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Central Nervous System Pharmacology- Part 1
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1. Guanfacine has recently been FDA-approved for managing attention-deficit hyperactivity disorder (ADHD) in patients between the ages of 6 and 17 In addition to i ts benefits for ADHD, i t appears to provide symptom relief in generalized anxiety disorder and post-traumatic stress disorder.
Although the newly approved indications for guanfacine focus on the central nervous system, the drug can cause many important peripheral autonomic effects. They are as follows:
- lowers total peripheral resistance (systemic vascular resistance);
- at usual doses i t does not block vasopressor responses to such drugs as phenylephrine;
- resting heart rate and ventricular stroke volume decline as effects of guanfacine build during long-term therapy;
- sympathetic-mediated increases of heart rate and stroke volume normally associated with such activities as exercise, or as a baroreceptor reflex response to a sudden fall of blood pressure, are blunted;
- miosis may occur; and
- guanfacine has no direct or indirect effects on airway smooth
- Based on this description, which one of the following drugs i s most s imilar to guanfacine?
The next five questions refer to the table below (shown earlier for Questions 2 to 8 in the chapter “Peripheral Nervous Systems/Autonomics”), which i s the anesthesia record from a patient undergoing two operative procedures during laparoscopic abdominal surgery. Here I ask you about some drugs not addressed before. Remember: This medication administration plan i s very typical of what you’ll see with many s imilar operative procedures.
2. You see that midazolam was the fi rst drug given to the patient—actually right before she was transported into the (The notation IVP next to midazolam means “IV push,” ie, a rapid bolus injection.) In addition to causing sedation, anxiety relief, and generally “smoothing” the induction of anesthesia, which of the following i s the most l ikely effect you would expect to achieve as a result of premedicating with midazolam?
- Potentiating the analgesic effects of the morphine
- Preventing an intraoperative fall of blood pressure
- Preventing seizures l ikely to be caused by the propofol
- Prophylaxis of cardiac arrhythmias
- Providing amnestic effects (suppressing recall of perioperative events)
3. The record shows that propofol was given for What i s/are the most l ikely adverse response(s) associated with the administration of this widely used drug?
- Hypotension and respiratory (ventilatory) depression
- Long-term memory loss
- Malignant hyperthermia Seizures
- Unintended or excessively prolonged skeletal muscle paralysis
4. Assume that instead of inducing anesthesia with propofol, the nurse anesthetist used a parenteral barbiturate (eg, methohexital, thiamylal, and thiopental) with an extremely fast onset of action and short duration (sometimes called “ultrashort”). These barbiturate induction agents are effective, but are associated with a fairly high incidence of a certain and rather unique adverse What best describes what that adverse effect i s?
- Hyperalgesia (heightened perception of pain)
- Hypertensive cris i s
- Malignant hyperthermia
- Seizures, typically monoclinic
5. The patient received an intravenous dose of ketorolac shortly before the wounds were closed and surgery was What i s the most l ikely purpose for which i t was given?
- Control of anticipated postoperative nausea and vomiting
- Postoperative pain control
- Reversal of CNS depression caused by multiple depressant drugs
- Reversal of drug-induced neuromuscular blockade (paralysis)
- Suppression of wound inflammation
6. Ondansetron was administered about an hour before the anticipated end of What was the most l ikely reason for giving this to the patient?
- Hasten recovery of consciousness while effects of anesthetics wear off
- Intensify pain-relieving effects of other analgesics given to the patient
- Lessen ri sks of postop urinary retention through effects on bladder musculature
- Prevent or reduce the ri sk of postoperative paralytic i leus
- Reduce the ri sk of postoperative nausea and vomiting
7. Two inhaled general anesthetics, A and B, have the following MAC values:
- Based only on this information (note that we have not named any drugs), which statement i s true?
- Drug A has a longer duration of action than Drug B
- Drug A i s more soluble in the blood than Drug B
- Drug B causes greater analgesia and skeletal muscle relaxation than Drug A
- The concentration of drug in inspired air that i s needed to cause adequate surgical anesthesia i s higher for Drug B than for Drug A
- The time to onset of adequate general anesthesia i s 50 times longer for Drug B than for Drug A
8. A patient with Parkinson disease has s igns and symptoms that can be considered “moderate” now, but they are worsening and not responding well to current drug The physician decides to empirically assess an antiparkinson drug that i s a selective inhibitor of monoamine oxidase type B (MAO-B). What drug would that be?
9. A patient who has been treated with levodopa i s switched to a regimen with a product that contains levodopa plus What i s the main action of carbidopa that provides the rationale for using i t in this dual-drug approach?
- Blocks ACh release in the CNS, thereby facilitating levodopa’s ability to restore a dopamine-ACh balance
- Helps activate dietary vi tamin B6, a deficiency of which occurs during levodopa therapy
- Increases permeability of the blood-brain barrier to levodopa, giving levodopa better access to the CNS
- Inhibits metabolic conversion of levodopa to dopamine outside the CNS
- Reduces levodopa-induced hypotension by blocking vascular dopamine receptors
10. A 34-year-old man with mild anxiety and depression symptoms has heard about buspirone on TV and asks whether i t might be suitable for him. According to the most diagnostic and treatment cri teria, the drug would be appropriate, particularly for short-term symptom control. Which phrase correctly describes an important property of buspirone?
- Associated with a withdrawal syndrome that, i f unsupervised or controlled, may be fatal
- Has a s ignificant potential for abuse
- Is l ikely to potentiate the CNS depressant effects of alcohol, benzodiazepines, and sedative antihistamines (eg, diphenhydramine), so such interactants must be avoided at all cost
- Requires almost daily dosage ti trations in order to optimize the response
- Seldom causes drowsiness
11. A physician considers placing a patient on long-term (months, years) phenobarbital for control of a relatively common medical For most of these indications, newer and arguably more efficacious drugs, which participate in fewer drug interactions, are available and preferred. For which one of the following uses, nonetheless, i s this barbiturate sti l l considered reasonable and appropriate?
- Alcohol withdrawal s igns/symptoms
- Anxiety management
- Certain epilepsies
- Endogenous depression (adjunct to SSRIs)
- Sleep disorders such as insomnia
12. One reason for the declining use of tri cyclic antidepressants such as imipramine, and the growing use of newer classes, i s the prevalence of common tri cyclic-induced s ide effects or adverse What s ide effect or adverse response, l i sted below, i s most l ikely to occur with usual therapeutic doses of a tri cyclic?
- Anticholinergic (antimuscarinic) effects
13. A 42-year-old woman develops akathisias, parkinsonian-like dyskinesias, galactorrhea, and amenorrhea, as a consequence of psychotropic drug What drug-receptor-based mechanism, occurring in the central nervous system, most l ikely caused these responses?
- Blockade of α-adrenergic receptors
- Blockade of dopamine receptors
- Blockade of muscarinic receptors
- Supersensitivity of dopamine receptors
- Stimulation of nicotinic receptors
14. A patient on the trauma-burn unit received a drug to ease the pain of debridement and dressing changes for several severe He experiences good, prompt analgesia, but despite the absence of pain sensation during the procedure his heart rate and blood pressure ri se considerably, consistent with sympathetic nervous system activation by the pain and not affected by the analgesic drug. As the effects of the drug develop his skeletal muscle tone progressively increases. He appears awake at times because his eyes periodically open. As drug effects wear off he hallucinates and behaves in a very agitated fashion. Hallucinations, “bad dreams,” and periods of delirium recur over several days after receiving the drug. What drug was most l ikely given?
15. A 17-year-old male was diagnosed with epilepsy after developing repeated episodes of generalized tonic-clonic seizures following a motor vehicle accident in which he received a closed-head After treating acute seizures with the proper injectable drugs, he i s started on a regimen of oral phenytoin, the daily dose ti trated upward until symptom control and a therapeutic plasma concentration were reached. The elimination half-life of the drug during initial treatment was measured to be 24 hours, a value that i s quite typical for otherwise healthy adults taking no other drugs.
Today he presents in the neurology cl inic with nystagmus, ataxia, diplopia, cognitive impairment, and other s igns and symptoms consistent with phenytoin toxicity. A blood sample, drawn at noon, has a plasma phenytoin concentration of 30 mcg/mL. That value i s 50% higher than typical peak therapeutic plasma concentrations, and twice the usual minimum effective blood level. These values are summarized in the figure below.
The attending orders discontinuation of further doses of phenytoin until plasma levels fall into the therapeutic range, and the patient i s largely free of s igns and symptoms of phenytoin toxicity. In the interim, what would you do or expect to occur next?
- Administer flumazenil, which will quickly reverse s igns and symptoms of phenytoin toxicity but may cause seizures to recur
- Anticipate that elimination of phenytoin from the plasma will follow zero-order kinetics for several days
- Give an amphetamine or other CNS stimulant to reverse generalized CNS depression due to the phenytoin excess
- Give phenobarbital to induce the P450 system, thereby hastening phenytoin’s metabolic elimination
- Plasma phenytoin concentrations will fall to 15 mcg/mL, in the middle of the therapeutic range, by noon tomorrow (24 hours later, per the usual half-life)
16. A 12-year-old boy has been treated with methylphenidate for the last 3 His younger s i ster finds the bottle of pills and consumes enough to cause s ignificant toxicity. Which of the following findings would you most l ikely expect?
- Hypertension, tachycardia, seizures
- Hypotension, bronchospasm
- Drowsiness, obtunded reflexes, diarrhea
- Miosis, bradycardia, profuse salivation, sweating
- Hypothermia, skeletal muscle weakness or paralysis, pupils that are not responsive to l ight
17. Meperidine i s s imilar to morphine in many ways, but has some decided differences that are cl inically relevant: with very high blood levels or with true overdoses, meperidine can cause s ignificant adverse responses that s imply aren’t seen with morphine or most other opioid What i s that rather unique effect of meperidine?
- Constipation leading to paralytic i leus
- Heightened response to pain (paradoxical hyperalgesia)
- Intense biliary tract spasm
- Psychosis-like state, possibly seizures
- Respiratory depression, apnea, ventilatory arrest
18. Chlorpromazine and haloperidol can be considered prototypes of two relatively old but sti l l -used antipsychotic drug classes: the phenothiazines and the butyrophenones, While many of the actions and s ide effects of these drugs are qualitatively s imilar, they are different quantitatively: that i s , in terms of incidence and severity. Which effect or s ide effect typically occurs more frequently, i s usually more severe, and has a relatively rapid onset, with haloperidol?
- Extrapyramidal reactions
- Intense atropine-like s ide effects
- Lethal blood dyscrasias
- Orthostatic hypotension
- Urinary retention necessitating bladder catheterization