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44 Cards in this Set
- Front
- Back
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AMINE HYPOTHESIS OF AFFECTIVE DISORDERS
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DEPRESSION results from a deficiency of brain monoamines, i.e. norepinephrine and perhaps serotonin, leading to decreased neuronal activity.
MANIA results from an excess of brain monoamines |
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Indirect Evidence for amine hypothesis of affective disorder
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Effective treatments for depresion increase concentration of NE/5HT in CNS.
Effective treatments for mania (Lithium) decreases synthesis of brain amines. Drugs that deplete brain amines (Reserpine) cause depression. |
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Problems w/ amine hypothesis
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time course delay- biochemical changes happen immediately, therapeutic results take weeks.
Amphetimines & cocaine act on brain amines but do not treat depression they cause euphoria. |
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Modification of Amine hypothesis
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Sustained use of ADs results in downregulation of presynaptic 5HT autoreceptors. In addition postsynaptic 5HT receptors become sensitized. This time course parallels clinical effect.
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Tricyclic ADs
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TERTIARY AMINES
imipramine (Tofranil )amitriptyline (Elavil) SECONDARY AMINES desipramine (Norpramin) nortriptyline (Aventyl; Pamelor) |
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Selective Serotonin Reuptake Inhibitors (SSRIs)
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fluoxetine (Prozac)
sertraline (Zoloft) paroxetine (Paxil) |
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Atypical (Second & Third-generation) Antidepressants: Heterocyclics
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amoxapine (Asendin)
trazodone (Desyrel) buproprion (Wellbutrin) venlafaxine (Effexor)mirtazapine (Remeron) |
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Monoamine Oxidase Inhibitors(MAOIs):
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phenelzine (Nardil)
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Lithium & other Mood-Stabilizing Drugs:
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lithium carbonate (Eskalith)
valproic acid (Depakene) carbamazepine (Tegretol) |
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MOA of TCAs
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big and bulky similar MOA to phenothiazines re: blockage of α1, H1, & muscarinic.
Block reuptake of NE & 5HT. Result in downregulation of presynaptic receptors and supersensitization of postsynaptic receptors. |
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TCAs: Results of blockage of α1, H1, & muscarinic.
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Sedation (H1)
Dry mouth, blurred vision, urinary retension, constipation, tachacardia (m) Orthostatic HT,cardiac arrythmias (α1) |
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Pharmacokinetics of TCAs:
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lipid soluble. Well absorbed orally. Tertiary amines are metabolized into active metabolites. 1/2 life can be 24 hrs or more in elderly patients.
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Clinical uses of TCAs
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1)depression (replaced by SSRIs)
2)enuresis (esp. imipramine) 3) OCD (SSRIs) 4)Panic disorder (BZDs & SSRIs 5)ADHD (imipramine) 6)Chronic pain |
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Side Effects of TCAs
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extension of unwanted receptor blockages.
Sedation (H1) Confusion & anticholinergic effects(m) Orthostatic HT & arrythmias(α 1) Siezures Seratonin syndrome (watch out for pts on MAOIs |
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Contraindications and Cautions of TCAs
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-hypersensitivity
-cardiac diseases -Liver impairment -Narrow-angle glaucoma; urinary retention History of seizure disorders Pregnancy, children, elderly Limit quantities/amount prescribed |
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Which TCA is most sedating?
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Amitryptiline
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Which TCA is used for Enuresis & ADHD?
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imipramine
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Fluoxitine MOA
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A selective inhibitor of 5-HT reuptake in the CNS
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PK of Fluoxitine
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Orally active. Metabolized to long acting metabolite. Long elimination half life.
Metabolized by Liver. |
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Clinical Uses of Fluoxitine
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Depression
Obsessive-compulsive disorder (OCD) Bulimia Bipolar depression:fluoxetine + olanzapine (Symbyax) |
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UNLABELLED Uses of Fluoxitine
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Alcoholism; ADHD, PMS, migraine & tension headache, Anorexia nervosa
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Adverse reactions of SSRIs
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Nausea, nervousness, agitation, insomnia, headache.
Decreased libido. INCREASED SUICIDAL TENDENCIES, EXTREME ANXIETY, VIOLENT BEHAVIOR– have been reported.—esp. in children and adolescents: MANIC OVERSHOOT *Prefered to TCAs because less side effects |
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Drug interactions of Fluoxetine (Prozac) and paroxetine (Paxil)
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can block metabolism of tricyclic antidepressants, benzodiazepines, carbamazepine
DO NOT give with MAO inhibitors–“Serotonin Syndrome” SUMATRIPTAN (IMITREX) |
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Atypical AD: amoxapine (Asendin)
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metabolite of antipsychotic so retains some dopamine antagonism and antipsychotic activity. Used for depression in psychotic patients. Can cause EPS side effects.
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Atypical AD: trazodone (Desyrel)
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5HT agonist. Also blocks 5HT uptake. Causes marked sedation. Used for Depression with anxiety & insomnia.
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Atypical AD: Bupropion (Wellbutrin)
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weak effect on NE & 5HT uptake. Also inhibits dopamine reuptake.
Used for smoking cessation. Can cause, CNS exitation, anxiety, & irritability. Risk of siezures. |
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Atypical AD: venlafaxine (Effexor)
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Inhibits both NE and 5-HT uptake equally.
intense withdrawal symptoms can occur. used in chronic pain |
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Atypical AD: mirtazapine (Remeron)
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Antihistamine with strong sedating effects. also blocks 5-HT2 ,α1 and muscarinic R. Blocks presynaptic α2–R to ↑ release of NE & 5-HT.
Causes sedation, weight gain, agranulocytosis--REVERSIBLE |
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MAOI: phenelzine (Nardil)
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Produce irreversible inhibition of MAO and ↑ biogenic amines in brain and periphery. It takes 1-2 weeks to restore MAO activity.
MAO inhibitors provide nonselective inhibition. They inhibit both MAO-A (NE, 5-HT and tyramine metabolism) & MAO-B (DA metabolism). |
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Cautions with MAOIs
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WAIT 2 wks before changing from a MAOI to a TCA or SSRI, or an OTC decongestant.
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Clinical use of MAOIs
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- refractory or atypical depressions
-panic disorders or phobias (BZs or SSRIs used more commonly) |
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Adverse reactions MAOIs
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stimulation, euphoria, restlessness
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Overdose toxicity of MAOIs
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Agitation, delirium, hallucination, convulsion
Coma, shock, hyperthermia Supportive and symptomatic treatment |
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Drug Interactions or food-drug interactions with MAOIs
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Sympathomimetic amines (e.g., OTC decongestant; EPHEDRINE)
SSRIs, tricyclic antidepressants– “Serotonin Syndrome” Food/beverages rich in tyramine: aged cheese, beer, certain wines, herring--Severe Hypertensive Crisis may occur |
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MOA of Lithium in manic patients
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prevents the recycling of second messangers (IP3 & DAG)
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Pharmacokinetics of Li+
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rate of Na+ intake is equal to rate of Li+ excretion
Na+ depletion, Li+ rise. Therefore Li+ levels depend on renal fx & Na+ levels |
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Clinical Uses of Li+
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DOC for treatment of acute mania and bipolar disorder (effective in 60-70% of pts) May require concurrent use of TCAs, antipsychotics, or BZs.
Drug has a slow onset of action. |
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Cautions of Li+
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Drug has many side effects and a low therapeutic index.
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Side effects of Li+
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Tremor (treat w/ propanolol)
Involuntary movements, motor hyperactivity,ataxia, dysarthria, aphasia, mental confusion Nephrogenic diabetes insipidus with polydipsia and polyuria Edema Depression of SA node. ECG changes. NVD, leukocytosis, acne. Thyroid problems (TSH every 6 mo) |
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Overdose toxicity of Li+
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NV, involuntary movements, confusion, stupor, seizures, coma, death.
Treatment: Discontinue drug; gastric lavage, moniter fluid and electrolytes; hemodialysis Teratogenic: CV and other birth defects have been reported; LOW RISK |
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Lithium precautions
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Avoid marked dehydration or sodium depletion
CAUTION in Renal and cardiac disease Moniter serum concentration Elderly Pregnancy |
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Lithium Drug Interactions
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Diuretics and NSAIDs: ↑ lithium toxicity by reducing excretion BY 25%
Sodium salts: ↑ renal excretion of lithium Antipsychotics |
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Carbamazepine (Tegretol)
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sxlly similar to TCAs
alternative to Li+ MOA: Inhibits voltage-sensitive sodium channels ↓ SENSITIZATION of brain to mood swings also used for Trigeminal neuralgia & Glossopharyngeal neuralgia |
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Valproic acid (Depakene)
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Alternative to Li+
Possible bipolar MOA: ↑ GABA Nausea is limiting factor |
