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case study scenarios

SCENARIO 1

Why are cytochrome P450 enzymes (CYPs) important in drug metabolism? The majority of medications are metabolized by what CYP enzyme? Utilizing the Medscape pill identifier, enter the following characteristics to identify the medication. What CYP enzyme metabolizes this medication? Write a sample prescription for it.

Imprint (ATO 40)  Shape (Oval)  Color (White)  Form (Tablet)  Scoring (None)

 

Response

Cytochrome P450 enzymes (CYPs) are crucial in drug metabolism for several reasons:

1. **Drug Metabolism**: CYPs are responsible for the oxidation of many drugs, which is a key step in their metabolism. This process helps convert lipophilic (fat-soluble) drugs into more hydrophilic (water-soluble) compounds that can be easily excreted from the body.

2. **Drug Interactions**: CYPs can be inhibited or induced by various substances, leading to significant drug interactions. For example, if a drug inhibits a CYP enzyme that metabolizes another drug, it can lead to increased levels of the second drug in the body, potentially causing toxicity.

3. **Genetic Variability**: There is considerable genetic variability in CYP enzymes among individuals, which can affect how different people metabolize the same drug. This variability can influence drug efficacy and the risk of adverse effects.

4. **Drug Development**: Understanding the role of CYPs in drug metabolism is essential for drug development. It helps in predicting how a new drug will be metabolized, its potential interactions with other drugs, and its overall safety profile.

In essence, CYPs play a pivotal role in determining the pharmacokinetics of drugs, which includes their absorption, distribution, metabolism, and excretion. This makes them a key focus in pharmacology and personalized medicine.

The majority of medications are metabolized by the enzyme **CYP3A4**. This enzyme is responsible for the metabolism of approximately 50% of all drugs that undergo hepatic metabolism. Its broad substrate specificity and high expression in the liver and intestines make it a key player in drug metabolism. Other important CYP enzymes include CYP2D6, CYP2C9, and CYP1A2, but CYP3A4 is the most significant in terms of the number of drugs it metabolizes.

The Medication is
Atorvastatin

Atorvastatin is primarily metabolized by the enzyme **CYP3A4**. This enzyme plays a significant role in the metabolism of many statins, including atorvastatin. It’s important to be aware of this because drugs that inhibit or induce CYP3A4 can affect the levels of atorvastatin in the body, potentially leading to adverse effects or reduced efficacy.

CASE 2

SCENARIO 2

JS is a 56-year-old female presenting with redness, warmth and tingling sensation in her neck and face. Current medications include semaglutide (Ozempic) 0.5 mg SC qWeek and Niacin 1,000 mg BID. She is 5’4” and weighs 175 lbs. Fasting lipid profile shows total cholesterol 200, LDL cholesterol 110, and Triglycerides 150. Blood pressure readings of 139/91 and 140/89. What is the patient’s HDL? BMI? What are goal Total Cholesterol, HDL, LDL, and Triglyceride levels for JS? What treatment plan would you implement (include complete medication orders)? How would you monitor the effectiveness of your treatment plan? How many risk factors for coronary artery disease does she have? Identify them specifically.

 

1. HDL Calculation

To calculate HDL, we use the formula:

Total Cholesterol=HDL+LDL+0.2×Triglycerides\text{Total Cholesterol} = \text{HDL} + \text{LDL} + 0.2 \times \text{Triglycerides}

Given:

· Total Cholesterol = 200 mg/dL

· LDL = 110 mg/dL

· Triglycerides = 150 mg/dL

HDL=200−110−(0.2×150)\text{HDL} = 200 – 110 – (0.2 \times 150)

HDL=200−110−30\text{HDL} = 200 – 110 – 30

HDL=60 mg/dL\text{HDL} = 60 \text{ mg/dL}

2. BMI Calculation

BMI is calculated using the formula:

BMI=Weight (lbs)Height (in)2×703\text{BMI} = \frac{\text{Weight (lbs)}}{\text{Height (in)}^2} \times 703

Given:

· Weight = 175 lbs

· Height = 5’4″ (64 inches)

BMI=175642×703\text{BMI} = \frac{175}{64^2} \times 703

BMI=1754096×703\text{BMI} = \frac{175}{4096} \times 703

BMI≈29.9\text{BMI} \approx 29.9

3. Goal Cholesterol Levels

·
Total Cholesterol: Less than 200 mg/dL

·
HDL: 50 mg/dL or higher (for women)

·
LDL: Less than 100 mg/dL

·
Triglycerides: Less than 150 mg/dL2

4. Treatment Plan

Given JS’s current medications and lipid profile, here is a potential treatment plan:

·
Continue Semaglutide (Ozempic): 0.5 mg SC qWeek

·
Adjust Niacin: Consider reducing the dose to 500 mg BID to minimize side effects like flushing, or switch to an extended-release formulation.

·
Add a Statin: Atorvastatin 20 mg PO daily to further lower LDL cholesterol.

·
Lifestyle Modifications: Encourage a heart-healthy diet, regular physical activity, and smoking cessation if applicable.

5. Monitoring Effectiveness

·
Lipid Profile: Recheck fasting lipid profile in 6-8 weeks to assess response to therapy.

·
Blood Pressure: Monitor regularly to ensure it remains controlled.

·
Side Effects: Monitor for any adverse effects from medications, especially niacin and statins.

6. Risk Factors for Coronary Artery Disease

JS has several risk factors for coronary artery disease:

1.
Age: 56 years old

2.
Hypertension: Blood pressure readings of 139/91 and 140/89

3.
Dyslipidemia: Elevated total cholesterol and LDL cholesterol

4.
Obesity: BMI of 29.9

These factors increase her risk for coronary artery disease4.

Given JS’s current condition and medication profile, here’s a comprehensive treatment plan:

Treatment Plan

1.
Continue Semaglutide (Ozempic):

·
Dose: 0.5 mg

·
Route: Subcutaneous (SC)

·
Frequency: Once a week (qWeek)

2.
Adjust Niacin:

·
Dose: 500 mg

·
Route: Oral (PO)

·
Frequency: Twice daily (BID)

·
Note: Consider switching to an extended-release formulation to minimize side effects like flushing.

3.
Add Atorvastatin:

·
Dose: 20 mg

·
Route: Oral (PO)

·
Frequency: Once daily (QD)

·
Purpose: To further lower LDL cholesterol.

4.
Lifestyle Modifications:

·
Diet: Encourage a heart-healthy diet rich in fruits, vegetables, whole grains, and lean proteins. Limit saturated fats, trans fats, and cholesterol.

·
Exercise: Recommend at least 150 minutes of moderate-intensity aerobic activity per week, such as brisk walking.

·
Smoking Cessation: If applicable, provide resources and support for quitting smoking.

Monitoring Effectiveness

1.
Lipid Profile: Recheck fasting lipid profile in 6-8 weeks to assess response to therapy.

2.
Blood Pressure: Monitor regularly to ensure it remains controlled.

3.
Side Effects: Monitor for any adverse effects from medications, especially niacin and statins.

Risk Factors for Coronary Artery Disease

JS has several risk factors for coronary artery disease:

1.
Age: 56 years old

2.
Hypertension: Blood pressure readings of 139/91 and 140/89

3.
Dyslipidemia: Elevated total cholesterol and LDL cholesterol

4.
Obesity: BMI of 29.9

These factors increase her risk for coronary artery disease.

Monitoring the effectiveness of the treatment plan for JS involves several key steps:

1. Lipid Profile

·
Frequency: Recheck fasting lipid profile in 6-8 weeks after initiating or adjusting therapy.

·
Parameters: Total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides.

·
Goal: Ensure that lipid levels are moving towards the target ranges:

· Total Cholesterol: Less than 200 mg/dL

· LDL: Less than 100 mg/dL

· HDL: 50 mg/dL or higher (for women)

· Triglycerides: Less than 150 mg/dL

2. Blood Pressure

·
Frequency: Regular monitoring, at least once a month.

·
Goal: Maintain blood pressure below 130/80 mmHg.

3. Blood Glucose Levels

·
Frequency: Regular monitoring, especially since JS is on semaglutide (Ozempic).

·
Goal: Maintain blood glucose levels within the target range as advised by her healthcare provider.

4. Side Effects

·
Frequency: Continuous monitoring for any adverse effects from medications.

·
Parameters: Look out for symptoms such as muscle pain or weakness (from statins), flushing (from niacin), and gastrointestinal issues (from semaglutide).

5. Lifestyle Modifications

·
Frequency: Regular follow-ups to assess adherence to lifestyle changes.

·
Parameters: Diet, exercise, and smoking cessation (if applicable).

6. Patient Feedback

·
Frequency: Regular consultations to discuss how JS is feeling and any concerns she may have.

·
Parameters: Overall well-being, medication adherence, and any new symptoms.

By closely monitoring these factors, we can ensure that JS’s treatment plan is effective and make any necessary adjustments to optimize her health outcomes.

CASE 3

CL is a 48-year-old African American male with blood pressure readings today of 159/91 and 165/95. He states he is taking Advil Cold & Sinus for a cold x 1 week. Additional medications include adalimumab 40 mg subcutaneous injection every other week, Wellbutrin XL 300 mg daily and pantoprazole 40 mg daily 30 minutes before breakfast. How would you treat CL? What would you prescribe (include complete medication order)? What is his goal blood pressure per JNC 8?

Goal Blood Pressure

According to the JNC 8 guidelines, the goal blood pressure for an African American male younger than 60 years old is less than 140/90 mm Hg2.

Current Medications and Interactions

1.
Advil Cold & Sinus (ibuprofen/pseudoephedrine): This medication can increase blood pressure and may interact with other medications.

2.
Adalimumab: No significant interactions with the current medications.

3.
Wellbutrin XL (bupropion): No significant interactions with the current medications.

4.
Pantoprazole: No significant interactions with the current medications.

Treatment Plan

Given CL’s elevated blood pressure readings and the potential impact of Advil Cold & Sinus, the first step would be to discontinue the Advil Cold & Sinus and monitor his blood pressure. If his blood pressure remains elevated, initiating antihypertensive therapy would be appropriate.

Medication Order

1.
Amlodipine 5 mg PO daily: A calcium channel blocker, which is recommended for African American patients.

2.
Hydrochlorothiazide 25 mg PO daily: A thiazide diuretic, also recommended for African American patients.

Complete Medication Order

·
Amlodipine 5 mg PO daily

·
Hydrochlorothiazide 25 mg PO daily

Monitoring and Follow-Up

· Recheck blood pressure in 1-2 weeks.

· Monitor for any side effects or adverse reactions.

· Adjust medications as needed based on blood pressure readings.

Would you like more details on any specific aspect of this treatment plan?

SCENARIO 4

Does nitroglycerin have a high or low first pass effect? Please discuss why this is important to know and how it relates to bioavailability. What route has 100% bioavailability? In addition to parenterally, how can this medication be given to counter the first pass effect? Write a sample prescription for this medication.

Nitroglycerin and First Pass Effect

Nitroglycerin has a
high first pass effect. This means that when taken orally, a significant portion of the drug is metabolized by the liver before it reaches systemic circulation, resulting in very low oral bioavailability2.

Importance of First Pass Effect and Bioavailability

Understanding the first pass effect is crucial because it directly impacts the
bioavailability of a drug. Bioavailability refers to the fraction of an administered dose that reaches the systemic circulation in its active form. For drugs with a high first pass effect, alternative routes of administration are often necessary to achieve therapeutic levels in the bloodstream.

Routes with 100% Bioavailability

The
intravenous (IV) route has 100% bioavailability because the drug is administered directly into the bloodstream, bypassing the liver and other metabolizing tissues4.

Alternative Routes to Counter First Pass Effect

To counter the first pass effect, nitroglycerin can be administered via:

·
Sublingual tablets: Placed under the tongue, allowing the drug to be absorbed directly into the bloodstream through the mucous membranes2.

·
Transdermal patches: Applied to the skin, providing a controlled release of the drug into the bloodstream.

·
Intravenous (IV) administration: Directly into the bloodstream, bypassing the liver.

Sample Prescription for Nitroglycerin

Here is a sample prescription for sublingual nitroglycerin:

Nitroglycerin 0.4 mg sublingual tablets

Take 1 tablet under the tongue at the onset of chest pain.

May repeat every 5 minutes as needed for a total of 3 doses in 15 minutes.

If pain persists after 3 doses, seek immediate medical attention.

Grading Criteria

Scenario 1: Appropriate medication is prescribed or changed. Rationale provided and includes current literature to support decision. All aspects of the patient history are considered in making the medication selection.

Written medication orders include all 5 aspects required for a valid order. The order is complete, accurate, and appropriate.

References for the scenario are within past 5 years and include the appropriate clinical practice guideline if applicable.

REFERENCES

Zhao, M., Ma, J., Li, M., Zhang, Y., Jiang, B., Zhao, X., Huai, C., Shen, L., Zhang, N., He, L., & Qin, S. (2021). Cytochrome P450 Enzymes and Drug Metabolism in Humans. 
International journal of molecular sciences
22(23), 12808.

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