Anxiety and Depression Drugs Flashcards
What do all anti-depressant drugs modulate?
All the antidepressant drugs now in use modulate monoamine neurotransmission
How long does it take for monoamines to exert their effects?
Monamines take six to eight weeks to exert their effects
What percentage of patients benefit from monamines?
60-70%
What neurological activities are monoamines active in?
Synaptic plasticity
Dendritic morphology
Neurogenesis
What is the mechanism of SSRIs (selective serotonin reuptake inhibitors)?
Blocks the serotonin reuptake molecule => keeping more of the serotonin monoamine in the synapse.
- Because of similar molecular form, can also block norepinephrine and dopamine uptake => leads to side effects
Where are cells located that use serotonin as the primary signaling messenger?
Raphe Nucleus (brainstem/midbrain)
What is Citalopram (Celexa)?
Citalopram is an SSRI used for depression and acts on the Raphe Nucleus
What are the major side effects of citalopram?
Weight gain, GI, loss of libido, sleep, sweating, hyponatremia, mania.
What is the major risk of citalopram?
Increase suicidal thinking in individuals 25yo and younger
What are the major interactions of citalopram?
- Weak 2D6 inhibition
- Can increase MAO-I’s and TCA levels (watch for synergistic effects)
What is the major cardiac precaution with citalopram?
QTc prolongation average 18msec at 60mg/day => can lead to Torsade’s
Where are norepinephrine dominant cells located?
Locus Coeruleus
What is Venlafaxine/ ER (Effexor/XR)?
Venlafaxine is an SNRI used for depression that acts on the locus ceruleus
What are the side effects of Venlafaxine?
- GI, sexual, sleep, sweating, hyponatremia, mania
- Diastolic blood pressure increase
What is the major risk of Venlafaxine for patients under 25?
Increased suicidal thoughts
What are the major interactions of Venlafaxine?
- Very weak 2D6 inhibition
- Can increase MAO-I’s and TCA levels (watch for synergistic effects)
What do TCA or tricyclic drugs do?
Modulate norepinephrine, but largely dual action drugs
What are the two types of TCAs (SNRIs)?
1) Tertiary Amines – having all three hydrogen replaced by other subgroups
2) Secondary Amines – where one of the 3 side groups is cleaved off and H again in its place
- Secondary Amines are metabolites of Tertiary Amines
What is Nortriptyline (Pamelor)?
A TCA used for depression
What are the major side effects of nortriptyline?
wt gain, sedation, ACh, hypotension, arrhythmia, sexual, sweating
What are the major interactions with nortriptyline?
- 2D6 inhibition
- MAO-I, TCA’s, tramadol
Why is it easier to overdose on nortriptyline?
The dose for nortriptyline is 75-150mg/day
Lethal in overdose (LD50 is 2000-3000mg) => easier to OD with a month supply of the drug
What is Bupropion (Wellbutrin/SR/XL, Zyban)?
Bupropion is an NDRI used for depression
[ Norepinephrine and dopamine reuptake inhibitor–mainly dopamine]
- Zyban is used for smoking cessation
What are the major side effects of bupropion?
Insomnia, tremor, tinnitus, seizures, restlessness, rare rash
* May reduce sexual side effects of anti-depressants because it doesn’t affect serotonin
What are the major interactions with bupropion?
2D6 -, MAO-I, TCA, tramadol, levodopa
Bupropion should be avoided in which patients?
Avoid in patients with eating disorders and seizure disorders
Why is bupropion a better anti-depressant in bipolar patients?
least likely to cause mania
How do MAO-Is work?
MAO inhibitors inhibit the activity of the monoamine oxidase enzyme family. They will affect serotonin, norepinephrine, and dopamine => broad spectrum drugs
What are the main adverse reactions with MAO-I?
1) Serotonin syndrome:
MS changes
Autonomic instability
Neuromuscular signs
2) Hypertensive crisis:
Especially when dietary tyramine is added (cheese syndrome)
- Excess Dopamine and NE because tyramine is a precursor – cause high blood pressure, headaches, seizures, stroke and death
What should be avoided in serotonin syndrome?
SSRI, SNRI, TCA Tramadol meperidine (dilaudid) Dextromethorphan Amphetamines
What is Mirtazapine (Remeron)?
A NaSSA (block reuptake of norepinephrine and serotonin) for depression
What is the major side effect of mirtazapine?
Sedating
Wt gain => especially beneficial in elderly populations
Sexual side effects
What are the major interactions of mirtazapine?
No P450 interactions
Do not combine w/ MAO-I
What are the major uses of benzodiazepines?
- Sedative – hypnotic
- Anxiolytic
- Seizure control
- Muscle relaxant
- Anterograde amnesia
Which receptors are benzodiazepine sensitive?
Receptors containing the α1, α2, α3or α5subunit are benzodiazepine sensitive
What are the major side effects of benzodizepine?
sedation, depression, amnesia, ataxia, dependence, withdrawal
What interactions should be noted with benzodiazepine?
CNS depressants, (opiates), cimetidine.
Describe the metabolism of benzodiazepine?
- Hepatically cleared ( watch for EtOH abuse/hepatic impairment)
- Active metabolites
- flumazenil reverses
What are the Z drugs?
Sedative hypnotics with preferential affinity for α1receptors
- zolpidem
- zalaplon
- eszopiclone
- NO anxiety reducing or muscle relaxing properties
What is buspirone/BuSpar?
It is an anti-anxiety drug that is a 5HT-1A partial agonist used for General Anxiety Disorder
- Acts on the hippocampus and cortex
- Will augment MDD
What are the major side effects of BuSpar?
Dizziness, HA, sedation, nervous/restless
What are major interactions with BuSpar?
Do not take with MAO-I
What are other interactions for BuSpar?
No sexual SE, No dependence, No withdrawal
Takes 4 weeks + to work
What are the indications for citalopram?
- Antidepressant
- Anxiolytic
- Panic
- PTSD
- Pain
- OCD
To what therapeutic class does Venlafaxine belong?
- Anxiety and depression
- Neuropathic pain
To what therapeutic class does Nortryptyline belong?
- Severe depression
- Anxiety
- ADHD
- Pain
What is the mechanism of action of nortryptyline?
Blocks the uptake of all monoamines, especially NE and serotonin
What cardiac risks are associated with nortryptyline?
Overdose of nortryptyline is lethal because it blocks the cardiac Na channels, leads to AV conduction block, causing sudden death
To what therapeutic class does buproprion belong (i.e. indications)?
- Depression without anxiety
- ADHD
- Nicotine cessation
- Bipolar disorder
