Pharmacology Flashcards
The route of administration associated with the lowest degree of bioavailability is:
- intravenous
- intramuscular
- intrathecal
- sublingual
intrathecal
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
- potency
- neurotoxicity
potency
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
- anticholinergic properties
- prokinetic properties on the GI tract
- a2-blocking properties
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:
- eplenerone
- methimazole
- metyrapone
- metyrosine
methimazole
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:
- vinca alkaloids
- angiotensin-converting enzyme inhibitors
- dantrolene
- amiodarone
amiodarone
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
μ-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:
- phentolamine
- phenoxygenzamine
- prazocin
- droperidol
phenoxybenzamine
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.
- A
- B
- C
- D
- Brain
- Muscle
- Fat
- Alveoli
Alveoli—>A
Brain—> B
Muscle—> C
Fat—>D
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.
1 2 3 4 Isoflurane Sevoflurane Nitrous Oxide Desflurane
Desflurane - 1
Nitrous Oxide - 2
Sevoflurane - 3
Isoflurane - 4
The onset of action of a local anesthetic agent is closely correlated to its:
- lipid solubility
- degree of protein binding
- ester or amide linkage
- pKa
pKa
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:
____%
3%
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:
- muscarinic receptors
- ganglionic nicotinic receptors
- glutaminergic receptors
- adrenergic receptors
muscarinic 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)
- analgesia
- bradycardia
- euphoria
- inhibition of ADH release
- pruritis
- antishivering
analgesia, inhibition of ADH release, antishivering
An infusion of 1.5 μg/kg/min of epinephrine would be expected to produce:
- mydriasis
- 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:
- coronary vasodilation
- 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:
- pH
- ester or amide linkage
- degree of protein binding
- pKa
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:
- desflurane
- nitrous oxide
- sevoflurane
- isoflurane
nitrous oxide
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)
- ventilatory rate
- tidal volume
- PaCO2
- hypoxic drive
- hypoxic vasoconstriction
- 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)
- acetylcholine
- succinic acid
- choline
- succinylmonocholine
- acetic acid
- succinyldicholine
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.):
0.6 L/Kg
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.
Clevidipine:
- 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:
- sigmoid shape
- hyperbolic shape
- parabolic shape
- bell shape
hyperbolic shape
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
- bupivacaine
- mepivacaine
- lidocaine
- ropivacaine
- prilocaine
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:
1500 mL
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:
- pregnancy
- thyroid disease
- severe burns
- patients receiving glucocorticoids
thyroid disease
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
- morphine
- oxycodone
- sufentanil
meperidine
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:
- B-blockers
- ACE inhibitors
- hydralazine
- a1 blockers
ACE inhibitors
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.
