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46 Cards in this Set
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major depression or unipolar depression: characterized by what |
depressed mood, anhedonia, changes in appetite or sleep, psychomotor agitation or retardation, fatigue or decreased energy, decreased concentration, increased indecisiveness, and recurring thoughts of death or suicide; for dx of major depression at least 5 or more of these sx must be present for 2 weeks of more; the incidence is 10-25% of females and 5-12% of males |
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dysthymia: characterized by what |
a depressed mood that is present on more days than not, for a period of two years or longer. The patient does not exhibit a major depressive episode(as described above) in the first two years of the disturbance. For a positive diagnosis, in addition to being depressed, the patient must have two or more of the following symptoms: poor appetite or overeating, insomnia or hypersomnia, low energy or fatigue, low self-esteem, poor concentration or difficulty making decisions, and feelings of hopelessness. The incidence is approximately 6%. Some patients will exhibit a "double depression", that is, they will have episodes of major depression superimposed on a baseline of dysthymia. |
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bipolar affective disorder: characterized by what |
previously called manic depression and is characterized by alternating periods of depression and mania or hypomania. During the manic phase, the patient will exhibit three or more of the following symptoms: inflated self esteem or grandiosity, decreased need for sleep, more talkative than normal, flight of ideas, distractible, increased goal-directed activity (work, school, sex), excessive involvement in pleasurable activities that have negative consequences (buying sprees, foolish business investments). In the most severe form of the manic phase, a patient may be desperate, panic stricken, incoherent, or have looseness of associations or hallucinations. During the depressive phase, the patient may experience varying degrees of depression related symptoms. The incidence is approximately0.4-1.6%, and there is a strong hereditary component. Patients are more likely to have a comorbid substance abuse disorder than are patients with other affective disorders. |
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in general: the treatment for major (unipolar) depression, dysthymia, and bipolar disorder |
In general, antidepressants (tricyclics, SSRIs) that are effective in treating major (unipolar depression) are effective in treating dysthymia. In some cases, lithium is used to treat major depression. In contrast, bipolar disorder is most typically treated with lithium,valproate, or carbamazepine. An antipsychotic drug, such as haloperidol, may be given acutely to reduce symptoms associated with mania |
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monoamine oxidase inhibitors (MAOIs): 1 name, what do they do, when are they used |
tranylcypromine non-selectively inhibit both types ofMAO (A and B). Long-duration (irreversible) inhibition of MAO results in increased tissue and brain levels of norepinephrine, dopamine and serotonin. Mood is elevated. Several weeks may be required to achieve the full therapeutic response. These agents are usually reserved for patients who do not respond to other treatments, primarily due to potential adverse effects; selegiline is also an MAOI |
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MAOIs: adverse effects |
MAO inhibitors can cause serious toxicities involving the liver, brain and cardiovascular system. Weight gain is a common side-effect. |
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MAOIs: interactions with other drugs |
MAO inhibitors may cause hypertensive crisis due to potentiation of sympathomimetic amines. These include direct acting agents in over-the-counter cold remedies, tryptophan, levodopa, dopamine, methyldopa, phenylpropanolamine, and tyramine in food and beverages; MAO inhibitors also inhibit metabolism of other drugs. Interaction with meperidine produces severe hypertension or hypotension, hyperpyrexia, and death; Use care when switching from an MAO inhibitor to another antidepressant |
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tricyclic antidepressants: pharmacological actions and what are the 4 TCAs |
antidepressant action; inhibition of amine uptake pumps; down regulation of biogenic amine receptors; sedation; anticholinergic effects; cardiovascular effects; imipramine, desipramine, amitriptyline, and nortriptyline |
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antidepressant action |
This effect depends upon the presence of depression. When given in the absence of depression, these compounds do not produce a mood elevation, but tend to produce unpleasant effects such as tiredness, light headedness, and difficulty in concentrating. |
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inhibition of amine uptake pumps |
Inhibition of uptake of norepinephrine, serotonin, or dopamine is responsible for several actions of these agents and may be related, either directly or indirectly, to their therapeutic effect. Currently available antidepressants in the tricyclic or second-generation group inhibit uptake of at least one of the monoamines. This effect is thought to develop rapidly, whereas antidepressant effects may require three or more weeks to develop with most agents |
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down regulation of biogenic amine receptors |
Beta-adrenergic and presynaptic serotonin receptors (5HT1A, 5HT1B/D) demonstrate down-regulation following chronic antidepressant treatment. There is also evidence for down-regulation and desensitization of presynaptic alpha-2 receptors with those drugs that inhibit norepinephrine uptake. These effects require time to develop, the delay being consistent with onset of clinical effects. The development of presynaptic receptor subsensitivity may occur as a result of increased synaptic concentrations of the amines secondary to uptake inhibition. Since the presynaptic receptors inhibit transmitter release, developing presynaptic receptor subsensitivity should reduce this inhibition, allowing continued release of transmitter and continued efficacy of reuptake blockade. |
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sedation |
In spite of having an antidepressant action, several of these compounds also produce sedation. The sedative effect of these agents may be related to their antagonism of histamine H1 receptors. |
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anticholinergic effects |
Like the phenothiazines, the tricyclic antidepressants have atropine like effects on cholinergic muscarinic receptors. This action accounts for several trouble some adverse effects including dry mouth, constipation, urinary retention, sexual dysfunction, blurred vision, paralytic ileus, precipitation of glaucoma, delirium, confusion, etc. These effects are additive with other agents that have anticholinergic activity (phenothiazines). |
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cardiovascular effects |
Heart= The tricyclic antidepressants have quinidine-like effects and anticholinergic effects which cause palpitations, tachycardia, ECG changes, conduction defects and arrhythmias (supraventricular and ventricular); Vascular: The tricyclic antidepressants produce varying degrees of alpha-adrenergic receptor blockade, similar to the phenothiazines. Therefore, orthostatic hypotension is a problem withmany of these agents (as high as 20% for some). Of the tricyclics, nortriptyline is thought toproduce the least orthostatic hypotension while the incidence is high with amitriptyline |
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adverse effects of tricyclic antidepressants: antichoinergic |
Use with caution in patients with glaucoma or prostatic hypertrophy. Exercise care when administering with other agents that have anticholinergic effects. Elderly patients are especially sensitive to the anticholinergic actions. Amitriptyline has the most anticholinergic activity |
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adverse effects of tricyclic antidepressants: cardiovascular |
Orthostatic hypotension= due to α1 -adrenergic blockade; Cardiac= The tricyclic antidepressants can produce ECG changes, tachycardia (inhibited NE uptake and antimuscarinic effect), conduction block (quinidine-like), congestive failure, or ventricular fibrillation. Since the quinidine-like effect is particularly dangerous for patients with heart block, such patients should be treated with a third-generation drug rather than a tricyclic |
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adverse effects of tricyclic antidepressants: CNS |
Weakness, fatigue, sedation, weight gain, headache, tremors, ataxia, agitation, precipitation of hypomanic excitement and psychosis in predisposed patients (i.e., bipolars); Central antimuscarinic syndrome= (delirium, confusion, decreased memory, excitement, hallucinations, delusions, disorientation, seizures). Confusion or delirium may be seen in 10% of patients; the incidence is considerably higher in older patients; Lowered seizure threshold= Enhanced possibility of seizure activity may necessitate increasing the dose of antiepileptic drug. This is similar to the effect of phenothiazines. These agents may precipitate first time seizures |
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adverse effects of tricyclic antidepressants: allergies |
Rarely, skin rashes, agranulocytosis, cholestatic jaundice |
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adverse effects of tricyclic antidepressants: drug interactions |
Tricyclics inhibit microsomal enzymes; Tricyclics inhibit uptake of guanethidine and methyldopa causing reduced antihypertensive action; Reduced seizure threshold may require increased antiepileptic medication; Synergistic anticholinergic effects; Enhancement of directly and indirectly-acting sympathomimetic agents (e.g., norepinephrine, l-dopa in Parkinsonian patients); Tricyclics reduce antihypertensive action of clonidine (antagonism of central alpha-2 receptors); Additive sedative effects with alcohol and depressants |
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adverse effects of tricyclic antidepressants: acute toxicity |
The antidepressant drugs are dangerous when taken in overdose, and depressed patients are likely to be suicidal. The lethal dose may be only 10-20X the therapeutic dose. Therefore, prescriptions should be limited, especially in an acutely depressed patient. The most serious results of overdose are cardiac arrhythmias, hypotension, convulsions and coma. Delirium, hyperpyrexia, bowel and bladder paralysis, hypertension (uncommon), and respiratory depression may occur |
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adverse effects of tricyclic antidepressants: treatment of acute overdose |
Treatment includes respiratory support, gastric aspiration and lavage, activated charcoal, cooling for hyperthermia (anticholinergic), fluid expansion for shock, etc |
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SSRIs: pros and what are the 6 SSRIs |
revolution in the treatment of depression= safer; less side effects= no effects on cholinergic, histamine, or alpha adrenergic receptors; fluoxetine is the most prescribed antidepressant out there; fluoxetine, sertaline, paroxetine, citalopram, escitalopram, vilazodone |
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SSRIs: side effects |
weak but significant statistical link between SSRIs and increased risk for suicide in adolescents; serotonin syndrome= SSRIs interaction with MAO inhibitors, altered mental status, fever, agitation, tremor, etc |
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fluoxetine (prozac): how does it work |
selective serotonin reuptake inhibitor (SSRI) with little effect on central norepinephrine or dopamine function, or on cholinergic, histamine or alpha-adrenergic receptors. With time, down-regulation of presynaptic 5-HT receptors develops. It is as effective as the tricyclics and has a similar onset of action. Fluoxetine is extensively converted to an active metabolite with a very long half-life (7-15 days) |
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fluoxetine: adverse effects |
nervousness, anxiety, agitation and restlessness resembling akathisia, headache, nausea, insomnia, urticaria or rash (4%), anorgasmia, precipitation of mania, and enhanced seizure activity in epileptic patients. Almost all of these effects are transient, with the exception of headache incidence which may actually increase over time in some patients (possible down regulation of presynaptic 5HT1D). Fluoxetine has fewer anticholinergic side effects than tricyclics, fewer cardiac effects, does not cause orthostatic hypotension, does not cause weight gain, and apparently does not potentiate CNS depressants such as alcohol. It may be less dangerous in overdose; Severe adverse reactions and death have resulted from concurrent use of fluoxetine and MAO inhibitors. MAOI's should be discontinued two weeks before starting fluoxetine, and fluoxetine should be stopped at least five weeks before initiating MAOI treatment; Another interaction is the worsening of extrapyramidal side effects when fluoxetine is taken with antipsychotic drugs. Fluoxetine inhibits the metabolism of several agents including tricyclic antidepressants, carbamazepine and antipsychotic drugs. Fluoxetine is strongly bound to plasma proteins, and may displace warfarin or digoxin; the Medical Letter recommends monitoring of prothrombin time or digoxin concentrations when starting or stopping fluoxetine |
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sertraline (zoloft): what is it, adverse effects |
Like fluoxetine, sertraline is a selective serotonin reuptake inhibitor. Some of the adverse effects of sertraline are similar to fluoxetine. Compared with the tricyclics, sertraline has a lower incidence of anticholinergic effects, dizziness, fatigue, sedation, weight gain or seizures. It has little effect on the EKG, and the akinesia and dyskinesia which have occurred with fluoxetine have not been reported. Suicidal and other violent behavior that have been associated with fluoxetine have not been reported with sertraline. Sertraline does not significantly inhibit metabolism of other drugs by the cytochrome P-450 system. The drug should not be used within 14 days before starting or after discontinuing an MAO inhibitor |
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paroxetine (paxil) : what is it, adverse effects |
selective serotonin reuptake inhibitor which is an effective antidepressant. Adverse effects include nausea, somnolence, sweating, tremor, insomnia, and ejaculatory disturbances. This new drug appears in large quantities in breast milk. Paroxetine inhibits cytochrome P-450 enzymes and causes interactions by reducing metabolism of other drugs. It cannot be given concurrently with MAO inhibitors, and an interval of at least two weeksshould elapse between changing from paroxetine to an MAO inhibitor and vice-versa |
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bupropion: how does it work, what is it used for |
blocks dopamine uptake without affecting serotonin or norepinephrine uptake (DA selective). Its mechanism of antidepressant effect is unknown, but in analogy to maprotiline-responders, it is possible that a dopamine-deficient subtype of depression may respond best to this drug. Buproprion can also be used to wean smokers away from tobacco, consistent with the notion that nicotine likewise elevates synaptic dopamine. Bupropion has been shown in clinical trials to be as effective as other antidepressants. It was introduced, withdrawn because of a high incidence of seizures, and then reinstated when it was found that the high seizure incidence was in a specific population of patients (bulimia). Bupropion has also been used in the treatment of attention-deficit hyperactivity disorder |
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bupropion: adverse effects |
causes fewer anticholinergic effects than tricyclics. It does not cause sedation, enhance the depressant effects of alcohol, cause weight gain, affect cardiac conduction, cause sexual dysfunction, or cause orthostatic hypotension. It does not antagonize the antihypertensive action of clonidine. Agitation is the most common reason for stopping the drug. Other adverse effects are headache, dizziness, tremor, insomnia, nausea, anorexia, weight loss, and constipation. Psychotic reactions can occur, and psychotic symptoms may worsen in depressed schizophrenic patients taking bupropion; THE PRIMARY CONCERN IS RISK OF SEIZURES which is higher with this drug than tricyclics. There is a very high incidence of drug-induced seizures in patients with bulimia. Caution should be exercised in prescribing bupropion to patients who are taking other drugs that lower seizure threshold; similarly, withdrawal from certain drugs (benzodiazepines) should not be undertaken while therapy with bupropion is being initiated or its dosage increased |
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bupropion: dosage |
It is recommended that dosage be started low and then increased by limited amounts.Four weeks or longer may be required for development of full therapeutic action |
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review of differences between tricyclic and 3rd gen drugs |
Trazodone, fluoxetine, sertraline and bupropion have little or no anticholinergic activity. Amoxapine and maprotiline have a low incidence of anticholinergic effects; The incidence of hypotension with bupropion, fluoxetine and sertraline is very low; Adverse cardiac effects are less frequent with trazodone, bupropion, sertraline and fluoxetine; Risk of seizures is the main concern with bupropion; Fluoxetine, sertraline and bupropion produce little additive sedative effects with alcohol and depressants |
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bipolar disorder: treatment |
Traditional treatment for bipolar disorder is lithium; Certain anticonvulsants such as carbamazepine and valproate are also very effective and mechanism of action is thought to be inhibition of G protein coupling to second messenger systems, perhaps through competition at a Mg++-sensitive site (these are safer than lithium); HALOPERIDOL (antipsychotic) can be used in acute manic phase; treatment with antidepressants during the depressive phase can induce the manic phase, consistent with the possibility that inhibition of adenylate cyclase activity occurs during the depressive phase, while overactivity of the cyclase might produce the manic phase; Lithium has a mood-leveling effect |
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lithium side effects |
Sodium depletion promotes lithium retention. Therefore, administration of lithium and diuretics should be avoided. Polydipsia and polyuria are sometimes seen due to lithium interference with renal water reabsorption. Hypothyroidism is seen in some patients since lithium may interfere with thyroxine synthesis. Weight gain, drowsiness and nausea are sometimes seen. Allergic reactions and fine tremor are rare side effects. The therapeutic concentration "window" for lithium is very small. |
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lithium is also effectively used for what |
MAJOR (UNIPOLAR DEPRESSION) IN SOME CASES |
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therapeutic uses of antidepressant drugs |
depression; cataplexy; OCD; chronic pain states; panic disorder; PTSD; enuresis; ADHD; eating disorders |
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treatment of cataplexy associated with narcolepsy |
imipramine |
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treatment of OCD |
clomipramine, fluoxetine, or flucoxamine |
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treatment of panic disorder |
desipramine, alprazolam, perhaps fluoxetine
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treatment of ADHD |
imipramine, desipramine, nortriptyline |
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treatment of eating disorders (bulimia, obesity) |
fluoxetine may help some pts lose weight; long term effectiveness not clear |
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A 73 y/o man has been in the clinic severaltimes in recent months displaying symptoms of depression as he deals with hishealthy issues (glaucoma) and the death of his wife after 50 years ofmarriage. You have diagnosed the pt assuffering from major depressive affective disorder. Which of the following antidepressant drugsis contraindicated in prescribing to this pt?a. imipramineb. trazadonec. bupropiond. sertralinee. paroxetine |
A imipramine because it is a TCA that has the cholinergic effects that you want to avoid in the elderly (it will effect the glaucoma) |
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what are the heterocyclics |
Amoxapine and maprotiline also have a three-ring basic structure and can be called tricyclics, although they are often classified as heterocyclics. Amoxapine inhibits reuptake of all threeamines, while maprotiline selectively inhibits norepinephrine uptake. The structures of trazodone, fluoxetine, sertraline and bupropion depart from the three-ring base. Trazodone, sertraline and fluoxetine alter serotonin uptake while bupropion inhibits dopamine uptake. Trazodone and bupropion are sometimes referred to as "atypical" antidepressants. Currently, the selective serotonin reuptake inhibitors such as fluoxetine, sertraline, or paroxetine are often the drugs of first choice, particularly for mild to moderate depression |
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amoxapine and maprotiline |
While the majority of unipolar depressed patients respond well to SSRI (see below) certain patients with low energy and persistent lethargy respond better to maprotiline. This suggests the existence of subtypes of depressed patients, e.g., patients with afunctional deficit in the noradrenergic system might respond better to agents such as maprotiline |
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trazodone |
Trazodone lacks anticholinergic activity but does produce marked sedative effects. Trazodone, but not the other antidepressants, may produce a high incidence ofpriapism in men. Priapism is a persistent, painful, and dysfunctional erection of the penis, involving only the corpora cavernosa. In some cases it may lead to permanent impotence. Male patients should be forewarned of this potential effect. In overdose, trazodone produces a different spectrum of effects than the tricyclic antidepressants, and may be safer. Symptoms include hypotension and CNS effects ranging from lethargy to coma. Cardiac effects are much less common than with the tricyclics, owing to less effect on excitable membranes and less tachycardia (less quinidine-like effect, less anticholinergic effect, no block of NE uptake). Maybe used as adjunctive drug |
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what are the 2 SNRIs |
vanlafaxine and duloxetine |
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what are the 4 treatments for bipolar disorder |
lithium, valproic acid, carbamazepine, and lamotrignine |
