NR566 Final Exam Study Guide Week 5 Latest Update, Exams of Nursing

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- Prevention of osteoporosis with hormone replacement therapy Tara (p.433) Hormone therapy reduces postmenopausal bone loss and thereby decreases the risk for osteoporosis and related fractures. Therapy is lifelong and the risk for harm is increased. Hormone therapy should only be considered for women with significant risk for osteoporosis, and only when that risk outweighs the risks of hormone therapy. Meds are: raloxifene (Evista), bisphosphonates (e.g., alendronate {Fosamax}), calcitonin (Miacalin), and teriparatide (Forteo). Encourage patients to prevent bone loss by ensuring adequate intake of calcium and Vit D, performing regular weight-bearing exercises, and avoiding smoking and excessive alcohol use. - When and when not to use progestin for hormone replacement therapy and why Tara (p.430-432) When : Menopausal hormone therapy Why : The primary noncontraceptive use of progestins is to counteract the adverse effects of estrogen on the endometrium in women undergoing menopausal HT. When : Dysfunctional uterine bleeding Why : Heavy irregular bleeding that occurs when progesterone levels are insufficient to balance the stimulatory influence of estrogen on the endometrium. Treatment goals with administration of progestins are to stop the bleeding and establish a regular monthly cycle. When: Amenorrhea Why: Progestins can induce menstrual flow in selected women who are experiencing amenorrhea. When: Endometrial hyperplasia and carcinoma Why: Progestins can provide palliation in women with metastatic endometrial carcinoma, but they do not prolong life. Endometrial hyperplasia, a potentially precancerous condition, can be suppressed with progestins. Benefits derive from counteracting the proliferative effects of estrogen. When: Other uses - Supports early pregnancies, prevention of preterm birth (Makena) Why: Progestins can be used to support early pregnancy in women with corpus luteum deficiency syndrome and in women undergoing in vitro fertilization (IVF). One progestin (hydroxyprogesterone acetate (Makena) is approved for preventing preterm birth in

women with a singleton pregnancy and a history of preterm delivery. When not to: Women with no uterus Why: Do not prescribe progestins to women who have undergone a hysterectomy.

- Local vs. systemic estrogen options and why one would be chosen over the other Tara Intravaginal : Estrogens for intravaginal administration are available as inserts, creams, and vaginal rings. The intravaginal inserts (Imvexxy, Vagifem, Yuvafem), creams (Estrace Vaginal, Premarin Vaginal), and one of the two available vaginal rings (Estring) are used only for local effects, primarily treatment of vulval and vaginal atrophy associated with menopause. The other vaginal ring (Femring) is used for systemic effects (e.g., control of hot flashes and night sweats) as well as local effects (e.g., treatment of vulval and vaginal atrophy). Parenteral : Although estrogens are formulated for intravenous (IV) and intramuscular (IM) administration, use of these routes is rare. IV administration is generally limited to acute, emergency control of heavy uterine bleeding. - Transdermal estrogen therapy has fewer adverse effects Tara Compared with oral formulations, the transdermal formulations have four advantages:

• The total dose of estrogen is greatly reduced (because the liver is bypassed).
• There is less nausea and vomiting.
• Blood levels of estrogen fluctuate less.
• There is a lower risk for DVT, pulmonary embolism, and stroke. - Management of oral contraceptives (OCs) Jennifer Jacques o How to change patients from one combination of oral contraceptives to another. When one combination OC is being substituted for another, the change is best made at the beginning of a new cycle. Pg 440 o How to initiate treatment (when in the cycle is it best to start- may vary based on type of contraceptive) The 28-day regimens are subdivided into four groups: monophasic, biphasic, triphasic, and quadriphasic (four-phasic) (see Table 51.5). In a monophasic regimen, the daily doses of estrogen and progestin remain constant throughout the cycle of use. In the other regimens, the estrogen, progestin, or both change as the cycle progresses. The biphasic, triphasic, and quadriphasic schedules reflect efforts to more closely simulate ovarian production of estrogens and progestins. However, these preparations appear to offer little or no advantage over monophasic OCs. Most 28-day cycle products are taken in a repeating sequence consisting of 21 days of an active pill followed by 7 days on which either (1) no pill is taken, (2) an inert pill is taken, or (3) an iron- containing pill is taken. The sequence begins on either the first day of the menstrual cycle or the first Sunday after the onset of menses. With the first option, protection is conferred

immediately; hence no backup contraception is needed. With a Sunday start, which is done to have menses occur on weekdays rather than the weekend, protection may not be immediate; hence an alternate form of birth control should be used during the first 7 days of the pill pack. With both options, each dose should be taken at the same time every day (e.g., with a meal or at bedtime). Successive dosing cycles should commence every 28 days even if there is breakthrough bleeding or spotting. Pg 441 o What teaching needs to be done Educate patients on proper protocol for missed doses (depending on medication type and cycle). Effectiveness of oral contraceptives can be reduced with some medications, including certain common antibiotics. Pg 446 o What baseline data is needed? Assess for history of hypertension, diabetes, thromboembolism, cerebrovascular or cardiovascular disease, breast cancer. Urine pregnancy test. Pg 446 o Contraindications for OCs Contraindications to use include current pregnancy, history of thromboembolus, breast cancer, and women over 35 years of age who continue to smoke tobacco. Use with caution in women with diabetes, hypertension, and cardiac disease. Pg 446

- How to achieve an extended cycle with oral contraceptives Jennifer Jacques To achieve an extended schedule, the user would simply purchase four packets of a 28-day product (each of which contains 21 active pills) and then take the active pills for 84 days straight. Pg 442 - What behaviors would make one birth control method more effective over another? Akunna Aguwa o Be able to evaluate a patient scenario and suggest an appropriate birth control method (type of prescribed contraception: OC, long-term methods, IUD, etc)

Page 437-438: Among women of higher weight oral contraceptive’s efficacy is somewhat reduced. Possible reasons include decreased blood levels of the hormones, sequestration in adipose tissue, and altered metabolism. Combination oral should be avoided by women with certain cardiovascular disorders as well as by women older than 35 years old who smoke. An alternative method is preferred: diaphragm, progestin-only pill, or IUD.

- What effect does CYP450 inhibitors or inducers have on OCs? Akunna Aguwa o Recall examples of CYP450 inhibitors and inducers from NR565 (Chapter 4 in textbook) o How does this impact prescribing of OCs? Page 441 : CYP450 inducers like Phenytoin, carbamazepine, Rifampin, alcohol and sulfonylureas can accelerate OC metabolism and thereby reduce OC effects. Women taking OC in combination with any of these agents should be alert for indications of reduced OC blood levels, such as breakthrough bleeding or spotting. It may be necessary to either:

1. Increase the estrogen dosage of the OC.
2. Combine the OC with a second form of birth control.
3. Switch to an alternative form of birth control. OC’s can decrease the benefits of warfarin and hypoglycemic agents. When combined with OC warfarin and hypoglycemic agents may require increased dosage. OC’s can impair the hepatic metabolism of several agents, including theophylline, tricyclic antidepressants, diazepam, and chlordiazepoxide. They may accumulate to toxic levels, with signs of toxicity doses of these drugs should be reduced. - Benefits and drawbacks of progestin-only contraception Krystal Paz Alvarez Pg. 442 Benefits for progestin-only : do not cause thromboembolic disorders, headaches, nausea, or most of the other adverse effects associated with combo OCs. Drawbacks : Less effective and are more likely to cause irregular bleeding (breakthrough bleeding, spotting, amenorrhea, inconsistent cycle length, variations in volume and duration of monthly flow). Must take the pill at the same time very day for effectiveness. Even taking it a few hours late can reduce their efficacy and a use of back up protection or emergency contraception is recommended. Guidelines for missed pill: -if one pill is missed, must be taken as soon as remembered and backup contraception should be used for at least 2 days. Pills should be resumed as scheduled on the next day

-if two pills are missed, the regimen should be restarted and backup contraception should be used for at least 2 days. -if two or more pills are missed and no beeding occurs, a pregnancy test should be done.

- What are the most effective forms of contraception? Krystal Paz Alvarez Pg. 437 The most effective methods are an etonogestrel implant (Nexplanon), an intrauterine device (IUD), and sterilization (vasectomy and tubal ligation). Oral contraceptives, depo, contraceptive ring and patch are close behind. Least reliable methods include barrier methods, periodic abstinence, spermicides, and withdrawal. - Testosterone replacement Bailey Ward o Administration ● Transdermal Patches - male hypogonadism ○ Applied daily to the upper arm, back, or abdomen. ● Testosterone gel is also available. o Patient Teaching ● Transdermal patches: ○ good hand washing is required after application ○ cover application site with clothing after medication has dried ○ wash the application site before skin-to-skin contact with another person ■ females and children may experience negative effects from exposure to testosterone ■ if cross contamination occurs, wash the affected area with soap and water to prevent absorption - Treatment of delayed puberty Bailey Ward o When is it appropriate to initiate androgen therapy (short course and long-term) ● Short term: The psychological pressures of delayed sexual maturation are causing a boy significant distress. In these cases, a limited course of androgen therapy is indicated. ○ Both fluoxymesterone (Androxy, Halotestin) and methyltestosterone (Methitest) are approved for this purpose. ● Long term: If delayed puberty is the result of true hypogonadism - Androgen therapy Shelby Bernaix Androgens and antiandrogens are commonly prescribed for men and women. (Hormone therapy) the main androgens in the body are testosterone and dihydrotestosterone (DHT)

o Effects ▪ Therapeutic - Endogenous androgens are responsible for key functions in the body such as the normal growth and maturation of sex organs, skeletal growth, activation of sebaceous glands during puberty, as well as enhancing the production of erythropoietic stimulating factor for red blood cell production and contributing to libido. ▪ Adverse - Hot flashes, bone fractures, disturbed libido, insulin resistance, erectile dysfunction, gynecomastia, acne, HTN, LDL Increase, HDL decrease, menstrual disturbances, sterility, hepatotoxicity, mood swings/ aggression. o Monitoring Needs- Lipids, blood glucose, androgen levels such as testosterone monitoring, Prostate specific antigen testing, H&H, CBC, BMP o Role of androgens in treating anemia - Androgen therapy will increase bone marrow stimulation to make more RBCs.

- Preferred administration route of alprostadil and why Shelby Bernaix Alprostadil is usually shot directly INTO the penis in order to achieve an erection. The medication comes as a power that is then mixed with water and inserted via syringe. Can also be administered IV in a hospital setting. - Treatment of hypogonadism Haley Herrera o Benefits o Administration methods for transdermal preparations Oral Androgens Only two androgens are approved for oral therapy of male hypogonadism. Despite the advantages of cost and ease of administration, these are not first-line agents. The androgenic effects of oral androgens are erratic. Furthermore, both fluoxymesterone and methyltestosterone are 17-α-alkylated androgens and therefore pose a risk for hepatotoxicity. Accordingly they should not be used long term. Transdermal Testosterone Testosterone is available in three transdermal formulations: patch, gel, and liquid. With all three formulations, testosterone is absorbed through the skin and then slowly absorbed into the blood.

Androgen INDICATIONS Hypogonadism (Male) Replacement Therapy (Male) Delayed Puberty (Male) Catabolic States Testosterone and Testosterone Esters Testoste rone

✓ ✓

Testoste rone cypionat e

✓ ✓

Testoste rone enantha te

✓ ✓

17-α-Alkylated Androgens Fluoxym esteron e

✓ ✓ ✓

Methylt estoster one

✓ ✓ ✓

Oxandro lone

✓

Male Hypogonadism

Hypogonadism is a condition in which the testes fail to produce adequate amounts of testosterone. Male hypogonadism may be hereditary, or it may result from other causes, including pituitary failure, hypothalamic failure, and primary dysfunction of the testes. Replacement Therapy Androgen replacement therapy is beneficial when testicular failure occurs in adult males. Some studies demonstrate that treatment restores libido, increases ejaculate volume, and supports expression of secondary sex characteristics. However, treatment will not restore fertility. The principal drugs employed for testosterone replacement are testosterone itself and two testosterone esters: testosterone enanthate and testosterone cypionate

- Treatment of BPH Haley Herrera o Know examples of drugs in each major drug class o Adverse effects of common therapies ▪ 5-α-Reductase Inhibitors ▪ α1 Blockers ▪ Phosphodiesterase-5 Inhibitor ▪ α1a Blocker/5-α-Reductase Inhibitor Generic Name Trade Name Actions in BPH Adverse Effects 5-α-Reductase Inhibitors Dutasteri Avodart Reduce Decreased de dihydrotesto ejaculate sterone volume and production, libido. Finasterid Proscar (^) which causes Teratogenic e (^) the prostate to the male to shrink, fetus. which reduces mechanical obstruction of the urethra. May

also delay BPH progression. Benefits take months to develop. α 1 Blockers Selective α1a Blockers Silodosin Rapaflo Blockade of α1a receptors relaxes smooth muscle in the bladder neck, prostate capsule, and prostatic urethra, and thereby decreases dynamic obstruction of the urethra. Benefits develop rapidly. Abnormal ejaculation (ejaculation failure, reduced ejaculate volume, retrograde ejaculation). Risk of floppy-iris syndrome during cataract surgery. Tamsulosi n Flomax Nonselective α 1 Blockers Alfuzosin Uroxatr al, Xatral Same as the selective α1a blockers. Hypotensio n, fainting, dizziness,

Doxazosi n Cardura , Cardura XL somnolence , and nasal congestion (from blocking α 1 receptors on blood vessels) Terazosin Hytrin Phosphodiesterase-5 Inhibitor Tadalafil Cialis Smooth muscle relaxation in the bladder, prostate, and urethra Hypotensio n, priapism α1a Blocker/5-α-Reductase Inhibitor Tamsulosi n/dutaste ride Jalyn Combination of the effects of 5-α- reductase inhibitors and selective α1a blockers Decreased libido and abnormal ejaculation (ejaculation failure, reduced ejaculate volume, retrograde ejaculation) o Therapeutic Effects -Two 5-α-reductase inhibitors are available: finasteride and dutasteride. Both drugs can reduce prostate size, although several months are required for a noticeable effect. There is no proof that one drug works better than the other.

- National STI/STD Curriculum Noel Machado o Treatment of STIs/STDs ▪ Chlamydia Azithromycin, 1 g PO once or Doxycycline, 100 mg PO 2 times/day × 7 days ▪ Uncomplicated gonococcal urethritis Ceftriaxone, 250 mg IM once, plus azithromycin, 1 g PO once ▪ Bacterial Vaginosis Metronidazole, 500 mg PO 2 times/day × 7 days or Metronidazole gel (0.75%), 1 full applicator (5 g) intravaginally once/day × 5 days or Clindamycin cream (2%), 1 full applicator (5 g) intravaginally at bedtime × 7 days ▪ Herpes Simplex Virus Noel Machado ▪ Trichomoniasis Noel Machado ▪ Syphilis Noel Machado **Week 6

• PD on exam is Parkinson Disease -** Dyskinesia (disorders of movement), tremors at rest, rigidity,postural instability, bradykinesia. - Management of PD ● Early stages -begin with MAO-B inhibitor, with severe start with levodopa with carbidopa or a dopamine agonist; N/V IS EXPERIENCED WITH PT’S DUE TO DOPAMINE RECEPTORS ACTIVATION; FOOD CAN DECREASE ABSORPTION OF LEVADOPA ● Combination therapy – LEVODOPA/CARBIDOPA: ○ CARBIDOPA – reduce peripheral conversion of levodopa to dopamine hence more drug cross the BBB; CARBIDOPA DOES NOT CROSS BBB ○ LEVODOPA – converted to dopamine to balance the dopamine and acetylcholine neurotransmitters ○ ENTACAPONE – COMT inhibitor and inhibits breakdown of levodopa BY COMT enzyme, ENTACOPONE decrease the WEARING OFF phenomenon ● ● Medications used to treat “off” times including “wearing off” experiences - Off times is when there is a loss of symptom relief which can be reduced with 3 types of drugs How to reduce “OFF TIMEs” 1. Dopamine agonist – a. Apomorphine (use trimethobenzamide (TIGAN) for antiemetic) b. Pramipexole, Ropinirole, Cabergoline

c. Rotigotine – PATCH FOR EARLY-STAGE PD, 2MG/WEEK THEN INCREASE, DO NOT PLACE ON SAME SIDE (TRANS PATCH)

**2. COMT inhibitor

3. MAO-B inhibitor** a. SELEGINE – BLACK BOX: HIHG RISK FOR SUICIDE IN YOUNGER **AGE (24), NOT FOR 12 YR OLD. ; INCREASE HTN CRISIS
4. Avoid high protein meals** Evidence of efficacy is strongest for entacapone (a COMT inhibitor) and rasagiline (an MAO-B inhibitor). The only drug recommended for dyskinesias is amantadine ● Wearing of f is a gradual loss that develops near the end of dosing interval which indicates the drug level has dropped to a subtherapeutic level. This is minimized in 3 ways
5. Shortening dose interval
6. Give a drug that prolongs levodopa’s half-life (entacapone)
7. Giving a direct-acting dopamine agonist o Adverse Effects ▪ Pramipexole - Dopamine agonist: non-ergot derivative used in early stages of PD. Side effects include nausea, dizziness, daytime somnolence, insomnia, constipation, weakness, and hallucinations. Some people have impulse control disorder (compulsive gambling, shopping, binge eating, and hypersexuality) which occurs depending on dose and about 9 months after patient is on medication. Few have reported sleep attacks (overwhelming and irresistible sleepiness that comes on without warning); **PT WITH HX OF ETOH ABUSE SHOULD NOT BE RX WITH THIS MED

• Management of seizures o** Which medication would be the safest choice for someone on an oral contraceptive? New antiseizure drugs are considered safer. 8 drugs that decrease effectiveness are carbamazepine, eslicarbazepine, lamotrigine, oxcarbazepine, phenytoin, phenobarbital, rufinamide, topiramate. Valproic acid should be avoided if no alternative medication is suitable and patient needs to take folic acid supplements; no valporic acid for preggos ABSENT SEIZURE- BLANK STARE (MOSTLY CHILDREN) o Purpose and timing of serum drug levels

The ability to measure serum levels of anticonvulsants has been a significant advance in the treatment of epilepsy. This technique enables practitioners to monitor a patient's plasma concentration, to detect potential toxicity, and to assess compliance with the prescribed regimen. o Patient teaching & Drug Interactions ▪ Phenytoin - Used for partial seizures and primary general tonic-clonic seizures. It was the first drug to suppress seizures without depressing the entire CNS. Mechanism of Action is it blocks sodium channels but limits to blocking sodium channels in hyperactive neurons. Treatment for all major forms of epilepsy except absent seizures. First drug of choice for adults and older children. Medication needs to be discontinued gradually or patient is at risk of seizures. Phenytoin Dosage Considerations: Dosing is highly individualized. Plasma drug levels are often monitored as an aid to establishing dosage. The dosing objective is to produce levels between 10 and 20 μg/mL. Levels below 10 μg/mL are too low to control seizures; levels above 20 μg/mL produce toxicity. Because phenytoin has a relatively narrow therapeutic range (between 10 and 20 μg/mL), and because of the nonlinear relationship between phenytoin dosage and phenytoin plasma levels, after a safe and effective dosage has been established, the patient should adhere to it rigidly Adverse effects include CNS side effects such as Nystagmus (continues back-and-forth movement of eyes), sedation, ataxia, diplopia, and cognitive impairment. Others are gingival hyperplasia (excessive growth of gum tissue), some patient require gingivectomy (removal of excess gum tissue) but can be prevented by good oral hygiene, flossing and gum massage. May need to supplement folic acid to reduce growth. Morbilliform (Measles-like) rash can develop and progress into Stevens-Johnson syndrome or toxic epidermal necrolysis (TEN). Check patients of Asian decent for human leukocyte antigen (HLA-B*1502) which is a genetic mutation known to develop this issues and should not be prescribed phenytoin.

- Management of Migraines Trina LHeureux o 1 st line therapy ▪ Preventative – FOR PTS WITH 3 OR MOMRE MIGRAINE ATTACKES QMONTH 1. propanolol and metoprolol – 1 st^ line drug for migraine prevention 2. antiepileptic drugs a. divalporex – black box warning: fatal pancreatitis, hepatitis, neural tube defects 3. topiramax – migraine prophylaxis; its benefits appear equal to those of the first line beta blockers

4. tricyclic antidepressants – NOT FOR PT WITH HYPOTENSION
5. ESTROGEN AND TRIPTANS -MENSTRUALY ASSOCIATED MIGRAINES a. ESTROGEN, FROVATRIPTAN, NAPROXEN SODIUM b. NASAL SPRAY IF OPIOD DOES NOT WORK i. SHOULD NOT BE TAKEN MORE THAN 2X/WEEK ▪ Abortive – USE AT START OF MIGRAINE
6. NSAIDS – ASA, NAPROXEN, DICLOFENAC
7. MIGRAINE SPECIFIC -SEROTONIN RECEPTOR AGONISTS a. MOA – DECREASAE RELEASE OF INFLAMMATORY NEUROPEPTIDES 3. ERGOTAMINE – NOT FOR PREGGOS a. NOT FOR HEPATIC OR RENAL IMPAIRED PTS, CAD, PVD b. Ergotism is a serious toxicity caused by acute or chronic overdose of ergotamine. The toxicity results in ischemia, causing the extremities to become cold, pale, and numb. o Contraindications for drugs 1. • Sumatriptan - NOT FOR PREGGOS, PT W/ ISCHEMIC HEART DISEASE, PRIOR MI, UNCONTROLLED HTN a. Some patients taking sumatriptan experience unpleasant chest symptoms, usually described as “heavy arms” or “chest pressure.” These symptoms are transient and are not related to heart disease. Patients experiencing angina-like pain when taking sumatriptan, as a result of coronary vasospasm, should be asked about hypertension or coronary artery disease (CAD) NOTE: SUMATRIPTAN AND OTHER TRIPTANS SHOULD NOT BE TAKEN TOGETHER WITH ERGOT ALKALOIDS WITHIN 24 HOURS DUE TO VASOCONSTRICTION

• Alternative preventative medication options o ERENUMAB – MOA -ANITBODY o BOTOX – FOR CHRONIC MIGRAINE, 15 QMONTH - Management of Alzheimer Disease – ACETYLCHOLINE ON AD PT’S IS BELOW 90% NORMAL B6,B12, FOLIC ACID – REDUCE LEVEL OF HOMOCYSTEINE SXS OF AD: MEMORY LOSS, PERSONALITY CHANGES, IMPAIRED JUDGEMENT LIFE EXPECTANCY FOR AD PT’S -4-8 YRS OR 20 YRS o Administration Considerations ▪ Memantine (FOR MODERATE - SEVERE AD)- Blocks neuronal receptors for N0- methyl-D-aspartate (NMDA) and is used to treat moderate to severe Alzheimer's. Can slow decline in function and can have some symptom improvement. Common side

effects are dizziness, headaches, and confusion and only occur 5-7% of the time in those taking it. Less common side effects include diarrhea or constipation.Adjust dose for renal impairment with creatinine clearance of less than 30mL/min. Avoid using it in patients with severe hepatic impairment or corneal conditions as they have worsened during treatment. ▪ Rivastigmine/ EXELON- Unlike donepezil, which causes reversible inhibition of AChE, rivastigmine causes irreversible inhibition. rivastigmine can cause peripheral cholinergic side effects but occurs more often than the others. With oral dosing, the most common cholinergic effects are nausea, vomiting, diarrhea, abdominal pain, tremors, and anorexia. Weight loss (7% of initial weight) occurs in 18% of male to 26% of female patients. By enhancing cholinergic transmission, rivastigmine can intensify symptoms in patients with peptic ulcer disease, bradycardia, sick sinus syndrome, urinary obstruction, and lung disease; caution is advised. Like other drugs in this class, rivastigmine can cause bradycardia, fainting, falls, and fall-related fractures. No significant drug interactions because it does not interact with hepatic drug-metabolizing enzymes. CHANGE PATCH Q2WEEKS (S/E: INCREASE CHOLINESTERASE)

• Dosing considerations o Donepezil is given for mild, moderate, and severe AD, and dosing may be increased, although it must be titrated up slowly ▪ Donepezil-Used to treat mild to severe AD. Mild to moderate AD: 5 mg daily. After 4–6 weeks, may increase to 10 mg daily Severe AD: 10 mg daily. After 3 months, may increase to 23 mg daily ▪ Memantine-Dosage must be increased gradually using the following schedule for IR and ER formulations. IR tablets and oral solution:
• 5 mg/day (5 mg once a day), for 1 week or more
• 10 mg/day (5 mg twice a day), for 1 week or more
• 15 mg/day (5 and 10 mg in separate doses), for 1 week or more
• 20 mg/day (10 mg twice a day), for maintenance ER capsules:
• 7 mg once daily for 1 week or more
• 14 mg once daily for 1 week or more
• 21 mg once daily for 1 week or more
• 21 mg once daily for maintenance Reduce dosage in patients with moderate renal impairment and discontinue in patients with severe renal impairment o Side Effects

▪ Cholinesterase Inhibitors- nausea, vomiting, diarrhea and dyspepsia often occur. Dizziness and headache also occur frequently. Can cause bronchoconstriction so use caution in patients with asthma or COPD. Cardiac effects are uncommon but include bradycardia, fainting, and falls. These patients may require a pacemaker or to withdrawl the drug.

- Additional Notes o If phenytoin (NOT FOR PREGGOS!!!) is administered in doses only slightly greater than those needed for therapeutic effects, the liver's capacity to metabolize the drug will be overwhelmed, causing plasma levels of phenytoin to rise dramatically. This unusual relationship between dosage and plasma levels is illustrated in Fig. 21.1A. As you can see, after plasma levels have reached the therapeutic range, small changes in dosage produce large changes in plasma levels. As a result, small increases in dosage can cause toxicity, and small decreases can cause therapeutic failure. This relationship makes it difficult to establish and maintain a dosage that is both safe and effective. For this reason, serum drug levels and trough levels are often used, along with assessments of seizure control, to determine dosage. PHENYTOIN LEVEL - 10-20 MG NEED TO TAPER OFF ; ABRUPT WITHDRAWAL CAN CAUSE SEIZURES!! IF PT ON TUBE FEEDING, TURN OFF PUMP 1H BEFORE AND AFTER ADMIN ▪ Examples: If a patient is taking phenytoin 300mg daily for seizures and their serum concentration is 8mg/L and they experience a considerable increase in seizure activity, their dose would only need to increase to 350mg daily. o When on medications for Alzheimer’s Disease (AD) and symptoms increase, it is better to increase the AD medication than to add things like herbal medications, vitamins, or NSAIDs **Week 7

• Management of Bipolar Disorder (BPD)** o Drugs from other classes that can be used to treat BPD BPD is treated with 3 major groups of drugs: mood stabilizers, antipsychotics, & antidepressants. In addition, benzodiazepines are frequently used for sedation. (p. 229) ● Mood stabilizers: Drugs that relieve symptoms during manic & depressive episodes, prevent the recurrence of manic & depressive episodes, & do not worsen symptoms of mania or depression or accelerate the rate of cycling. The

principle mood stabilizers are lithium & 2 drugs originally developed for epilepsy: divalproex sodium (valproate) & carbamazepine. Lamotrigine (Lamictal) is another antiepileptic drug indicated for long-term maintenance therapy of BPD. (pp. 230-232) ● Antipsychotics: Drugs given in BPD to help control ACUTE symptoms during severe manic episodes, even if psychotic symptoms are absent. They are also given LONG TERM to help stabilize mood. Although they can be used alone, they are usually employed in combination with a mood stabilizer. The 2nd generation (atypical) antipsychotics (olanzapine, risperidone) are generally preferred to the 1st generation (conventional) agents (haloperidol) because they carry a lower risk for extrapyramidal side effects, including tardive dyskinesia. (Currently, only 3 atypical agents are approved for long-term use to prevent the recurrence of mood episodes: aripiprazole, olanzapine, & ziprasidone. (p. 233) ● Antidepressants: In patients with BPD, antidepressants are almost always combined with a mood stabilizer because of the long-held belief that when used alone they may elevate mood so much that a hypomanic or manic episode will result. Among clinicians with extensive experience in BPD, the following are considered antidepressants of choice: bupropion (Wellbutrin) , venlafaxine (Effexor XR) , & the serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac) & sertraline (Zoloft). NOTE: The use of tricyclic antidepressants (TCAs) appears to promote more incidents of mania, therefore they are not recommended in the treatment of BPD. (pp. 229-230) o Drug Interactions (pp. 231-232) ▪ Lithium: Diuretics: Diuretics promote sodium loss & 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. NSAIDs: NSAIDs can increase lithium levels by as much as 60%. By suppressing prostaglandin synthesis in the kidney, NSAIDs can increase renal reabsorption of lithium (& also sodium), causing lithium levels to rise. (EXCEPTION: Aspirin & Sulindac do NOT increase lithium levels!) Anticholinergics: Anticholinergic drugs can cause urinary hesitancy. Coupled with lithium-induced polyuria, this can result in considerable discomfort. Accordingly, patients should avoid drugs with prominent anticholinergic actions (antihistamines, phenothiazine antipsychotics, TCAs).

o Monitoring (pp. 230-231) ▪ Lithium: Lithium has a low therapeutic index. As a result, toxicity can occur at blood levels only slightly greater than therapeutic levels. Accordingly, the monitoring of lithium levels is mandatory & an essential component of treatment. Lithium levels must be kept below 1.5 mEq/L--levels greater than this can produce significant toxicity. Lithium levels should range from 0.4 to 1 mEq/L. Generally levels should be between 0.6 & 0.8 mEq/L as these levels are effective for most patients. Levels of 0.8 to 1 mEq/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. Lithium levels should be measured every 2-3 days during initial therapy & every 3-6 months during maintenance. BLACK BOX WARNING: Lithium toxicity is closely related to serum lithium levels & can occur at doses close to therapeutic levels. Facilities for prompt & accurate serum lithium determinations should be available before initiating therapy. Signs of Lithium Toxicity: Less than 1.5 mEq/L: N/V/D, thirst, polyuria, lethargy, slurred speech, muscle weakness, fine hand tremor. 1.5-2 mEq/L: Persistent GI upset, coarse hand tremor, confusion, hyperirritability of muscles, EKG changes, sedation, incoordination. 2-2.5 mEq/L: Ataxia, giddiness, high output of dilute urine, serious EKG changes, fasciculations, tinnitus, blurred vision, clonic movements, seizures, stupor, severe hypotension, coma, death (usually secondary to pulmonary complications). More than 2.5: Symptoms may progress rapidly to generalized convulsions, oliguria, & death.

- Management of Major Depressive Disorder (pp. 214-216) Drugs are the primary therapy for major depression. However, benefits are limited mainly to patients with severe depression. In patients with mild to moderate depression, antidepressants have little or no beneficial effect. Available antidepressants fall into 5 major classes: ***selective serotonin reuptake inhibitors (SSRIs) *serotonin-norepinephrine reuptake inhibitors (SNRIs) *tricyclic antidepressants (TCAs) monoamine oxidase inhibitors (MAOIs) atypical antidepressants

ALL OF THESE CLASSES ARE EQUALLY EFFECTIVE, AS ARE ALL THE INDIVIDUAL DRUGS WITHIN

EACH CLASS. Differences among these drugs relate mainly to side effects & drug interactions. o Know example drugs ▪ SSRIs: The most commonly prescribed antidepressants, they are indicated for major depression as well as several other psychological disorders. Compared with the TCAs & MAOIs, they are equally effective, better tolerated, & much safer. They work by blocking 5-HT reuptake & thereby increase 5-HT in the synapse. (pp. 216-219) Citalopram (Celexa) Escitalopram (Lexapro) Fluoxetine (Prozac) Paroxetine (Paxil) Sertraline (Zoloft) Vortioxetine (Trintellix) o Adverse Effects ▪ Venlafaxine (Effexor XR) : The 1st serotonin-norepinephrine reuptake inhibitor (SNRI) available & the prototype drug for this class of antidepressants. (pp. 219-220) Venlafaxine can cause a variety of adverse effects. The most common is nausea (37% to 58%), followed by headache, anorexia, nervousness, sweating, somnolence, & insomnia. Dose-dependent weight loss may occur secondary to anorexia. It can also cause dose-related sustained diastolic hypertension , so blood pressure should be monitored. Sexual dysfunction may also occur. 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, it may increase the risk for suicide , especially in children & young adults. The combined use of venlafaxine with MAOIs & other serotonergic drugs increases the risk for serotonin syndrome , a potentially fatal reaction. Because of this, use with an MAOI is contraindicated. 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, & possibly seizures. Symptoms 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, & 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 Inhibitors (MAOIs): Isocarboxazid (Marplan), Phenelzine (Nardil), Tranylcypromine (Parnate), Selegiline (Emsam) Are 2nd or 3rd choice antidepressants, because although as effective as the SSRIs & TCAs, they are more hazardous. At this time, MAOIs are drugs of choice ONLY for atypical depression

- depressed mood can be brighten up w/ positive events. s/sx: increase appetite, sleeping too much, arms and legs heavy, feeling rejected. Central nervous system stimulation: MAOIs cause direct CNS stimulation (in addition to their antidepressant effects). Excessive stimulation can produce anxiety, insomnia, agitation, hypomania, & even mania. Orthostatic hypotension: MAOIs reduce blood pressure when administered in usual therapeutic doses. Patients should be informed about signs of hypotension ( dizziness, lightheadedness ) & advised to sit or lie down if these occur. This can be minimized by moving slowly when assuming an erect position. 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 norepinephrine (NE) from sympathetic neurons. Hypertensive crisis is characterized by severe headache, tachycardia, hypertension, nausea, vomiting, confusion, & profuse sweating--possibly leading to stroke & death. o Food & Drug Interactions ▪ Monoamine Oxidase Inhibitors (MAOIs): (pp. 223-225) Food Interactions: Dietary tyramine can produce a life-threatening hypertensive crisis when taken with MAOIs. In the absence of MAO inhibition, dietary tyramine is not a threat.

1. Inhibition of neuronal MAO augments NE levels within the terminals of sympathetic neurons that regulate cardiac function & vascular tone.
2. Inhibition of intestinal & hepatic MAO allows dietary tyramine to pass directly through the intestinal wall & liver, & then enter the systemic circulation intact.
3. On reaching peripheral sympathetic nerves, tyramine stimulates the release of the accumulated NE, thereby causing massive vasoconstriction & intense stimulation of the heart. Foods That Contain Tyramine Vegetables : Avocados; fermented bean curd; fermented soybean; soybean paste Fruits : Figs; bananas (in large amounts) Meats : Meats that are fermented, smoked, or otherwise aged; spoiled meats; liver (unless very fresh) Sausages : Fermented varieties: bologna, pepperoni, salami, others Fish : Dried or cured fish; fish that is fermented, smoked, or otherwise aged; spoiled fish Milk/Milk Products : Practically all cheeses Foods with Yeast : Yeast extract Beer/Wine : Some imported beers, Chianti wine Other Foods : Protein dietary supplements; soups (may contain protein extract); shrimp paste; soy sauce Foods That Contain Nontyramine Vasopressors Chocolate, Fava beans, Ginseng, Caffeinated beverages Drug Interactions: Indirect-acting sympathomimetic agents : Drugs that promote the release of NE from sympathetic nerves. Patients should be instructed to avoid all sympathomimetic drugs,

including ephedrine, methylphenidate, amphetamines, & cocaine. Sympathomimetic agents may be present in cold remedies, nasal decongestants, & asthma medications--all of these should be avoided unless approved by the prescriber. Interactions secondary to inhibition of hepatic monoamine oxidase : Inhibition of MAO in the liver can decrease the metabolism of several drugs, including epinephrine, norepinephrine, & dopamine. These drugs must be used with caution because their effects will be more intense & prolonged. Tricyclic antidepressants : The combination of a TCA with an MAOI may produce hypertensive episodes or hypertensive crisis. As a result, this combination of antidepressants is not employed routinely. However, although potentially dangerous, the combination can benefit certain patients. If concurrent use is employed, caution must be exercised. Serotonergic drugs : Combining MAOIs with SSRIs & other serotonergic drugs poses a risk for serotonin syndrome. Accordingly, these combinations should be avoided. Antihypertensive drugs : Combined use of MAOIs & antihypertensive agents may result in excessive lowering of blood pressure. o Suicide Risks and Considerations for Major Depressive Disorder Safety measures ▪ Concerns about antidepressant-induced suicide apply mainly to children, adolescents, and adults younger than 25 years.

- To reduce the risk for suicide, patients taking antidepressant drugs should be observed closely for suicidality, worsening mood, and unusual changes in behavior. Close observation is especially important during the first few months of therapy and whenever antidepressant dosage is changed (either increased or decreased). Ideally, The patient or caregiver should meet with the prescriber at least weekly during the first 4 weeks of treatment, then biweekly for the next 4 weeks, then once 1 month later, and periodically thereafter. Phone contact may be appropriate between visits. In addition, family members or caregivers should monitor the patient daily, being alert for symptoms of decline (e.g., anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, hypomania, and, of course, emergence of suicidality). If these symptoms are severe or develop abruptly, the patient should see his or her prescriber immediately.

• What should be done if suicidal thoughts emerge during drug therapy, or if depression is persistently worse while taking drugs? One option is to switch to

another

antidepressant. Another option is to stop antidepressants entirely. If the risk for suicide appears high, temporary hospitalization may be the best protection o Administration and Cessation of Medication Considerations ▪ Selective serotonin reuptake inhibitors (SSRIs)

• What do patients need to know about starting and stopping SSRIs? SSRIs are indicated for major depression as well as several other psychological disorders.Abrupt discontinuation of selective serotonin reuptake inhibitors can cause a withdrawal syndrome. Symptoms include dizziness, headache, nausea, sensory disturbances, tremor, anxiety, and dysphoria. These begin within days to weeks of the last dose and then persist for 1 to 3 weeks. Resumption of drug use will make symptoms subside. The withdrawal syndrome can be minimized by tapering the dosage slowly. ▪ MAOIs
• What patient type would be appropriate for MAOIs?

1. Because MAOIs can be hazardous, they are generally reserved for patients who have not responded to SSRIs, TCAs, and other safer drugs. There is one group of patients—those with atypical depression—for whom MAOIs are the treatment of choice.
2. Identifying High-Risk Patients: Monoamine oxidase inhibitors are contraindicated in patients taking SSRIs, patients with heart failure, severe renal impairment, hypertension, and cardiovascular disease. Also use with caution in patients taking serotonergic drugs. o Baseline Data Needed to prescribe and strategies to minimize adverse effects for the following: (you will use each option only once on the exam) ▪ SSRI/SNRI – serum sodium should b checked in older adults and pts on diuretic therapy; do not abruptly stop meds, report any suicidal ideation ▪ Tricyclic Antidepressants – EKG, esp for pts with dysrhythmia, older than 40 yrs, educated pt re: ortho b/p, anticholinergic effects: dry mouth, blurred vission, constipation, and urinary hesitancy ▪ MAOIs – b/p check, NO FOODS CONTAINING TYRAMINE, REPORT SIGNS OF HTN CRISIS. - Management of Panic Disorder o Medications used to treat ▪ Exam will note mg in choices but if you know the med, the mg will be irrelevant. ▪ BENZOS(alprazolam, cloncazepam), SSRIs(paroxetine, sertraline), SNRIs (effexor). - Management of social anxiety disorder (SAD)