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PHARMACOLOGY > PCOL M2.5 > Flashcards

PCOL M2.5 Flashcards

1
Q

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.

A

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

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2
Q

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

A

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

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3
Q

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

A

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

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4
Q

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

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

A

PATHOPHYSIOLOGY OF MAJOR DEPRESSION:
3. ELEVATED GLUTAMATE

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5
Q

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

A

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

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6
Q

release in the dexamethasone
suppression test

A

nonsuppression of adrenocorticotropic
hormone (ACTH)

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7
Q

chronically elevated levels

A

corticotropin-releasing hormone

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8
Q

has been reported in depressed
patients

A

Thyroid dysregulation

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9
Q

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

A

Estrogen deficiency

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10
Q

In men is sometimes
associated with depressive symptoms.

A

testosterone deficiency

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11
Q

What are the 4 MAJOR CATEGORIES OF ANTIDEPRESSANTS:

A
  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
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12
Q

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

Fewer in ——, ——-, ——-

Safer than TCA’s following an overdose

A
  1. Selective Serotonin Reuptake Inhibitors (SSRI’s)

Fewer sedative, autonomic, & cardiovascular side
effects

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13
Q

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

A

Flouxetine

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14
Q
  1. SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRI’S)
    EXAMPLES:
A

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

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15
Q
  1. SEROTONIN-NOREPINEPHRINE REUPTAKE INHIBITORS EXAMPLE
A

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

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16
Q

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

A

SEROTONIN-NOREPINEPHRINE REUPTAKE INHIBITORS

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17
Q

tx of MDD and pain syndromes

A

Favored over TCA’s

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18
Q

EXAMPLE OF TERTIARY AMINE

A

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

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19
Q

EXAMPLE OF SECONDARY AMINE

A

o Protriptyline
o Desipramine
o Nortriptyline

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20
Q

o Primarily block serotonin
uptake.
*↑ SE

A

TERTIARY AMINE

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21
Q

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

A

SECONDARY AMINE

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22
Q

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

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

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
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23
Q

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

A
  1. 5-HT2 ANTAGONISTS
    * Nefazadone & Trazodone
24
Q

EXAMPLE OF 3. 5-HT2 ANTAGONISTS

A
  1. 5-HT2 ANTAGONISTS
    * Nefazadone & Trazodone
25
Q

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

A
  1. 5-HT2 ANTAGONISTS
    - Nefazodone
26
Q

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

A
  1. 5-HT2 ANTAGONISTS
    - Trazodone
27
Q

EXAMPLE OF TETRACYCLIC AND UNICYCLIC ANTIDEPRESSANTS

A

Bupropion
Mirtazapine
Amoxapine and Maprotiline

28
Q

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

A

TETRACYCLIC AND UNICYCLIC ANTIDEPRESSANTS
* Bupropion

29
Q

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

A

Mirtazapine

30
Q

o Same as TCA’s.
*↑ NE, SE, dopamine

A

Amoxapine and Maprotiline

31
Q

*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

A
  1. MONOAMINE OXIDASE INHIBITORS (MAOIS)
32
Q
  1. MONOAMINE OXIDASE INHIBITORS (MAOIS)
    - HYDRAZINE DERIVATIVES
A

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

33
Q
  1. MONOAMINE OXIDASE INHIBITORS (MAOIS)
    - NON-HYDRAZINE DERIVATIVES
A

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

34
Q

TYPES OF MAO

A
  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
35
Q

CLINICAL INDICATIONS OF ANTIDEPRESSANTS

A
  1. DEPRESSION
  2. ANXIETY DISORDERS
  3. PAIN DISORDERS
  4. PREMENSTRUAL DYSPHORIC DISORDER (PMDD)
  5. SMOKING CESSSATION
  6. EATING DISORDERS
  7. OTHER USES FOR ANTIDEPRESSANTS
36
Q

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.

A
  1. DEPRESSION
37
Q

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

A
  1. ANXIETY DISORDERS
    o PTSD
    o OCD
    o GAD
    o panic disorder
38
Q

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: ——–

A

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

39
Q

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

A

OCD (OBSESSIVE-COMPULSIVE DISORDER)

40
Q

OCD (OBSESSIVE-COMPULSIVE DISORDER)
—— and several of the —— are approved for
the treatment, and they are moderately effective.

Behavior therapy + antidepressant =

A

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

= additional benefits

41
Q

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.

A

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.

42
Q

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

A

D. GAD (GENERALIZED ANXIETY DISORDER

43
Q

Characterized by recurrent episodes of brief overwhelming
anxiety, which often occur without precipitant

SSRIs and SNRIs have largely replaced ——
and ———

A

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.

44
Q

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

A

PAIN DISORDERS

45
Q

Approved for the treatment of chronic joint and
muscle pain

A

PAIN DISORDERS - Duloxetine

46
Q

Approved for the treatment of fibromyalgia.

A

PAIN DISORDERS - Milnacipran

47
Q

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

A

PAIN DISORDERS - Desvenlafaxine

48
Q

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

A

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

49
Q

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

A

SMOKING CESSSATION
Bupropion

50
Q

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

A

SMOKING CESSSATION
Nortriptyline

51
Q

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

A

BULIMIA NERVOSA

52
Q
  • 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 ————————————-
A

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
53
Q

About EATING DISORDERS

A

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)

54
Q

o —— was approved for the tx of bulimia

A

Fluoxetine

55
Q
  • —— may have some benefits in treating obesity.
A

Bupropion

56
Q
A

PHARMACOLOGY (16 decks)

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