Chapter 3 CNS - tricyclic antidepressants and monoamine oxidase inhibitors Flashcards
Major depression
- 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
mania
- 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)
biogenic amine hypothesis
- 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)
Tricyclic antidepressants
- 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
Amitriptyline (elavil)
- 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
Imipramine (tofranil)
- 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
Doxepin (sinequan)
- 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
Desipramine (norpamin)
- 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
Nortiptyline (pamelor, aventyl)
- 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
Amoxapine (asendin)
- 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
Protriptyline (vivctil)
- 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
clomipramine (anafranil)
- 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
trimipramine (sumontil)
- 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
tranylcypromine (parnate)
Isocarboxazid (marplan)
Phenelzine (nardil)
- 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
