Deja Review Pharmacology, 2nd Edition

CHAPTER 5. CNS Agents

 

GENERAL AND LOCAL ANESTHETICS

 

State which stage of anesthesia each of the following descriptions refers to?

Delirium; violent behavior; increased blood pressure; increased respiratory rate; irregular breathing rate and volume; amnesia; retching and vomiting with stimulation; disconjugate gaze

Stage II (excitement)

Depression of vasomotor center; depression of respiratory center; death may occur

Stage IV (medullary depression)

Eye movements cease; fixed pupils; regular respiration; relaxation of skeletal muscles

Stage III (surgical anesthesia)

Loss of pain sensation; patient is conscious; no amnesia in early part of this stage

Stage I (analgesia)

Give examples of inhaled anesthetics:

Halothane; nitrous oxide; isoflurane; enflurane; sevoflurane; desflurane; methoxyflurane

With regard to inhaled anesthetics, what does MAC stand for?

Minimum alveolar concentration. Note: this is not to be confused with monitored anesthesia care also commonly referred to as MAC, which is a combination of regional anesthesia, sedation, and analgesia.

What is MAC in regard to inhaled anesthetics?

The concentration of inhaled anesthetic required to stop movement in 50% of patients given a standardized skin incision; a measure of potency for inhaled anesthetics

For potent inhaled anesthetics, is the MAC small or large?

Small (inverse of the MAC is used as an index of potency for inhaled anesthetics)

Which inhaled anesthetic has the largest MAC?

Nitrous oxide (>100%)

Which inhaled anesthetic has the smallest MAC?

Halothane (0.75%)

As lipid solubility of an inhaled anesthetic increases, what happens to the concentration of inhaled anesthetic needed to produce anesthesia, that is, does it increase or decrease?

It decreases.

What is the blood/gas partition coefficient?

The ratio of the total amount of gas in the blood relative to the gas equilibrium phase. It refers to an inhaled anesthetic’s solubility in the blood.

If an inhaled anesthetic has a high blood/gas partition coefficient, will times of induction and recovery be increased or decreased?

It will be increased because the time to increase arterial tension is longer.

Give an example of an inhaled anesthetic with a low blood/gas partition coefficient (low blood solubility):

Nitrous oxide (0.5); desflurane (0.4)

Give an example of an inhaled anesthetic with a high blood/gas partition coefficient (high blood solubility):

Halothane (2.3); enflurane (1.8)

Which inhaled anesthetic, halothane or nitrous oxide, will take longer to change the depth of anesthesia when the concentration of the inhaled anesthetic has been changed?

Halothane

Are MAC values additive?

Yes

Are MAC values higher or lower in elderly patients?

They are lower, thus elderly patients generally require lower concentrations of inhaled anesthetics.

Are MAC values higher or lower when opioid analgesics and/or sedative hypnotics are used concomitantly?

They are lower.

Do inhaled anesthetics increase or decrease the response to Pco2 levels?

Decrease

Do inhaled anesthetics increase or decrease cerebral vascular flow?

Increase

Do inhaled anesthetics increase or decrease intracranial pressure?

Increase

Do inhaled anesthetics relax or strengthen uterine smooth muscle contractions?

Relax (except methoxyflurane when briefly inhaled, therefore, can be used during childbirth)

Which of the inhaled anesthetics is not a halogenated hydrocarbon?

Nitrous oxide

Are the inhaled halogenated hydrocarbon anesthetics volatile or nonvolatile gases?

Volatile gases

Which inhaled anesthetic is associated with malignant hyperthermia?

Halothane

What characterizes malignant hyperthermia?

Hyperthermia; muscle rigidity; acidosis; hypertension; hyperkalemia

Should a patient with a family history positive for malignant hyperthermia be concerned?

Yes, because a genetic defect in ryanodine receptors may be inherited.

What drug is given to treat malignant hyperthermia?

Dantrolene

Which inhaled anesthetic is associated with increased bronchiolar secretions?

Isoflurane

Which inhaled anesthetic is associated with hepatitis?

Halothane

Halothane is not hepatotoxic in what patient population?

Pediatric patients

Which inhaled anesthetic is the least hepatotoxic?

Nitrous oxide

Which inhaled anesthetic is associated with increased bronchiolar spasms?

Isoflurane

Which inhaled anesthetic relaxes bronchial smooth muscle?

Halothane

Which inhaled anesthetic is associated with cardiac arrhythmias?

Halothane

Which inhaled anesthetics increase heart rate (via reflex secondary to vasodilation)?

Isoflurane; desflurane

Which inhaled anesthetics decrease heart rate?

Halothane; enflurane; sevoflurane

Which inhaled anesthetic decreases renal and hepatic blood flow?

Halothane

Give examples of intravenous (IV) anesthetics:

Propofol; fentanyl; ketamine; midazolam; thiopental; etomidate

Which of the previously mentioned IV anesthetics is a barbiturate?

Thiopental

Which of the previously mentioned IV anesthetics is a benzodiazepine?

Midazolam

Which of the previously mentioned IV anesthetics is an opioid?

Fentanyl

Is thiopental used for induction, maintenance, or both?

Induction

Pharmacodynamically, how does recovery occur with the rapid-acting barbiturates?

Rapid redistribution from the central nervous system (CNS) to peripheral tissues

State whether thiopental increases, decreases, or does not change each of the following physiologic effects:

Cerebral blood flow

No change

Respiratory function

Decreases

Blood pressure

Decreases

Why should caution be taken when administering thiopental to asthmatic patients?

May cause laryngospasm

Midazolam offers which type of amnesia making it useful for monitored anesthesia care?

Anterograde amnesia

What is the antidote for midazolam-induced respiratory depression?

Flumazenil, which is also the antidote for any benzodiazepine overdose

What adverse drug reaction may be caused by fentanyl when given intravenously?

Chest wall rigidity

Does propofol have good analgesic properties?

No

About which allergies should a patient be questioned before administration of propofol?

Egg and soybeans. Propofol is prepared as a lipid emulsion using egg and soybean lecithin. This gives propofol its white color and can cause allergic reactions in patients with sensitivities to these substances.

Does propofol increase or decrease blood pressure?

It decreases blood pressure.

Is propofol used for induction, maintenance, or both?

It is used for both.

Which IV anesthetic causes dissociative anesthesia?

Ketamine

What is dissociative anesthesia?

The patient is unconscious and feels no pain, yet appears awake. Eyes may open and the swallowing reflex is present, but the patient is sedated, immobile, and usually amnestic. Hallucinations and delirium are common.

Which anesthetic has antiemetic properties?

Propofol

Which IV anesthetic is a cardiovascular stimulant (increases blood pressure and cardiac output)?

Ketamine

Which IV anesthetic causes vivid dreams and hallucinations?

Ketamine

Does ketamine increase or decrease cerebral blood flow?

Increase

What is the most cardiac-stable IV anesthetic agent?

Etomidate

Are local anesthetics weak acids or weak bases?

Weak bases

Give examples of amide local anesthetics:

Lidocaine; prilocaine; articaine; mepivacaine; bupivacaine (all have >1 “i” in their generic name)

Give examples of ester local anesthetics:

Cocaine; benzocaine; procaine (all have only one “i” in their generic name)

Which medication, when used in combination, reduces systemic toxicity and increases the duration of action of local anesthetics?

Epinephrine, by inducing a local vasoconstriction

Epinephrine should not be combined with local anesthetics when injecting near which anatomic sites?

Digits; nose; ears; penis; and any end-artery circulation

Which type of enzymes metabolize amide local anesthetics and where are they located?

Amidases located in the liver

Which type of enzymes metabolize ester local anesthetics and where are they located?

Esterases located in tissues and blood

What is the mechanism of action of local anesthetics?

Inhibition of sodium channels in axonal membranes via binding to the channels in their inactivated state and preventing a structural change to the resting state

Do local anesthetics need to be in the ionized or nonionized form to bind to the sodium channel?

Ionized form

Do local anesthetics need to be in the ionized or nonionized form to gain access to the sodium channel, which is located on the inner side of the axonal membrane?

Nonionized form (must be able to cross lipophilic axonal membrane)

All local anesthetics cause vasodilation with the exception of which drug?

Cocaine (causes vasoconstriction)

Nerve fibers most sensitive to blockade are of smaller or larger diameter?

Smaller diameter

Nerve fibers most sensitive to blockade have low or high firing rates?

High firing rates

Which nerve fibers are most sensitive to local anesthetics?

Type B fibers; type C fibers

Which nerve fibers are least sensitive to local anesthetics?

Type A α-fibers

What are the adverse effects of local anesthetics?

Hypotension (except cocaine); nystagmus; seizures; dizziness; allergic reactions (rare)

Allergic reactions are more associated with ester or amide local anesthetics?

Esters (via para-aminobenzoic acid [PABA] formation)

OPIOID ANALGESICS AND ANTAGONISTS

 

Which neurotransmitter binds to the δ-opioid receptor?

Enkephalin

Which neurotransmitter binds to the δ-opioid receptor?

Dynorphin

Which neurotransmitter binds to the β-opioid receptor?

β-Endorphin

What is the mechanism of action of medications that activate presynaptic opioid receptors?

Inhibits calcium influx through voltage-gated ion channels, thereby inhibiting neurotransmitter release

What is the mechanism of action of medications that activate postsynaptic opioid receptors?

Increases potassium efflux from cells leading to membrane hyperpolarization and thereby inhibition of neurotransmitter release

Opioid receptors are coupled to what type of proteins?

Inhibitory G-proteins (inhibits adenylyl cyclase)

What is the prototype opioid analgesic?

Morphine

Why must caution be taken when using opioids in patients with head injuries?

Opioids may increase intracranial pressure

Where in the midbrain are opioid receptors located?

Periaqueductal gray region (binding to these receptors leads to activation of descending pathways to the raphe nuclei, thereby decreasing transmission throughout pain pathways)

Where in the dorsal horn of the spinal cord are opioid receptors located?

Primary afferent fibers (binding to these receptors leads to inhibition of substance P release)

Are opioid analgesics better at relieving intermittent or persistent pain?

Persistent pain

What is the mechanism of morphine-induced hypotension and pruritus?

Increased histamine release from mast cells

Do opioid analgesics increase or decrease gastrointestinal (GI) peristalsis?

Decrease (they cause constipation)

Which two opioids are used specifically to treat diarrhea?

 

  1. Loperamide
  2. Diphenoxylate

 

Which opioid analgesic does not increase the tone of the biliary tract, bladder, and ureter?

Meperidine (antagonizes muscarinic receptors)

Do opioid analgesics increase or decrease uterine contractions during pregnancy?

They decrease uterine contractions, thus a good contraction pattern should be achieved before placement of an epidural catheter during labor.

Do opioid analgesics cause miosis or mydriasis of the pupils?

Miosis (common sign of opioid overdose is pinpoint pupils)

What is the mechanism of opioid-induced miosis?

Increased parasympathetic (cholinergic) activity in the pupilary constrictor muscles

Which opioid analgesic does not cause miosis?

Meperidine (antagonizes muscarinic receptors)

Which two opioids are used specifically to treat cough?

 

  1. Codeine
  2. Dextromethorphan

 

Opioids suppress the cough reflex.

Synthetic

Is dextromethorphan a natural or synthetic opioid?

Synthetic

What is the mechanism of opioid-induced urinary retention?

Increases antidiuretic hormone (ADH)

Do opioid analgesics promote emesis or act as antiemetics?

Promote emesis

What is the mechanism of opioid-induced emesis?

Activation of the chemoreceptor trigger zone (CTZ)

Where is the CTZ located?

Area postrema

What is the mechanism of opioid-induced respiratory depression?

Reduced sensitivity of respiratory center to carbon dioxide levels

What is the most common cause of death in opioid overdose?

Respiratory depression

What are the two most lipophilic opioids?

 

  1. Heroin
  2. Fentanyl

 

These two medications rapidly cross the blood-brain barrier (BBB) to produce euphoric effects.

Which opioid is the least lipophilic?

Morphine

Is morphine metabolized via phase I or phase II reactions?

Phase II metabolism (glucuronidation)

Does morphine-3-glucuronide have analgesic activity?

No

Does morphine-6-glucuronide have analgesic activity?

Yes

Which two opioid-induced effects do patients not develop tolerance to?

 

  1. Constipation
  2. Miosis

 

What are the signs and symptoms of opioid withdrawal?

Lacrimation; rhinorrhea; diaphoresis; yawning; goose bumps; anxiety; muscle spasms; diarrhea; increased pain sensation

Which medication is used to counteract the respiratory depression seen in opioid overdose?

IV naloxone (may need to give multiple doses as naloxone has a shorter half-life than morphine)

What is the mechanism of action of naloxone?

(μ,-Receptor antagonist

Which opioid antagonist is given orally to decrease cravings in alcoholism?

Naltrexone

Which opioid analgesic is used to prevent withdrawal symptoms in patients discontinuing heroin use?

Methadone

Which central-acting α2-agonist is used to prevent withdrawal symptoms in patients discontinuing heroin use?

Clonidine

Give examples of strong opioid agonists:

Morphine; fentanyl; heroin; methadone; meperidine; hydrocodone; hydromorphone

Give examples of weak opioid agonists:

Codeine; propoxyphene

Give examples of partial opioid agonists:

Buprenorphine; pentazocine

Propoxyphene is a derivative of which opioid analgesic?

Methadone

Name two synthetic opioid analgesics:

 

  1. Meperidine
  2. Methadone

 

Fentanyl is chemically related to which synthetic opioid analgesic?

Meperidine

Does morphine have a high or low oral bioavailability?

Low

Which two opioids should not be given in combination with monoamine oxidase inhibitors (MAOIs)?

 

  1. Meperidine
  2. Dextromethorphan

 

These combinations may produce serotonin syndrome.

What drug do you get by acetylating morphine?

Heroin

Is codeine itself an active opioid analgesic?

No (must be metabolized via cytochrome β-450 2D6 to active morphine)

Which medication is commonly given in combination with codeine for the treatment of pain?

Acetaminophen

ANXIOLYTIC AND SEDATIVE-HYPNOTIC AGENTS

 

For each of the following sedative-hypnotic-induced CNS effects, place in order from effect caused by lowest to highest dose of drug: coma; anesthesia; hypnosis; sedation/anxiolysis; medullary depression.

Sedation/anxiolysis; hypnosis; anesthesia; medullary depression; coma

What is the first step in ethanol metabolism?

Alcohol dehydrogenase converts ethanol to acetaldehyde.

What is the second step in ethanol metabolism?

Acetaldehyde dehydrogenase converts acetaldehyde to acetate.

What enzyme does disulfiram inhibit?

Acetaldehyde dehydrogenase, leading to a build up of acetaldehyde

Which metabolite of ethanol is responsible for causing headache, hypotension, nausea, and vomiting (“hangover”)?

Acetaldehyde

What does GABA stand for?

Gamma-aminobutyric acid

How many subunits make up the GABA receptor?

Five subunits

Which subunit does GABA bind to?

α-Subunit

Which subunit on the GABA receptor do benzodiazepines bind to?

γ-Subunit (binding potentiates the affinity of the GABA receptor for GABA; does not activate the receptor alone without GABA)

Which subunit on the GABA receptor do barbiturates bind to?

β-Subunit (binding potentiates the affinity of the GABA receptor for GABA; does not activate the receptor alone without GABA)

What physiologic process takes place when GABA binds to the GABAAreceptor?

Increased chloride ion influx into cells leading to membrane hyperpolarization and subsequent decreased neuronal firing

What physiologic process takes place when GABA binds to the GABABreceptor?

Increased potassium ion efflux out of cells leading to membrane hyperpolarization and subsequent decreased neuronal firing

What medication binds specifically to the GABAB receptor?

Baclofen

What is baclofen used for?

Muscle relaxation

Do benzodiazepines potentiate GABA by increasing the duration or frequency of chloride ion channel opening?

Frequency

Do barbiturates potentiate GABA by increasing the duration or frequency of chloride ion channel opening?

Duration

Name three nonbenzodiazepine sleep aids that specifically bind to the BZ1-receptor subtype:

 

  1. Eszopiclone
  2. Zolpidem
  3. Zaleplon

 

Does zolpidem display anticonvulsant, antianxiety, or muscle relaxant properties?

No, it is a selective hypnotic along with zaleplon and eszopiclone.

Do benzodiazepines have good analgesic properties?

No

What types of actions do benzodiazepines display?

Muscle relaxant; anticonvulsant; antianxiety; sedative-hypnotic; anterograde amnesia (midazolam); alcohol withdrawal

Give examples of benzodiazepines:

Diazepam; lorazepam; alprazolam; chlordiazepoxide; clonazepam; clorazepate; midazolam; flurazepam; flunitrazepam; temazepam; triazolam; oxazepam

What is the name of the prototype benzodiazepine?

Chlordiazepoxide

What benzodiazepine is colloquially referred to as the “date rape” drug and is illegal in the United States?

Flunitrazepam (trade name: Rohypnol; slang: “roofies”)

Which benzodiazepine is the longest acting?

Diazepam

Which benzodiazepine is the shortest acting?

Midazolam

What three benzodiazepines undergo phase II metabolism?

 

  1. Lorazepam
  2. Oxazepam
  3. Temazepam

 

Which benzodiazepines are commonly used as anticonvulsants?

Diazepam; clonazepam

Which benzodiazepines are commonly used to treat alcohol withdrawal?

Oxazepam; lorazepam; diazepam; chlordiazepoxide

Which benzodiazepines are commonly used as sleep aids?

Temazepam; triazolam; flurazepam

Which benzodiazepines are commonly used as anxiolytics?

Diazepam; lorazepam; alprazolam

Why is alprazolam not the drug of choice when treating patients with chronic anxiety?

It has a short half-life, and therefore may cause withdrawal symptoms, such as anxiety, which subsequently worsens the condition and leads to higher addiction rates.

Give examples of long-acting benzodiazepines (duration of action of 1-3 d):

Diazepam; chlordiazepoxide; flurazepam; clorazepate

Give examples of intermediate-acting benzodiazepines (duration of action of 10-20 h):

Lorazepam; temazepam; alprazolam

Give examples of short-acting benzodiazepines (duration of action of 3-8 h):

Midazolam; oxazepam; triazolam

Give examples of benzodiazepine withdrawal signs and symptoms:

Insomnia; anxiety; agitation; seizures; restlessness; confusion

What are the adverse effects of benzodiazepines?

Confusion; drowsiness; ataxia; cognitive impairment; amnesia; respiratory depression

Is withdrawal more likely to occur with long-acting or short-acting benzodiazepines?

Short-acting benzodiazepines (abrupt withdrawal may ensue as drug levels are rapidly decreased versus long-acting benzodiazepines which offer a “self-tapering” mechanism which decreases the chance of withdrawal)

What is the antidote for benzodiazepine-induced CNS depression?

Flumazenil (short half-life; therefore, multiple administrations may be necessary)

What is the mechanism of action of flumazenil?

Benzodiazepine receptor antagonist

Will flumazenil decrease the effects of barbiturates?

No (barbiturates act at a different GABA receptor subtype than benzodiazepines)

Which two sedative-hypnotic drug classes are potentially fatal with overdose and/or withdrawal?

 

  1. Barbiturates
  2. Alcohols

 

Benzodiazepines may be potentially fatal but to a lesser extent than barbiturates and alcohols.

Give examples of long-acting barbiturates (duration of action of 1-2 d):

Phenobarbital; pentobarbital

Give examples of short-acting barbiturates (duration of action of 3-8 h):

Amobarbital; secobarbital

Give an example of an ultra-short-acting barbiturate (duration of action of 30 min):

Thiopental

What is phenobarbital commonly used to treat?

Seizures (generalized tonic-clonic and partial seizures)

What is thiopental commonly used for?

Induction of anesthesia

What are short-acting barbiturates commonly used for?

Sedation; hypnosis

What kind of drug interactions can barbiturates produce?

Induction of cytochrome β-450 enzymes

What are the adverse effects of barbiturates?

Drowsiness; impair cognitive function (especially in pediatric patients); “hangover” effect; nausea; dizziness; increase heme synthesis (contraindicated in patients with acute intermittent porphyria); coma; respiratory depression; cardiovascular depression; addiction

Give examples of barbiturate withdrawal signs and symptoms:

Insomnia; tremors; anxiety; restlessness; nausea; vomiting; seizures; cardiac arrest; delirium; hyperreflexia; agitation

What drug class is used to prevent barbiturate withdrawal?

Long-acting benzodiazepines

Over-the-counter (OTC) sleep aids have what types of medications in them?

Sedating antihistamines

Give examples of sedating antihistamines:

Diphenhydramine; doxylamine; hydroxyzine (prescription only)

Give examples of antidepressants that have been used for sedation and hypnosis:

Trazodone; amitriptyline

Which medication is a partial agonist at 5-HT1A receptors and is effective in treating generalized anxiety disorder?

Buspirone

Does buspirone have anticonvulsant and muscle relaxant properties?

No

Is buspirone sedating?

No

How long does it take for buspirone to exert its anxiolytic effects?

1 to 2 weeks (therefore, not useful in treating an acute anxiety attack)

What types of withdrawal signs and symptoms does buspirone cause?

None

ANTIDEPRESSANT AGENTS

 

According to the biogenic amine theory, depression is due to a deficiency of which two neurotransmitters in the brain?

 

  1. Serotonin (5-HT)
  2. Norepinephrine (NE)

 

MAOA inactivates which neurotransmitters?

5-HT; NE

MAOB inactivates which neurotransmitter?

Dopamine (DA)

What is the mechanism of action of MAOIs?

Inactivation of MAO, thereby increasing levels of 5-HT, NE, and DA in presynaptic neurons with subsequent leakage of neurotransmitter into the synaptic cleft

Name three nonselective MAOIs:

 

  1. Tranylcypromine
  2. Phenelzine
  3. Isocarboxazid

 

Selegiline is commonly used in the treatment of which disease?

Parkinson disease

MAOA also inactivates which monoamine commonly found in certain cheeses (aged), alcoholic beverages, fish, chocolates, red wines, and processed meats?

Tyramine (inactivated by MAO in the GI tract)

MAOIs are the drugs of choice for treating what type of depression?

Atypical depression

How long does it take to see antidepressant effects in patients who are started on an MAOI?

2 to 4 weeks

How long should a patient wait from the time of discontinuing an MAOI to the time of starting a new antidepressant medication?

At least 2 weeks

What are the adverse effects of MAOIs?

Orthostatic hypotension; xerostomia; blurred vision; drowsiness; constipation; urinary retention

What life-threatening condition may develop when MAOIs and selective serotonin reuptake inhibitors (SSRIs) are used concomitantly?

Serotonin syndrome

What characterizes serotonin syndrome?

Rigidity; diaphoresis; hyperthermia; seizures; autonomic instability; myoclonus

What life-threatening condition may develop when patients taking MAOIs ingest foods containing tyramine?

Hypertensive crisis

What characterizes hypertensive crisis?

Hypertension; headache; tachycardia; nausea; vomiting; stroke; cardiac arrhythmias

A serotonin-like syndrome may develop when MAOIs are used concomitantly with what common OTC medication used to suppress cough?

Dextromethorphan

A serotonin-like syndrome may develop when MAOIs are used concomitantly with which opioid analgesic?

Meperidine

What is the mechanism of action of tricyclic antidepressants (TCAs)?

Inhibits reuptake of 5-HT and NE into presynaptic neurons, thereby increasing neurotransmitter concentrations in the synaptic cleft

What other types of neurotransmitter and hormonal receptors, other than 5-HT and NE, are inhibited by TCAs?

Muscarinic; α-adrenergic; histaminergic

How long does it take to see antidepressant effects in patients who are started on a TCA?

4 to 6 weeks

Give examples of TCAs:

Amitriptyline; imipramine; clomipramine; nortriptyline; protriptyline; desipramine; doxepin

What is the name of the active metabolite of amitriptyline that selectively inhibits NE reuptake?

Nortriptyline

What is the name of the active metabolite of imipramine that selectively inhibits NE reuptake?

Desipramine

Which TCA is also used for the treatment of certain types of neuropathic pain and for the prevention of migraine headaches?

Amitriptyline

Which TCA is commonly used to treat obsessive-compulsive disorder (OCD)?

Clomipramine

Which TCA is also used to treat pediatric nocturnal enuresis?

Imipramine

Why is imipramine used for childhood enuresis?

Increases contraction of internal sphincter of bladder; decreases stage 3 and 4 sleep

What are the adverse effects of the TCAs?

Xerostomia; blurred vision; urinary retention; constipation; precipitation of acute glaucoma attacks; cardiac arrhythmias; seizures (lowers seizure threshold); orthostatic hypotension with reflex tachycardia; sedation; serotonin syndrome when combined with MAOIs and/or SSRIs; coma

What are the “3 C,’s” of TCA toxicity?

Coma, convulsions, and cardiotoxicity

Compare TCA toxicity to SSRI toxicity.

SSRI toxicity is much lower than that seen with TCAs, and mortality is most often reported only when SSRIs are used in combination with another agent, such as alcohol. This is in contrast to TCAs, which can lead to death at much lower concentrations as compared to SSRIs.

What is the treatment for TCA overdose?

Activated charcoal to absorb the drug in the GI tract; sodium bicarbonate to correct acidosis and cardiac arrhythmias; phenytoin; magnesium

What is the mechanism of action of trazodone and nefazodone?

Inhibits reuptake of 5-HT into presynaptic neurons, thereby increasing neurotransmitter concentrations in the synaptic cleft

What adverse effect is unique to trazodone?

Priapism

What is the mechanism of action of bupropion?

Weak inhibitor of DA, 5-HT, and NE reuptake

Bupropion is also used in what settings (other than depression)?

Smoking cessation; OCD

Does bupropion cause sexual dysfunction?

No, making it a useful alternative in patients that experience sexual dysfunction with other antidepressant medications such as SSRIs

Is bupropion safe to use in patients with epilepsy?

No, because it lowers the seizure threshold.

What is the mechanism of action of mirtazapine?

α2-Adrenoceptor antagonist (results in increased release of NE and 5-HT)

What is the major side effect of mirtazapine?

Weight gain via appetite stimulation (may be beneficial in depressed patients who become anorexic)

Name an α2-antagonist that is used in the treatment of erectile dysfunction:

Yohimbine

What is the mechanism of action of venlafaxine?

Potent inhibitor of 5-HT and NE reuptake; weak inhibitor of DA reuptake

What is the major side effect of venlafaxine?

Hypertension

What is the mechanism of action of duloxetine?

Selective serotonin and norepinephrine reuptake inhibitor (SSNRI)

Give examples of SSRIs:

Fluoxetine; paroxetine; fluvoxamine; sertraline; citalopram; escitalopram

What is the prototype of the SSRI drug class?

Fluoxetine

What is the longest-acting SSRI?

Fluoxetine

Fluoxetine is also used in what settings (other than depression)?

Premenstrual dysphoric disorder (PMDD); bulimia nervosa; OCD; panic disorder; selective mutism

What kind of drug interactions may SSRIs produce?

Inhibition of cytochrome β-450 enzymes

Do SSRIs cause sexual dysfunction?

Yes, they can cause anorgasmia.

Do SSRIs cause cardiac arrhythmias?

No, they do not, in contrast to TCAs.

What are the adverse effects of SSRIs?

Sexual dysfunction; agitation; anxiety; seizures (with overdose); nausea; vomiting; diarrhea; sedation

Which SSRI is also FDA approved for social anxiety disorder (SAD), generalized anxiety disorder (GAD), and posttraumatic stress disorder (PTSD)?

Paroxetine

Which SSRIs cause the least amount of drug-drug interactions?

Citalopram; escitalopram; sertraline

AGENTS FOR MANIC-DEPRESSION

 

Manic-depression is also known as what?

Bipolar disorder

What is the traditional drug of choice for treating manic-depression?

Lithium

When is lithium used in the treatment of manic-depression (what phases of the disease)?

Prevention; treatment of manic episodes

Does lithium have a narrow or wide therapeutic window?

Narrow. Therapeutic levels range from 0.6 to 1.2 mEq/L and toxicity is seen at 1.5 mEq/L (and at 0.8 mEq/L in elderly patients).

Lithium is eliminated renally in a similar fashion to which other salt?

Sodium

Is lithium toxicity exacerbated by low or high sodium plasma levels?

Low sodium levels

What is the mechanism of action of lithium?

Unknown; may decrease cAMP levels thereby decreasing its function as a second messenger; may inhibit dephosphorylation of IP3 to IP2 and IP2 to IP thereby interfering with the recycling of inositol

What are the adverse effects of lithium?

Acne; seizures; visual disturbances; edema; ataxia; drug-induced nephrogenic diabetes insipidus; hypothyroidism; tremors

How does lithium cause drug-induced nephrogenic diabetes insipidus?

Uncoupling of the vasopressin V2 receptor in the kidney

Which diuretic is usually used to treat nephrogenic diabetes insipidus?

Thiazide diuretics

Which drug is used to treat lithium-induced nephrogenic diabetes insipidus?

Amiloride (thiazide diuretics cause increased reabsorption of lithium which may lead to lithium toxicity)

How does lithium cause hypothyroidism?

Inhibition of 5’-deiodinase

What is 5’-deiodinase responsible for?

Converting thyroxine (T4) to triiodothyronine (T3)

What is the name of the cardiac anomaly that may be found in neonates born to mothers using lithium?

Ebstein anomaly

What characterizes Ebstein anomaly?

Malformation of the tricuspid valve leaflets (partly attached to the fibrous tricuspid valve annulus; partly attached to the right ventricular endocardium; inferior displacement of the tricuspid leaflets)

What other medications (mood stabilizers) may be used in the treatment of manic-depression?

Carbamazepine; valproic acid; benzodiazepines; gabapentin; topiramate

Why are antidepressant agents not used to treat the depression phase of manic-depression?

May cause patients to enter into the manic phase

ANTIPSYCHOTIC AGENTS

 

According to the dopamine (DA) hypothesis of schizophrenia, do symptoms arise due to an excess or a lack of DA in the CNS?

An excess of DA

What characterizes the positive symptoms of schizophrenia?

Hallucinations; delusions; thought disorders

What characterizes the negative symptoms of schizophrenia?

Speech disorders; flat affect; amotivation; social withdrawal

What is the mechanism of action of “typical” antipsychotic agents?

Inhibition of D2 receptors in the mesolimbic system of the brain

What is the mechanism of action of “atypical” antipsychotic agents?

Inhibition of 5-HT2 receptors (D2 receptors are still involved to some extent)

Give examples of typical antipsychotics:

Haloperidol; chlorpromazine; thioridazine; fluphenazine; pimozide

Give examples of atypical antipsychotics:

Clozapine; risperidone; aripiprazole; olanzapine; ziprasidone; quetiapine

Name two typical antipsychotics commonly used in the treatment of Tourette syndrome:

 

  1. Haloperidol
  2. Pimozide

 

What are extrapyramidal symptoms (EPS)?

Parkinsonian-like symptoms (dystonia, rigidity, tremor, and bradykinesia); akathisia; tardive dyskinesia (TD)

What is akathisia?

Motor restlessness

What is tardive dyskinesia (TD)?

Inappropriate movements of the tongue, neck, trunk, and limbs (associated with long-term use of DA antagonists)

What is the mechanism of anti-psychotic-induced TD?

Long-term DA receptor inhibition leads to an upregulation and supersensitivity of DA receptors, thereby leading to DA overstimulation, especially when the antipsychotic has been discontinued.

Which antipsychotics are more likely to cause EPS?

High potency typical antipsychotics such as haloperidol and fluphenazine secondary to their weak anticholinergic activity

Why do thioridazine and chlorpromazine have a lower EPS potential?

They have high anticholinergic activity.

What medications are used to treat antipsychotic-induced EPS?

Benztropine; amantadine; diphenhydramine (due to its anticholinergic action)

How do antipsychotics cause parkinsonian-like symptoms?

Inhibition of DA receptors in the nigrostriatal pathway

How do antipsychotics cause orthostatic hypotension?

Inhibition of α-adrenergic receptors in the vasculature

How do antipsychotics cause prolactinemia?

Inhibition of DA receptors in the anterior pituitary

Which two antipsychotics possess the highest antimuscarinic activity?

 

  1. Chlorpromazine
  2. Thioridazine

 

Characterize the antimuscarinic activity of chlorpromazine and thioridazine:

Xerostomia; blurred vision; confusion; constipation; urinary retention

What is xerostomia?

Dry mouth

Which antipsychotic agents are more effective at treating negative symptoms?

Atypical antipsychotics

Which phenothiazine antipsychotic is also used to treat intractable hiccups?

Chlorpromazine

Which phenothiazine antipsychotic may cause priapism, agranulocytosis, blue-gray discoloration of the skin, and lower seizure threshold?

Thioridazine

Which two typical antipsychotics can be formulated as depot intramuscular injections that may last up to 3 weeks?

 

  1. Haloperidol
  2. Fluphenazine

 

Which atypical antipsychotic is usually reserved as a third-line agent to treat schizophrenic patients refractory to traditional therapy?

Clozapine

What is the major dose-limiting side effect of clozapine?

Agranulocytosis

How are patients receiving clozapine therapy monitored?

WBCs obtained at baseline and weekly for the first 6 months of therapy, every other week for the second 6 months, and monthly thereafter

What adverse effect is more common with clozapine, agranulocytosis, or seizures?

Seizures (occur in 10% of patients, whereas agranulocytosis occurs in l%-2% of patients)

Why is gynecomastia a common adverse effect of risperidone?

Risperidone induces prolactinemia (only atypical antipsychotic that increases prolactin levels significantly)

What is a potential life-threatening adverse effect of antipsychotic medications?

Neuroleptic malignant syndrome (NMS)

What characterizes NMS?

Hyperthermia; rigidity; altered mental status; cardiovascular instability

What is the treatment for NMS?

Dantrolene + bromocriptine (DA agonist)

What are the additional adverse effects of olanzapine?

Weight gain; hyperglycemia; sialorrhea

What are the additional adverse effects of quetiapine?

Hypercholesterolemia; hypertriglyceridemia; weight gain; hepatotoxicity

What is the mechanism of action of aripiprazole?

Antagonist at S-HT2A receptors; partial agonist at D2 and 5-HT1A receptors

What are the additional adverse effects of aripiprazole?

Weight gain; rash; sialorrhea; hepatotoxicity

Which antipsychotic has the highest incidence of sialorrhea?

Clozapine β1%-48%)

AGENTS FOR PARKINSON DISEASE

 

What are the signs of Parkinson disease (PD)?

Bradykinesia; muscular rigidity; tremors; gait abnormalities; postural instability

What neurotransmitter pathway is affected in PD?

Dopaminergic pathway (inhibitory neurons) in the substantia nigra and corpus striatum (neurotransmitter ratio shifts toward decreased DA and increased acetylcholine [ACh])

What does increased levels of DA in the tuberoinf undibular tract lead to?

Decreased prolactin levels

What does increased levels of DA in the CTZ lead to?

Increased emesis

What does increased levels of DA in the mesolimbic-mesocortical tracts lead to?

Increased psychomotor activity; psychosis; schizophrenia; increased reinforcement

Which DA receptor subtype is implicated in PD?

D2 receptor subtype (inhibitory receptor subtype that decreases cyclic adenosine monophosphate [cAMP] levels in the corpus striatum)

Given the abnormal DA/ACh shift in the striatum, give two pharmacologic strategies in the treatment of PD:

 

  1. Medications that will increase DA levels
  2. Medications that will decrease ACh levels

 

Do anti-Parkinson medications effect pathology, symptoms, or both?

Symptoms

Name two antimuscarinic medications that are used in the treatment of PD:

 

  1. Benztropine
  2. Trihexyphenidyl

 

Is benztropine more or less lipid soluble than atropine?

More lipid soluble (therefore, greater CNS penetration)

Which characteristic of PD is not affected by anticholinergics?

Bradykinesia

Is benztropine useful in the treatment of tardive dyskinesia?

No, it may actually exacerbate tardive dyskinesia.

What are the adverse effects of benztropine and trihexyphenidyl?

Xerostomia; blurred vision; constipation; urinary retention; sedation; mydriasis

How does amantadine work in the treatment of PD?

May inhibit reuptake of DA into presynaptic neurons; may increase DA release from presynaptic fibers

Amantadine is used to treat what condition other than PD?

Influenza A

What is the name of the dermatologic adverse effect caused by amantadine?

Livedo reticularis

What is livedo reticularis?

A network-patterned discoloration of the skin caused by dilation of capillaries and venules

Which characteristic of PD is not affected by amantadine?

Tremors

Which selective MAOB inhibitor is commonly used as first-line treatment for PD?

Selegiline

What is the mechanism of action of selegiline?

Inhibition of DA metabolism in presynaptic neurons located in the CNS via inhibition of MAOB

What are the two active metabolites of selegiline?

 

  1. Amphetamine
  2. Methamphetamine

 

What are the main adverse effects of selegiline?

Cardiovascular stimulation (hypertension, tachycardia, palpitations; arrhythmias; angina)

Name two ergot derivatives that act as DA agonists in the nigrostriatal system:

 

  1. Bromocriptine
  2. Pergolide

 

Bromocriptine is used to treat what conditions other than PD?

Prolactin-secreting microadenomas; NMS; acromegaly; postpartum lactation

What are the adverse effects of bromocriptine?

Headache; dizziness; nausea; orthostatic hypotension; dyskinesia; hallucinations; confusion; psychosis

Name two nonergot DA agonists:

 

  1. Pramipexole
  2. Ropinirole

 

What are the adverse effects of the nonergot DA agonists?

Sedation; syncope; nausea; vomiting; hallucinations; dyskinesia

What is the mechanism of action of tolcapone and entacapone?

Inhibition of peripheral catechol-O-methyltransferase (COMT), thereby increasing CNS uptake of L-dopa

What reaction does COMT catalyze?

Conversion of L-dopa to 3-O-methyldopa (partial DA agonist) in peripheral tissues

What are the adverse effects of COMT inhibitors?

Orthostatic hypotension; headache; fatigue; nausea; diarrhea; anorexia; dyskinesia; muscle cramps; brown-orange urine discoloration; hallucinations; diaphoresis

Which of the COMT inhibitors is hepatotoxic?

Tolcapone

Are COMT inhibitors used as first-line therapy, adjunctive therapy, or both in the treatment of PD?

Adjunctive therapy (in combination with carbidopa/levodopa)

Are the nonergot DA agonists used as first-line therapy, adjunctive therapy, or both in the treatment of PD?

Both

What is the precursor of DA?

Levodopa (L-dopa)

What enzyme converts L-dopa to DA?

Dopa decarboxylase (DDC)

Does DA cross the BBB?

No

Does levodopa cross the BBB?

Yes, it does and is subsequently converted to DA by dopaminergic neurons in the substantia nigra.

Is levodopa effective in treating PD when all of the dopaminergic neurons in the substantia nigra have been destroyed?

No, since dopaminergic neurons in the substantia nigra are required to convert levodopa to DA.

What is the mechanism of action of carbidopa?

Inhibition of peripheral DDC, thereby increasing the amount of levodopa that is available to cross the BBB into the CNS. This allows for lower doses of levodopa needed, thereby decreasing levodopa adverse effects.

Does carbidopa cross the BBB?

No, it does not and therefore only inhibits peripheral DDC.

How does levodopa work in the treatment of PD?

Decreases symptoms of PD, such as rigidity, bradykinesia, and tremors

What is the “on-off” phenomenon?

Levodopa has such a short half-life (1-2 h) that plasma concentrations may decline rapidly causing the patient to experience sudden rigidity, bradykinesia, and tremors.

Which amino acids compete with levodopa for GI absorption?

Isoleucine; leucine

What are the adverse effects of levodopa?

Anorexia; nausea; vomiting; tachycardia; hypotension; discoloration of saliva and urine; mydriasis; hallucinations; dyskinesia; increased intraocular pressure; cardiac arrhythmias

Why should vitamin B6 (pyridoxine) not be used in combination with levodopa?

Pyridoxine enhances peripheral metabolism of levodopa, thereby rendering the medication ineffective.

ANTICONVULSANT AGENTS

 

What are the two types of partial seizures?

 

  1. Simple
  2. Complex

 

What are the three types of general seizures?

 

  1. Tonic-clonic
  2. Absence
  3. Myoclonic

 

What is another name for tonic-clonic seizures?

Grand mal seizures

What is another name for absence seizures?

Petit mal seizures

Does hypoventilation or hyperventilation lower the seizure threshold?

Hyperventilation (via alkalinization of blood pH)

What is the most common seizure type?

Tonic-clonic seizure

What type of seizure is associated with “febrile seizures”?

Tonic-clonic seizure

What type of seizure most commonly presents during childhood?

Absence seizure

What is status epilepticus?

Epileptic seizure lasting longer than 30 minutes or absence of full recovery of consciousness between seizures (can be life threatening)

In general, how do antiepileptic agents work?

Inhibit initiation of an abnormal electrical discharge from the focal area; prevent dissemination of abnormal electrical discharge to surrounding areas of the brain

What is the mechanism of action of phenytoin?

Inhibition of axonal sodium channels to produce membrane stabilization

Does phenytoin inhibit the axonal sodium channel in its activated or inactivated state?

Inactivated state

What antiarrhythmic class does phenytoin belong to?

Class Ib

What type of drug interactions can phenytoin produce?

Induces cytochrome β-450 metabolic enzymes; highly protein bound, therefore, can potentially displace other medications from plasma proteins

What are the adverse effects of phenytoin?

Diplopia; sedation; ataxia; gingival hyperplasia; acne; hirsutism; megaloblastic anemia (interferes with folate absorption); granulocytopenia; hypotension (IV); osteomalacia; drug-induced lupus; hyperglycemia; nystagmus; Stevens-Johnson syndrome; hepatotoxicity

Is phenytoin safe to use during pregnancy?

No, it causes fetal hydantoin syndrome characterized by cleft lip and palate.

What prodrug is hydrolyzed to phenytoin and is commonly given intravenously secondary to its superior water solubility versus phenytoin?

Fosphenytoin

Name two other medications that may cause gingival hyperplasia:

 

  1. CyclosporinA
  2. Nifedipine

 

Which types of seizures does phenytoin treat?

Simple partial; complex partial; tonic-clonic; status epilepticus

What is the mechanism of action of carbamazepine?

Inhibition of axonal sodium channels to produce membrane stabilization

What type of drug interactions can carbamazepine produce?

Induces cytochrome β-450 metabolic enzymes; auto-induces its own metabolism

What conditions, other than epilepsy, can carbamazepine be used in?

Manic-depression; trigeminal neuralgia

What are the adverse effects of carbamazepine?

Diplopia; sedation; ataxia; osteomalacia; aplastic anemia; hyponatremia; Stevens-Johnson syndrome; alopecia; pancreatitis; hepatotoxicity; nystagmus

Is carbamazepine safe to use in pregnancy?

No, it causes neural tube defects and craniofacial abnormalities.

Which types of seizures does carbamazepine treat?

Simple partial; complex partial; tonic-clonic

What antiepileptic medication can cause alopecia?

Valproic acid (VPA)

What is the mechanism of action of VPA?

Inhibition of axonal sodium channels; inhibition of T-type calcium channels; inhibition of GABA transaminase

What type of drug interactions can VPA produce?

Inhibition of cytochrome β-450 enzymes

What conditions, other than epilepsy, can VPA be used in?

Manic-depression; migraine

What are the adverse effects of VPA?

Hepatotoxicity; pancreatitis; alopecia; nausea; vomiting; photosensitivity; sedation; diarrhea; abdominal pain; thrombocytopenia; rash; amenorrhea; dysmenorrhea; weight gain; tinnitus

Is VPA safe to use in pregnancy?

No, it causes neural tube defects.

Which types of seizures does VPA treat?

Simple partial; complex partial; tonic-clonic; absence; myoclonic

Which antiepileptic medication is used to treat partial and tonic-clonic seizures during pregnancy?

Phenobarbital

Which benzodiazepines are used in the treatment of status epilepticus?

Diazepam; lorazepam

Which benzodiazepine is used to treat myoclonic and absence seizures?

Clonazepam

Which antiepileptic medication is the drug of choice for treating absence seizures and its only FDA indication is for absence seizures?

Ethosuximide

What is the mechanism of action of ethosuximide?

Inhibition of T-type calcium channels in the thalamus

What are the adverse effects of ethosuximide?

EPS; nausea; vomiting; diarrhea; abdominal pain; fatigue; hirsutism; Stevens-Johnson syndrome; drug-induced lupus; hiccups

Which antiepileptics decrease the efficacy of oral contraceptives?

Phenytoin; carbamazepine

How do phenytoin and carbamazepine decrease the efficacy of oral contraceptives?

Induction of cytochrome β-450 enzymes

Overdose or abrupt withdrawal of antiepileptics may cause what adverse effect?

Seizures

Give examples of newer antiepileptic medications:

Gabapentin; pregabalin; lamotrigine; topiramate; tiagabine; vigabatrin; felbamate; levetiracetam

Name two antiepileptics that are considered free of drug-drug interactions:

 

  1. Levetiracetam
  2. Gabapentin

 

Which of the newer antiepileptics may inhibit carbonic anhydrase, thereby causing a metabolic acidosis?

Topiramate

What conditions, other than epilepsy, can topiramate be used in?

Migraine; manic-depression; neuropathic pain

What is the mechanism of action of topiramate?

Inhibition of glutamate (AMPA) receptors; increases GABA effects; blocks neuronal voltage-gated sodium channels

Which types of seizures does topiramate treat?

Simple partial; complex partial; seizures associated with Lennox-Gastaut syndrome

What are the adverse effects of topiramate?

Impaired cognition; word finding difficulty; sedation; weight loss; renal stones; metabolic acidosis

Which of the newer antiepileptics may cause Stevens-Johnson syndrome?

Lamotrigine

What is the mechanism of action of lamotrigine?

Inhibition of sodium channels; inhibition of glutamate receptors

Which types of seizures does lamotrigine treat?

Absence; simple partial; complex partial; seizures associated with Lennox-Gastaut syndrome

What are the adverse effects of lamotrigine?

Stevens-Johnson syndrome; sedation; headache; dizziness; ataxia; nausea; diplopia; amenorrhea; dysmenorrhea

What neurotransmitter is gabapentin structurally related to?

GABA

Does gabapentin bind to the GABA receptor?

No

What is the mechanism of action of gabapentin?

Unknown (may bind to voltage-gated calcium channels specifically possessing the α-2-δ-1 subunit)

Which types of seizures does gabapentin treat?

Simple partial; complex partial

What conditions, other than epilepsy, can gabapentin be used in?

Migraine; neuropathic pain; manic-depression; insomnia; chronic pain; social phobia

What are the adverse effects of gabapentin?

Sedation; ataxia; viral infection (in children); weight gain; diarrhea; nausea; vomiting

AGENTS FOR MIGRAINE

 

What antihypertensive medication is used in the prophylaxis of migraine headache?

Propranolol

Give examples of medications in the “triptan” drug class:

Sumatriptan; almotriptan; naratriptan; rizatriptan; zolmitriptan

What is the mechanism of action of sumatriptan?

5-HT1D-receptor agonist which causes vasoconstriction in cranial arteries

Why should sumatriptan be used with caution in a patient with angina?

Can precipitate an anginal attack secondary to vasospasm of coronary arteries

How long after the first dose can a second dose of sumatriptan be given if migraine headache has not resolved?

Dose may be repeated once after 2 hours.

What is the mechanism of action of the ergot alkaloids?

Causes vasoconstriction of cranial arteries less selectively than “triptans” by acting as an agonist at various 5-HT receptors throughout the body

Give examples of ergot alkaloids:

Ergotamine; ergonovine

What are some common side effects of ergotamine?

Nausea; vomiting; diarrhea; chest pain; toxic levels can cause gangrene

Why is ergotamine sometimes given with caffeine?

Caffeine increases gut absorption of ergotamine.

Are opioid analgesics usually effective against migraine headache?

No

CLINICAL VIGNETTES

 

A 39-year-old man is unsatisfied with the results he is seeing from his current antidepressant therapy. He decides to stop taking the medication and to start seeing a new psychiatrist. To avoid repeating the same therapy he does not reveal that he was previously treated for his major depressive disorder. The new psychiatrist prescribes a first-line SSRI to treat the patient. Shortly after taking the SSRI, the patient becomes tachycardic, diaphoretic, and experiences myoclonic twitches. He develops a generalized tonic-clonic seizure shortly after admission to the emergency room. What class of medication was the patient most likely taking previously?

This patient was most likely taking a monoamine oxidase inhibitor (MAOI) prior to his arrival at his new psychiatrist. Results may not be seen for up to a month after initiation of treatment with an MAOI, leading to patient dissatisfaction and the belief that the medication is not effective. Should the MAOI therapy be discontinued, adequate time should be allowed for complete clearance of the drug before alternate therapy is initiated. SSRIs are particularly dangerous when combined with MAOIs because of their risk for causing serotonin syndrome, which this patient has developed.

An 80-year-old man has come to a cocktail party celebrating the end-of-the-year holidays. At the party he enjoys some hors d’oeuvres including small sausages and cheeses. In a few minutes, however, he collapses and is rushed to the emergency room. There he is found to have a blood pressure of 200/98. His wife informs the physician that he only takes one antihypertensive medication. What medication does he most likely take, and how has it contributed to his current condition?

He has suffered a hypertensive crisis due to the combination of tyramine and MAOIs. Cured meats and aged cheeses, such as those consumed by the patient contain tyramine, which may displace norepinephrine from storage vesicles and cause a buildup of catecholamines, leading to extreme hypertension.

A 29-year-old man is undergoing abdominal surgery. Shortly after induction and successful intubation, the patient’s peak airway pressures begin to rise. Bilateral auscultation confirms equal breath sounds, and stat chest x-ray reveals no pneumothorax. What intravenous anesthetic agent is most likely responsible for this development?

Fentanyl, a synthetic high-potency opioid, is frequently used as a part of balanced anesthesia and can cause chest wall and laryngeal rigidity, interfering with mechanical ventilation. Low doses of opiates should be used to avoid this complication.

A 72-year-old woman with Parkinson disease is unable to move after sitting through a film at the movie theater with her family. What is the most likely therapy she is receiving for her disease, and why might the medication be responsible for her current situation? What fast-acting dopamine agonist would be appropriate for use in such a situation?

The patient is most likely on levodopa therapy. Levodopa has a very short half-life leading to the “on-off” phenomenon frequently seen with its use. Patients may find they are suddenly unable to stand or walk and may require rescue therapy with a fast-acting dopamine agonist. Apomorphine is such an agent, and is useful in emergency situations such as that presented in the vignette. It does not require enzymatic conversion to an active product, and so works quickly—about 10 minutes after injection. Nausea and vomiting limit its use to rescue situations, as does dyskinesia and hypotension.