PCOL M2.5

Question 1

o depressed mood (most of the time for at least ——)
o loss of interest or pleasure in most activities
o disturbances in sleep and appetite
o deficits in cognition and energy
o thoughts of guilt, worthlessness, and suicide.

Answer 1

MAJOR DEPRESSIVE DISORDER (MDD)
(most of the time for at least 2
weeks)

Question 2

Based on this hypothesis, depression is related to a
deficiency in the amount or function of cortical and limbic —-, ——, ——-

Answer 2

PATHOPHYSIOLOGY OF MAJOR DEPRESSION:
1. MONOAMINE HYPOTHESIS
serotonin (5-HT), norepinephrine (NE), and dopamine
(DA)

Question 3

Proposes that depression is associated with loss of
——-, the brain-derived neurotrophic factor
(BDNF)
- Critical in regulation of neural plasticity,
resilience, and neurogenesis

Answer 3

PATHOPHYSIOLOGY OF MAJOR DEPRESSION:
2. NEUROTROPHIC HYPOTHESIS
brain-derived neurotrophic factor
(BDNF)
*↓ BDNF = depression; severe ↓ BDNF = thoughts of suicide

Question 4

↑ glutamate content in the —— —– of depressed
patients; decreased glutamine/glutamate ratios in the
——-.

higher levels of glutamate are observed —— (CSF)
rather than —– (neurons)

Answer 4

PATHOPHYSIOLOGY OF MAJOR DEPRESSION:
3. ELEVATED GLUTAMATE

Question 5

*lack of sleep; stress eating = —– cortisol =
depression

Answer 5

elevated cortisol levels
- lack of sleep; stress eating = ↑ cortisol =
depression

Question 6

release in the dexamethasone
suppression test

Answer 6

nonsuppression of adrenocorticotropic
hormone (ACTH)

Question 7

chronically elevated levels

Answer 7

corticotropin-releasing hormone

Question 8

has been reported in depressed
patients

Answer 8

Thyroid dysregulation

Question 9

states are thought to play a role in the
etiology of depression in some women.
o occurs in the postpartum and postmenopausal
periods.

Answer 9

Estrogen deficiency

Question 10

In men is sometimes
associated with depressive symptoms.

Answer 10

testosterone deficiency

Question 11

What are the 4 MAJOR CATEGORIES OF ANTIDEPRESSANTS:

Answer 11

1. Selective Serotonin Reuptake Inhibitors (SSRI’s)
2. Serotonin-Norepinephrine Reuptake Inhibitors
   a. SNRI’s (newer)
   b. TCA’s (older)
3. 5-HT2 Antagonists
4. Monoamine oxidase inhibitors

Question 12

PHARMACOLOGICAL ACTIONS:
* As effective as the TCA’s in the treatment of depression

Fewer in ——, ——-, ——-

Safer than TCA’s following an overdose

Answer 12

1. Selective Serotonin Reuptake Inhibitors (SSRI’s)

Fewer sedative, autonomic, & cardiovascular side
effects

Question 13

is a potent inhibitor of hepatic CYP-450
isoenzyme.
*it prolongs the action of other drugs

Answer 13

Flouxetine

Question 14

1. SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRI’S)
   EXAMPLES:

Answer 14

EXAMPLES:
* Fluoxetine – prototype
* Sertraline
* Citalopram
o Escitalopram: S-enantiomer of citalopram
* Paroxetine
* Fluvoxetine

Question 15

2. SEROTONIN-NOREPINEPHRINE REUPTAKE INHIBITORS EXAMPLE

Answer 15

Include:
o Venlafaxine
o Desvenlafaxine: active metabolite of venlafaxine
o Duloxetine
o Milnacipran
o Levomilnacipran: active enantiomer of racemic
SNRI, milnacipran

Question 16

Differ from the TCA’s in that they lack:
o Antihistamine
o Alpha-adrenergic blockade
o Anticholinergic effects

Answer 16

SEROTONIN-NOREPINEPHRINE REUPTAKE INHIBITORS

Question 17

tx of MDD and pain syndromes

Answer 17

Favored over TCA’s

Question 18

EXAMPLE OF TERTIARY AMINE

Answer 18

o Amitriptyline
o Imipramine (prototype)
*represents both primary and
secondary amines
o Doxepin
o Clomipramine
o Trimipramine

Question 19

EXAMPLE OF SECONDARY AMINE

Answer 19

o Protriptyline
o Desipramine
o Nortriptyline

Question 20

o Primarily block serotonin
uptake.
*↑ SE

Answer 20

TERTIARY AMINE

Question 21

o Block NE uptake more than
serotonin uptake.
*↑ NE
▪ less likely to cause
sedation, hypotension, &
anticholinergic effects.
▪ More likely to induce
psychosis

Answer 21

SECONDARY AMINE

Question 22

TCA’s Actions
* Possess ——— effects
give also example

• Potent ——– receptor.
  o Sedative effects
• ———- receptor.
  o Orthostatic hypotension

Answer 22

Possess antimuscarinic effects
o dry mouth
o constipation
o tachycardia
o blurred vision
o urinary retention (dysuria)

• Potent antagonists of H1 receptor.
  o Sedative effects
• Block alpha-adrenergic receptor.
  o Orthostatic hypotension

Question 23

block 5-HT2A receptor
o Associated with antianxiety, antipsychotic and
antidepressant effects.

Answer 23

3. 5-HT2 ANTAGONISTS
   * Nefazadone & Trazodone

Question 24

EXAMPLE OF 3. 5-HT2 ANTAGONISTS

Answer 24

3. 5-HT2 ANTAGONISTS
   * Nefazadone & Trazodone

Question 25

weak inhibitor of both SERT and NET. ** ↑ both serotonin & NE

Answer 25

3. 5-HT2 ANTAGONISTS - Nefazodone

Question 26

weak but SELECTIVE inhibitor of SERT. ** ↑ serotonin only

Answer 26

3. 5-HT2 ANTAGONISTS - Trazodone

Question 27

EXAMPLE OF TETRACYCLIC AND UNICYCLIC ANTIDEPRESSANTS

Answer 27

Bupropion Mirtazapine Amoxapine and Maprotiline

Question 28

o In animal studies, it is a modest-to-moderate inhibitors of NE and Dopamine reuptake. o Causes presynaptic release of catecholamines. *catecholamines: NE, Epi, Dopa

Answer 28

TETRACYCLIC AND UNICYCLIC ANTIDEPRESSANTS * Bupropion

Question 29

o Has a complex pharmacology. o Enhances release of both NE and 5-HT. *↑ NE, SE (effect is similar to nefazodone) ▪ Antagonist of alpha-autoreceptor, 5- HT2 and 5-HT3 receptors; potent H1 antagonist *alpha-autoreceptor (a2): presynaptic receptor; regulate the release of neurotransmitters from the presynaptic neuron →when NE binds, it inhibits further release of NE = ↓ NE levels in synapse

Answer 29

Mirtazapine

Question 30

o Same as TCA’s. *↑ NE, SE, dopamine

Answer 30

Amoxapine and Maprotiline

Question 31

*MAO: responsible for metabolism of monoamines = inhibit release of catecholamines = ↓ monoamines in synaptic space X *MAOIs: they only act inside the presynaptic = prevents release of active monoamines

Answer 31

5. MONOAMINE OXIDASE INHIBITORS (MAOIS)

Question 32

5. MONOAMINE OXIDASE INHIBITORS (MAOIS) - HYDRAZINE DERIVATIVES

Answer 32

o Phenelzine o Isocarboxazid o Bind irreversibly and nonselectively with MAO-A and MAO-B. *↑ dopamine, NE, SE

Question 33

5. MONOAMINE OXIDASE INHIBITORS (MAOIS) - NON-HYDRAZINE DERIVATIVES

Answer 33

o Tranylcypromine ▪ MOA same as phenelzine. *↑ dopamine, NE, SE o Selegiline ▪ Irreversible MAO-B inhibitor. *↑ dopamine o Moclobemide ▪ Reversible and selective MAO-A inhibitor. *↑ NE and SE but not dopamine

Question 34

TYPES OF MAO

Answer 34

1. MAO-A * Responsible for the inactivation of any serotonin or NE that may leak out of presynaptic storage vesicles. 2. MAO-B * Responsible for the metabolism of dopamine

Question 35

CLINICAL INDICATIONS OF ANTIDEPRESSANTS

Answer 35

1. DEPRESSION 2. ANXIETY DISORDERS 3. PAIN DISORDERS 4. PREMENSTRUAL DYSPHORIC DISORDER (PMDD) 5. SMOKING CESSSATION 6. EATING DISORDERS 7. OTHER USES FOR ANTIDEPRESSANTS

Question 36

Most antidepressants are approved for BOTH acute and long-term treatment of major depression. The goal of acute treatment of MDD is remission of all symptoms.

Answer 36

1. DEPRESSION

Question 37

SSRIs and SNRIs have been approved for all the major anxiety disorders, including

Answer 37

2. ANXIETY DISORDERS o PTSD o OCD o GAD o panic disorder

Question 38

Manifested when a traumatic or life-threatening event results in intrusive anxiety-provoking thoughts or imagery, hypervigilance, nightmares, and avoidance of situations that remind the patient of the trauma. * ------- are considered first-line treatment * Other tx: --------

Answer 38

PTSD (POST-TRAUMATIC STRESS DISORDER) [SSRIs] Other tx: psychotherapeutic interventions + antidepressants

Question 39

Characterized by repetitive anxiety-provoking thoughts (obsessions) or repetitive behaviors aimed at reducing anxiety (compulsions)

Answer 39

OCD (OBSESSIVE-COMPULSIVE DISORDER)

Question 40

OCD (OBSESSIVE-COMPULSIVE DISORDER) ------ and several of the ------ are approved for the treatment, and they are moderately effective. Behavior therapy + antidepressant =

Answer 40

Clomipramine and several of the SSRIs are approved for the treatment, and they are moderately effective. = additional benefits

Question 41

Patients experience severe anxiety in social interactions. o Limit the ability to function adequately in their jobs or interpersonal relationships. what are the approved tx Efficacy of the ----- in the treatment of social anxiety is ----- in some studies than their efficacy in the treatment of MDD.

Answer 41

SOCIAL ANXIETY DISORDER Several SSRIs and venlafaxine = approved for the treatment Efficacy of the SSRIs in the treatment of social anxiety is GREATER in some studies than their efficacy in the treatment of MDD.

Question 42

Characterized by a chronic, free-floating anxiety and undue worry that tends to be chronic in nature.

Answer 42

D. GAD (GENERALIZED ANXIETY DISORDER

Question 43

Characterized by recurrent episodes of brief overwhelming anxiety, which often occur without precipitant SSRIs and SNRIs have largely replaced ------ and ---------

Answer 43

PANIC DISORDER SSRIs and SNRIs have largely replaced sedative-hypnotics and older antidepressants BZDs provide much more rapid relief of both generalized anxiety and panic. o Antidepressants appear to be as effective or more effective than BZDs in the long-term treatment GAD.

Question 44

Antidepressants possess analgesic properties independent of their mood effects. * TCAs: used in tx of neuropathic & other pain conditions. * Medications that possess both NE and 5-HT reuptake blocking properties are often useful in treating pain disorders *↑ NE and SE

Answer 44

PAIN DISORDERS

Question 45

Approved for the treatment of chronic joint and muscle pain

Answer 45

PAIN DISORDERS - Duloxetine

Question 46

Approved for the treatment of fibromyalgia.

Answer 46

PAIN DISORDERS - Milnacipran

Question 47

Being investigated for a variety of pain conditions from postherpetic neuralgia to chronic back pain.

Answer 47

PAIN DISORDERS - Desvenlafaxine

Question 48

Prominent mood and physical symptoms during the late luteal phase of almost every cycle.

Answer 48

PREMENSTRUAL DYSPHORIC DISORDER (PMDD) May include anxiety, depressed mood, irritability, insomnia, fatigue, and a variety of other physical symptoms. * Symptoms are more severe than those typically seen in premenstrual syndrome (PMS) and can be quite disruptive to vocational and interpersonal activities * Fluoxetine and sertraline = approved for this indication

Question 49

Approved as a treatment for smoking cessation. o Experience fewer mood symptoms and possibly less weight gain while withdrawing from nicotine dependence. o As effective as nicotine patches in smoking cessation

Answer 49

SMOKING CESSSATION Bupropion

Question 50

Shown to be helpful in smoking cessation but the effects have not been as consistent as those seen with bupropion.

Answer 50

SMOKING CESSSATION Nortriptyline

Question 51

Characterized by episodic intake of large amounts of food (binges) followed by ritualistic purging through emesis, the use of laxatives, or other methods. *binge-purge

Answer 51

BULIMIA NERVOSA

Question 52

* Reduced food intake results in a loss of weight of 15% or more of ideal body weight. * The person has a morbid fear of gaining weight and a highly distorted body image. * The primary treatment for anorexia at this time is -------------------------------------

Answer 52

ANOREXIA NERVOSA * The primary treatment for anorexia at this time is refeeding, family therapy, and cognitive behavioral therapy. *currently, there’s no approved medication for anorexia

Question 53

About EATING DISORDERS

Answer 53

Antidepressants appear to be helpful in the treatment of bulimia BUT NOT anorexia o Other antidepressants have also shown benefit in reducing the binge-purge cycle (bulimia)

Question 54

o ------ was approved for the tx of bulimia

Answer 54

Fluoxetine

Question 55

* ------ may have some benefits in treating obesity.

Answer 55

Bupropion