Psych pharm Flashcards
Lorazepam
Clonazepam - *most common treatment of REM behavior disorder
Oxazepam
Diazepam
Acute Anxiety Benzos
• GABAergic in that they potentiate the actions of the inhibitory neurotransmitter GABA • Bind to GABAA receptors in CNS neuronal synapses, thereby facilitating GABA-mediated Cl- ion channel opening and enhancing membrane hyperpolarization.
• Anxiolytic doses result in CNS depression that is manifested by a calming effect with concomitant reduction of anxiety.• 1st-line agents for rapid relief of acute anxiety states in generalized anxiety disorder (GAD) or panic disorder.• Should be used for short periods, no longer than 2-4 weeks.
Midazolam
acute anxiolytic benzo
• Midazolam is labeled for sedation prior to medical or surgical procedures.
Benzo: refer to other slides
Adverse effects of Benzos
- Risk of dependence (schedule IV controlled substances).• Taper slowly (over weeks) to avoid precipitation of withdrawal symptoms.• Additive effects with ethanol, anticholinergics, and antihistamines.
- abrupt cessation can lead to withdrawal states
ManifestationsofCNS
-depressant effects: Drowsiness - Impaired judgement - Diminished motor skills - Anterograde amnesia - Lethargy - Confusional states in the elderly (slower metabolism)
Clorazepate
Benzo acute anxiolytic
- GABAergic in that they potentiate the actions of the inhibitory neurotransmitter GABA • Bind to GABAA receptors in CNS neuronal synapses, thereby facilitating GABA-mediated Cl- ion channel opening and enhancing membrane hyperpolarization.
- Anxiolytic doses result in CNS depression that is manifested by a calming effect with concomitant reduction of anxiety.• 1st-line agents for rapid relief of acute anxiety states in generalized anxiety disorder (GAD) or panic disorder.• Should be used for short periods, no longer than 2-4 weeks.
Alprazolam
aka Xanax - acute anxiety benzo
- GABAergic in that they potentiate the actions of the inhibitory neurotransmitter GABA • Bind to GABAA receptors in CNS neuronal synapses, thereby facilitating GABA-mediated Cl- ion channel opening and enhancing membrane hyperpolarization.
- Anxiolytic doses result in CNS depression that is manifested by a calming effect with concomitant reduction of anxiety.• 1st-line agents for rapid relief of acute anxiety states in generalized anxiety disorder (GAD) or panic disorder.• Should be used for short periods, no longer than 2-4 weeks.
Escitalopram
Seriously Escaping From Very Dull Pakistan
Lexapro
SSRI
Clinical uses: major depression, anxiety disorder, OCD, PTSD, PMDD, bulimia
Mechanism of action for anti-anxiety is unclear.• Implicated in the modulation of receptor activation of neuronal signal transduction pathways connected to serotonin, dopamine, and norepinephrine.• Theorized to activate stress-adapting pathways.
- Reduce somatic anxiety symptoms and the general distress associated with those symptoms.
- 1st-line agents for the chronic management of GAD, particularly with comorbid depression.• Anti-anxiety response requires 2 to 4 weeks or longer.• Assessment of initial response should be after 4 to 6 weeks of therapy at adequate doses.
Adverse effects of SSRIs and SNRIs
First Aid:
SNRI: increase BP, stimulant effects, sedation, nausea
SSRI: fewer than TCA’s. GI distress, SIADH, sexual dysfunction (anorgasmia, decreased libido)
Most common adverse effects include: Diarrhea Nausea and vomiting Sexual dysfunction Insomnia Weight gain Headache Diaphoresis
seizures with gross overdose
Thediaphoresis are often transient, whereas weight gain and sexual dysfunction may continue in long-term treatment.• Discontinuation rates secondary to side effects tend to be higher with the SNRIs than the SSRIs.
Paroxetine
SSRI
Clinical uses: major depression, anxiety disorder, OCD, PTSD, PMDD, bulimia
*potent inhibitor of CYP2D6
Mechanism of action for anti-anxiety is unclear.• Implicated in the modulation of receptor activation of neuronal signal transduction pathways connected to serotonin, dopamine, and norepinephrine.• Theorized to activate stress-adapting pathways.
- Reduce somatic anxiety symptoms and the general distress associated with those symptoms.
- 1st-line agents for the chronic management of GAD, particularly with comorbid depression.• Anti-anxiety response requires 2 to 4 weeks or longer.• Assessment of initial response should be after 4 to 6 weeks of therapy at adequate doses.
Sertraline
aka Zoloft
SSRI
Clinical uses: major depression, anxiety disorder, OCD, PTSD, PMDD, bulimia
Mechanism of action for anti-anxiety is unclear.• Implicated in the modulation of receptor activation of neuronal signal transduction pathways connected to serotonin, dopamine, and norepinephrine.• Theorized to activate stress-adapting pathways.
- Reduce somatic anxiety symptoms and the general distress associated with those symptoms.
- 1st-line agents for the chronic management of GAD, particularly with comorbid depression.• Anti-anxiety response requires 2 to 4 weeks or longer.• Assessment of initial response should be after 4 to 6 weeks of therapy at adequate doses.
Duloxetine
aka Cymbalta
SNRI Uses: major depression chronic pain fibromyalgia menopausal symptoms
Mechanism of action for anti-anxiety is unclear.• Implicated in the modulation of receptor activation of neuronal signal transduction pathways connected to serotonin, dopamine, and norepinephrine.• Theorized to activate stress-adapting pathways.
- Reduce somatic anxiety symptoms and the general distress associated with those symptoms.
- 1st-line agents for the chronic management of GAD, particularly with comorbid depression.• Anti-anxiety response requires 2 to 4 weeks or longer.• Assessment of initial response should be after 4 to 6 weeks of therapy at adequate doses.
Venlafaxine XR
SNRI
*metabolized extensively via CYP2D6 - so inhibitors or inducers need to be considered
major depression
chronic pain
fibromyalgia
menopausal symptoms
Mechanism of action for anti-anxiety is unclear.• Implicated in the modulation of receptor activation of neuronal signal transduction pathways connected to serotonin, dopamine, and norepinephrine.• Theorized to activate stress-adapting pathways.
- Reduce somatic anxiety symptoms and the general distress associated with those symptoms.
- 1st-line agents for the chronic management of GAD, particularly with comorbid depression.• Anti-anxiety response requires 2 to 4 weeks or longer.• Assessment of initial response should be after 4 to 6 weeks of therapy at adequate doses.
Buspirone
First AID: GAD, does not cause sedation, addiction or tolerance. Does not interact with alcohol as opposed to barbituates and benzodiazepines.
It does not interact with GABAergic systems.• Mechanism uncertain. Partial agonist at 5- HT1A receptors Also has affinity for dopamine D2receptors.
Selective anxiolytic without causing marked sedative, hypnotic, or euphoric effects.
2nd-line agent for the chronic management of GAD.• Classified as 2nd-line due to inconsistent reports of long-term efficacy and lack of suitability for comorbid disorders (e.g., panic disorder or depression).• Anxiolytic effects take 2 weeks or longer to become established.
Adverse effects Buspirone
Most common adverse effects are typically transient, and include:
Nausea
Abdominal pain
Drowsiness
Dizziness
• Interacts with inducers and inhibitors of CYP3A4 as well as monoamine oxidase (MAO) inhibitors.
Pregabalin
aka Lyrica
GABAergic agent that does not interact with the GABAA receptor.• Thought to potentiate GABA activity in two ways:1. Increasing presynaptic GABA release by binding to the alpha2delta subunit of voltage- gated calcium channels and altering calcium influx.2. Increasing GABA biosynthesis by modulating the actions glutamate decarboxylase and branched chain aminotransferase.
Produces anxiolytic effects similar to the benzodiazepines and antidepressants.
2nd-line agent for the chronic management of GAD.• Not currently approved as a 1st-line agent for GAD in the US, due to a lack of sufficient clinical experience.
Adverse effects Pregabalin
Most common adverse effects include: -Dizziness -Somnolence - Incoordination - Dry mouth -Blurred vision - Weight gain • More idiosyncratic adverse effects include: Peripheral edema Thrombocytopenia• Lower risk of dependence than the benzodiazepines (schedule V controlled substance) but you can still get withdrawal symptoms with abrupt discontinuation
Imipramine
TCA (acts like an SNRI) Uses: major depression, chronic pain, OCD
inhibit NE and 5 HT reuptake, more selective for 5HT!
Produces anxiolytic effects similar to the newer antidepressants.
2nd-line agent for the chronic management of GAD.• Classified as 2nd-line due to higher toxicity and adverse effect rates than the newer antidepressants.
Adverse effects imipramine
Adverse effects are related to blockade of histamine, muscarinic/cholinergic, and alpha -adrenergic receptors.
• Antihistamine effects include:
Sedation Somnolence
• Anticholinergic (muscarinic block) effectsinclude: Dry mouth, Constipation, Blurred/double vision, Tachycardia
• Antiadrenergic effects include: Orthostatic hypotension
• Risk of serious toxicity (including seizures, tachycardia, and cardiac arrest) with high doses.
First AID: TriC’s: Convulsions, Coma, Cardiotoxicity (arrhytmia)
Hydroxyzine
potent H1 antihistamine that also acts as a strong antagonist at 5-HT2a receptors.• Antiserotonergic activity is thought to underlie its anxiolytic properties.
Produces anxiolytic effects similar to buspirone and the benzodiazepines.
Alternative agent for the treatment of GAD.• Although commonly used in the primary care setting, it is considered an alternative agent due to adverse effects and lack of efficacy for comorbid disorders.• Used as a sedative prior to dental procedures.
Adverse effects Hydroxyzine
Adverse effects are related to blockade of histamine, muscarinic/cholinergic, and dopamine receptors.
• Antihistamine effects include:
Sedation Somnolence
- Anticholinergic effectsinclude: Dry mouth Constipation Blurred/double vision
- Antidopaminergic effects include: Extrapyramidal symptoms (dyskinesias and tremors)
- Overdose can result in hallucinations and cardiac effects (QT prolongation and Torsades des Pointes).
Quetiapine XR
Atypical antipsychotic
Antagonist activity at 5-HT2a receptors is thought to underlie its anxiolytic properties.
• Produces anxiolytic effects similar to the newer antidepressants, but with an earlier onset of action.• Alternative agent for the treatment of GAD.• It is considered an alternative agent due to adverse effects and insufficient clinical experience with regard to long-term risks and benefits.
Quetiapine XR adverse effects
Adverse effects are related to blockade of alpha-adrenergic, muscarinic/cholinergic, and dopamine receptors.
• Antiadrenergic effects include: Orthostatic hypotension
- Anticholinergic effectsinclude: Dry mouth Constipation Tachycardia
- Antidopaminergic effects include: Extrapyramidal symptoms (tardive dyskinesia and akathisia)
Estazolam
Sleep Benzo
Decrease sleep latency (time to fall asleep) and the number of awakenings.• Increase total sleep time.
Sleep disorders characterized by difficulty in falling asleep.• Hypnotic doses are higher than those used for anxiolytic applications.• Should be used at the lowest possible dose for the shortest possible time period.• Typically maintain hypnotic efficacy for 1 month, but tolerance can develop with time.
Flurazepam
Sleep Benzo
Decrease sleep latency (time to fall asleep) and the number of awakenings.• Increase total sleep time.
Sleep disorders characterized by difficulty in falling asleep.• Hypnotic doses are higher than those used for anxiolytic applications.• Should be used at the lowest possible dose for the shortest possible time period.• Typically maintain hypnotic efficacy for 1 month, but tolerance can develop with time.
Quazepam
Sleep Benzo
Decrease sleep latency (time to fall asleep) and the number of awakenings.• Increase total sleep time.
Sleep disorders characterized by difficulty in falling asleep.• Hypnotic doses are higher than those used for anxiolytic applications.• Should be used at the lowest possible dose for the shortest possible time period.• Typically maintain hypnotic efficacy for 1 month, but tolerance can develop with time.
Temazepam
Sleep Benzo
Decrease sleep latency (time to fall asleep) and the number of awakenings.• Increase total sleep time.
Sleep disorders characterized by difficulty in falling asleep.• Hypnotic doses are higher than those used for anxiolytic applications.• Should be used at the lowest possible dose for the shortest possible time period.• Typically maintain hypnotic efficacy for 1 month, but tolerance can develop with time.
Triazolam
Sleep Benzo
Decrease sleep latency (time to fall asleep) and the number of awakenings.• Increase total sleep time.
Sleep disorders characterized by difficulty in falling asleep.• Hypnotic doses are higher than those used for anxiolytic applications.• Should be used at the lowest possible dose for the shortest possible time period.• Typically maintain hypnotic efficacy for 1 month, but tolerance can develop with time.
Adverse effects of 'Estazolam Flurazepam Quazepam Temazepam Triazolam
ManifestationsofCNS
1. depressant effects: Daytime sedation Psychomotorincoordination
- Cognitive deficits Anterograde amnesia
- • Risk of dependence(schedule IV controlled substances).• After prolonged use, abrupt cessation can result in withdrawal symptoms, with associated rebound insomnia.• Additive effects with ethanol and other CNS depressants.
Zolpidem (Ambien) Zaleplon (Sonata) Eszopiclone (Lunesta
Similar GABAergic mechanism to the benzodiazepines.• More selective than the benzodiazepines with regard to the specific GABAA receptor isoform they bind.
All decrease time to persistent sleep.• Zolpidem and eszopiclone increase total sleep time, while zaleplon does not.• Reduced potential for amnesic effects and day-after psychomotor depression relative to the benzodiazepine hypnotics.
Sleep disorders characterized by difficulty in falling asleep.• Should be used at the lowest possible dose for the shortest possible time period.
Adverse effects of Z drugs
Adverse effects are dose related and can include: Somnolence Dizziness Headache GI upset Muscle pain• Risk of dependence(scheduleIV controlled substances).• After prolonged use, abrupt cessation can result in withdrawal symptoms and rebound insomnia, though typically of less intensity than those associated with the benzodiazepine hypnotics.
Ramelteon (Rozerem) Tasimelteon (Hetlioz)
Agonists at MT1 and MT2 receptors in the brain.• No GABAergic activity.
Decrease sleep latency and increase sleep periods, with no rebound insomnia or risk of dependence.
Ramelteon is approved for sleep disorders characterized by difficulty in falling asleep.
• Tasimelteon is approved for non-24 hour sleep- wake disorder.
Side effects of Melatonin Receptor agonists
Ramelteon, Tasimelteon
Most common adverse effects of ramelteon include: Somnolence Dizziness Fatigue Endocrine changes(↓testosterone and ↑prolactin)
• Most common adverse effects of tasimelteon include: Drowsiness Headache Abnormal dreams ornightmares Urinary tract infection
Suvorexant
Antagonist at OX1 and OX2 receptors in the brain.• No GABAergic activity.
Decreases sleep latency and increases sleep periods.
Sleep disorders characterized by difficulty in falling asleep.
Adverse effects of Suvorexant
Most common adverse effects include: Day-after somnolence Dizziness Headache• Can cause “sleep-driving” behavior and amnesic effects.• Risk of dependence (schedule IV controlled substance).
Flumazenil
GABAa receptor antagonist
Acts as a competitive antagonist at the benzodiazepine binding site on the GABAA receptor.
• Antagonizes the CNS depressant effects of benzodiazepines and the non- benzodiazepine GABAergic hypnotics (zolpidem, zaleplon, and eszopiclone).
It is approved for use in reversing the CNS depressant effects of benzodiazepine overdose.• Hastens recovery after benzodiazepine use in medical procedures.• Typically requires repeated administration, due to its shorter half- life (0.7 to 1.3 hours) relative to the benzodiazepines.
Adverse effects of Flumazenil
Agitation and confusion.• Potential for precipitating withdrawal symptoms in cases of drug dependence.w
which is why it is controversial
Reserpine
a compound that was found to induce depression and its MOA was used to model depression
Reserpine inhibits VMAT on vesicles which prevents NT from concentrating in the presynaptic neuron. Little or no NT is released
Fluoxetine
aka Prozac
SSRI
Clinical uses: major depression, anxiety disorder, OCD, PTSD, PMDD, bulimia
Inhibit 5-HT reuptake
selectively as compared to NE
reuptake
- *metabolite of fluoxetine - norfluoxetine has a half life of 7 to 9 days, be wary when transition to MAOI
- potent inhibitor of 2D6.
• Relatively selective for 5-HT transporter, thus side effects limited to effects on 5-HT- mediated responses \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ -also used as treatment for ADHD
-also used in treatment of BULIMIA- regardless if patient has depression, it is the only FDA approved medication
fluvoxamine
SSRI
Clinical uses: major depression, anxiety disorder, OCD, PTSD, PMDD, bulimia
**Potent inhibitor of CYP3A4
Inhibit 5-HT reuptake
selectively as compared to NE
reuptake
• Relatively selective for 5-HT transporter, thus side effects limited to effects on 5-HT- mediated responses
Citalopram
SSRI
Clinical uses: major depression, anxiety disorder, OCD, PTSD, PMDD, bulimia
Inhibit 5-HT reuptake
selectively as compared to NE
reuptake
• Relatively selective for 5-HT transporter, thus side effects limited to effects on 5-HT- mediated responses
