Antidepressants

Vilazodone (viibryd) - "____" antidepressant: - low incidence of ___

- "dual action": blocks serotinin reuptake transporter and is partial agonist at 5-HT1a receptor - sexual side effects

Reboxetine (edronax) - Selectively inhibits ______ uptake

- Norepinephrine (NRI)

Mirtrazapine (remeron) - ____ _one of its most prominent adverse effects due to its capacity for blocking histamine recepotrs - Also has capacity to block _____, ____ and ____

- Sedation - 5-HT2A receptors, alpha-1 receptors, alpha-2 autoreceptors

Trazodone (desyrel) - 50mg widely prescribed as _____ for difficulty sleeping - Advantages: virtual absence of what side effects owing to its prominent serotonergic properties; however ___ has been reported

- Sedative hypnotic - virtual absence of cardiac and anticholinergic side effects - priapism

Blocking muscarinic- Blocking histamine- Blocking alpha1-

- anti-SLUDE - sedation - orthostatic hypotension

Buproprion (wellbutrin/zybna) - known for its ability to ... - 3-fold increase in incidence of ___ - No _____ (bc don't affect serotonin system)

- block reuptake of dopamine AND NE (like cocaine) - seizures - sexual side effects

Advantage of SSRIs

- cut out autonomic effects from increase NE reuptake by only inhibiting serotonin reuptake - safer drugs - good for older people who may already have high bp, etc. - can use to treat anti-depressive EPISODE

As a class, antidepressants: - Administration - PP bound - Metabolized/excreted - Half life durations - Therapeutic index

- orally administered - 90-95% PP bound- drug interactions - Metabolized by liver; excreted in urine - Long half-lives - Relatively small therapeutic index

Nefazodone (serzone) - Prominent effects are through _______ mechanisms - Caution:

- serotonergic mechanisms - Black box warning on label- rare but life threatneing liver failure can occur

Effects of acut Lithium intoxication - can be seen at what levels; experienced by 75-90% treated with it - Effect CNS, heart, GI tract, kidneys

- therapeutic levels 1. Altered mental status 2. Vomiting 3. Profuse diarrhea 4. Coarse tremor ataxia 5. Coma 6. Convulsions

Adverse Effects: Serotonin Syndrome

1. Agitation 2. Hallucinations 3. Coma (other changes mental status) 4. coordination problems 5. muscle twitching/stiffness/tightness 6. fast heartbeat 7. high/low BP 8. sweating/fever 9. N/V/D

Adverse effects of lithium

1. GI tract- N/D 2. Drowsiness 3. Polyuria 4. dry mouth> polydipsia 5. Acquired nephrogenic diabetes 6. weight gain 7. insomnia 8. benign thyroid enlargement (rare) 9. benign sustained increase in circulating polymorphonuclear leukocytes - reversed within week terminating treatment

Adverse Effects: Manic Episodes

1. Greatly increase energy 2. Severe trouble sleeping 3. Racing thoughts 4. Reckless behavior 5. Unusual grand ideas 6. Excessive happiness/irritability 7. Talking more/faster than usual

5 Classes of Antidepressants

1. Tricyclics (TCAs) 2. Selective Serotonin Reuptake inhibitors 3. Selective Serotonin and Norepi. Reuptake inhibitors (SNRIs) 4. Atypical 5. MAO Inhibitors

Tricyclics attempt to remedy depression by inactivating the ______ on the ______ nerve terminal and thus limiting the reuptake of ____ and _____.

"amine" pump on the presynaptic nerve terminal norepinephrine and serotonin

Adverse effects: Heme (4)

1. Agranulocytosis (rare) 2. bone marrow depression 3. thrombocytopenia/eosinophilia 4. Elderly- low Na levels in blood Symptoms: HA, weakness, fatigue, unsteady, confusion, issues concentrating, thinking/memory problems - may increase risk of bleeding especially take blood thinner (warfarin-coumadin, jantoven, NSAID, aspirin)

Adverse effects: cardiovascular (2)

1. Orthostatic hypotension > tachycardia 2. Antimuscarinic effects at SA node> sympathetic influences

Desipramine (norpram) - Class - Naturally occurring metabolite of _____

Secondary Amine Tricyclic - imipramine

All the medications above except ______, _____, _____ and ____ do not have FDA approval for bipolar disorder and are used "off label

valproic acid, olanzapine, and lamotrigine

SSRI's commonly used to treat depression in ____ with ____ - IF an SSRI is needed for depression, ___ and ___ should be used because these SSRI's only weak inhibitors of CYP2D6

women with breast cancer Citalopram and escitalopram

Antidepressants are prescribed for ____ disorders characterized by (2) - Tx takes _____ with ___ remission

Affective Disorders; extreme depression (dysphoria), extreme elation (mania), or both - 2-4 weeks with 85% remission

Valproic Acid (depakote) Carbamazepine (tegretol)

Anticonvulsants- treat bipolar disorder

Circadian clock of antidepressants

Day- lots of serotoninergic activity- sleepy Night- Not a lot of serotoninergic activity- can't sleep

Most problematic interaction with lithium> ___ - Increase excretion - Decrease excretion

Diuretics- because most will increase Na+ excretion and indirectly decrease Li+ excretion> increased/toxic levels of lithium - osmotic diuretics and acetazolamide - Loops and thiazides that deplete Na

Lamotrigine - 1st drug...without indication of... - particularly effective against ____ with minimal risk of inducing ____

First drug FDA approval for long-term prophylactic treatment of bipolar disorder without an indication of acute mania - bipolar depression; inducing mania

Isocarboxazid (marplan)

MAOI

Phenelzine (nardil)

MAOI

Tranylcypromine (parnate)

MAOI

Bipolar Depression common tx

Mood Stabilizer (anti-convulsant) + Antipsychotic (2nd generation- increase mood- better compliance)

Lithium blocks ___ - so toxicity>

Na+ Arrythmias, attracts water in kidney and GI tract> poluria/polydipsia, diarrhea

Affective disorders results from chemical imbalance between ...

Norepinephrine, Serotonin, Dopamine Possibly beta-adrenergics

Too much serotonin> ___ behavior

OCD (could be suicide)

Duloxetine (cymbalta) - approved for ______

SNRI - Approved for tx fibromyalgia

Milnacipran (ixel)

SNRI - approved for tx of fibromyalgia

Venlafaxine (effexor) - _____ that has shown to produce ___ following chronic treatment and ______ effects

SNRI - phenethylamine; withdrawal; rebound

Fluvoxamine (luvox)

SSRI

Sertaline (zoloft)

SSRI

Citalopram (celexa) - used for...

SSRI - used for depression in women with breast cancer

Escitalopram (lexapro) - also approved for ______ - used for...

SSRI Also approved for adolescents - used for depression in women with breast cancer

Paroxetine (Paxil) - Notes for its ____ side effects; recently approved for _____

SSRI anticholinergic social phoobia

Fluoxetine (prozac)

SSRI too long T.5=72hr...don't use much anywmore

Nortryptyline (Pamelor) - Class - Metabolite of _____ (tertiary amine tricyclic)

Secondary Amine Tricyclic - amitryptyline (tertiary amine tricyclic)

Maprotiline (ludiomil) - Class - Very new with increased potential for ___

Secondary Amine Tricyclic - seizure

Amoxapine (asendin) - Class - A ____ that is a metabolite of the antipsychotic ____ therefore has a ___ as well as ____ mechanism

Secondary Amine Tricyclics dibenzodiazepine; loxapine; dopaminergic; adrenergic

Protryptyline (vivactil) - Class - Lacks ______ properties; often prescribed for ______

Secondary Amine Trycyclic - sedative; "Sleepy depressives"

Would you give sleepy depressant tertiary or secondary amine tricyclic?

Secondary- need stimulation

Tertiary Amine Tricyclics- Predominately block reuptake of _____

Serotonin

Adverse effects: very troubling/leads to non-compliance

Sexual dysfunction (serotonin)

M of A of bipolar depression meds - Alters...

Slow down neuronal activity in brain (block Na, Ca channel)> block neurotransmission> generalized neuronal dampening> straight line-no highs/lows (pts hate it) - need to give something for some mood elevation alters reuptake of serotonin, norepinephrine and dopamine, and decreases release. We also know that it decreases protein kinases in brain tissue such as PKC and directly affects neuronal inositol levels by directly inhibiting inositol monophosphatase.

Imipramine (Tofranil) - Class - Admin - Long-acting ___ formulation is available

Tertiary Amine Tricyclic - IM - "pamoate"

Doxepin (Seinequan) - Class - Increase ___ - Absence of ____

Tertiary Amine Tricyclic - Increased sedation - Absence of cardiovascular effects

Trimipramine (surmontil) - Class - Very ___ - Moderately _____

Tertiary Amine Tricyclic - very sedating - moderately anticholinergic

Clomipramine (anafranil) - class - usually given for _____ - Not very ____ - Can cause ____

Tertiary amine tricyclic - Usually given for obsessive compulsive disorder - not very selective - can cause seizures

Amitrypyline (Elavil) - Class - Admin.

Tertiary amine tricyclic Can be given IM

Desvenlafaxine (pritiq) - Isomer of _____ with similar pharmacologic properties

Venlafaxine

Selective Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs) - In general, have fewer _____ and ____ effects than tricyclics and have more ___ effect compared to SSRIs

antimuscarinic, antihistaminic effects adrenergic effect

SNRI's are different from Secondary Tricyclics because...

different chemical backbone- don't go as many places (not tricyclic-like big structure)

Potential for local anesthetic solutions containing ____ to cause ____ in patients receiving ____

epinephrine; hypertensive crisis; MAOIs

*note that lithium toxicity, neuroleptic malignant syndrome (NMS) and serotonin syndrome can all present with a number of symptoms that are similar; one factor that may distinguish lithium toxicity from NMS or serotonin syndrome is _______. Patients with lithium toxicity are not usually ______.

hyperthermia; febrile

5-HT; Serotonin System Increase serotonin>

increase mood, increase sedation, decrease libido, decrease appetite

Some depressants need NE component for

increased alertness/mood effect- from NE

Amphetamine Tyramine

indirect-acting sympathomimetic

Adverse effects: CNS

lower seizure threshold (increase chances)

Psuedoephedrine

mixed-acting sympathomimetic (often found OTC)

Selective Serotonin Reuptake Inhibitors (SSRI's) - Often first choice for _____ depression and appear to be most effective agents in treatment of _________

monopolar depression premenstrual dysphoric disorder (PMDD)

Most common tx for bipolar depression are _____- one of the most prescribed- _____

mood stabilizers; Lithium

Many tricyclics have effects at _____, _____, and _____

muscarinic receptors, histamine type-1 receptors, and alpha-1 receptors big, bulky structure

Lithium - Admin - Absorption - Length of action - Excretion (2) - ineffective in __% pts who take it

orally administered and absorbed - long acting - 95% excreted in urine unchanged- doesn't bind to PP - Also excreted in milk- on lithium- dont breast feed - 30%

Antidepressants should not be given with _____, _____, ____

other CNS depressants, antimuscarinic agent, or MAOI

Bipolar Depression: mix of ____ and ____ - Cycle between _______ between _____ periods of time - ____ can be associated with some forms of depression at times (no true cycling like bipolar)

psychoses and major depressive disorder - high and low moods between long or short periods of time - mania

Monoamine Oxidase Inhibitors (MAOI's) - Usually only use to treat ____ - M of A - don't take with ____

refractory depression - inactivates enzyme that metabolizes norepinephrine and serotonin- more NE and Serotonin to release - Tyramine> hypertensive crisis

Adverse effects: ____ largest problem

sedation

Secondary Amine Tricyclics block reuptake of _____________

serotonin AND norepinephrine

Antidepressants increase risk of _______ in children, teens, young adults compared to placebo. - Should be..

suicidal thinking and behavior (suicidality) - Should be monitored closely for clinical worsening, suicidiality, unusual changes in behavior

Interactions with various _____ is very problematic

sympathomimetics