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NSG 533 ADVANCED PHARMACOLOGY EXAM 1 2025/
QUESTIONS AND ANSWERS GRADED A+ WILKES
UNIVERSITY
A patient with type 1 diabetes reports taking propranolol for hypertension. What concern does this information present for the provider?
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."
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)?
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)?
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?
Cimetidine
What lifestyle modifications should be recommended?
-losing weight if overweight
-elevating head of bed while asleep
-eating smaller meals
-avoid foods/meds that exacerbate gerd
-stop smoking
-stop drinking alcohol
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 diabetes. Which drug therapy would be the best for JR to trial?
Discuss your opinion of JR's lipid management.
Discuss your opinion of JR's blood pressure management.
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-
- 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. $$$
GLP-1 analog and has data to support an A1C reduction necessary to gain glycemic control and may assist with weight loss goals for this patient. New information suggests these agents may provide benefits in those with ASCVD. JR has a past history of pancreatitis and GLP-1 analogs are not recommended due to this contraindication
TZDs have data to support an A1C reduction necessary to gain glycemic control, but are associated with weight gain, negative effects on lipids and increased risk of fracture. Until recently, TZDs have also been linked to increased CV events and use has fallen out of favor
Sulfonylureas provide excellent A1C lowering, but are also associated with weight gain. They also have the potential to cause hypoglycemia, so patient education is crucial. Because of his allergies to "sulfa", use would be contraindicated
SGLT2 inhibitors have data to support an A1C reduction necessary to gain glycemic control. In addition, they are associated with weight loss and blood pressure lowering. New information demonstrates these agents may be beneficial in those with ASCVD, heart failure and / or CKD. They are also associated with dyslipidemias as well. Prior to starting therapy, renal function and electrolytes would have to be assessed. $$$
Based on the ASCVD recommendations (which are now paralleled by the 2015 ADA recommendations), all patients with type I or II DM ages 40-75 should be on a moderate intensity statin. If the patients 10 years ASCVD risk is greater than 7.5%, a high intensity statin can be considered. Since all information needed to perform the estimate is not present, we can assume JR need at least moderate intensity statin. ACCE/ACE guidelines still resemble those of ATPIII. Even so, the recommendation is for a statin regardless of LDL-C in diabetics over 40 with at least 1 risk factor of ASCVD.
-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?
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?
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)?
-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 both hemodynamic and tissular effects of angiotensin II.
Finally, there are a growing number of arguments favoring the use of ACE inhibitors very early in patients with diabetes mellitus.
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
What are the various types of oral and non-insulin medications and what represents a rational combination of medications?
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:
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)).
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 2-3 agents at maximally tolerated doses
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
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)
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?
Small therapeutic effect in magnitude
thyrotoxicosis
Why does amiodarone pose a unique concern to thyroid disorders
"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?
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: 3-4 days for full inhibition
Duration of action up to 24 hours due to covalent, irreversible inhibition of proton pump
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
Final thoughts on GERD:
◦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
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
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
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
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
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
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)!
C diff -
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.
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
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"
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
