Week 9 - Anxiolytics, Sedatives, Hypnotics, Antidepressants

First line pharm tx for Anxiety

SSRIs and SNRIs

Can use Benzo's (short-term)

Goal of anxiety tx?

Symptom relief

What are neurotransmitters involved in Anxiety & Depression?

- Serotonin (5-HT)

- Norepinephrine (NE)

- Gamma-Aminobutyric Acid (GABA)

- Dopamine (DA)

What is the function of serotonin?

- Regulate mood, anxiety and emotional stability

What does low serotonin lead to?

Possible depression and anxiety disorders

What is norepinephrine?

A neurotransmitter involved in alertness, stress response & mood regulation

Function of GABA

the primary inhibitory neurotransmitter in the brain that reduces neuronal excitability

Function of Dopamine

Modulates motivation, reward and mood

Drug classes of Anxiety Disorder Treatment (5)

- Benzodiazepines

- Antidepressants (e.g. SSRIs/SNRIs)

- Pregabalin

- Bupropion

- Misc. Agents (Hydroxyzine, Beta Blockers, 2nd gen antipsychotics)

Drugs within the class of Benzodiazepines?

End in "lam" or "pam"

- Alprazolam

- Lorazepam

- Clonazepam

- Diazepam

MOA of Benzos?

enhance effects of GABA at the GABA receptor

ADRs of Benzos? (** = most important)

- Sedations**

- Tolerance

- Incoordination

- Impaired Memory

- Cognitive Impairment**

- Respiratory Depression**

- Amnesia

- Paradoxical effects

Your pt ODs on a benzo. What is the reversal agent for this OD?

Flumazenil

OD Toxicity for Benzos? (7)

- Sedation

- Apnea

- Confusion

- Ataxia

- Hypotension

- Coma

- Death

Benzo drug interactions

- Anything that adds CNS depression (ex. alcholol, TCAs, Antihistamines, Opiods, Sedative-hynotics)

What benzos are preferred in liver dysfunction?

- Lorazepam

- Oxazepam

- Temeazepam

What considerations are needed when considered benzo tx?

- Not first line; using a bridging therapy

- Caution with elderly/dementia patients

- Tolerance and dependence use

Benzo: Fastest onset (oral)

• diazepam (most lipophilic)

Benzo: Slowest onset (oral):

• clonazepam, oxazepam, temazepam (CLOT)

Benzo: Shortest duration (single dose):

• diazepam

Benzo: Shortest duration (multiple dose):

• alprazolam, triazolam

Benzo: Long duration (multiple dose):

• diazepam (and others)

What is the recommended tapering guidelines for Benzos?

Decrease does by 10-25% every 1-2 weeks

what types of benzo txts can cause Withdrawal for Benzos? (so taper slowly in)

- High doses

- Short half-life

- Prolonged use (> 2 months)

What pts are at increased risk for abuse of Benzos?

Pts w/:

- Family hx of Alcohol use disorder

- Polydrug abuse

- Antisocial personality disorder

What are the drugs w/i the Antidepressant SSRI class?

- Sertraline

- Escitalopram

- Citalopram

- Fluoxetine

- Paroxetine

What are the drugs w/i the Antidepressant SNRI class?

- Venlafaxine

- Duloxetine

Onset and Titration of Antidepressants?

- Onset: Slower onset (4-6 weeks on avg.)

- Titration: Start low and go slow

What is the MOA of Pregabalin (Lyrica)?

Binds to alpha2-delta subunit of Ca channels reducing neurotransmitter release (Glutamate, Substance P, norepinephrine)

Indications of Pregabalin?

- Anxiolytic

- Fibromyalgia

- Neuropathy/Neuraglia

- Seizure Disoder

ADRs of Pregabalin

- Respiratory Depression

- Weight Gain

- Cogntive effects (confusion, attention problems)

- Somnolence

- Dizziness

Key drug interactions of Pregabalin?

- CNS depressants

- Additive sedation & respiratory depression (Opioids, Benzodiazepines, Alcohol, Sedating antihistamines)

- Thiazolidinediones (Pioglitazone)

Who should you be careful to use pregabalins with?

elderly, patients with sleep apnea, COPD, respiratory conditions

MOA of Buspirone

- 5HT1A partial agonist

- Weak antagonists at Dopamine D2 receptors

ADRs of Buspirone

- Dizziness

- Headache

- Nausea/GI upset

- Nervoness/agiation

- Insomina/restlessnes

Hydroxyzine - MOA

H1 histamine receptor antagonists - produces sedation and calming effects

What is Hydroxyzine?

A 1st gen antihistamine that has anxiolytic properties

Side effects of Hydroxyzine

- Sedation/Drowsiness

- Anticholinergic effects

- Dizziness/confusion

- QT prolongation

What are the treatment options for Major Depression?

- SSRIs

- SNRIs

- TCAs

- MAOIs

MOA of SSRIs

inhibit the reuptake of serotonin, thereby increasing serotonin activity

ADRs of SSRIs

- GI upset

- Sexual Dysfunction

- Insomnia

- Headache

- Bleeding risk

Drug interactions of SSRIs (4)

- MAO inhibitors

- Antiplatelets/Anticoags

- Lithium and tricyclic antidepessants

- CYP450 inhibitors

What is Serotonin Syndrome?

A life-threatening condition caused by excess serotonergic activity in the CNS usually due to drug interactions, OD or increased dose of serotonin containing drugs

Clinical Presentation of Serotonin Syndrome

- Rapid onset

- Classic Triad:

- 1) AMS

- 2) Autonomic instability (sweating, tachycardia)

- 3) Neuromusucular abonormalities (clonus, hyperreflexia, etc.)

Meds within TCA class?

- Amitriptyline (main one)

MOA of TCAs

Inhibit reuptake of NE and 5-HT + anticholinergic and antihistamine effects

TCA side effects

Anticholingeric effects

Sedation

Weight gain

orthostatis

-cardiac toxicity

Drugs within the class of MAOIs?

- Phenelzine

- Tranylcypromine

MOA of MAOIs

• MOA: inhibit MAO-A and/or MAO-B which leads to decreased metabolism of monoamines (NE, 5-HT, DA, etc.)

MAOI side effects

- Sexual dysfunction

- HTN crisis

- Edema

- Serotonin sydrome

- Weight gain

Key drug interactions of MAOIs

- Tyramine-containing food (aged cheese, wine, beer, picked meats, fish, smoking meat) -> HTN crisis

- SSRIs/SNRIs, TCAs

- Other antidepressants

MOA of Mirtazapine

selective alpha-2 antagonist that enhances the release of NE & serotonin

MOA buproprion

NE/DA reuptake inhibitor may increase anxiety

side effects of bupropion

- Increased seizure risk

- Dry mouth

- Insomnia

- GI upset

MOA of Trazadone

Inhibits 5HT reuptake and blocks 5HT-2 receptors

Side effects of Trazadone

- Sedation

- Orthostatic hypotension

- Priapism

- Dizziness, headache

MOA of Vilazodone

SSRI and 5HT1A partial agonist

Side effects of Vilazodone

nausea and diarrhea

headache

insomnia

sex dysfunction

serotonin syndrome

What non-SRRI may be an initial therapy for depression?

- Buproprion (if there is a ADHD dx)

- Duloxetine (if fibromylagia or back pain is present)

- TCAs (useful if hx of migraines)

- Paroxetine or Venlafaxine (vasomotor symptoms in post-menopausal women)

Drugs for sleep disorders

Benzos

Non-benzos

Melatonin receptor agonists

Trazadone

Doxepin