Term
Typical Antipsychotics (TA)
MOA?
Therapeutic Efficacy & pathway?
TA also block muscarinic, alpha-adrenergic, and histamine-1 receptors |
|
Definition
MOA: antagonism at dopamine D2 receptors
-nigrostriatal pathway blockade --> EPS
-tuberoinfundibular pathway blockade --> hyperprolactinemia
-mesocortical pathway blockade --> worse negative Sx (alogia, avolition) and cognitive Sx (poor attention)
Therapeutic against positive symptoms (delusions & hallucinations) due to D2 blockade of mesolimbic DA pathway. |
|
|
Term
TA
list high potency, mid potency, and low potency agents
high potency - cause worse EPS
mid potency - balanced prolife
low potency - cause more anticholinergic, antihistaminergic, and antiadrenergic side effects |
|
Definition
High potency:
haloperidol (haldol)
fluphenazine (prolixin)
pimozide (Orap)
thiothixene (Navane)
trifluoperazine (stelazine)
Mid potency:
perphanazine (Trilafon)
Molindone (Moban)
Loxapine (Loxitane)
Low Potency:
Chlorpromazine (Thorazine)
Mesoridazine (Serentil)
Thioridazine (Mellaril) |
|
|
Term
|
Definition
Psychotic d/o
-Schizophrenia
-Schizoaffective d/o
-brief psychotic d/o
-substance and medication induced psychosis
Psychotic symptoms in mood d/o
-major depression w/ psychotic fx
-acute manic, depressed, and mixed manic states of bipolar d/o
Tourette's d/o
Huntington's d/o |
|
|
Term
|
Definition
EPS (akathisia, dystonic rxn, parkinsonism)
Hyperprolactinemia (gynecomastia, impotence, amenorrhea)
Sedation
Weight gain
Anticholinergic SE (dry mouth, constipation, blurry vision, urinary retention, confusion, ECG changes)
Antiadrenergic SE (orthostatic hypotension)
decreased seizure threshold (more low potency)
sexual dysfxn
dermatologic SE (dermatitis and photosensitivity) |
|
|
Term
Treating EPS caused by TA
hours: Dystonic Rxns? (painful muscle spasms)
days-wks: Akathisia? (intense restlessness)
wks-months: Parkinsonism? (tremor, bradykinesia, masked facies, festinating gait, cogwheel rigidity) |
|
Definition
Akathisia: benztropine (anticholinergic), propranalol (beta blocker), benzodiazepines
Dystonia: PO or IM anticholinergics
Parkinsonism: anticholinergics, dopaminergics (amantadine), beta-blockers |
|
|
Term
Serious Adverse Effects of TA
occurs months-years after taking |
|
Definition
Tardive Dyskinesia - involuntary choreoathetoid movements of face, neck, trunk, and extremeties
Neuroleptic Malignant Syndrome - hyperpyrexia, autonomic instability, muscle rigidity, delerium. Uncommonly occurs with atypical antipsychotics as well
Treat with dantrolene & bromocriptine
dantrolene (muscle relaxant, abolishes excitation-contraction coupling in muscle cells by acting on the ryanodine receptor)
bromocriptine (dopamine agonist) |
|
|
Term
Atypical Antipsychotic (AtA)
MOA?
Therapeutic Efficacy & pathway?
AtA also block muscarinic, alpha-adrenergic, and histamine-1 receptors |
|
Definition
MOA: antagonism at dopamine D2 receptors and serotonin 2A receptors
-DA transmision normally suppressed by serotonin in nigrostriatal, mesocortical, and tuberoinfundibular tracts. Thus serotonin 2A blockade increases DA transmission a bit mitigating EPS.
Therapeutic against positive Sx due to D2 blockade of mesolimbic pathway |
|
|
Term
| Compare TA to AtA TA indications also apply to AtA indications CATIE Trial? |
|
Definition
AtA
-higher rates of metabolic problems (hyperglycemia, T2D, hyperlipidemias)
-lower incidences of tardive dyskinesia, NMS, and EPS (except risperidone!!)
-all AtA indicated for acute mania (except clozapine)
-olanzapine & aripiprazole indicated for prophylaxis of recurrent mania...aka bipolar maintenance
CATIE Trial:
-olanzapine, was slightly better than the other drugs but also was associated with significant weight-gain as a side-effect.
-Surprisingly, the older, less expensive medication (perphenazine) used in the study generally performed as well as the four newer medications (risperidone, quetiapine, and ziprasidone).
-newer medications have no substantial advantage over the older medication used in this study. An important issue still to be considered is individual differences in patient response to these drugs |
|
|
Term
|
Definition
clozapine (clozaril)
Risperidone (Risperdal)
Olanzapine (Zyprexa)
Quetiapine (Seroquel)
Ziprasidone (Geodon)
Aripiprazle (Abilify)
Paliperidone (Invega)
Iloperidone (Fanapt)
Asenapine (Saphris)
Lurasidone (Latuda) |
|
|
Term
| General Adverse Effects of AtA |
|
Definition
sedation
weight gain
metabolic problems
depending on the medication: anticholinergic effects or orthostatic hypotension |
|
|
Term
Antidepressants
Drug Classes |
|
Definition
Tricyclic Antidepressants (TCAs)
Monoamine Oxidase Inhibitors (MAOIs)
Selective Serotonin Reuptake Inhibitors (SSRIs)
Selective Serotonin Reuptake Inhibitor and Serotonin Partial Agonist (falls under SSRI)
Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs)
Noradrenergic and Specific Serotonergic Antidepressants (NaSSAs)
Serotonin Antagonists and Reuptake Inhibitors (SARIs)
(serotonin rctpr antagonist and agonist)
Noradrenergic and Dopamine Reuptake Inhibitors (NDRI) |
|
|
Term
TCAs
MOA?
tertiary vs secondary amines?
TCAs also block muscarinic, alpha-adrenergic, and histamine 1 rcptrs
therapeutic effect beings 3-4 wks after administration
TCAs can be lethal in overdose. blood monitoring common. |
|
Definition
MOA: antagonism at 5HT and NE presynaptic reuptake pumps (so increased serotonin and norep at synapse)
tertiary amines: greater alpha-1, H1, and muscarinic blockade
secondary amines: fewer SE, less sedating, safe in overdose |
|
|
Term
TCAs
list agents:
tertiary amines
secondary amines |
|
Definition
tertiary amines:
Amitriptyline (Elavil)
Clomipramine (Anafranil)
Doxepin (Sinequan)
Trimipramine (Surmontil)
Imipraprime (Tofranil)
secondary amines:
Desipramine (Norpramin)
Nortriptyline (Pamelor)
Protriptyline (Vivactil) |
|
|
Term
TCAs
indications
contraindications
rarely 1st line agents b/c of SE and lethal in overdose |
|
Definition
indications:
MDD
BP depression
panic d/o
Generalized Social Phobia
GAD
OCD (clomipramine)
Pain disorders (migrains, neuralgias)
Contraindications:
cardiac conduction delays
arrhythmias |
|
|
Term
|
Definition
anticholinergic
sedation
weight gain
orthostatic hypotension
sexual dysfxn (erectile dysfxn, delayed ejaculation, anorgasmia)
Mania in BP pts
seizures (rare) |
|
|
Term
TCAs
Serious Adverse effects? |
|
Definition
Cardiotoxicity: TCAs slow cardiac conduction --> ECG changes, arrythmias, AV block
Neurotoxicity: tremor, ataxia
In overdose: agitation, delerium, coma, death |
|
|
Term
MAOIs
MOA?
MAOIs block both MAO-A and MAO-B but onyl MAO-A blockade is necessary for antidepressant effect
MAOIs also block alpha-1 adrenergic and H1 rcptrs |
|
Definition
MOA:
irreversible monoamine oxidase inhibitors (MAO).
MAO metabolizes monoamines (5HT, DA, NE) in presynaptic neuron
MAO inhibition disables monoamine degradation, thus increasing serotonin, dopamine, and norep |
|
|
Term
|
Definition
Phenelzine (Nardil)
Tranylcypromine (Parnate)
Transdermal selegiline (Emsam) |
|
|
Term
|
Definition
orthostatic hypotension (may require support stockings, hydration, increased salt intake)
weight gain
sexual dysfxn
insomnia
myoclonus, muscle pain, paresthesia
mania |
|
|
Term
MAOIs
serious adverse effects |
|
Definition
tyramine induced hypertensive crisis
-Tyramin causes release of monoamine stores (dopamine, NE, epineph)
-Tyramine normally broken down by MAO-A in GI tract.
-MAOIs increase NE, DA,5HT
Tyramine + MAOI ==> sudden, catastrophic rise in blood pressure
pts on MAOIs must be on low tyramine diet (avoid aged cheese, fava beans, liver, red wine).
Also, don't take MAOI w/ SSRI |
|
|
Term
SSRI
MOA?
Therapeutic effect begins 3-4 wks after administration
Most commonly prescribed antidepressant b/c:
-low incidence of SE
-no food restrictions
-safer in OD |
|
Definition
MOA: selective antagonism at serotonin (5HT) presynaptic reuptake pumps. Site of action = frontal serotonin projection.
SSRIs have fewer SE than TCAs and MAOIs due to serotonin selectivity (they don't act on histamine, adrenergic, and muscarinic rcptrs) |
|
|
Term
|
Definition
Fluoxetine (Prozac)
Paroxetine (Paxil)
Sertraline (Zoloft)
Fluvoxamine (Luvox)
Citalopram (Celexa)
Escitalopram (Lexapro) |
|
|
Term
SSRI
Indications?
Contraindications? |
|
Definition
indications:
MDD
Premenstrual dysphoric d/o (PMDD)
PTSD
Bulimia
Panic d/o
Social Phobia
OCD |
|
|
Term
SSRI
adverse effects
SE due to over-stimulation of various 5HT rcptrs widely distributed throughout the body |
|
Definition
weight gain
mania
Serotonergic SE
-5HT3 - GI system, overstimulation --> diarrhea, nausea, vomiting
-5HT2c - CNS, overstimulation --> anxiety, mental agitation
-5HT2a - CNS & spinal cord, overstimulation --> anxiety, mental agitation, akathisia, insomnia, myoclonus, sexual dysfxn
Serotonin Discontinuation Syndrome: headache, dizziness, irritability, fatigue upon abrupt discontinuation |
|
|
Term
SSRI
Serious adverse effects
Don't take SSRI with MAOI or triptan
(triptans for migraines, they are agonists at 5HT rcptrs in cranial BV) |
|
Definition
Serotonin Syndrome
If take SSRI with MAOI:
hyperthermia, myoclonus, autonomic instability, rigidity, coma, death
MAOI washout of 2 wks prior to SSRI treatment |
|
|
Term
SNRI (serotonin and NE reuptake inhibitor)
MOA?
no alpha-1, H1, muscarinic blockade
(avoids many SE common w/ TCAs) |
|
Definition
MOA:
selective antagonism at NE and serotonin presynaptic reuptake pumps
Additional dopamine reuptake inhibition at higher doses, yielding a curvilinear dose response. |
|
|
Term
|
Definition
Venlafaxine (Effexor)
Duloxetine (Cymbalta)
Desvenlafaxine (Pristiq) |
|
|
Term
SNRI
Indications
Contraindications |
|
Definition
I:
MDD
GAD
PD
Generalized Social Phobia |
|
|
Term
|
Definition
tremor
agitation
tachycardia
HTN
diarrhea, nausea, vomiting
anxiety, mental agitation
akathisia
insomnia
myoclonus
sexual dysfxn
seizures (rare)
mania
discontinuation syndrome (headache, dizziness, irritability, fatigue upon abrupt discontinuation) |
|
|
Term
NaSSA (Noradrenergic and Specific Sertonergic Antidepressants)
MOA? (dual) |
|
Definition
Dual MOA:
1) antagonism at central alpha-2 autoreceptors (& subsequent disinhibition of NE and 5HT release)
2) stimulation of alpha-1 somatodendritic rcptrs on serotonin neurons (boosts 5HT release) |
|
|
Term
NaSSA agent?
think alpha-2 receptor antagonist
also blocks 5HT2a, 2c, 3, and H1 rcptrs |
|
Definition
|
|
Term
NaSSA
Indications
Contraindications |
|
Definition
Mirtazapine (remeron)
I:
MDD
Refractory MDD (especially in pts that need to gain weight)
C:
co-administration w/ MAOIs |
|
|
Term
NaSSA
Adverse effects
serious adverse effects |
|
Definition
Mirtazapine (remeron)
sedation (serious, can be used as sleep aid)
increased appetite and weight gain
serious SE:
agranulocytosis and other blood dyscrasias |
|
|
Term
SARIs (Serotonin antagonist and reuptake inhibitors)
MOA?
essentially serotonin rctpr antagonist & agonist |
|
Definition
MOA:
selective antagonism of serotonin (5HT) presynaptic reuptake pumps with simultaneous 5HT2A blockade |
|
|
Term
|
Definition
Trazadone (Desyrel)
Nefazadone (Serzone) |
|
|
Term
SARI
Indications
Contraindications |
|
Definition
trazadone
nefazadone
I:
MDD
Dysthymia
C:
co-administration w/ MAOIs |
|
|
Term
SARI
adverse effects
-due to 5HT2a blockade sexual dysfxn is avoided
and serious AE |
|
Definition
sedation
nausea
dizziness
mania
Serious SE:
trazadone: priapism, "trazadone raises the bone"
nefazadone: liver toxicity (black box warning) |
|
|
Term
NDRI (Noradrenergic and Dopamine Reuptake Inhibitors)
MOA?
Agent? |
|
Definition
MOA: antagonism of presynaptic NE and DA reuptake pumps
Bupropion (Wellbutrin) |
|
|
Term
|
Definition
bupropion (wellbutrin)
I:
MDD
Dysthymia (chronic depression, less severe, but longer sx than MDD, almost daily over 2 yrs)
BP depression
ADHD
smoking cessation
C:
co-administration w/ MAOIs
Anorexia
Bulimia nervosa
seizure d/o |
|
|
Term
|
Definition
activation
insomnia
nausea
tremor
serious SE:
seizures at high doses |
|
|
Term
SSRI and serotonin partial agonist
agent?
I and C?
SE? |
|
Definition
Vilazadone (Viibryd)
I: MDD
C: co-administration w/ MAOIs
SE: similar to SSRIs (lower risk of sexual dysfxn and weight gain) |
|
|
