Transcript Chapter 16 Cholinesterase Inhibitors

Chapter 32
Antidepressants
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Antidepressants
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Primarily used to relieve symptoms of
depression
Can also help patients with anxiety disorders
Not indicated for uncomplicated bereavement
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Depression
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Most common psychiatric disorder
30% of the U.S. population will experience
some form during their lifetime
Approximately 5% of adult population is
depressed
Incidence in women twice as high as in men
Risk of suicide is high in depression
Often untreated
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Clinical Features
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Depressed mood
Loss of pleasure or interest
Insomnia (or sometimes hypersomnia)
Anorexia (or sometimes hyperphagia)
Mental slowing and loss of concentration
Feelings of guilt, worthlessness, helplessness
Thoughts of death and suicide
Overt suicidal behavior (patient with plan or serious
intent should be hospitalized for therapy)
Symptoms must be present most of the day, nearly
every day, for at least 2 weeks
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Pathogenesis
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Complex and incomplete
Possible contributing factors
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Genetic heritage
Difficult childhood
Chronic low self-esteem
Monoamine hypothesis of depression
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Depression is caused by functional insufficiency of
monoamine neurotransmitters
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Treatment Modalities
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Pharmacotherapy
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Primary therapy
Depression-specific psychotherapy (eg, cognitive
behavioral therapy)
The two together are better than either one alone,
consider psychotherapy/counseling while waiting for
antidepressants to work, which may be 4-8 weeks
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Suicide Risk with Antidepressants
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May increase suicidal tendency early in the
treatment
Patients should be observed closely for:
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Suicidality
Worsening mood
Changes in behavior
Precautions
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Prescriptions should be written for the smallest
number of doses consistent with good patient
management
Dosing of inpatients should be directly observed
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Selective Serotonin Reuptake
Inhibitors (SSRIs)
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Introduced in 1987
Most commonly prescribed antidepressants
As effective as TCAs, but do not cause
hypotension, sedation, or anticholinergic
effects
Overdose does not cause cardiac toxicity
Death by overdose is extremely rare
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Selective Serotonin Reuptake
Inhibitors (SSRIs)
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Fluoxetine (Prozac, Sarafem)
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Most widely prescribed SSRI in the United States
Other SSRIs
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Mechanism of Action
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Produce selective inhibition of serotonin
reuptake
Produce CNS excitation
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Therapeutic Uses
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Primarily used to treat major depression
Other uses
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Obsessive-compulsive disorder
Bulimia nervosa
Premenstrual dysphoric disorder
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Adverse Effects
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Serotonin syndrome (agitation, sweating, hyperreflexia)
 2–72 hours after treatment
Withdrawal syndrome – therapy is generally continued for a 912 months, but withdraw from meds gradually)
Neonatal effects when used in pregnancy
Teratogenesis
Extrapyramidal side effects
Bruxism
Bleeding disorders
Sexual dysfunction- drug holiday Friday/Saturday may be
prescribed
Weight gain
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Drug Interactions
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Monoamine oxidase inhibitors
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Risk of serotonin syndrome- discontinue MAOI 2
weeks prior to starting SSRI
Warfarin
Tricyclic antidepressants and lithium
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Can elevate levels of these drugs
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Other SSRIs
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Sertraline (Zoloft)
Paroxetine (Paxil)
Citalopram (Celexa)
Escitalopram (Lexapro)
Fluvoxamine (Luvox)
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Serotonin/Norepinephrine
Reuptake Inhibitors (SNRIs)
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Venlafaxine (Effexor)
Duloxetine (Cymbalta)
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Venlafaxine (Effexor)
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Indications
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Major depression
Generalized anxiety disorder
Social anxiety disorder (social phobia)
Blocks NE and serotonin uptake
Does not block cholinergic, histaminergic, or
alpha1-adrenergic receptors
Serious reactions if combined with MAOIs
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Venlafaxine (Effexor)
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Side effects
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Nausea
Headache
Anorexia
Nervousness
Sweating
Somnolence
Insomnia
Weight loss/anorexia
Diastolic hypertension
Sexual dysfunction
Hyponatremia (in older adult patients)
Neonatal withdrawal syndrome
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Tricyclic Antidepressants
(Imipramine, amitriptyline)
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Drugs of first choice for many patients with
major depression
Most common adverse effects: sedation,
orthostatic hypotension, and anticholinergic
effects
Most dangerous adverse effect: cardiac
toxicity
May increase risk of suicide early in treatment
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Chemistry
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Nucleus of the tricyclic antidepressants has
three rings
Similar to phenothiazine antipsychotics
Produce varying degrees of:
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Sedation
Orthostatic hypotension
Anticholinergic effects
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Mechanism of Action
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Block neuronal reuptake of two monoamine
transmitters
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Norepinephrine (NE)
Serotonin
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Fig. 32–2. Mechanism of action of tricyclic antidepressants.
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Adverse Effects
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Orthostatic hypotension
Anticholinergic effects
Diaphoresis
Sedation
Cardiac toxicity
Seizures
Hypomania
“Yawngasm”
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Drug Interactions
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Monoamine oxidase inhibitors
Direct-acting sympathomimetic drugs
Indirect-acting sympathomimetic drugs
Anticholinergic agents
CNS depressants
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Toxicity
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Clinical manifestations
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Primarily from anticholinergic and cardiotoxic
actions
• Dysrhythmias
• Tachycardia
• Intraventricular blocks
• Complete atrioventricular block
• Ventricular tachycardia
• Ventricular fibrillation
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Toxicity
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Treatment
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Gastric lavage
Ingestion of activated charcoal
Physostigmine
Propranolol, lidocaine, or phenytoin
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Monoamine Oxidase Inhibitors
(phenelzine, isocarboxacid)
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2nd- or 3rd-choice antidepressants for most
patients
As effective as TCAs or SSRIs, but more
dangerous
Risk of triggering hypertensive crisis if patient
eats foods rich in tyramine (see page 32-6)
Drug of choice for atypical depression
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Monoamine Oxidase Inhibitors
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Mechanism of action
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Block MOA, the enzyme that converts monoamine
neurotransmitters (NE, serotonin, and dopamine)
into inactive products
Inactivate tyramine and other biogenic amines
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Fig. 32–3. Mechanism of action of monoamine oxidase inhibitors.
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Monoamine Oxidase Inhibitors
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Therapeutic uses
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Depression
Other uses
• Bulimia nervosa
• Obsessive-compulsive disorder
• Panic attacks
Adverse effects
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CNS stimulation
Orthostatic hypotension
 Hypertensive crisis from dietary tyramine
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Monoamine Oxidase Inhibitors
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Drug interactions
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Sympathomimetic agents
Interactions secondary to inhibition of hepatic
MAO
Antidepressants: TCAs (risk of hypertensive
episodes) and SSRIs (increased risk of serotonin
syndrome)
Meperidine- hyperpyrexia
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Fig. 32–4. Interaction between dietary tyramine and MAOIs.
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