockade include:
-pseudohypterophic muscular dystrophy
-amyotrophic lateral sclerosis
Patients with myasthenia gravis are usually resistant to succinylcholine, with larger than usual doses required to produce complete blockade. This effect might be offset by the inhibition of plasma cholinesterase activity provided by pyridostigmine. Sensitivity to nondepolarizing neuromuscular blocking drugs is increased to a variable extent, depending on the severity of the disease
Zero-order drug elimination:
-is the most common method of elimination of narcotics
-is more efficient as compared to first-order elimination
-results in the removal of a constant amount of drug per unit time
-results in the removal of a constant fraction of drug per unit time
results in the removal of a constant amount of drug per unit time
First-order drug elimination implies that a constant fraction of drug is being eliminated per unit time. This is the most common method of elimination of anesthetic drugs. Zero-order elimination implies the removal of a constant amount of drug per unit time. This is a much less efficient method of drug elimination and implies saturation of the metabolic or elimination pathway.
Diuresis, through the competitive inhibition of aldosterone, can be achieved with the administration of:
By blocking the action of aldosterone, which normally stimulates Na+ reabsorption and K+ excretion by the collecting duct, spironolactone causes sodium and water loss with potassium retention.
Metabolic acidosis, increased mixed venous oxygen content, tachyphylaxis and tachycardia may be seen with the high-dose administration of:
In general, when nitroprusside is administered faster than 2 μg/kg/min, cyanide is generated faster than the patient can eliminate it. Clinically, the development of metabolic acidosis, increased mixed venous oxygen content, tachycardia and tachyphylaxis during nitroprusside use are signs of cyanide toxicity.
Nerve fibers showing the least sensitivity to the effects of local anesthetics are the:
-A alpha fibers
-A beta fibers
A αlpha fibers
Although some controversy exists regarding the relative sensitivity of the nerve fibers to local anesthetics, the Aα fibers have consistently shown the least sensitivity. Aα fibers are responsible for motor functions and proprioception.
Hypoglycemic agents that inhibit dipeptidyl peptidase-4 (DPP-4), thereby slowing the degradation of incretin hormone and improving postprandial glucose control include
Dipeptidyl-peptidase-4 inhibitors, such as sitagliptin [Januvia], slow degradation of incretin hormones and improve postprandial hyperglycemia.