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Nervous System Pharm

Affective Disorders I and II

genetic studies show that people homozygous for polymorphisms in this gene may be more vulnerable to developing major depression and suicidal behavior, and are less likely to repsond to anti depressants. Serotonin transporter gene
all available anti depressants affect the monoamine system and enhance synaptic availability of these three neurotransmitters Serotonin, NE, Dopamine
what are some abnormalities in the HPA axis that are seen with depression elevated cortisol levels, chronically elevated CRH, can be due to dysregulation of the stress hormone axis. some have thyroid dysregulation. hypogonadal men and women can also have depression
describe the integration of the neurotropic and monoamine hypotheses HPA and steroid abnormalities in depression can lead to suppression of BDNF transcription, which causes depression. The chronic activation of monoamine receptors by antidepressants increase BNDF transcription.
list the primary clinical indications for Antidepressants major depressive disorder
describe the secondary clinical indications for antidepressant therapy panic attacks, GED, PTSD, OCD
what is another use for anti-depressants not discussed previously? pain disorders (neuropathic and fibromyalgia) some can be used for PMDD, hot flashes in menopause, stress urinary incontinence
list some classes of antidepressants SSRI, SNRI, tricyclic antidepressants, serotonin antagonists, MAO inhibtors, tetracyclic and unicyclic antidepressants
this class of anti depressants is most commonly used SSRIs
list some common SSRI's Fluoxetine (prototype), Sertraline, Paroxetine, Escitalopram
what is the mechanism of action of SSRIs Serotonin normally binds to SERT, inducing conform change in transporter alowing NaCl to enter cell, and K+ to leave, another conform change happens, allowing serotonin into the cell. SSRI binds to SERT and inhibits all this.
what is one major advantage to SSRIs? most all generic, cheap, they are good at specifically targeting SERT
describe the half life of SSRIs short
list some clinical indications for SSRIs major depression, GEd, PTSD, OCD, panic disorder, PMDD, bulimia
list some adverse drug interactions to SSRIs enhanced serotonergic tone in the brain and body: gut: N/D, GI upset, GI symtoms, spinal cord and above: decreased sexual function and interest, delayed orgasm. CNS: increased headaches, hypo/hypersomnia, weight gain, discontinuous syndrome
which SSRI is especially known to cause weight gain? paroxetine
which cyp enzymes do SSRIs inhibit? CYPD2D6 (metabolizes cardiac and neuro drugs), CYP3A4
SSRIs cause serotonin syndrome when given in combination with what? monoamine oxidase inhibitor
what are some common symptoms of serotonin syndrome? hypertension, hyperreflexia, tremor, clonus, hyperthermia, mydriasis, agitation
what is the main use for SNRIs? mainly used for pain disorders, but also used for depression
what is the general mechanism of action for SNRIs? they bind both SERT and NET transporters,and have little affinity for other recetors.
list some of the SNRIs Duloxetine, Minacipran, (Venlafaxine)
which SNRIs are balanced inhibitors of SERT and NET Duloxetine, Minacipran
in general, do SNRIs have a greater affinity for SERT or NET? SERT
list some of the clinical indicaitons for SNRIs major depression, pain disorders (neuropathies and fibromyalgia), generalied anxiety, stress urinary incontinence, hot flashes in menopause
which SNRI is more commonly used for fibromyalgia? milnacipran
which SNRI is more commonly used for fibromyalgia and diabetic neuropathic pain, and chronic musculoskeletal pain? Duloxetine
describe the SERT inhibition adverse effects of SNRIs similar to that of SSRIs, as well as discontinuation syndrome
describe NET blocking adverse effects of SNRIs increased BP, HR, CNS activation (insomnia, anxiety, agitation)
there is more cardiac toxicity associated with this SNRI than any other SNRI or SSRI vanlafaxine
SNRI with simulataneous use of what other class of drugs is contraindicated due to development of serotonin syndrome? SSRI
this class of antidepressants work by inhibiting both SET and NET, but with considerable variability Tricyclic antidepressants
TCA's have what ending? "mine" or "line"
what are the clinical indications for TCADs? treatment of depression unresponsive to SSRIs and SNRIs, pain conditions, enuresis, insominia
what TCAD is used specifically for bed wetting? imipiramine
what is a potent adverse reaction to TCAD? potent antimuscarinic effects: dry mouth and constipation: ANTI-DUMBBells (constipation, no urination, mydriasis, bronchodilation, tachycardia, no emesis, no tearing, dry mouth, no sweat)
list some drug interactions with TCAD levels elevated with other drugs that inhibit cyp2D6, slow/ultrarapid/normal metabolizers because of polymorphisms, can have additive effects with drugs that also have anticholine or antihistam effects, can exacerbate orthostatic hypotension with anti HT
list the serotonin antagonist Trazodone
what are clinical uses for serotonin antagonists? it is used for major depression, and also has off label use as a hypnotic.
what are some common adverse drug reactions for serotonin antagonists common: sedation and Gi upset, Gi disturbance is dose dependent. there is also dose related orthostatic hypotension.
describe a drug interaction of Trazedone it is a CYP3A4 substate, so inhibitors of this enzyme can increase its concentration
what is the general mechansm of action of MAOIs? they specifically target MAO-A (in DOPA and NE neurons) and MAO-B ( in SRT and HIST neurons)selectively. some structurally resemble amphetamines, so CNS stimulation is increased
list the MAOI drugs phenelzine
what are some substrates for MAO-A? NE, EPI, SRT
what are some substrates for MAO-B? tyramine, phenylethylamine, benzylamine
MAO-A and MAO-B both metabolize what? tryptamine and dopamine
what is the clinical indication for MAOIs? treatment of depression unresponsive to other drugs
list some adverse drug reactions to MAOIs orthostatic hypotension (most common), weight gain, confusion, sexual effects (anorgasmia), suden discont syndrome that resembles delirium like prsentation (psychosis, excitement, confusion). phenelzine is more sedating than amphetamine like drugs.
what are the most common drug interactions with MAOIs? serotonin syndrome when given with SSRIs, SNRIs, most TCAD, analgesics. when given with tyramine, can result in enhanced peripheral noradrenergic effects. this can also happen when given with sympathomimetics (pseudoephedrine, phenylpropanolamine)
what are some foods that contain tyramine aged cheese, tap beer, soy products, dried sausages
what is the main clinical indicaiton for unicyclic/tetracyclic drugs? mainly used if a person wasn't responding to the other previously mentioned medications.
name the most commonly used unicyclic/tetracyclic drug buproprion. this resembles an amphetamine. it has a unique side effect profile, and has few sexual side effects. actions are poorly understood.
what are adverse drug reactions to buproprion occasionally produces agitation, insomnia, and anorexia, and can lead to seizures in overdose.
which enzyme is buproprion metabolized by? CYP2B6
choosing an antidepressant depends on these factors... indication, practical considerations (cost, availability, adverse reactions, potential drug interactions, patient history and patient preference), patient age, gender, medical status
these classes of drugs are mainly used for pain conditions TCAD and SNRIs
these classes of drugs are mainly used for treatment of OCD SSRI and clomipramine
this drug is used for smoking cessation buproprion
describe the general dosing o fthese drugs start at the lowest dose within normal range, and if no change occurs after four weeks, dose can be increased and titrated to maximum dose.
in general, does anxiety require high or low doses? high
in general does pain require high, moderate, or low doses? moderate
what is a common method of suicide with these drugs? via overdose
what can be used in cases of overdose with TCADs? sodium bicarbonate
antidepressants are black boxed for what? increased risk of suicidality in patients under age 25 (suicidal ideation and gestures, not complete suicides)
antideprssants fall under which category of pregnancy? C
is there a protective benefit for using Anti-depressants for major depression long term? yes
is there always a benefit seen when using anti depressants with bipolar disorder? no. it is often given with a mood stabilizer
has there been success with using anti-depressants with unipolar depression no
antidepressants are often given in combination with what other therapy? cognitive behavioral therapy
which class of antidepressants are used mainly for chronic pain? TCAD, SNRI
what drugs are used to treat PMDD? fluoxetine, sertraline
what drug is known for use in smoking cessation? what is the MOA? Bupropion, MOA unknown. it is two times better than placebo for reducing urge to smoke, and also improves and minimizes mood swings.
this drug is used to treat this type of eating disorder fluoxetine, treats bulemia, NOT anorexia
this drug is used to help treat euresis in children Imipramine
this is an OTC herbal used to treat mild to moderate depression, anxiety, nervous tensin, insomnia, seasonal affective disorder. it works by inducing this enzyme St. John Wort, induces CYP 3A4
this drug is used to treat symptoms of manic phase of bipolar disorder. lithium
how does lithium work? directly inhibits inositol signaling through depletion of intracellular inositol and inhibits glycogen synthase kinsase-3 (GSK3). Decreased inositol leads to mood stabilization.
can lithium be used for maintenance therapy? yes
is lithium use common today? no
in severe manic situations, lithium is often substituted with what? antipsychotics or potent benzodiazapines
list some adverse effects of lithium tremor (occurs with therapeutic dose, treated with propanolol, atenolol), choreothetosis, motor hyperactivity, ataxia, dysarthria, aphasia. psychiatric: mental confusion, withdrawal, decreased thyroid function, edema, acne
what renal side effect is lithium known for? nephrogenic diabetes insipidus
what cardiac conditions is lithium contraindicated in? bradycardia-tachycardia syndrome ("sinus sickness")
besides lithium, what other class of drugs can be used to treat bipolar disorder? antipsychotics, anticonvulsants.
Created by: aferdo01