Apex Unit 4 Pharmacology I Flashcards
A drug has a volume of distribution of 0.35 L/kg. In a 70-kg patient, what IV loading dose must be administered to achieve a plasma concentration of 8 mg/L?
(Enter your answer as mg and round to the nearest whole number)
196 mg
The loading dose is the amount of drug that must be administered to quickly achieve a therapeutic plasma concentration.
Loading dose = (Vd x desired Cp) / Bioavailability
If Vd is 0.35 L/kg and the patient weights 70 kg, the theoretical volume in which this drug will distribute in this patient is 24.5 L. Now we can input this into our equation.
Loading dose = (24.5 L x 8 mg/L) / 1 = 196 mg
Clearance is directly proportional to: (Select 2.)
half-life.
concentration in the central compartment.
extraction ratio.
blood flow to clearing organ.
Blood flow to clearing organ
Extraction ratio
Clearance is the volume of plasma that is cleared of drug per unit time.
Cl is directly proportional to blood flow to the clearing organ, extraction ratio, and drug dose.
Cl is inversely proportional to half-life and drug concentration on the central compartment.
Click on the part of the curve that correlates with drug elimination from the plasma.
The steepest portion of the curve represents redistribution from the plasma to the tissues. This is called the alpha phase.
The less steep portion of the curve represents elimination from the plasma. This is called the beta phase.
After administering an IV drug that distributes into a 1 compartment model, the patient’s serum contains 6.25 percent of the original dose. How many half-lives have elapsed?
(Enter your answer as a whole number)
Four
The elimination half-life (t ½) is the time required for a drug’s plasma concentration to decline by 50 percent.
After four half-lives have elapsed, the patient’s serum will contain 6.25 percent of the original dose.
In which circumstance is a drug more likely to pass through a lipid membrane? (Select 2.))
A weak base where the pH of the solution is < the pKa of the drug
A weak base where the pH of the solution is > the pKa of the drug
A weak acid where the pH of the solution is > the pKa of the drug
A weak acid where the pH of the solution is < the pKa of the drug
A weak acid where the pH of the solution is < the pKa of the drug
A weak base where the pH of the solution is > the pKa of the drug
Ionization describes the process where a molecule gains a positive or negative charge, and this molecular change affects a molecule’s ability to diffuse through lipid membranes.
Remember that like dissolves like, therefore the correct answers are a weak base in a basic solution and a weak acid in an acidic solution.
Which circumstance creates the STRONGEST gradient for passage of local anesthetic from the mother to the fetus?
Maternal acidosis and fetal acidosis
Maternal acidosis and fetal alkalosis
Maternal alkalosis and fetal acidosis
Maternal alkalosis and fetal alkalosis
Maternal alkalosis
Fetal acidosis
This question tests your understanding of ion trapping, which happens to be a terrific way to apply what you learned in the last question.
Local anesthetics are weak bases, and the acid-base status of the mother and fetus affects how these drugs transfer across the placenta.
Maternal alkalosis increases the unionized fraction in the maternal circulation; more local anesthetic is available to diffuse across the placenta.
Fetal acidosis increases the ionized fraction inside the fetus. This prevents the local anesthetic from crossing the placenta (back to the mother), thus “trapping” it inside the fetus.
If a drug is usually 98 percent bound by plasma protein and the bound fraction is reduced to 96 percent, the free fraction will increase by:
(Enter your answer as a percentage)
100
This question is really a percent change calculation in disguise. The kind of question you probably saw on the GRE. And you thought you could purge all of that from your memory?
We asked about the free fraction, although we gave you values for the bound fraction.
Percent change = [(New value - Old value) / Old value] x 100
Percent change = [(4 - 2) / 2] x 100 = 100%
Which kinetic model describes the process that metabolizes a constant amount of drug per unit time?
Zero order
First order
Second order
Third order
Zero order
Kinetic models help us predict a drug’s plasma concentration over time.
Zero order kinetics describes a situation where a constant amount of the drug is metabolized per unit time.
First order kinetics describes a situation where a constant fraction of the drug is metabolized per unit time.
Which process is a phase 2 reaction? Hydrolysis Reduction Conjugation Oxidation
Conjugation
Drug metabolism is divided into three phases:
Phase 1 = Modification (oxidation, reduction, hydrolysis)
Phase 2 = Conjugation
Phase 3 = Excretion
Identify the drugs that undergo perfusion-dependent hepatic elimination. (Select 3.) Remifentanil Fentanyl Propofol Lidocaine Rocuronium Diazepam
Fentanyl
Propofol
Lidocaine
You’ll need to be able to identify drugs that undergo perfusion-dependent hepatic elimination vs those subject to capacity-dependent hepatic elimination.
Drugs that undergo perfusion-dependent hepatic elimination include: fentanyl, lidocaine, and propofol.
Drugs that undergo capacity-dependent hepatic elimination include: diazepam and rocuronium.
Remifentanil is metabolized by nonspecific esterases in the plasma (not the liver).
Which drug inhibits codeine metabolism? Fluoxetine Rifampin Phenytoin Diltiazem
Fluoxetine
Codeine is biotransformed to its active metabolite (morphine) by CYP 2D6. Therefore, the Cp of its active metabolite is affected by alterations in CYP 2D6 activity.
Quinidine and selective serotonin reuptake inhibitors (particularly fluoxetine and paroxetine) profoundly inhibit CYP 2D6.
Therefore, codeine, oxycodone, and hydrocodone will not be effectively metabolized to morphine and will fail to provide adequate pain relief. The clinical correlation is that these analgesics are poor choices for patients taking SSRIs or quinidine.
Which statement regarding renal clearance is true?
Acidic urine promotes thiopental excretion.
Organic anion transporters secrete drug into the distal convoluted tubule.
Basic urine enhances morphine reabsorption.
Protein bound drugs are filtered at the glomerulus.
Basic urine enhances morphine reabsorption.
This is a complex question that requires a solid understanding of renal physiology, acid/base chemistry, and a bit of pharmacology.
Morphine is a weak base. As a weak base, the unionized fraction increases in an alkalotic environment. Therefore, basic urine enhances morphine reabsorption.
Thiopental is a weak acid. Acidic urine enhances its reabsorption (not excretion).
Protein bound drugs do not freely pass through the glomerulus – only the free fraction is filtered.
Organic anion transporters are present in the proximal (not distal) convoluted tubule. They actively secrete anions into the urine.
Identify the drugs that are metabolized by nonspecific plasma esterases. (Select 3.) Remifentanil Atracurium Cocaine Esmolol Succinylcholine Fospropofol
Esmolol
Remifentanil
Atracurium
Enzymatic drug metabolism in the plasma tends to occur via one of three pathways:
Pseudocholinesterase: succinylcholine, cocaine (+ hepatic)
Nonspecific esterases: esmolol, remifentanil, atracurium (+ Hofmann)
Alkaline phosphatase: fospropofol
For completeness, Hofmann elimination also takes place in the plasma, but is dependent on pH and temperature (not enzymatic function).
Pharmacodynamics is the study of:
plasma concentration and effect site concentration.
drug dose and plasma concentration.
tissue concentration and efficacy.
effect site concentration and clinical effect.
Effect site concentration and clinical effect
Pharmacodynamics describes the relationship between the effect site concentration and the clinical effect.
Pharmacokinetics describes the relationship between drug dose and plasma concentration.
Pharmacobiophasics unites PK and PD by examining the relationship between plasma concentration and effect site concentration.
On the dose response curve, the x-axis correlates with: percentage of receptors occupied. individual variability. efficacy. potency.
Potency
Potency is the dose required to achieve a given clinical effect. It is depicted by the x-axis.
Efficacy is the intrinsic ability of a drug to elicit a given clinical effect. It is depicted by the y-axis.
The slope tells us how many receptors must be occupied to elicit a clinical effect
We can compare the dose response curves from multiple patients to learn about the individual variability of each patient.
Click the curve that represents an antagonist.
Curve A: An agonist binds to a receptor and turns on a specific cellular response.
Curve B: A partial agonist binds to a receptor, but it is only capable of eliciting a partial cellular response.
Curve C: An antagonist binds to a receptor but does not elicit a clinical response.
Curve D: An inverse agonist binds to a receptor and causes the opposite effect of the agonist.
A new induction agent has a median effective dose of 125 mg and the median lethal dose of 1500 mg. Calculate the therapeutic index for this drug.
(Round your answer to the nearest whole number)
12
The therapeutic index is a measure of drug safety.
To calculate TI, you need to divide the LD50 by ED50.
The LD50 was 1500 mg and the ED50 was 125 mg.
TI = 1500 mg / 125 mg = 12
Click on the molecule that is one half of a racemic mixture.
Chirality is a division of stereochemistry. It deals with molecules that have a center of three-dimensional asymmetry. In biologic systems, this type of asymmetry generally stems from the tetrahedral bonding of carbon – carbon binds to 4 different atoms.
A molecule with 1 chiral carbon will exist as 2 enantiomers. The more chiral carbons in a molecule, the more enantiomers that are created.
A racemic mixture contains 2 enantiomers in equal amounts.
A patient is experiencing a prolonged recovery from midazolam sedation. What is the initial dose of flumazenil?
(Enter your answer as milligrams)
0.2 mg
Flumazenil is a competitive antagonist of the GABA-A receptor. It is used to reverse benzodiazepine overdose.
The initial dose is 0.2 mg IV.
It is titrated in 0.1 mg increments until a desired response is achieved.
Propofol infusion syndrome is categorized by the presence of: (Select 2.) bradycardia. metabolic acidosis. hypokalemia. respiratory failure.
Bradycardia
Metabolic acidosis
Propofol contains long chain triglycerides, and an increased LCT load impairs oxidative phosphorylation and fatty acid metabolism. This starves cells of oxygen, particularly in cardiac and skeletal muscle.
Propofol infusion syndrome presents with acute refractory bradycardia → asystole + at least one of the following:
Metabolic acidosis (base deficit > 10 mmol/L)
Rhabdomyolysis
Enlarged or fatty liver
Renal failure
Hyperlipidemia
Lipemia (cloudy plasma or blood) may be an early sign
Fospropofol is: (Select 2.) associated with pain at the injection site. metabolized by alkaline phosphatase. a prodrug. prepared as a lipid emulsion.
A prodrug
Metabolized by alkaline phosphatase
Fospropofol (Lusedra) is a prodrug that is metabolized to propofol in the systemic circulation. Alkaline phosphatase is the enzyme that carries out this reaction. Because the drug is activated inside the body, it has a prolonged onset and longer duration of action (it takes time to convert the prodrug to propofol).
Unlike propofol, fospropofol is prepared as an aqueous solution and is not associated with pain at the injection site. Interestingly, fospropofol does cause burning in the genital and anal regions.
Ketamine: (Select 3.)
increases the cerebral metabolic rate of oxygen consumption.
causes emergence delirium.
increases the risk of depression.
relieves somatic pain.
agonizes the N-methyl-D-aspartate receptor.
promotes bronchoconstriction.
Relieves somatic pain
Causes emergence delirium
Increases the cerebral metabolic rate of oxygen consumption
Ketamine is an NMDA receptor antagonist (not agonist). Its pharmacologic profile is much different from the other IV induction agents, making it a great topic for boards.
It causes emergence delirium.
It provides good analgesia (somatic pain > visceral pain).
It increases CMRO2.
It promotes bronchodilation (not bronchoconstriction).
It is gaining popularity in the treatment of severe depression (it doesn’t cause it).
Central nervous system effects of etomidate include: (Select 2.) decreased intracranial pressure. myoclonus. cerebral vasodilation. analgesia.
Myoclonus
Decreased intracranial pressure
Central nervous system effects of etomidate include:
Myoclonus
↓ Cerebral blood flow (cerebral vasoconstriction)
↓ Intracranial pressure
Etomidate does not provide analgesia.
Which anesthetic agent increases mortality in the patient with Addisonian crisis? Etomidate Midazolam Propofol Dexmedetomidine
Etomidate
Cortisol and aldosterone synthesis are dependent on the enzyme 11-beta-hydroxylase (located in the adrenal medulla). Some texts also add 17-alpha-hydroxylase.
Etomidate is a known inhibitor of 11-beta-hydroxylase and 17-alpha-hydroxylase.
A single dose of etomidate suppresses adrenocortical function for 5-8 hours (some books say up to 24 hrs).
For this reason, etomidate should be avoided in patients reliant on the intrinsic stress response (sepsis or acut
Choose the statements that demonstrate an accurate understanding of thiopental. (Select 2.)
It provides neuroprotection against global ischemia.
There is a sulfur molecule in the second position.
It causes a reflex tachycardia.
Prompt awakening is the result of hepatic metabolism.
It causes a reflex tachycardia
There is a sulfur molecule in the second position
Although sodium thiopental isn’t available in the US, its place in anesthetic history makes it fair game on the NCE.
Thiopental is a thiobarbiturate with a sulfur molecule in the second position.
Hypotension is primarily the result of venodilation and decreased preload; myocardial depression is a secondary cause. Because the baroreceptor reflex remains intact, there is a reflex tachycardia. This explains why thiopental tends to cause less hypotension compared to propofol (propofol impairs the baroreceptor reflex).
Although thiopental is metabolized by the hepatic P450 enzymes, rapid awaking following a single IV induction dose is the result of redistribution out of the brain (not metabolism).
Which anesthetic agent produces sedation that MOST closely resembles natural sleep? Propofol Dexmedetomidine Ketamine Midazolam
Dexmedetomidine
Dexmedetomidine is an alpha-2 agonist. Of all of the IV anesthetic agents, it produces sedation that most closely resembles natural sleep.
Sedation is the result of decreased SNS tone and decreased level of arousal.
Patients are easily aroused.
It does not provide reliable amnesia.
Rank each benzodiazepine according to its elimination half-life.
Midazolam
Lorazepam
Diazepam
(One is the shortest and three is the longest)
Midazolam + 1
Lorazepam + 2
Diazepam + 3
Comparative elimination half-lives: diazepam > lorazepam > midazolam
Diazepam undergoes enterohepatic recirculation, which explains why it remains in the body for such a long time (elimination t1/2 = 43 hrs).
A patient is experiencing a prolonged recovery from midazolam sedation. What is the initial dose of flumazenil?
(Enter your answer as milligrams)
0.2 mg
Flumazenil is a competitive antagonist of the GABA-A receptor. It is used to reverse benzodiazepine overdose.
The initial dose is 0.2 mg IV.
It is titrated in 0.1 mg increments until a desired response is achieved.
Match each inhaled anesthetic with its chemical structure.
review nitrous, des 6
iso - cl
sevo 7
Match each inhaled anesthetic with its physiochemical property.
Isoflurane + Vapor pressure = 240 mmHg
Desflurane + Boiling point = 22 degrees
Sevoflurane + Unstable even in hydrated soda lime
Nitrous oxide + Molecular weight = 44 g
Match each inhalation anesthetic to its blood gas partition coefficient.
Desflurane + 0.42
Nitrous oxide + 0.46
Sevoflurane + 0.65
Isoflurane + 1.46
Click on the FA/FI curve that represents nitrous oxide.
The FA/FI curves are listed from top to bottom:
Nitrous oxide Desflurane Sevoflurane Isoflurane So if desflurane has the smallest blood:gas partition coefficient, then why is it below nitrous oxide on this graph?
Which factor reduces the rate of rise of FA/FI? (Select 3.)
Increased FRC Increased cardiac output Decreased time constant Decreased fresh gas flow Increased alveolar ventilation Decreased anatomic dead space
Increased cardiac output
Increased functional residual capacity
Decreased fresh gas flow
A decreased rate of rise of FA/FI means a slower induction. This can be caused by an increased cardiac output, increased FRC, or decreased fresh gas flow.
An increased rate of rise of FA/FI means a faster induction. This can be caused by a decreased time constant, decreased anatomic dead space, or an increased alveolar ventilation.
What percentage of body weight is accounted for by the vessel rich group? 10% 20% 50% 75%
10%
when considering the distribution of anesthetics throughout the body, we can conceptualize 4 tissue groups: vessel rich group, muscle group, fat group, and vessel poor group.
The vessel rich group accounts for only 10% of body weight, yet it receives 75% of the cardiac output!
Match each inhalation anesthetic to its amount of hepatic metabolism.
Nitrous oxide + 0.004%
Desflurane + 0.02%
Isoflurane + 0.2%
Sevoflurane + 2% (up to 5%)
Which concept BEST explains why the rate of rise of FA/FI is faster for nitrous oxide than desflurane? Augmented inflow effect Concentrating effect Ventilation effect Second gas effect
Concentrating Effect
Even though desflurane has a lower blood gas partition coefficient than nitrous oxide, the concentrating effect explains why the rate of rise of FA/FI is faster for nitrous oxide than desflurane.
Assuming that the functional residual capacity remains constant, which concept explains a temporary increase in alveolar oxygen concentration when nitrous oxide is turned on during an inhalation induction?
Ventilation effect
Diffusion hypoxia
Concentration effect
Second gas effect
Second Gas Effect
Not only does the second gas effect explain how nitrous oxide hastens the onset of a second gas, but it also explains why alveolar oxygen might transiently increase.
We all know that FRC may become smaller during anesthetic induction with a halogenated agent, so in clinical practice the PaO2 may not always increase. This is why we specifically stated that the FRC remained constant.`
A patient has a right-to-left intracardiac shunt. The rate of rise of FA/FI of which drug will be affected MOST?
FA/FI is unaffected by a right-to-left intracardiac shunt
Desflurane
Isoflurane
Sevoflurane
Desflurane
This is the kind of question where the rubber meets the road. You need to know something about cardiac shunts as well as how they impact the pharmacokinetics of the inhalation anesthetics.
A right-to-left cardiac shunt slows the speed of induction with a volatile agent. It takes longer for FA to equilibrate with FI.
Agents with low solubility (desflurane) are affected the most.
Agents with high solubility (isoflurane) are affected the least.
