Depression/ Mania Drugs For Block III Flashcards
Definition of a:
Receptor-
Neurotransmitter-
Nueromodulator-
Receptor: a cellular macromolecule or a macromolecule complex with which a medication interacts to elicit a cellular response
Neurotransmitter: Substance that enables neurons to communicate with each other
Neuromodulator: Any substance that has an effect on neurotransmission
What is the current understanding of neurotransmittion
Current understanding that the brain has a combination of voltage and chemical transmission
What is the pathway of a neurotransmitter from Synthesis to reuptake
Synth- realease- Effect/activation of receptor- degradation- reuptake
Neurotransmitters action is terminated by what two methods
Degradation via enzymes
Reuptake into the presynaptic neuron
What is the major NT in the PNS and SNS and what degrades it
Acetylcholine:
Major NT in Parasympathetic & Sympathetic systems (activates Nicotinic & Muscarinic receptors and degraded by Acetylcholinesterase)
What are the three Amino Acid NTs and what degrades them
GABA, Glutamate/aspartate, Glycine/taurine
Degraded by Transaminase
What is the effect of GABA stimulation
Inhibitory/ Sedative
What is the effect of Gluatmamte/ aspartate NTs
Excitatory, Stimulating
What are the 4 types of amines NTs and what degrades them
Dopamine, NE, Seretonin, Histamine
Degraded by Monoamine Oxidase
What are the two Neuropeptide NTs and what degrades them
Opiods and Techykins
Degraded by peptidases
What does amantadine do
Increase the release of Dopamine
What does long term antagonism or reduction of NT release cause
Up-regulation of receptors
What does sustained release or slow elimination of NTs cause
Down regulation of receptor
Dx Criteria for MDD
Depression + 5 S/s of SIGECAPS
What is SIGECAPS
Sleep, Interest, Guilt, Energy, Concentration, Appetite, Psychomotor, Suidice
What are the gender differences as it relates to depression
Females have less serotonin, earlier onset, longer episodes, greater recurrence and more seasonal
More likely to attempt suicide (but less likely to complete the suicide), 2-4 x increase during menopause
What are the three main classifications of depression
Reactive/ Secondary
Unipolar
Bipolar affective
What is the option for refractory depression, depression in therapy, or psychotic depresssion
Electro therapy
T.I.D.
What do all medications classified as Antidepressants do
increase the synaptic concentration of norepinephrine, dopamine, and/or serotonin
Three ways to increase these neurotransmitters:
- Inhibit the reuptake of neurotransmitters
- Block the metabolic degradation
- Increase the release of the neurotransmitters
Serotonin is released from what kind of neuron
Raphe neurons
TCAs, SSRIs, and SNRIs, have what MOA
block the reuptake of 5-HT and increase synaptic concentrations
How are BZDs used with antidepressants
Not classified as an anti-depressant
Used short-term in acute anxiety management while SSRIs are initiated
What is the difference between tertiary and secondary amines (TCAs)
Tertiary amines:
More potent at blocking reuptake of serotonin > norepinephrine
Include: amitriptyline, clomipramine, doxepin, imipramine
Secondary amines:
More potent in blocking reuptake of norepinephrine > serotonin
Include: nortriptyline, desipramine, and protriptyline
TCAs have effect on what Receptors
Presynaptic SERT and NET
Postsynaptic A1 blocker
What is the MOA of TCAs
Block the reuptake of norepinephrine and serotonin (precursors to SNRI) into the presynaptic neuron which increases the concentrations of monoamines in the synaptic cleft (debated theory)
Also block alpha adrenergic, histamine and muscarinic receptors (anticholinergic side effects)
What is the ADE of TCAs
Anticholinergic S/e
Are TCAs first line Tx
seldom used as 1st line depression treatment; due to adverse effects and new agents available
What can TCAs be used for
Depression
Anxiety Disorders
(NOT 1st LINE!)
Numerous off labeled uses such as:
Treatment for pain syndromes: useful in chronic pain
Migraine prophylaxis
What is the Onset of TCAs
2-4 weeks
What are the cautions and warnings for TCAs
Most commonly used drug in an overdose
(Avoid in suicidal pts)
Can produce serious, life-threatening cardiac arrhythmias, delirium, coma, seizures, and psychosis
(T.C.A These Cause Arrhythmia’s)
Should not be used in patients with suicidal ideations
Should avoided in patients with cardiovascular conditions, closed angle glaucoma, urinary retention, or severe prostate hypertrophy (Anticholinergic Effects)
What are Anticholinergic Fx
Anticholinergic Effects: dry mouth, urinary retention, constipation, blurred vision
Dry mouth is a suggested link to weight gain due to the tendency for patients to drink excessive caloric beverages
The anticholinergic effects will make BPH worse
Are TCAs sedating?
Yes they block Histamine
Which TCAs cause the most sedation, Anticholinergic efffects, and Alpha blockade
Amitryptyline, Doxepin, Clomipramine
What is Doxepin indicated for
Depression and insomnia
What is clomipramine approved for
OCD
What TCA can be used for childhood bed wetting in chlidren older than 6
Imipramine
Which two TCAs specifically mention weight gain
Notriptyline (2kgs) and Amitriptlyine (1.5kgs)
What receptors do SSRIs effect
Presynaptic SERT
What is the MOA of SSRI
Inhibit serotonin reuptake, without affecting reuptake of norepinephrine or dopamine into the presynaptic neuron
SSRI’s do not significantly effect histamine, muscarinic or other receptors
What is the onset of SSRI
3-8 weeks
1st line for depression
SSRI
1st line for OCD
SSRI
1st line for Panic DO
SSRI
1st line for social phobia
SSRI
1st line for PTSD
SSRI
1st line for Premenstral Dysphoric DO
SSRI
1st line for GAD
SSRI
What is the advantage of SSRI over TCAs in Tx depression
Not as lethal in cases of overdose
Low cost and better pt outcomes
Which SSRI has the longest 1/2 life
Fluoxetine
1-3 days for parent drug and active metabolites are 4-16 days
What is the 1/2 life of most SSRI
About 1 day, except fluoxetine
Which SSRI has the shortest 1/2 life
Fluvoxamine is the shortest with half-life at 15 hours
All SSRI interact with CYP 450 except for
Citalopram and escitalopram
What are the SSRI that are most activating
Fluoxetine and Sertaline
Which SSRI are most sedating
Paroxetine and Fluvoxamine
Which SSRI has the worst wt gain
Paroxetine
What are the ADE for SSRI
Gastrointestinal: nausea, diarrhea, constipation
CNS: agitation, anxiety, tremor, or panic may be seen in during the early phase of therapy
Sexual Dysfuntion
Serotonin Syndrome
EPS
What are the interventions that can be used to combat the sexual dysfunction of SSRIs
Wait-and-see method
Lowering the dose of the SSRI
Switching to bupropion or adding ED medication (i.e. sildenafil)
What are the severe ADE of SSRIs
Serotonin Syndrome
Syndrome of Inappropriate Anti-Diuretic Hormone (SIADH)
Especially with elderly
EPS side effects:
Include akathisia, dystonias, and parkinsonian symptoms
Reported with all SSRI’s, but paroxetine has the most reported
What is a severe ADE of SSRIs in elderly pts
SIADH
What is EPS
Include akathisia, dystonias, and parkinsonian symptoms
Which SSRI has the most risk for EPS
Paroxetine
How does Seretonin syndrome present
Cognitive effects (thinking) Neuromuscular dysfunction (movements) Autonomic dysfunction (reflexes, breathing, hr)
What is the Tx for seretonin syndrome
Withdraw offending agent(s)!
Supportive care:
Anxiety/seizures -benzodiazepines
Hyperthermia- ice, cooling blankets
Cyproheptadine :
1st generation antihistamine, and 5HT1A and 5HT2 antagonist
What is the warning with Citalopram
QT prolongation
Can SSRIs be used with Aspirin or NSAIDS
No, DDI, increases bleeding
What enzyme does fluoxetine inhibit
2D6
What is the clinical use of sertraline
PTSD and MDD