NR 565 NR565 Week 7 Exam review Completed A+++

NR 565 NR565 Week 7 Exam review Completed A+++ Week 7 review  Management of Bipolar Disorder (BPD) o Drugs from other classes that can be used to treat BPD BPD is treated with three major groups of drugs: mood sta ...

NR 565 NR565 Week 7 Exam review Completed A+++ Week 7 review  Management of Bipolar Disorder (BPD) o Drugs from other classes that can be used to treat BPD BPD is treated with three major groups of drugs: mood stabilizers, antipsychotics, and antidepressants. In addition, benzodiazepines are frequently used for sedation. Mood Stabilizers Mood stabilizers are drugs that (1) relieve symptoms during manic and depressive episodes, (2) prevent the recurrence of manic and depressive episodes, and (3) do not worsen symptoms of mania or depression or accelerate the rate of cycling. The principal mood stabilizers are lithium and two drugs originally developed for epilepsy: divalproex sodium (valproate) and carbamazepine. These drugs are the mainstays of treatment. The pharmacology of lithium and the antiepileptic drugs is discussed later. Antipsychotics In patients with BPD, antipsychotic drugs are given to help control symptoms during severe manic episodes, even if psychotic symptoms are absent. Although antipsychotics can be used alone, they are usually employed in combination with a mood stabilizer. For reasons discussed later, the second-generation antipsychotics (e.g., olanzapine, risperidone) are generally preferred to the firstgeneration agents (e.g., haloperidol). Antidepressants Antidepressants may be needed during a depressive episode. However, in patients with BPD, antidepressants are almost always combined with a mood stabilizer because of the long-held belief that, when used alone, antidepressants may elevate mood so much that a hypomanic or manic episode will result. However, data indicate that the risk for inducing mania may be much lower than previously thought. Nonetheless, the current guidelines suggest continuing the traditional practice of using an antidepressant only if a mood stabilizer is being used as well. Although antidepressants have been studied extensively in patients with major depression, research is still lacking in patients with BPD. At this time there are insufficient data on which to base drug selection. Even so, experts do have theirpreferences. Among clinicians with extensive experience in BPD, the following are considered antidepressants of choice: bupropion (Wellbutrin), venlafaxine (Effexor XR), and the selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac) and sertraline (Zoloft). One thing we do know is that the use of tricyclic antidepressants (TCAs) appears to promote more incidents of mania; therefore TCAs are not recommended in the treatment of BPD.  o Drug Interactions ▪ Lithium Drug Interactions Diuretics. Diuretics promote sodium loss and can thereby increase the risk for lithium toxicity. Toxicity can occur because renal excretion of lithium is reduced in the presence of low sodium, causing lithium levels to rise. Nonsteroidal antiinflammatory drugs. Nonsteroidal antiinflammatory drugs (NSAIDs) can increase lithium levels by as much as 60%. By suppressing prostaglandin synthesis in the kidney, NSAIDs can increase renal reabsorption of lithium (and also sodium), causing lithium levels to rise. NSAIDs known to increase lithium levels include ibuprofen (Motrin, others), naproxen (Naprosyn), piroxicam (Feldene), indomethacin (Indocin), and celecoxib (Celebrex). Interestingly, aspirin (the prototype NSAID) and sulindac (Clinoril) do notincrease lithium levels. Accordingly, if a mild analgesic is needed, aspirin or sulindac would be a good choice. Anticholinergics o Monitoring ▪ Lithium Monitoring plasma lithium levels. Measurement of plasma lithium levels is an essential component of treatment. Lithium levels must be kept below1.5 mEq/L; levels greater than this can produce signifcant toxicity. Lithum levels should range from 0.4 to 1 mEq/L. Generally levels should be between 0.6 and 0.8 mEq/L. Levels of 0.8 to 1mEq/L may be more effective but carry a greater risk of adverse effects. Blood for lithium determinations should be drawn in the morning, 12 hours after the evening dose. During maintenance therapy, lithium levels should be measured every 3 to 6 months.  - Management of Major Depressive Disorder o Know example drugs ▪ SSRIs Citalopram (Celexa) Escitalopram (lexapro, cipralex) Fluoxetine (Prozac, Sarafem) Fluvoxamine (Luvox) Paroxetine (Paxil, Pexeva) Sertraline (Zoloft) Vortioxetine (Trintellix) o Adverse Effects ▪ Venlafaxine Venlafaxine Venlafaxine (Effexor XR), the first SNRI available, is approved for major depression, generalized anxiety disorder, social anxiety disorder, and panic disorder. The drug produces powerful blockade of NE and 5-HT reuptake and weak blockade of dopamine reuptake. The relationship of these actions to therapeutic effects is uncertain. Venlafaxine does not block cholinergic, histaminergic, or α1-adrenergic receptors. Despite impressions that venlafaxine may be superior to SSRIs, when compared directly in clinical trials, the drugs were about equally effective—and SSRIs are probably safer.Venlafaxine is well absorbed after oral administration, in both the presence and absence of food. In the liver, much of each dose is converted to desvenlafaxine, an active metabolite. The half-life is 5 hours for the parent drug and 11 hours for the active metabolite. Venlafaxine can cause a variety of adverse effects. The most common is nausea (37% to 58%), followed by headache, anorexia, nervousness, sweating, somnolence, and insomnia. Dose-dependent weight loss may occur secondary to anorexia. Venlafaxine can also cause dose-related sustained diastolic hypertension; blood pressure should be monitored. Sexual dysfunction may occur too. Some patients experience sustained mydriasis, which can increase the risk for eye injury in those with elevated intraocular pressure or glaucoma. Like the SSRIs, venlafaxine can cause hyponatremia, especially in older adult patients taking diuretics. Like all other antidepressants, venlafaxine may increase the risk for suicide, especially in children and young adults. The combined use of venlafaxine with MAOIs and other serotonergic drugs (see Table 27.3) increases the risk for serotonin syndrome, a potentially fatal reaction. If the clinical situation demands, venlafaxine may be cautiously combined with an SSRI or another SNRI. However, combined use with an MAOI is contraindicated. Accordingly, MAOIs should be withdrawn at least 14 days before starting venlafaxine. When switching from venlafaxine to an MAOI, venlafaxine should be discontinued 7 days before starting the MAOI. As with the SSRIs, the use of venlafaxine late in pregnancy can result in a neonatal withdrawal syndrome, characterized by irritability, abnormal crying, tremor, respiratory distress, and possibly seizures. Symptoms, which can be managed with supportive care, generally abate within a few days. Abrupt discontinuation can cause an intense withdrawal syndrome. Symptoms include anxiety, agitation, tremors, headache, vertigo, nausea, tachycardia, and tinnitus. Worsening of pretreatment symptoms may also occur. Withdrawal symptoms can be minimized by tapering the dosage over 2 to 4 weeks. Warn patients not to stop venlafaxine abruptly. ▪ Monoamine Oxidase InhibitorsAdverse effects Central nervous system stimulation. MAOIs cause direct CNS stimulation (in addition to exerting antidepressant effects). Excessive stimulation can produce anxiety, insomnia, agitation, hypomania, and even mania. Orthostatic hypotension. Despite their ability to increase the NE content of peripheral sympathetic neurons, the MAOIs reduce blood pressure when administered in usual therapeutic doses. Patients should be informed about signs of hypotension (dizziness, lightheadedness) and advised to sit or lie down if these occur. Also, they should be informed that hypotension can be minimized by moving slowly when assuming an erect posture. MAOIs reduce blood pressure through actions in the CNS. The following sequence has been proposed: (1) Inhibition of MAO increases the NE content of neurons within the vasomotor center. (2) When NE is released, it binds to postsynaptic α receptors on neurons within the vasomotor center, thereby decreasing the firing rate of sympathetic nerves that control vascular tone. (3) This reduction in sympathetic activity results in vasodilation, causing blood pressure to fall. Hypertensive crisis from dietary tyramine. Although the MAOIs normally produce hypotension, they can be the cause of severe hypertension if the patient eats food that is rich in tyramine, a substance that promotes the release of NE from sympathetic neurons. Hypertensive crisis is characterized by severe headache, tachycardia, hypertension, nausea, vomiting, confusion, and profuse sweating—possibly leading to stroke and death. Before considering the mechanism by which hypertensive crisis is produced, let's consider the effect of dietary tyramine under drug-free conditions. In the absence of MAO inhibition, dietary tyramine is not a threat. Much of the tyramine in food is metabolized by MAO in the intestinal wall. Furthermore, as shown in Fig. 27.3A, any dietary tyramine that gets through the intestinal wall intact will then pass directly to the liver through the hepatic portal circulation. When in the liver, tyramine isimmediately inactivated by MAO there. Hence, as long as intestinal and hepatic MAO is functioning, dietary tyramine is prevented from reaching the general circulation and therefore is devoid of adverse effects. o Food & Drug Interactions Monoamine Oxidase Inhibitors (MAOIs) Foods That Can Interact With Monoamine Oxidase Inhibitors Foods That Contain Tyramine Category Foods With High Tyramine Content Foods With Little or No Tyramine Vegetables Avocados, especially if overripe; fermented bean curd; fermented soybean; soybean paste Most vegetables Fruits Figs, especially if overripe; bananas, in large amounts Most fruits Meats Meats that are fermented, smoked, or otherwise aged; spoiled meats; liver, unless very fresh Meats that are known to be fresh (exercise caution in restaurants; meat may not be fresh)Sausages Fermented varieties: bologna, pepperoni, salami, others Nonfermented varieties Fish Dried or cured fish; fish that is fermented, smoked, or otherwise aged; spoiled fish Fish that is known to be fresh; vacuum-packed fish, if eaten promptly or refrigerated only briefly after opening Milk, milk products Practically all cheeses Milk, yogurt, cottage cheese, cream cheese Foods with yeast Yeast extract (e.g., Marmite, Bovril) Baked goods that contain yeast Beer, wine Some imported beers, Chianti wine Major domestic brands of beer, most wines