Sedative Hypnotic And Anxiolytic Drugs Flashcards
A 43-year-old man with severe hepatic cirrhosis requires a sedative for insomnia. Which of the following sedatives would be the best choice for this patient?
A
Phenobarbital
B
Diazepam
C
Lorazepam
D
Secobarbital
E
Flurazepam
C
Lorazepam
A 19-year-old college student has overdosed on phenobarbital. After standard supportive care, the physician in the ER should do which of the following to hasten the elimination of phenobarbital?
A
Acidify the urine
B
Acidify the blood
C
Alkalinize the blood
D
Alkalinize the urine
E
Use a drug to stimulate hepatic CYP 2C19
D
Alkalinize the urine
A 32-year-old woman is taking ramelteon for chronic insomnia. Ramelteon binds to
A
melatonin receptors M1 and M2.
B
muscarinic receptors M3.
C
nicotinic receptors.
D
α1-adrenergic receptors.
E
D2 dopaminergic receptors.
A
melatonin receptors M1 and M2.
A 43-year-old woman is prescribed a benzodiazepine for anxiety. The choice of which benzodiazepine to prescribe should be based on
A
volume of distribution.
B
plasma half-life.
C
protein binding.
D
the indications approved by the FDA.
E
creatinine clearance.
B
plasma half-life.
53-year-old man with 15 years of alcohol abuse has developed weakness in his legs and the onset of heart failure. The primary treatment is
A
digoxin.
B
metoprolol.
C
creatine.
D
abstinence from alcohol.
E
thiamine.
D
abstinence from alcohol.
A 33-year-old Japanese man becomes flushed and light-headed after one glass of wine. This reaction is likely due to
A
the rate he drank the glass of wine.
B
increased absorption of the alcohol.
C
inhibition of monoamine oxidase.
D
decreased renal excretion of alcohol.
E
a variant in aldehyde dehydrogenase.
E
a variant in aldehyde dehydrogenase.
Which of the following molecular processes best
describes the mechanism of action of benzodiazepines?
(A) potentiating the effect of GABA at chloride ion channels
(B) blocking glutamate excitation
(C) blocking the inactivation of sodium ion channels
(D) binding to opioid receptors to produce sedation
(E) potentiating the action of the inhibitory amino acid, glycine
(A) potentiating the effect of GABA at chloride ion channels
Benzodiazepines are noted for altering which one of the following aspects of sleep?
(A) increasing the time to sleep onset
(B) decreasing stage 2 NREM sleep
(C) increasing slow-wave sleep
(D) decreasing the REM stage of sleep
(E) increasing sleep awakenings
(D) decreasing the REM stage of sleep
Which one of the following statements best describes flumazenil?
(A) does not produce withdrawal seizures
(B) has the longest elimination half-life
(C) is not metabolized into an active agent
(D) is also used for the treatment of epilepsy
(E) is a selective benzodiazepine antagonist
(E) is a selective benzodiazepine antagonist
Zaleplon differs from zolpidem in which one of the following ways?
(A) produces withdrawal seizures
(B) has a shorter elimination half-life
(C) has a different chemical structure than benzodiazepines
(D) shows less tolerance to sedative effects
(E) produces greater morning sedation
(B) has a shorter elimination half-life
Which one of the following anxiolytic drugs is noted for its lack of sedation?
(A) hydroxyzine
(B) diazepam
(C) oxazepam
(D) alprazolam
(E) buspirone
(E) buspirone
Clinical antipsychotic potency for “typical” antipsychotics correlates with actions at which receptor?
(A) dopamine D2 receptors
(B) α2-adrenergic receptors
(C) muscarinic receptors
(D) histamine receptors
(E) serotonin
(A) dopamine D2 receptors
Which of the following agents is an antipsychotic that can improve both positive and negative symptoms of schizophrenia?
(A) chlorpromazine
(B) haloperidol
(C) thiothixene
(D) risperidone
(E) thioridazine
(D) risperidone
Which one of the following is not a class of antidepressant medications?
(A) SNRIs
(B) TCAs
(C) MAOIs
(D) acetylcholinesterase inhibitors
(E) SSRIs
(D) acetylcholinesterase inhibitors
The older TCAs share all of the following adverse effects except which one?
(A) orthostatic hypotension
(B) sedation
(C) seizures
(D) weight gain
(E) sexual dysfunction
(E) sexual dysfunction
Foods containing tyramine should be avoided when taken with which class of medications?
(A) TCAs
(B) MAOIs
(C) SSRIs
(D) atypical antidepressants
(E) antihypertensive medications
(B) MAOIs
A 38-year-old man is taking Tranylcypromine an MAO inhibitor, for depression. After a celebratory dinner, he develops a severe headache and chest pain. At hospital his blood pressure is 190/135 mm Hg. His hypertensive crisis is likely due to the ingestion of
A. Green salad
B. Chocolate cake
C. Red wine
D. Broiled salmon
E. Wheat bread
C. Red wine
A 32-year-old woman is taking sertraline for mild depression. This drug increases the availability of serotonin (5-HT) at the postsynaptic membrane because it
A. Stimulates 5-HT4 receptors
B. Enhances the release of 5-HT from presynaptic nerve endings
C. Inhibits the presynaptic uptake of 5-HT
D. Blocks MAO which degrades 5-HT
E. Enhances the synthesis of 5-HT
C. Inhibits the presynaptic uptake of 5-HT
Which of the following can greatly enhance the toxicity when combined with the use benzodiazepines or barbiturate medications?
A. Cocaine
B. Alcohol
C. Methamphetamine
D. Marijuana
B. Alcohol
How is MOA different than other Benzodiazepines?
Oxazepam, Temazepam, and Lorazepam
bypass phase I oxidation and are metabolized only by phase II conjugation and are safer to use in the elderly
Shorter acting Benzodiazepines are….
alprazolam, estazolam, midazolam and triazolam
Longer acting Benzodiazepines are…
chlordiazepoxide, diazepam, flurazepam
Drugs of choice for Insomia are…..
Zolpidem, Zaleplon, Eszopiclone, Ramelteon
Benzodiazepines: MOA
- facilitating the activity of y-aminobutyric acid (GABA) at various sites in the CNS.
- binding site is located at the interface between a and y subunits at a different site of binding than GABA and bind to a1 and a2 subunits.
- BDZ increase the frequency with which the channel is opened.
Benzodiazepines: Side Effect
anterograde amnesia
Midazolam (Versed)
- Benzodiazepines
- Used IV as an anesthetic for patients undergoing procedures (EGD/Colonoscopy)
Clonazepam (Klonopin)
- Benzodiazepines
- Used for treatment of panic disorder, anxiety, and seizure disorders
- It does not have active metabolites
- One of the easier drugs in this class to taper off of in cases of dependence
Triazolam
Triazolam is short acting and coming off of this medication may cause rebound insomnia
Flurazepam
- Benzodiazepines
- is long acting and may cause significant hangover effect with somnolence the next day
Flumazenil (Romazicon)
- Competitive benzodiazepine receptor antagonist
- Used to counteract the adverse effects of benzodiazepine such as respiratory depression in cases of accidental or intentional overdose
- Adverse effects include seizures, arrhythmia, blurred vision, emotional lability, and dizziness
Barbiturates: MOA
- Bind to allosteric site on the GABAa receptor chloride ion channel that is distinct from the site BDZ bind.
- Increases the affinity of the receptor for GABA and the duration of time the chloride channel remains open
- Directly increases chloride influx in the absence of GABA
Phenobarbital
- Used to treat seizure disorders.
- Considered a Narrow Therapeutic Index Drug
- less lipid soluble and is absorbed slowly and distributed slowly hence it carries a longer half life
Thiopental
- Administered IV
- rapid onset of action and short duration of action
Antihistamines: MOA
(Diphenhydramine, Hydroxyzine, Doxepin)
- Bind to H1 receptors and reduce acetylcholine released by neurons in the reticular nuclei
Other Sedative hypnotic drugs
(Zolpidem, Zaleplon, Eszopiclone)
More selective as it binds to GABAa1 subunits
Melatonin
Neuroendocrine hormone synthesized in the pineal gland that interacts with specific receptors in the CNS and is believed to be the principal mediator of the biologic clock that determines circadian, seasonal, and productive rhythm
Ramelteon (Rozerem)
- that selectively acts at melatonin receptors and is approved to treat sleep onset insomnia
- Does not produce dependence with little potential for abuse
- No evidence of rebound insomnia with this drug
- Has significant drug interaction with Fluvoxamine (Luvox) through Cyp1A2
Tasimetleon (Hetlioz)
- Melatonin agonist used for the treatment of insomnia for non 24 hour sleep wake disorder
- Blind people
Buspirone (Buspar)
- Unique anxiolytic agent
- Drug is used to treat chronic anxiety and produces an anxiolytic effect without causing marked sedation, amnesia, tolerance, dependence, or muscle relaxation
- Side effects include headache, dizziness, nervousness, and are usually mild and temporary
- Partial agonist of 5HT1a receptors and provides activation feedback inhibition of serotonin release
- May cause up regulation of postsynaptic serotonin receptors
- This effect takes time to develop consistent with 3-4 week delay in onset of the anxiolytic effect
Typical antipsychotic agents:
- Chlorpromazine
- Thioridazine
- Fluphenazine
- Haloperidol
Chlorpromazine
is considered low potency phenothiazine agent that causes moderate sedation and EPS
Thioridazine
is considered low potency, has greater anticholinergic effects and less EPS effects
Fluphenazine
is considered higher potency produces fewer autonomic side effects but more EPS and comes in an IM formulation given every 1-3 weeks
Haloperidol
is considered high potency and may cause significant EPS and is also available in IM formulation. Haloperidol is also used in the treatment of Tourette’s syndrome
What drugs can you adminster to manage EPS?
- Benztropine (Cogentin)
- Diphenhydramine (Benadryl)
- Amantadine (Symmetrel)
Atypical anti-psychotic agents
- Clozapine
- Olanzapine
- Risperidone (Risperdal)
Clozapine
- causes less EPS and also has greater activity against negative symptoms. It also has significant sedation and autonomic side effects.
*has a 1.3% risk of first year incidence of fatal agranulocytosis. - FDA requires weekly monitoring of leukocyte counts for first 6 months then biweekly thereafter with a registry
Olanzapine
- Causes fewer autonomic side effects and has not been reported to have agranulocytosis
- Olanzapine is as effective as haloperidol in alleviating positive symptoms of schizophrenia and is superior to haloperidol in alleviating the negative symptoms and produces less EPS than haloperidol
- Most common side effects to olanzapine includes sedation and weight gain
- Olanzapine is available in combination with fluoxetine
Risperidone (Risperdal)
- Acts as an antagonist of both D2 and Serotonin 5HT2A receptors
- Newer atypical antipsychotic
- Causes less sedation, more orthostatic hypotension, and a higher incidence of EPS
- May elevate prolactin levels
- Lengthens the QT interval potentiating risk of causing Torsades
Atypical antipsychotic agents: Agents acting similar to risperidone
- Paliperidone (Invega)
- Ziprasidone (Geodon)
- Lurasidone (Latuda)
- Iloperidone (Fanapt)
- Asenapine (Saphris)
- Aripiprazole (Abilify)
** Partial agonist at dopamine and 5HT1A receptors but is an antagonist of 5HT2A
**First drug approved to treat irritability in Autistic children*
Types of Antidepressant drug classes:
- Tricyclic anti-depressants (TCA)
- Selective Serotonin Reuptake Inhibitors (SSRI)
- Serotonin and Norepinephrine Reuptake Inhibitors (SNRI)
- Monoamine Oxidase Inhibitors (MAOI)
TCAs
- block the neuronal reuptake of norepinephrine and serotonin through the reuptake transporters
- Antidepressant effect occurs 2-4 weeks after treatment
- Adverse effects include autonomic effects, marked sedation, lowering of the seizure threshold,
- Overdose can cause life threatening cardiac dysrhythmias manifests as a wide complex QRS tachycardia
- Treatment for overdose can be treated by IV sodium bicarbonate
Types of TCAs
Amitriptyline, Clomipramine, Desipramine, Imipramine, Nortriptyline
Types of SSRIs
fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, escitalopram
SSRI: Adverse effects
nervousness, dizziness, insomnia, sexual dysfunction, priaprism, impotence, inability to reach orgasm
Citalopram/Escitalopram
- SSRI
- Citalopram is a racemic mixture of Rand S enantiomers of the drug molecule and is highly selective for serotonin
- Citalopram may cause prolonged QT interval with risk of Torsades
- Escitalopram is 100% S enantiomer and is 100 x more potent at inhibiting 5HT reuptake
Paroxetine/Sertraline
- SSRI
- Sertraline undergoes extensive first pass effect in liver
- Sertraline is preferred in the elderly because its elimination is not substantially affected by aging
- Paroxetine is associated with significant weight gain
Fluvoxamine
- SSRI
- Approved for obsessive-compulsive disorder
- Associated with having sedation side effects
Fluoxetine
- Used to treat depression, anorexia, bulimia, and obsessive-compulsive disorder
- Can impair regulation of blood glucose levels and can cause inappropiate antidiuretic hormone secretion causing hyponatremia and elevated urine osmolality
Types of SNRI Serotonin and Norepinephrine Reuptake inhibitors:
- Duloxetine (Cymbalta)
- Venlafaxine (Effexor)
- Desvenlafaxine (Pristiq)
- Milnacipran (Savella)
Duloxetine (Cymbalta)
- SNRI
- Indicated for major depressive disorder, diabetic peripheral neuropathy, generalized anxiety, fibromyalgia, chronic pain syndromes
Venlafaxine (Effexor)
- SNRI
- Clinically does not cause significant sedation and is not associated with weight gain
Desvenlafaxine (Pristiq)
- SNRI
- Newer agent in the class touted as the go to for treatment failures of other medications
Milnacipran (Savella)
- SNRI
- Indicated for treatment of fibromyalgia
Types of MAO Inhibitors:
Isocarboxazid, Phenelzine, Tranylcypromine
MAO Inhibitors
- Irreversibly bind to and inhibit monoamine oxidase
- Increase serotonin levels more than the do norepinephrine
- Antidepressant effects are caused by down regulation of presynaptic autoreceptors and subsequent increased firing of serotonergic neurons
- Effects are delayed several weeks after therapy
- Major adverse effect is the occurrence of hypertensive crisis characterized by occipital headache that may radiate frontally, palpitation, neck stiffness, or soreness, nausea, vomiting, sweating and photophobia
- Foods containing tyramine and use of sympathomimetic amines co-administered with a MAOI may potentiate the hypertensive crisis
- Selegiline (Eldepryl) third generation MAOI is used in the treatment of Parkinson’s disease
Bupropion (Wellbutrin) (Zyban)
- Causes very little sedation, rarely produces cardiovascular effects, or sexual dysfunction
- Produces few anticholinergic effects but may cause agitation, insomnia, nausea, and weight loss
- Used to assist in patients who are attempting nicotine cessation
Mirtazepine (Remeron)
- Tetracyclic antidepressant and has antidepressant and anti anxiety properties
- Blocks presynaptic a2 adrenergic auto-receptors and heteroreceptors increasing neuronal release of NE and 5HT
- May cause increase in hepatic enzymes and has been associated with a few cases of agranulocytosis
Trazodone (Desyrel)
- Inhibits neuronal reuptake of serotonin and acts as an antagonist at the 5HT 2a receptor
- Causes significant sedation and orthostatic hypotension but does not cause anticholinergic effects or impact cardiac conduction
Vilazodone (Viibryd)
- Serotonine reuptake inhibitor and partial agonist of the 5HT1A receptor
- MOA is shared with Buspirone and Aripraprazole
TCA Adverse drug interactions
- TCA levels are elevated by: Antipsychotic drugs, Ca Channel blockers, Cimetidine, and SSRIs
- TCA levels are reduced by: Barbiturates, Carbamazepine, Phenytoin
- TCA should not be used in conjunction with MAOI’s
SSRIs Adverse drug reactions
- SSRIs interact with a variety of drugs CYP2D impacted by Fluoxetine
- SSRIs Sertraline has the least effect and drug interactions
- SSRIs should not be used in conjunction with MAOI’s or triptans for migraine
MAOI Adverse drug reactions
may cause hypertensive crisis if intake of tyramines occur (aged cheese, beer, wine, meats, raisins, chocolate, coffee)
Lithium
- reduces the formation of inositol triphosphate IP3 by inhibiting myoinositol 1 phosphatase an enzyme in the inositol phosphate pathway.
- reduces the neuronal response to serotonin and norepinephrine whose effects are partly mediated by IP3
- High levels can cause neurotoxicity and cardiotoxicity leading to dysrhythmia
- Side effects include drowsiness, weight gain, tremor, polyuria, and hypothyroidism
Ethanol
is a CNS Depressant similar to barbiturates and benzodiazepines and potentiates the actions of GABA producing sedative hypnotic anxiolytic amnesic and anticonfulsant effects.
Thiamine deficiency
- leads to nerve demyelination and neuropathy
- Thiamine deficiency may lead to Wernicke-Korsakoff syndrome characterized by confusion, amnesia, ataxia, nystagmus, and ophthalmoplegia
CNS Stimulants
- Amphetamine and derivatives increase the synaptic concentration of norepinephrine and dopamine by gaining entry into the presynaptic terminal through the reuptake transporter protein and increasing amount of catecholamines packaged into vesicles
- Methamphetamine is often preferred by abusers because it causes less norepinephrine to be released and can be more easily burned and smoked
- Known as ice or crystal meth produced from otc cough and cold preparations
- 3,4methylene-dioxy-methamphetamine MDMA know as ecstasy
- Ecstasy produces euphoria, increases empathy, enhances pleasure, heightens sexuality, and expands consciousness without loss of control
- Unpleasant effects include nausea, vomiting, anorexia, anxiety life threatening due to cardiac arrhythmias, hyperthermia, rhabdomyolysis, and disseminated intravascular coagulation
- MDMA likely destroys serotonergic brain neurons contributing to associated psychiatric complications such as panic reactions, psychosis, depression and suicide
COCAINE
- Psychostimulant and local anesthetic with limited clinical use
- Stimulant effects caused by inhibition of the neuronal reuptake of norepinephrine and dopamine
- Use of purified forms of cocaine are associated with drug dependence as well as cardiovascular, pulmonary, and neural toxicity
- Crack cocaine inhaled from smoke has the same concentration effect as given IV
- Cocaine alters tactile sensation causing its users to feel as if insects were crawling under their skin
- Cocaine stimulates respiration at lower doses and at high doses can produce irregular breathing and apnea known as Cheyne-Stokes respiration
- Cocaine overdose often experience delirium and become aggressive and violent
- Other adverse effects include tonic-clonic seizures, malignant encephalopathy, myocardial infarction, subdural hemorrhage
