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Pharmacology Questions and Answers: Case Studies and Treatment Strategies, Exams of Nursing

A series of case studies and scenarios related to pharmacology, focusing on the diagnosis and treatment of various conditions. It explores the use of different medications, their mechanisms of action, potential side effects, and contraindications. The document also includes questions and answers that test the reader's understanding of the presented concepts and clinical applications. It is a valuable resource for students and professionals in the field of pharmacology.

Typology: Exams

2024/2025

Available from 12/30/2024

michael-abonyo
michael-abonyo 🇺🇸

106 documents

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Advanced Pharmacology NSG 533

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EP is a 38-year-old female patient that comes in for diabetes education and management. She was diagnosed 12 years ago and states lately she is not able to control her diet although she continues a 1600 calorie diet with appropriate daily carbohydrate intake (per dietitian prescription) and walks 40 minutes every day of the week. She states compliance with all medications. She denies any history of hypoglycemia despite being able to identify signs and symptoms and describe appropriate treatment strategies. PMH: T2DM, HTN, obesity, depression, s/p thyroidectomy due to thyroid cancer FmHx: Noncontributory SHx: (−) Smoking, alcohol use, past marijuana use while in high school Medications: Metformin 850 mg tid, glipizide 20 mg bid, lisinopril 20 mg daily, sertraline 100 mg daily, multivitamin daily Vitals: BP 128/82 mg Hg; P 72 beats/min; BMI 31 m/kg Laboratory test results: Na 134 mEq/L, K 5.4 mEq/L, Cl 106 mEq/L, BUN - ANSWER-Exenatide - Exenatide (Bydureon) once weekly has been able to demonstrate weight loss and decrease A1C% by 0.7% to 1.2% in clinical trials; however it is contraindicated for EP due to the self-reported history of thyroid cancer. Dapagliflozin - Dapagliflozin (Farxiga) is contraindicated in this patient due to hyperkalemia which could be made worse by this drug. The package insert does not indicate a specific potassium concentration cut off to no longer use this medication; however, there are better choices in this patient. Sitagliptin - Sitagliptin (Januvia) is able to obtain an A1C goal of less than 7% based on clinical trials and currently the patient does not have any cautionary objective measures to not use this medication. DPP-IV inhibitors are weight neutral. DPP-IV inhibitors can be used in patients taking sulfonylureas; however, it may be recommended to reduce or stop the sulfonylurea dose.

Acarbose - Acarbose (Precose) is not recommended for initial management and is associated with significant GI side effects. More information would be needed regarding fasting and post-prandial numbers. In addition, adding acarbose would only lower A1c by 0.8% at best and therefore would not achieve the desired A1C goal of <7% JR is a 68-year-old African American man with a new diagnosis of T2DM. He was classified as having prediabetes (at risk for developing diabetes) 5 years before the diagnosis and has a strong family history of type 2 diabetes. JR's blood pressure was 150/92 mm Hg. His laboratory results revealed an A1C of 8.1%, normal cholesterol panel, and normal renal/hepatic function were noted with today's laboratory test results. Past medical history: Hypertension (diagnosed 4 y ago) Hyperlipidemia (diagnosed 2 y ago) Pancreatitis (idiopathic) (acute hospitalization 3 y ago) Family history: Type 2 diabetes Medication: HCTZ 25 mg daily, simvastatin 10 mg daily Allergies: SMZ/TMP Vitals: BP: 150/92 mm Hg P: 78 beats/min RR: 12 rpm Waist Circumference: 46 in Weight: 267 lb Height: 5 ′ 6 ″ BMI: 43.1 kg/m 2 Despite improvements in the past six weeks due to lifestyle changes and exercise, drug therapy is to be started for JR's diabet - ANSWER-Metformin is the drug of choice recommended for most patients with diabetes in addition to lifestyle modifications assuming no contraindications or intolerabilities are present upon evaluation. Metformin has also shown to provide positive weight neutral/loss effects in obese patients. It is crucial to know the renal status of patients commencing metformin therapy to limit the risk of lactic acidosis (JR is without contraindication). Since his entry A1C is >7.5%, dual therapy is indicated. There are several potential choices. The second step can be a dipeptidyl peptidase-4 inhibitor, it can be a glucagon-like peptide-1 (GLP-1) receptor agonist, it can be a TZD, it can be a sulfonylurea agent, it can be a SGLT2 inhibitor, or it could be basal insulin. Anything next can be tried depending on what suits the circumstance DPP4 inhibitors are weight neutral bet relatively benign side effect profile. Sitagliptin has been associated with case reports of pancreatitis, so this specific agent should be avoided. $$$ GLP-1 analog and has data to support an A1C reduction necessary to gain glycemic control and may assist with weight loss goals for this patient. New

information suggests these agents may provide benefits in those with ASCVD. JR has a past history of pancreatitis and GLP-1 analogs are not recommended due to this contraindication TZDs have data to support an A1C reduction necessary to gain glycemic control, but are associated with weight gain, negative effects on lipids and increased risk of fracture. Until recently, TZDs have also been linked to increased CV events and use has fallen out of favor Sulfonylureas provide excellent A1C lowering, but are also associated with weight gain. They also have the potential to cause hypoglycemia, so patient education is crucial. Because of his allergies to "sulfa", use would be contr A patient with type 1 diabetes reports taking propranolol for hypertension. What concern does this information present for the provider? - ANSWER-A patient with Type 1 DM is insulin dependent for glucose control and at high risk for hypoglycemic episodes. Propanolol causes prolonged hypoglycemic episodes. Needs to switch to ACE or ARB. A provider teaches a patient who has been diagnosed with hypothyroidism about a new prescription for levothyroxine. Which statement by the patient indicates a need for further teaching? a. "I should not take heartburn medication without consulting my provider first." b. "I should report insomnia, tremors, and an increased heart rate to my provider." c. "If I take a multivitamin with iron, I should take it 4 hours after the levothyroxine." d. "If I take calcium supplements, I may need to decrease my dose of levothyroxine." - ANSWER-D. Calcium may reduce levothyroxine absorption. Further education is needed if the patient feels she can take half of a prescribed medication. MC has undiagnosed multiple gastric ulcers. Shortly after consuming a large meal and alcohol he experiences significant GI distress. He takes an OTC heartburn remedy. Within a minute or two he develops what he will later describe as "belching, nausea and a bad bloated feeling". Several of the ulcers began to bleed and he becomes profoundly hypotensive from the blood loss and is taken to the ED. Endoscopy confirms multiple bleeds; the endoscopist remarks that it appears as if the lesions had been literally stretched apart causing additional tissue damage. What did the patient most likely take (i.e. what was the OTC remedy)? - ANSWER-I would accept

Alka-Selzer. I contains NaHCO3 (as well as ASA). In the presence of HCL it Liberates CO2, that can cause gastric distention, belching and nausea. The reaction is fairly swift allowing little time for dissipation. Tums, its primary ingredient calcium carbonate which when taken cause a reaction with the stomach acid such as production of carbon dioxide gas which can cause bloating and the stomach to stretch to tear the ulcers open. On your way to this examination, you experience the vulnerable feeling that an attack of acute diarrhea is imminent! If you stop at a drug store, which anti-diarrheal drugs could you buy without a prescription even though it is chemically related to the strong opioid analgesic meperidine (but acts only on the peripheral opioid receptor)? - ANSWER-Loperamide JA has multiple medical problems and is taking several drugs including theophylline, warfarin and phenytoin. His conditions were well controlled, but recently he started to experience some GI distress for which of his "well intentioned friends" gave him some medication. He presents to you with toxic effects of all his other medications and plasma levels of those medications elevated. What was most likely the medication he took? - ANSWER-Cimetidine What lifestyle modifications should be recommended? - ANSWER--losing weight if overweight -elevating head of bed while asleep -eating smaller meals -avoid foods/meds that exacerbate gerd -stop smoking -stop drinking alcohol What medications / foods can contribute to GERD? - ANSWER--Medications: anticholinergics, barbituates, dopamine, estrogen, opioids, progesterone, theophylline, nitrates -Foods: cirus fruits/juices, coffee, tomatoes, spicy food, carbonated drinks Fried/fatty foods, garlic, onions, chocolate What is the most effective PPI or H2RA within each of these classes? - ANSWER--PPI- bismuth quadruple therapy combined with proton pump inhibitors -H2RA- Famotidine 80mg

Other products such as antacids are also available. What are some of these and what is their place in therapy? - ANSWER--Reflux symptoms <2 times a week (infrequent) -Effective for immediate relief -Magnesium/Aluminum Hydroxide (Maalox)- can cause constipation -Alginic Acid Why would antibiotics be used for PUD caused by H Pylori? What is a typical regimen and duration of therapy? What patient specific factors should be considered and how should treatment be monitored? - ANSWER- Considerations before regimen choice: -penicillin allergy -previous exposure to macroglide antibiotics Strongest Reccomendation: -Bismuth Quadruple Therapy 10-14 days do not drink alcohol w/ metronidazole -Salvage regimen should be different than first regimen Who would be a candidate for prophylaxis of NSAID induced ulcer and what agents are appropriate? What if the patient is on cardio-protective (low dose) aspirin? What if an NSAID induced ulcer does develop. How should it be treated? - ANSWER-Candidate: -Candidates: Chronic Nsaid Use, Hx ulcers, Zollinger-Ellison Prevention Treatment- PPI, standard doses (most effective & best tolerated), Misoprostol (better than H2RA's, No Pregnancy) What if an NSAID induced ulcer does develop. How should it be treated? - ANSWER-Ulcer Treatment- -PPI (most effective) -H2RA (Famotidone 40mg daily) -Sucralfate (binding paste, requires multiple doses, adverse med reactions, abdominal side effects) Who is a candidate for stress ulcer prophylaxis (SUP)? - ANSWER--ICU patients -Trauma, including spinal cord injuries -Mechanical ventilation -Thermal injuries >35% (almost half the body)

Of the agents available to control the complications of diabetes mellitus, cardiovascular drugs, and particularly ACE inhibitors, have a pre-eminent place. Experimental and epidemiological data suggest that activation of the renin-angiotensin-aldosterone system plays an important role in increasing in the micro- and macrovascular complications in patients with diabetes mellitus. Not only are ACE inhibitors potent antihypertensive agents but there is a growing body of data indicating that also they have a specific 'organ-protective' effect. For the same degree of blood pressure control, compared with other antihypertensive agents, ACE inhibitors demonstrate function and tissue protection of considered organs. ACE inhibitors have been reported to improve kidney, heart, and to a lesser extent, eye and peripheral nerve function of patients with diabetes mellitus. These favorable effects are the result of inhibition of bo - ANSWER- There is a "compelling" indication in patients with hypertension and DM. These should be the 1st class of antihypertensive medications used in those with DM + HTN Recommended for the treatment of the patient with CKD (modestly elevated (30-299 mg/24 h) or higher levels (>300 mg/24 h) of urinary albumin excretion), even in those without DM Delay progression of nephropathy in Type 1 with or without HTN and any degree of albuminuria Delay progression of nephropathy in Type 2 with or without HTN and microalbuminuriaReduce development of microalbuminuria (kidney disease) in Type 2 with or without HTN ARBs are considered a reasonable alternative for those intolerant of ACEI - ANSWER- Cardioprotective dose ASA (IE baby aspirin or clopidrogel as alternative)For SECONDARY PREVENTION of CV Events- Use in ALL diabetics with CV diseaseFor PRIMARY PREVENTION of CV EventsUSE in: high CV risk patients (10-yr CV risk > 10%) - Typically: male > 50 yo or female >60 yo with 1 additional major risk factor (FH of CVD, HTN, smoker, dyslipidemia or albuminuria)MAY consider: intermediate CV risk patrients 10-yr CV risk of 5-10%) - younger patients with 1 or more risk factors, older patients with no risk factorsNOT recommended: low CV risk patients - men <50 yo or women <60 yo without major CV risk factors or 10-yr CV risk < 5%Note - Many authorities consider DM to be an ASCVD risk equivalentThis is basically everyone with DM - ANSWER-

What are the goals set by ACE /ACCE and are they written in stone for all patients? - ANSWER-Primary target for glycemic control is HbA1C Individualize HbA1C goal - based on...Duration of DMAge/life expectancyComorbid conditions Known CVD or advanced comorbid conditionsHypoglycemic unawareness Individual patient considerations Please note when transitioning from oral therapy for type II DM to insulin, metformin is retained! Secretagogues are discontinued possibly when basal insulin is initiated, but definitely when prandial (fast/rapid) insulin is to be added - ANSWER-Options to add to basal insulin for prandial coverage... Fast-acting insulin DPP-4 inhibitors Incretin mimetics Glinides Alpha-glucosidase inhibitors Colesevelam What are the various types of oral and non-insulin medications and what represents a rational combination of medications? - ANSWER-Combinations should have different mechanism of action Combinations should avoid overlapping ADRs Combinations should ideally be selected based on need for better basal vs post-prandial control Selection should account for patient specific concerns (eg. weight, CVD risk, etc) What antidiabetic medications have compelling indications: - ANSWER-for those with underlying ASCVD or at high risk for CVD for those with CKD for those with a compelling need to avoid hypoglycemia for those where weight is an important consideration (ie which are associated with weight loss, gain or are weight neutral) What are the various insulins and describe the pharmacokinetics (onset, peak, duration)and how are they used (eg basal, basal-bolus, split-mixed, sliding scale (..Ask if you don't understand)). - ANSWER-Basal-bolus (long acting basal + rapid/fast acting bolus) provides the greatest flexibility and control of all regimens Sliding Scale Should NOT be used

Difficult to do in home setting, requires education and understanding of patient and caregiver Allows patient to become hyperglycemic, better to schedule dosing and prevent rises in BG Requires frequent blood glucose monitoring, $$$ and compliance issues Can be used as monotherapy or as add-on therapy for T2DM .. Presenting A1C of 9 + symptoms or failure to achieve goal A1C on adequate trial of 2- agents at maximally tolerated doses - ANSWER-Often starting with a long acting insulin When glycemic goals aren't reached despite basal insulin (Good FBG and pre-prandial BG, but elevated HbA1C), Consider prandial therapy with fast- acting insulin. Begin fast-acting insulin before largest meal.Variation exists between ADA and ACCE in their recommendations If HbA1C still elevated, add fast-acting to another mealSulfonylurea can continue up until the point where prandial (rapid) insulin is addedMetformin can / should continue !! What agents are used to treat hypothyroid disease? What makes the medications different and what do the guidelines recommend for use - ANSWER-Recommendation 22.1: Patients with hypothyroidism should be treated with Levothyroxine monotherapy. Grade Aother forms of thyroid replacement may be associated with necessary cost, lack of therapeutic rationale, increase adverse effects and allergenicity (animal based products) Starting therapyNormal adult dose: 1.6 mcg/kg/day (~100-125 mcg/day) based on IBW (LBW)Titration by 25-50 mcg every 4-6 weeks until TSH normalizesEXCEPTIONS include elderly, chronically ill patients or history of cardiovascular disease. Initially 12.5-25 mcg/day, then titrate to maintenance dose until TSH normalizesExpect higher requirements during pregnancyThyroid hormone demandIncreases in TBGDestruction of T4 by placental deiodinases How is treatment monitored and how should results be interpreted as far as therapy changes (the relationship between TSH and T3-4) - ANSWER- Monitoring should be every 6-8 weeks after starting or dose/product change. If TSH is not in target range (0.5-2.5 mIU/L) alter dose in 10% to 20% increments. .. levothyroxine has a T 1/2 of 6-10 days (and NTI .. see below). How does this relate to the fact that after initiating or changing a does or changing a

product (IE brand to generic, generic to brand or one generic brand to another), TSH should be checked in about 6 weeks? Why are thyroid replacement drugs considered to have a narrow therapeutic index ( NTI )and what does that mean clinically? - ANSWER-The therapeutic index (TI) is the range of doses at which a medication is effective without unacceptable adverse events. Drugs with a narrow TI (NTIs) have a narrow window between their effective doses and those at which they produce adverse toxic effects. Oral Bioavailability: (erratic) 40- 80%brand vs generic Highly protein bound (99%)Half-lifeEuthyroid = 6- daysHypothyroid = 9-10 daysSteady State: @ 6 weeks or 4-5 t1/2 's ... this is the bases for monitoring @ six weeks from start or changes! Consider changes such as brand to generic, different generics manufactures, different pharmacies, etcAny such change will require repeat lab monitoring @ ~ 6 weeks to confirm the same clinical response What are some drug-drug, drug-food interactions associated with thyroid replacement - ANSWER-drug binding interactions, di-valent cations, amiodarone, certain antibiotics RECOMMENDATION 13 Methimazole should be used in virtually every patient who chooses antithyroid drug therapy for GD, except during the first trimester of pregnancy when propylthiouracil is preferred, in the treatment of thyroid storm (inhibition of peripheral conversion), and in patients with minor reactions to methimazole who refuse radioactive iodine therapy or surgeryDelayed onset - ANSWER- Beta-blockers role in therapy? - ANSWER-So .. beta blockers are used for Symptomatic relief of hyperthyroidism until more definative therapy is instituted and thyroid levels retun to normal or near normal.. Reduction of peripheral manifestations Tachycardia, sweating, severe tremor, nervousness Inhibition of peripheral conversion of thyroid hormones at higher doses (propranolol ONLY) Small therapeutic effect in magnitude thyrotoxicosis Why does amiodarone pose a unique concern to thyroid disorders - ANSWER-"Amiodarone-normal thyroid autoregulation is lost because of the relatively high iodine content" .. this fact can lead to a situation where

amiodarone can cauase BOTH hyper- and hypo- thyroidism, depending on the patient, through several process blocking thyroid peroxidase blocking proteolysis of Tg and thyroid hormone altering organification, etc What would you recommend if a patient is taking Nexium and Plavix together? - ANSWER-As we have seen through our discussions, there is a lot of information (including an FDA issued statement in the package insert) describing the drug interaction and reduced efficacy of clopidogrel if used with a PPI (primarily omeprazole) (or in patients who are genetically slow CYP2C19 metabolizers); however there is also evidence based information indicating the interaction is not as significant as originally thought. Bottom line: Despite pharmacokinetic evidence that omeprazole interferes with clopidogrel metabolism, COGENT trial found addition of omeprazole to clopidogrel reduced gastrointestinal events without increasing cardiovascular events. Note there is no significant difference in efficacy among the H2RAs when given at equipotent dosesCimetidine is associated with numerous clinically significant DIs Dose reduction in renal and hepatic insufficiency and in the elderly Duration of suppression ranges from 6-10 hours and varies with dose Note there is no significant difference in efficacy among the PPIs when given at equipotent doses Food may affect absorption. Given 30-60' before a meal. More flexibility in term of dosing with newer agents (eg. dexlansoprazole)Delayed onset: 3- days for full inhibition Duration of action up to 24 hours due to covalent, irreversible inhibition of proton pump - ANSWER- Patients with known osteoporosis can remain on PPI therapy. Concern for hip fractures and osteoporosis should not affect the decision to use PPI long-term except in patients with other risk factors for hip fracture - ANSWER- Final thoughts on GERD: - ANSWER-◦Therapy for GERD other than acid suppression, including prokinetic therapy and/or baclofen, should not be used in GERD patients without diagnostic evaluation.

◦For patients with partial response to once daily therapy with a PPI, tailored therapy with adjustment of dose timing and/or twice daily dosing should be considered in patients with night-time symptoms, variable schedules, and/or sleep ◦In patients with partial response to PPI therapy, increasing the dose to twice daily therapy or switching to a different PPI may provide additional symptom relief. ◦ Maintenance PPI therapy should be administered for GERD patients who continue to have symptoms after the PPI is discontinued, and in patients with complications including erosive esophagitis and Barrett's esophagus ◦Histamine-receptor antagonists (H2RA) therapy can be used as a maintenance option in patients without erosive disease if patients experience heartburn relief. Bedtime H2RA therapy can be added to daytime PPI therapy in selected patients with objective evidence of night- time reflux if needed, but may be associated with the development of tachyphylaxis after several weeks of usage Peptic ulcers (gastric and duodenal) are defects in the GI mucosa that extend through the muscularis mucosa. Causal relationships associate with H. Pylori infection, NSAIDs and SRMD. - ANSWER-Therapy includes non- pharmacological interventions (similar to GERD) and pharmacological with acid suppression (antacids, H2RAs, PPIs) and/or mucosal protection (sucralfate, colloidal bismuth, misoprostol), and if present, H Pylori eradication Acid suppression - see treatment modalities under GERD (Duration / dosages may be different based on indication) Mucosal protectionSucralfate - In acid environment it turns into a viscous, sticky polymer that binds selectively to ulcers and erosions creating a protective layerEfficacy comparable to H2RAsChemically, contains Al(OH)3, thus behaves as Aluminum as far as ADRs (eg constipation), DIs (eg chelation)Bismuth - MOA unclearBismuth coats ulcers and erosions, creating a protective layer against acid and pepsinIt may stimulate PG and mucus secretionIt binds bacterial endotoxins and has direct antimicrobial activity against pylori H Pylori eradication - Because of the critical role of H. Pylori in the pathogenesis of peptic ulcer, eradication of this infection is a standard care in patients with gastric or duodenal ulcers All regimens include 2 antibiotics & Acid suppression therapy (PPI or H2RA)May include Bismuth preparation

Note especially duration and comments sections of the table below! - ANSWER- In patients aged 55 yr or younger with no alarm features, the clinician may consider two approximately equivalent management options: (i) test and treat for H. pylori and a trial of acid suppression if eradication is successful but symptoms do not resolve or (ii) an empiric trial of acid suppression with a proton pump inhibitor (PPI) for 4-8 wk - ANSWER- NSAID induced ulcers Prevention: - ANSWER-Misoprostol or PPI. H2RAs not recommended for prophylaxis.COX-2 inhibitors are associated with a significantly lower incidence of gastric and duodenal ulcers when compared to traditional NSAIDs. However, this beneficial effect is negated when the patient is taking concomitant low-dose aspirin. The usefulness of these agents has also been reduced by their association with myocardial infarction and other thrombotic CV eventsCOX-2 inhibitors and NSAIDs to be discussed in more detail later in the semester Candidate for prophylaxis Candidate for prophylaxis - ANSWER-History of prior gastrointestinal event Age over 60 (5x greater risk) High NSAID dosage Concurrent use of corticosteroids (4x greater risk) Concurrent use of anticoagulants, antiplatelets or low dose ASA (12x greater risk) Treatment: Discontinue NSAID If possibleEradicate H Pylori if (+)H2RAs or PPIsPPIs heal NSAID-related ulcers more effectively as compared with H2RAs and are therefore the antisecretory drug of choice for treating NSAID-related ulcers, especially when NSAIDs are continuedPatients with NSAID-associated ulcers should be treated with a PPI for a minimum of eight weeksSucralfate is an option for healing only if NSAID will be stopped Constipation - ANSWER-Approach to treatment should begin with determination of cause(including medications a patient may be on table 21- 1)OpiatesAnticholinergics (eg. tricyclic antidepressant (amitryptiline), diphenhydramine, benztropine, etc.)NDHP-CCB (eg verapamil)Oral iron preparationsCalcium or aluminum antacidsNSAIDsClonidineDiuretics

Constipation treatment - ANSWER-Non-pharmacological interventions first (diet (fiber), exercise, fluids)Probiotics - limited data Best Pract Res Clin Gastroenterol. 2011;25:119- PharmacologicalBulk forming agents (eg. methylcellulose (Citrucel))Administer 240 mL of water with each dose to prevent esophageal / GI obstruction and worsening symptomPhysical binding of other substances including medicationsSafe in pregnancyEmollients (softeners) (eg. docusate (Colace)Facilitate mixing of aqueous and fatty materials in the intestinal tractUsed for prevention, NOT treatment. Commonly prescribed with medications that may cause constipation (chronic opiate use, iron supplementation)Safe in pregnancyLubricant laxative (mineral oil / castor oil)Coats stool to allow easy passage / Prevents colonic water absorptionSystemic absorption - can generate immune responseAspiration - may lead to lipoid pneumoniaDecreases absorption of fat-soluble vitamins à DO NOT use in pregnancyHyperosmotics (eg. polyethylene glycol (Miralax))Osmotic effects to retain fluid in GI tractSafe in pregnancySaline laxatives - Composed of relatively poorly absorbed ions (Mg+ - sulfate, - phosphate, - citrate)(eg. MOM)Osmotic effects to retain fluid in GI tractMay be used occasionally to treat constipation in otherwise healthy adultADRs: fluid and electrolyte disturbances: Mg (renal dysfunction) or Na (CHF) accumulationStimulant laxatives (Senna, Bisacodyl) (eg Sennokot, Dulcolox)Only recommended for intermittent use

  • daily use strongly discouragedNew agents available for specific use ONLY (eg. IBS-C, OIC)NOT discussed in this course Summary of constipation recommendations - ANSWER-Slow Transit ConstipationHyperosmotic laxativesSenna, Bisacodyl and other stimulants are second line Those who need to avoid straining (eg hemorrhoids, hernia, MI)Stool softeners or PEG ChildrenDiet, fluid exerciseAvoid under 6 years without evaluationGlycerin suppository, docusate Goal of diarrhea treatment - ANSWER-Goal of treatment: Identify and Treat primary cause, Manage secondary causes, prevent electrolyte & acid/base disturbances & dehydration , provide symptomatic relief , Note the primary goal is NOT ALWAYS to stop diarrhea (see below, Infectious diarrhea)! Non-pharmacologicalRehydration , oral preferredAvoid Soda products, Gatorade*, Chicken broth, TeaDietResume age-appropriate diet once

rehydratedSecondary causes can include medications. An evaluation of medications an possible substitution of offending medications should be considered (if possible)Magnesium containing antacids, metformin (1/3 of patients), antibiotics (25% incidence), anti-inflammatory / anti-gout agents (eg. colchicine), etc. Pharmacological agents for diarrhea: - ANSWER-Opiates and derivatives - Acts on peripheral (eg loperamide (Imodium)) and central (eg diphenoxylate/atropine (Lomotil)) opioid receptors depending on the agent. Those that act on central mu receptors are control substances and prescription onlyNoninfectious diarrhea (acute & chronic)Adverse effects: constipation, fatigue, dizziness Adsorbents = Works through non-selective adsorption, providing bulk in digestive tractNot systemically absorbedBinds 60 times its weight in waterAlso used for constipation (absorbs water / fluids)Can also bind drugs leading to altered drug bioavailability Bismuth subsalicylate - see GERDContraindicationsASA allergyNursing or pregnant womenGI bleedingImmunocompromised patientsDrug interactionsDecrease protein binding of warfarinDecrease absorption of TCN, quinolones Octreotide - Prevents the release of secretory substances, Stimulates intestinal absorptionSymptomatic treatment of carcinoid tumors & VIPomas that produce violent watery diarrheaAdverse effects:Nausea , abdominal pain, QT prolongationCholelithiasis (d/t inhibition of gall bladder activity)Hyper - / Hypoglycemia ( d/t altered insulin, glucagon GH balance) Crofelemer - FDA approved for symptomatic relief of non-infectious diarrhea in patients with HIV/AIDS on anti-retroviral therapy Probiotics - Help maintain normal GI flora, reduce colonization of disease- causing bacteriaEvidence - Vary based on intended use (acute treatment, prevention, antibiotic associated, adults, children), strain of bacterium and timing of administration Digestive enzymes (lactaid)Use in patients with lactase deficiency who are lactose intolerant We do not routinely use empiric antibiotics in patients with acute diarrhea. Infectious diarrhea: C diff - - ANSWER-The initial step in the treatment of Clostridium difficile infection (CDI) is cessation of the inciting antibiotic as soon as possible Therapy for non-severe difficile infection (CDI) consists of oral metronidazole >> oral vancomycinLimitations of metronidazole include

dose-dependent peripheral neuropathy and side effects of nausea and metallic taste.Use of oral vancomycin is appropriate for initial therapy of non-severe disease in patients who are pregnant, breastfeeding, or intolerant/allergic to metronidazoleRifaximin— Small case series have suggested that sequential therapy with vancomycin followed by Rifaximin may be effective for the treatment of recurrent CDI Traveler's diarrhea - the classic travelers' diarrhea due to enterotoxigenic Escherichia coli (ETEC) generally produces malaise, anorexia, and abdominal cramps followed by the sudden onset of watery diarrhea. The illness is generally self-limited with symptoms lasting for approximately one to five days. - ANSWER-Antibiotics are warranted to treat diarrhea in those who develop severe diarrhea, characterized by more than four unformed stools daily, fever, or blood, pus, or mucus in the stool. In addition, some travelers desire antibiotic treatment for milder disease if the illness is a large burden on a business trip or vacation.For mild to moderate disease, anti-motility drugs(eg. loperamide) may be used as monotherapyFor sever disease, anti-motility drugs(eg. loperamide) may be used cautiously as adjunctive therapyuse in combination with simethicone may provide faster relief of symptoms For adults, several different antibiotic options are effective for travelers' diarrhea. In general, fluoroquinolones (eg ciprofloxacin) are the first choice for their efficacy and tolerability. However, for travelers to Asia, azithromycin is preferable because of increasing resistance to fluoroquinolones among enteric pathogens in that region. Azithromycin is also the preferred agent for pregnant women and children. We only use Rifaximin if a fluoroquinolone or azithromycin is not available or appropriate because its efficacy for invasive disease is unknown Nausea / Vomiting When choosing an agent - ANSWER-Focus on individual patient, evaluate risk factors, and rule out other causes. Agent related variables (efficacy, ADR's, cost) Please review mechanisms, ADRs and Promethazine -Block DA2 receptors in the CTZ + have antihistaminic and anticholinergic effects.ADR's: EPS, sedation, hypotension Place in therapy: "general purpose antiemetics". not very effective in severe n/v (i.e. chemotherapy induced n/v (CINV)Example Lorazepam - Benzodiazepines bind to GABA-A receptors. GABA is the major inhibitory NT in the CNS

benzodiazepines are sedatives, not antiemetic agents Sedative and anti-anxiety effects → reduce anticipatory N/V associated with chemotherapy ADRs - CNS - sedation, hallucinations, euphoria; CV - hypotension CINV - Evaluate emetogenic potential of regimen Mono therapy for chemotherapy with low and moderate emetogenic risk Aggressive (combination of agents with different mechanisms) antiemetics for highly emetogenic regimens and delayed CINV Examples Dexamethasone + metoclopramide + diphenhydramine + lorazepam Ondansetron + dexamethasone Ondansetron + metoclopramide Metoclopramide + dexamethasone Ondansetron + dexamethasone + prochlorperazine Ondansetron + dexamethasone + aprepitant Erectile dysfunction -"The inability to attain or sustain an erection adequate for sexual stimulation" - ANSWER-Can be the result of age related changes (e.g. diminished testosterone, altered response to NO, etc), comorbidities (e.g. DM, BPH, depression, etc .. Table 51-1), and medications (e.g. 5-alpha reductase inhibitors, beta-blockers, TCAs, etc. .. Table 51-2) Before initiating treatment for ED - ANSWER-a physical examination and thorough medical, social, and medication histories with emphasis on cardiac disease must be taken to assess for ability to safely perform sexual activity and to assess for possible drug interactions Diagnosis should include PE (including a check for signs of hypogonadism), medication review, Hx, and labs ( HbA1C, PSA, FLP, testosterone) ED treatment should include: - ANSWER-Non-pharmacological interventions Reduce fat and cholesterol in diet Decrease or limit alcohol consumption Eliminate tobacco use and substance abuse Weight loss if appropriate Regular exercise Co-morbidity (DM, HTN, etc.) management - including (if possible) removal of causal medications If a medication is removed, consider that it probably will have to be replaced with a reasonable alternative - ANSWER-Examples: SSRIs are a potential cause of ED. A reasonable replacement might be bupropion (assuming no contraindications)

Dutasteride (for BPH) is a common cause of ED. Tardenafil as a replacement for or in combination with a 5-alpha reductase might be reasonable (assuming no contraindications) ED Note: - ANSWER-There are occasions where an offending medication can NOT be discontinued because of a compelling indication and / or lack of a reasonable alternative (eg Beta-blockers in heart failure or SIHD). PDE5Is - Often considered drug of choice when pharmacotherapy is necessary. There is no convincing evidence that one agent in this class is superior to another. Choice may be based on patient preference, cost, and formularies - ANSWER-There is no drug effect without some type of sexual stimulation because these drugs do not cause penile erections; they only provide the ability of the penis to respond to sexual stimulation. Varying duration of action (most 4-5 h, tadalafil 36h). Headache and flushing most common ADRs. Serious cardiac events possible Significant DIs exist - ANSWER-+) nitrates - severe hypotensionIn an emergent situation, a patient who has taken sildenafil may be given a nitrate after 24 hours; for tadalafil, after 48 hours. Vardenafil does not have a suggested time interval, but blood pressure and heart rate did not change when the drug was taken 24 hours before nitrate administration. These suggested intervals are a direct correlation to half-life and duration of action Prolonging of QT interval Serious cardiovascular events have been associated with PDE5 inhibitors; therefore, they should not be used in patients in whom sexual intercourse is inadvisable because of poor cardiac status. Testosterone replacement (Low-T) - ANSWER-Testosterone replacement regimens should never be administered to men with normal serum testosterone levels, or in patients with isolated erectile dysfunction as the only sign of hypogonadism. Before initiating any testosterone replacement regimen in patients 40 years and older, patients should be screened for breast cancer, benign prostatic hyperplasia, and prostate cancer. All are testosterone-dependent conditions and theoretically could be worsened by exogenous administration of testosterone

Alprostadil - PgE1 analog administered by intracavernosal injection & intraurethral inserts - ANSWER-Because PGs bypass many steps in the erectile cascade, they are quite effective at producing an erection, even in cases where PDE5 inhibitors cannot do so. Most invasive and low patient acceptance. Reserved as second or third line treatment BPH - ANSWER-BPH increases urethral resistance, resulting in compensatory changes in bladder function. Obstruction-induced changes in detrusor function, including smooth muscle hypertrophy, compounded by age-related changes in the functioning of the bladder, lead to urinary frequency, urgency, and nocturia, the most bothersome BPH-related complaints. Not all patients with LUTS have BPH and not all men with BPH have LUTS. BPH diagnosis - ANSWER-Diagnosis includes components such as symptom assessment (AUA score), PE and PSA PSA is present in small quantities in the serum of men with healthy prostates, but is often elevated in the presence of prostate cancer or other prostate disorders. PSA is not uniquely an indicator of prostate cancer, but may also detect prostatitis or BPH. PSA correlates with prostate size and can be used as a prognostic marker Non-pharmacologic interventions for BPH - ANSWER-Lifestyle modification

  • limiting EToH, caffeine, avoid certain medications (Table 52-4)(e.g. decongestants, androgens, etc) as well as addressing co-morbidities (weight loss, etc) Watchful waiting is the most conservative approach for patients with mild symptoms or those with moderate symptoms without bother ◦Appropriate option for patients with mild symptoms (AUA-SI score ≤ 7), and for many with moderate to severe symptoms (AUA-SI ≥ 8) if they are not bothered ◦Behavior modification includes restricting fluids close to bedtime, minimizing caffeine, sweetened drinks and alcohol intake, frequent emptying of the bladder during waking hours (to avoid overflow incontinence and urgency), and avoiding drugs that could exacerbate voiding symptoms (e.g. antihistamines, decongestants). ◦At each visit, assess the patient's risk of developing acute urinary retention by evaluating the patient's prostate size or using PSA as a surrogate marker of prostate enlargement

The level of symptom distress that individual men are able to tolerate is variable Alpha-blockers - ANSWER-fairly rapid onset (2-4 weeks) with relatively rapid symptom resolution , durable effect (years) with AUA symptom index (AUASI) improving 30-45%. No effect on prostate size (PSA) or disease progression. Relax smooth muscle in bladder neck, urethra & prostate(Blue dots indicate the distribution of alpha receptors surrounding the bladder and prostate). It is clear why these agents would provide rapid relief of symptoms New second generation (alfuzosin) and third generation (tamsulosin and silodosin) agents are preferred because of uroselectivity, no need for dose titration and limited orthostasis Alpha-blockers - ANSWER-Older agents also have an indication for hypertension and have more CV ADRs (e.g. orthostasis, reflex tachycardia, etc). e.g. terazosin. doxazosin dose titration should follow the "start low, go slow" paradigm Most guidelines advocate for the individual management of BPH and hypertension Note that the ACC / AHA recommends that that for those with the comorbidities of hypertension and BPH, each of those conditions should be treated independently based on GDMT. For those with persistent HTN on maximized first line therapies, alpha-blockers with vascular effects may provide benefit in terms of additional BP lowering 5 alpha reductase inhibitors - ANSWER-Management of moderate to severe BPH in patients with enlarged prostate glands. Management of patients who desire medical therapy but cannot tolerate alpha-1-adrenergic antagonists and do not have predominately irritant symptoms or concomitant erectile dysfunction (Symptoms are non- bothersome, so the delay in onset would not interfere with Qol) Reduce prostate size (and PSA) and thus outlet obstruction Reverse / Slow disease progression Decrease the risk of disease complications Note: although dutasteride blocks both the Type I and Type II iso-enzymes of 5-alpha reductase while finasteride only blocks Type II, there is not a clinically significant difference in outcomes when either is used

Peak effect 6-12 months, effect is only durable as long as drug is continued (prostate will return to pre-treatment size (or larger) when / if 5ARIs are stoppedFinasteride & Dutasteride reduces, but does not stop the prostate from producing PSA If PSA fails to decline by 50% after 6-12 months or an increase of 0.3 ng/L or more above the baseline nadir level, patient should be evaluated for prostate cancer. May also indicate worsening condition or non-compliance with 5 a-reductase inhibitors ADRs - ANSWER-(androgen insufficiency) decreased libido, impotence & ejaculatory disorder, breast tenderness & enlargement PDE5Is (tadalafil) - ANSWER-Treatment of the signs and symptoms of benign prostatic hyperplasia +/- ED Relaxes smooth muscle of urethra, prostate and bladder neck Tadalafil may be prescribed alone, or along with an α1-adrenergic antagonist and/or 5α-reductase inhibitor. Although other phosphodiesterase type 5 inhibitors share the same mechanism of action as tadalafil and can improve the AUA Symptom Score, tadalafil (which is the only PDE5I approved by the FDA for this indication) is preferred because of its longer plasma half-life, which is theoretically beneficial in the management of BPH, a chronic disease. Comparable efficacy to alpha-blockers for LUTS, but does not increase flow rate or reduce PVR Peak onset 1-4 weeks $$$ Tadalafil adverse reactions: - ANSWER-◦Use with alpha-blockers, antihypertensives or substantial amounts of alcohol may lead to hypotension ◦headache, dizziness, flushing, back pain, myalgia, and cyanopsia Precautions ◦Unstable angina, uncontrolled or high-risk arrhythmias, persistent hypotension, poorly controlled hypertension, or New York Heart Association Classification IV congestive heart failure Contraindication ◦Current use of nitrates BPH combination therapy - ANSWER-Alpha-blocker offer immediate relief; 5 alpha-RIs reduce prostate enlargement over time

◦In patients with an enlarged prostate gland and an elevated PSA ≥1.4 ng/mL, combination drug therapy with an α1-adrenergic antagonist and a 5α-reductase inhibitor is more beneficial than single drug therapy. ◦Rationale a-blocker offer immediate relief 5a-RIs reduce prostate enlargement ◦Works better for those with obstructive symptoms ◦May consider stopping a-blocker after 6-12 months, but should continue in those patients with severe symptoms as long as they are responding BPH combination therapy - ANSWER-◦-blocker and anticholinergic (or β3 agonist) For men with low post-void residual urine volumes and irritative symptoms (e.g., frequency, urgency) that persist during treatment with an alpha- adrenergic antagonist, combination treatment with an anticholinergic agent can be tried ◦Improved storage voiding parameters and frequency compared with alpha- 1-adrenergic antagonist therapy alone ◦For patients who poorly tolerate anticholinergic adverse effects, an alternative is Mirabegron The risk of side effects, increased post-void residual urine volume, decreased maximal urinary flow rate, or acute urinary retention is low BPH combination therapy - ANSWER-◦ a-blocker and PDE-5Is For men with moderate symptoms of BPH and erectile dysfunction, treatment with daily tadalafil (5 mg/day) alone or in combination with tamsulosin (0.4 mg/day) can be considered Addition of PDE-5Is to alpha blockers may improve lower urinary tract symptoms ◦PDE-5i and 5a-RIs Addition of PDE-5i to 5a-RIs can offset erectile dysfunction commonly seen with 5a-RIs Red Flag medications in pregnancy

  • Commonly used / teratogenic - ANSWER-Warfarin, Phenytoin, Valproic Acid, Carbamazepine, Lithium, ACE inhibitors/ARBs, Thalidomide, Ethanol, statins .. etc Considerations must be given to not only those who ARE pregnant, but all women of child bearing years where pregnancy is possible (planned or un- planned)

Note: this is NOT a comprehensive list, but a good representation for exam purposes Combined Oral Contraception: - ANSWER-choosing a formulation based on fertility goals, patient preference, discussion of risk/benefits, Hx (to rule out contraindications .. see US MEC attached) World Health Organization and the Food and Drug Administration recommend using the lowest dose pill that is effective (as noted below, efficacy can be impacted by several factors .. including other medications. Thus, the lowest dose available is not always the lowest most effective dose) Combined Oral Contraceptives - ANSWER-Risks can include, but not limited to cancers, CV events/HTN, VTE, drug interactions Concomitant use of broad spectrum antibiotics and combination contraceptives may result in decreased contraceptive efficacy; however this is Category 1 under US MEC If a typical failure rate of 1% to 3% is a concern for the patient, consider additional or alternative forms of birth control Concomitant use of P450 enzyme inducers (rifampin, phenytoin, carbamazepine, phenobarbital) may result in decreased contraceptive efficacy If use COC - use higher doses (at least 35 mcg EE) + high progestin, shorten hormone free interval to 4 days or less Avoid low progestin - the patch, POP Consider additional or alternative forms of birth control Concomitant use of Anti-HIV protease inhibitors can either increase or decrease serum levels of estrogens and progestins - may need backup method Drospirenone can cause hyperkalemia, especially if used with other agents that can increase potassium (ACEIs, heparin, aldosterone antagonists, etc) Benefits can include favorable effect on bone, menstrual effects, improved acne, improved PMDD, etc Managing hormone concerns - ANSWER-Estrogen Excess - N/V, cervical mucorrhea, hypertension, headache, breast tenderness, edema, melasma, bloating Deficiency - Early or mid-cycle breakthrough bleeding, increased spotting, hypomenorrhea, vasomotor symptoms Progestin

Excess - breast tenderness, headache, fatigue, changes in mood Deficiency - Late break through bleeding, hypermenorrhea, dysmenorrhea Androgen Excess - increased appetite, weight gain, acne, oily skin, hirsutism, decreased libido, increased breast size, breast tenderness, increased LDL, decreased HDL Amenorrhea - rule out other causes. Can increase to more estrogenic formulation or to triphasic formulation to decrease amenorrhea.Not a concern if patient is happy. Acne/ oily skin/ hirsutism - Rule out other causes. Switch to less androgenic formulation of progestin (or decrease progestin content)3rd generation Desogestrel, norgestimate4th generation drospirenone Dienogest Managing hormone concerns - ANSWER-GI- typically resolves in 1-3 months. Decrease estrogen component will help with nausea. Decrease progestin component to help with bloating and constipation Bleeding /spotting - Common (30-50%) when first initiated. Often resolves by 3rd or 4th cycle Other manipulations of estrogen and progestin depend at the point of the cycle bleeding / spotting occurs First rule out other causes including medications (eg. Medications that increase metabolism)If spotting or bleeding before completing active pills (late cycle (days10-21)) - increase progestin to enhance endometrial support Monophasic with higher progestin or triphasic with ing progestin If spotting after withdrawal bleeding (early cycle (days 1-9))- increase estrogen or decrease progestin in the early pills(triphasic)If mid-cycle spotting/bleeding - increase both estrogen/progestin midcycle Headaches - If headaches start or worsen after starting OC, need to rule out other causes (take BP, ask about headache, any focal neurologic symptoms)If related to OC use and are not serious - Discontinue OC, Lower estrogen dose, Lower progestin, Eliminate pill free interval (only if HA occur during pill free interval) Decreased Libido Ask about depression If due to decrease in vaginal lubrication, switch to vaginal ring contraception Increase estrogen Hypertension - COCs can cause small increases (i.e., 6 to 8 mm Hg) in blood pressure, regardless of estrogen dosage

Low -dose COCs is acceptable in women younger than 35 years with well- controlled and frequently monitored hypertension Discontinuing the COC usually restores blood pressure to pretreatment values within 3 to 6 months VTE / Thromboembolism Estrogens - increase hepatic production of factor VII, factor X, and fibrinogen in the coagulation cascade, therefore increasing the risk of thromboembolic events Progestins Newer 3rd Progestin Only oral contraceptives - ANSWER-- indicated in Breastfeeding (post-partum phase), older women, women who cannot take estrogen The failure rate is higher than other progestin-only methods or COCs Effectiveness is lowered when taken as little as a few hours late DM I/II/GDM in pregnancy: - ANSWER-DM I / II / GDM TreatmentADA diet Insulin - drug of choice Regular insulin or NPH Insulin lispro (Humalog) Insulin aspart (Novolog)◦Insulin requirements will increase beginning around 28 weeks gestation and continue to increase due to placental hormones Increasing data on safety of insulin glargine in pregnancy Oral agents (metformin / glyburide) 2nd line. Reasonable alternative for women who decline to take, or are unable to comply with, insulin therapy. HTN in pregnancy: - ANSWER-HTN when SBP reaches 160 or DBP reaches 110 Continue treatment when multiple hypertensive's were required before pregnancy or when end organ damage is present methyldopa / labatolol / nifedipine ER 1st line Hypothyroidism in pregnancy: - ANSWER-hypothyroidism ◦Levothyroxine - DOC ◦Attain normal thyrotropin concentrations ◦Women who received thyroid replacement prior to pregnancy can expect an increased dosage requirement of 25-50% during pregnancy

Depression in pregnancy: - ANSWER-depression Pregnant patients with severe unipolar major depression who were successfully treated with antidepressants prior to pregnancy should generally receive the same drug during pregnancy. For patients who have not been treated with antidepressants in the past, we suggest selective serotonin reuptake inhibitors (SSRIs) as initial treatment, rather than other antidepressants No psychotropic drugs with labeling approved by the FDA for use during pregnancy and lactation 1st line - psychotherapy, but not always an option SSRI's ◦Avoid paroxetine (D) during first trimester CV malformations ◦Fluoxetine (C) citalopram (C) sertraline (C) -->Literature is reassuring, best data for use during pregnancy ◦Risk of PPHTN after 20 weeks gestation with SSRI's ◦Risk of neonatal withdrawal or adaptation syndrome1 d/c 2 weeks before term TCA's ◦Literature is reassuring ◦Possible withdrawal symptoms Atypical antidepressants ◦Limited data Dyslipidemia in pregnancy: - ANSWER-Dyslipidemia Women who are on statin therapy and anticipate becoming pregnant should stop statins three months prior to attempting to conceive. Maternal consumption of fish and marine omega-3 fatty acid supplement is an active area of investigation because of potential favorable effects on pregnancy and offspring outcome. Menopause nonpharmacological interventions: - ANSWER-Goals - Alleviate or reduce symptoms, Improve QOL, Minimize ADRs Non-pharmacological interventions - avoid vasomotor triggers (hot beverage, spicy food, EToh, etc), exercise, water based lubricants Pharmacotherapy menopause - ANSWER-Pharmacotherapy - hormone therapy remains the most effective treatment for vasomotor symptoms and vulvovaginal atrophy, especially in women with moderate to severe