Chapter 3 CNS - tricyclic antidepressants and monoamine oxidase inhibitors

Question 1

Major depression

Answer 1

• intense sadness or loss of interest in usual activities
• accompanied by
  1) poor appetite
  2) insomnia
  3) hypersomnia
  4) psychomotor retardation
  5) decrease in sex drive
  6) fatigue
  7) worthlessness
  8) decreased concentration
  9) thoughts of death or suicide

Question 2

mania

Answer 2

• another affective d/o
• elevated, expansive or irritable mood
• accompanied by
  1) increased activity
  2) pressured speech
  3) FOI
  4) grandiosity
  5) decreased need for sleep
  6) distractiblity
  7) involvment in high risk activities w/ consequences

pts tend to cycle between depression and mania (bipolar affective disorder)

Question 3

biogenic amine hypothesis

Answer 3

• suggests that depression is d/t paucity (scarce) of NE, dopamine, or 5-HT in brain whereas mania is d/t excess monoamine neurotransmission (D, NE, 5-HT)
• faces criticism due to onset of drug action (hours) and clinical response (weeks)
• possibly d/t downregulation (lack of receptors at synaptic membrane)

Question 4

Tricyclic antidepressants

Answer 4

• most block reuptake of monoamine NTs (NE, 5-HT)
• subsequent downregulation (reduction in number in the number of receptors) in resposne to long term antidepressant use l/t less negative feedback on ABOVE NT

As a response to serotonin stimulation, the serotonergic neuron reduces the number of 5HT1A receptors, this phenomenon is known as downregulation. Since downregulation is mediated by genomic mechanisms, the reduction of 5HT1A receptors is not immediate, this occurs in weeks. This has been proposed as a possible explanation of antidepressants’ delay in therapeutic effects.

“dirty”/“sloppy” antidepressants, in that they also: Block muscarinic receptors, producing anticholinergic effects such as dry mouth, blurry vision, constipation, and urinary retention. Block histamine-1 (H1) receptors, which causes sedation.

indications
1) major depressive episodes
2) enuresis
3) agoraphobia (fear of open spaces) w/ panic attacks
4) Obessive compulsive neurosis
5) Chronic pain
6) neuralgia
7) migraine headaches

Undesirable effects
* anticholinergic effects
Red as a beet (flushing of the skin)

Dry as a bone (dry mouth, eyes, and skin)

Blind as a bat (dilated pupils)

Mad as a hatter (confusion, delirium, agitation)

Hot as a hare (overheating and fever)

Full as a flask (trouble peeing)

• cardiotoxicity (NE)
• sedation (Block histamine-1 (H1) receptors, which causes sedation.)
• orthostatic hypotension
• mania
• hypomania
• weight gain
• impotence
• obstructive jaundice (able to impair liver fx)

abuse potential
* tolerance to anticholinergic side effects may develop
* physical and psychic dependence develops occasionally
* sudden withdrawal l/t malaise, chills, coryza (inflammation of the mucous membrane in the nose, and muscle aches

drug interactions
* don’t give w/ monoamine oxidase inhibitors (lethal w/ potentiation)
* some other drugs (bind to plasma proteins) can displace TCAs)
* can make CNS depressants stronger
* Potentiate actions of other anticholinergic drugs

NOTE
can shorten cycle betwen mania and depression w/ pts w/ bipolar
patient coming out of depression are at increased risk of committing suicide

Question 5

Amitriptyline (elavil)

Answer 5

• most block reuptake of monoamine NTs (NE, 5-HT)\
• downregulation
• “dirty”/“sloppy” antidepressants, in that they also: Block muscarinic receptors, producing anticholinergic effects such as dry mouth, blurry vision, constipation, and urinary retention. Block histamine-1 (H1) receptors, which causes sedation.

indications
1) major depressive episodes
2) enuresis
3) agoraphobia (fear of open spaces) w/ panic attacks
4) Obessive compulsive neurosis
5) Chronic pain
6) neuralgia
7) migraine headaches

undesireable effects
* most severe anticholinergic effects
Red as a beet (flushing of the skin)

Dry as a bone (dry mouth, eyes, and skin)

Blind as a bat (dilated pupils)

Mad as a hatter (confusion, delirium, agitation)

Hot as a hare (overheating and fever)

Full as a flask (trouble peeing)

• highly sedating (Block histamine-1 (H1) receptors, which causes sedation.)

abuse + drug interactions + notes refer to TCA card hehe

PO/M

Question 6

Imipramine (tofranil)

Answer 6

• most block reuptake of monoamine NTs (NE, 5-HT)\
• downregulation
• “dirty”/“sloppy” antidepressants, in that they also: Block muscarinic receptors, producing anticholinergic effects such as dry mouth, blurry vision, constipation, and urinary retention. Block histamine-1 (H1) receptors, which causes sedation.

indication
* original TCAD; prescribed less often b/c of side effects
* enuresis in children (involuntary urination)

undesireable effects
* less sedating than amitryptiline
* significant anticholinergic effects

Red as a beet (flushing of the skin)

Dry as a bone (dry mouth, eyes, and skin)

Blind as a bat (dilated pupils)

Mad as a hatter (confusion, delirium, agitation)

Hot as a hare (overheating and fever)

Full as a flask (trouble peeing)

• may induce arrhythmias (quinidine-like actions? – Antiarrhythmic and Anti-parasite)

abuse + drug interaction + notes refer to main card!

PO/IM

Question 7

Doxepin (sinequan)

Answer 7

• most block reuptake of monoamine NTs (NE, 5-HT)\
• downregulation
• “dirty”/“sloppy” antidepressants, in that they also: Block muscarinic receptors, producing anticholinergic effects such as dry mouth, blurry vision, constipation, and urinary retention. Block histamine-1 (H1) receptors, which causes sedation.

indications
1) major depressive episodes
2) enuresis
3) agoraphobia (fear of open spaces) w/ panic attacks
4) Obessive compulsive neurosis
5) Chronic pain
6) neuralgia
7) migraine headaches

undesireable effects:
* very sedating (Block histamine-1 (H1) receptors, which causes sedation.)
* substantial anticholinergic effects

abuse + drug interactions + notes refer to main card

PO

Question 8

Desipramine (norpamin)

Answer 8

• most block reuptake of monoamine NTs (NE, 5-HT)\
• downregulation
• “dirty”/“sloppy” antidepressants, in that they also: Block muscarinic receptors, producing anticholinergic effects such as dry mouth, blurry vision, constipation, and urinary retention. Block histamine-1 (H1) receptors, which causes sedation.

indications
increasing use d/t fewer anticholinergic effets

undesirable effects
* less sedation
* fewer anticholinergic effects
Red as a beet (flushing of the skin)

Dry as a bone (dry mouth, eyes, and skin)

Blind as a bat (dilated pupils)

Mad as a hatter (confusion, delirium, agitation)

Hot as a hare (overheating and fever)

Full as a flask (trouble peeing)

• sudden death in children has occurred

PO

Question 9

Nortiptyline (pamelor, aventyl)

Answer 9

• most block reuptake of monoamine NTs (NE, 5-HT)\
• downregulation
• “dirty”/“sloppy” antidepressants, in that they also: Block muscarinic receptors, producing anticholinergic effects such as dry mouth, blurry vision, constipation, and urinary retention. Block histamine-1 (H1) receptors, which causes sedation.

indications
use increasing d/t clear relation between plasma levels and clinical efficacy than other TCAs

Undesireable effects:
* anticholinergic
* sedating

PO

Question 10

Amoxapine (asendin)

Answer 10

• most block reuptake of monoamine NTs (NE, 5-HT)\
• downregulation
• “dirty”/“sloppy” antidepressants, in that they also: Block muscarinic receptors, producing anticholinergic effects such as dry mouth, blurry vision, constipation, and urinary retention. Block histamine-1 (H1) receptors, which causes sedation.

indication
* depression

undesireable effects:
* moderate anticholinergic
* sedative effects
* neuroleptic malignant syndrome

PO
shortest half life

Question 11

Protriptyline (vivctil)

Answer 11

• most block reuptake of monoamine NTs (NE, 5-HT)\
• downregulation
• “dirty”/“sloppy” antidepressants, in that they also: Block muscarinic receptors, producing anticholinergic effects such as dry mouth, blurry vision, constipation, and urinary retention. Block histamine-1 (H1) receptors, which causes sedation.

indications
1) major depressive episodes
2) enuresis
3) agoraphobia (fear of open spaces) w/ panic attacks
4) Obessive compulsive neurosis
5) Chronic pain
6) neuralgia
7) migraine headaches

effects
* lesast sedation
* some anticholinergic effects

PO
longest half life; thus lower daily dose

Question 12

clomipramine (anafranil)

Answer 12

• most block reuptake of monoamine NTs (NE, 5-HT)\
• downregulation
• “dirty”/“sloppy” antidepressants, in that they also: Block muscarinic receptors, producing anticholinergic effects such as dry mouth, blurry vision, constipation, and urinary retention. Block histamine-1 (H1) receptors, which causes sedation.
• VERY EFFECTIVE serotonin uptake blocker

indication
* obsessive compulsive disorder

undesireable effects
* very sedating

Question 13

trimipramine (sumontil)

Answer 13

• most block reuptake of monoamine NTs (NE, 5-HT)\
• downregulation
• “dirty”/“sloppy” antidepressants, in that they also: Block muscarinic receptors, producing anticholinergic effects such as dry mouth, blurry vision, constipation, and urinary retention. Block histamine-1 (H1) receptors, which causes sedation.

indication
* depression

effect
* very sedating

Question 14

tranylcypromine (parnate)
Isocarboxazid (marplan)
Phenelzine (nardil)

Answer 14

• blocks metabolism of biogenic amines (NE, 5-HT, D) l/t inc synaptic concentration
• suppresses REM sleep

indication
* used to tx depression if TCA fail and when ECT fail or is refused
* can be used to treat narcolepsy, phobic/anxiety stress + parkinson’s disease

effects
* hepatotoxic
* excessive CNS stimulation
* orthostatic hypotension

Overdose can cause:
* agitation
* hallucinations
* hyperreflexia
* hyperpyrexia
* convulsions
* altered blood pressure

PO
* binds irreversibily to MAO causing pharmacologic effects for weeks (inactivated by acetylation)
* therefore, pts who are genetically “slow acetylators” will have elevated serum levels!

low likelihood of abuse

drug interactions
* potentiate effects of sympathomimetics (tyramine in dairy and yeast products, amephatmines in diet pills, and sympathomimetics in cold remedies)
* Cured, smoked, or processed meats include dried sausages like pepperoni and salami, hot dogs, bologna, bacon, and smoked fish. Sauerkraut, kimchi, pickled beets, pickled cucumbers, and pickled peppers have high tyramine levels. Also, fermented soy products like tofu, miso, and soy sauce contain tyramine
* Medications called monoamine oxidase inhibitors (MAOIs) block monoamine oxidase, which is an enzyme that breaks down excess tyramine in the body. Blocking this enzyme helps relieve depression.

If you take an MAOI and you eat high-tyramine foods, tyramine can quickly reach dangerous levels. This can cause a serious spike in blood pressure and require emergency treatment.

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• amphetamine-like structure