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