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Therapeutic Effects

Unit 1 Lesson 2.3

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Student Learning Outcomes

Define Therapeutic Window, Peak, Trough, and Therapeutic Index
Describe therapeutic blood level testing and evaluation of drugs
Discuss the nurse’s role in evaluating medications

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Therapeutic Window 1

The range of drug dosage between the minimally effective dose (Effective Concentration) and the toxic dose (Toxic Concentration)
The "perfect dose" where the desired therapeutic effect is achieved without causing toxicity

(Ernstmeyer & Christman, 2023)

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Therapeutic Window 2

Example:

Warfarin's therapeutic window is monitored using the International Normalized Ratio (INR) blood test to prevent clotting and bleeding

INR range

2.0 - 3.0 for most indications, 2.5 - 3.5 for mechanical heart valves

(Ernstmeyer & Christman, 2023)

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Peak and Trough Levels 1

Peak level

Highest drug concentration in the bloodstream after administration

Typically obtained between 30 minutes and 2 hours after drug administration (depends on drug pharmacokinetics)
Trough level

Lowest drug concentration in the bloodstream before the next dose

Typically measured just before the next dose (within 30 minutes of the next scheduled dose)

(Ernstmeyer & Christman, 2023)

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Peak and Trough Levels 2

Medications have predicted reference ranges for peak and trough levels
Nurses must plan the administration of IV medications according to the timing of blood draws for peak and trough levels
Example

Gentamicin requires peak and trough levels to monitor nephrotoxicity and ototoxicity

(Ernstmeyer & Christman, 2023)

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Peak and Trough Levels 3

Peak level

5-10 mcg/mL (30 minutes after completion of a 30-minute infusion)

Trough level

< 2 mcg/mL (within 30 minutes before the next dose)

(Ernstmeyer & Christman, 2023)

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Interpreting Peak and Trough Levels 1

Peak levels above the therapeutic range may indicate toxicity and require dose reduction
Peak levels below the therapeutic range may indicate inadequate dosing and require dose increase

(Ernstmeyer & Christman, 2023)

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Interpreting Peak and Trough Levels 2

Trough levels above the therapeutic range may indicate accumulation and require dose reduction or increased dosing interval
Trough levels below the therapeutic range may indicate inadequate dosing and require dose increase or decreased dosing interval

(Ernstmeyer & Christman, 2023)

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Critical Thinking Question

A client is receiving gentamicin for a severe infection. The nurse is reviewing the client's peak and trough levels. Which result would indicate that the gentamicin dose needs to be adjusted?

Peak: 6 mcg/mL, Trough: 1.5 mcg/mL
Peak: 8 mcg/mL, Trough: 1.8 mcg/mL
Peak: 12 mcg/mL, Trough: 3 mcg/mL
Peak: 9 mcg/mL, Trough: 1 mcg/mL

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Therapeutic Index 1

Quantitative measurement of the relative safety of a drug
Compares the amount of drug that produces a therapeutic effect versus a toxic effect
A high therapeutic index indicates a wide margin of safety, as the toxic dose is much higher than the therapeutic dose
A low therapeutic index indicates a narrow margin of safety, as the toxic dose is close to the therapeutic dose

(Ernstmeyer & Christman, 2023)

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Therapeutic Index 2

High therapeutic index

Wide therapeutic window, relatively safe drug

Low therapeutic index

Narrow therapeutic window, dosage titrated according to blood levels

(Ernstmeyer & Christman, 2023)

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Therapeutic Index 3

Example

Phenytoin has a narrow therapeutic index and requires frequent peak and trough drug level monitoring

Therapeutic range

10 - 20 mcg/mL

Toxic level

> 30 mcg/mL

Subtherapeutic level

< 10 mcg/mL (increased risk of seizures)

(Ernstmeyer & Christman, 2023)

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Critical Thinking Question

A client with epilepsy is prescribed phenytoin. The nurse is reviewing the client's phenytoin levels and notes that the most recent level is 8 mcg/mL. What is the most appropriate nursing action?

Continue the current phenytoin dose
Increase the phenytoin dose
Decrease the phenytoin dose
Stop the phenytoin and notify the provider

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Answer: B. Increase the phenytoin dose

Explanation: The therapeutic range for phenytoin is 10-20 mcg/mL. In this question, the client's phenytoin level is 8 mcg/mL, which is below the therapeutic range (subtherapeutic). Subtherapeutic levels of phenytoin may not provide adequate seizure control. Therefore, the most appropriate nursing action is to increase the phenytoin dose to achieve a therapeutic level.

Options A, C, and D are incorrect because:

A. Continuing the current dose would not address the subtherapeutic level and may leave the client at risk for seizures.

C. Decreasing the dose would further lower the phenytoin level, making it even more subtherapeutic.

D. Stopping the phenytoin is not necessary as the level is not toxic, and abruptly stopping the medication could put the client at risk for seizures. The provider should be notified, but the medication should not be stopped without an alternative anti-epileptic medication in place.

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Therapeutic Drug Monitoring 1

Involves measuring drug concentrations in the blood to optimize therapy
Used for drugs with a narrow therapeutic index or high variability in client response
Peak levels are measured shortly after a dose to assess the maximum concentration

(Ernstmeyer & Christman, 2023)

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Therapeutic Drug Monitoring 2

Trough levels are measured just before the next dose to assess the minimum concentration
Nurses should be familiar with the therapeutic range for monitored drugs and alert the healthcare team if levels are outside this range

(Ernstmeyer & Christman, 2023)

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Comparison of Drugs with Broad and Narrow Therapeutic Indexes

Drug	Therapeutic Index	Therapeutic Range
Amoxicillin	Broad	N/A
Warfarin	Narrow	INR 2.0 - 3.0
Digoxin	Narrow	0.5 - 2.0 ng/mL
Acetaminophen	Broad	N/A

(Ernstmeyer & Christman, 2023)

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The Nurse's Role in Therapeutic Drug Monitoring

Understand the reasons for therapeutic drug monitoring and the drugs that commonly require it
Collect peak and trough levels as appropriate
Interpret the results in the context of the client’s clinical condition
Collaborate with the healthcare team to adjust medication doses as appropriate
Monitor the client for signs of toxicity or inadequate therapeutic response

(Ernstmeyer & Christman, 2023)

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Evaluating the Effects of Medications

Dosages should be verified to ensure they are within recommended safe ranges and potency
Potency

The amount of drug required to produce the desired effect

Selectivity

The separation between the desired and undesired effects of a drug

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Drug Selectivity Targeting Specific Cellular Pathways 1

Drug selectivity

The ability of a drug to specifically target a desired receptor, enzyme, or cellular process

Highly selective drugs interact only with their intended biological target, reducing off-target effects and adverse reactions
Less selective drugs may affect multiple targets

Increases the risk of side effects

(Ernstmeyer & Christman, 2023)

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Drug Selectivity Targeting Specific Cellular Pathways 2

Example

Beta-blockers selectively block beta-1 adrenoceptors in the heart, while minimizing effects on beta-2 receptors in the lungs

Clinical relevance

High selectivity → Fewer side effects and safer pharmacological profile
Low selectivity → Higher risk of adverse effects due to off-target interactions

(Ernstmeyer & Christman, 2023)

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Drug Potency: How Much Drug is Needed to Achieve an Effect? 1

Potency

The amount of drug needed to produce a specific therapeutic effect

Highly potent drugs require a lower dose to achieve the desired effect
Less potent drugs require higher doses for the same effect

(Ernstmeyer & Christman, 2023)

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Drug Potency: How Much Drug is Needed to Achieve an Effect? 2

Example

Fentanyl (highly potent opioid) → Effective at microgram doses
Morphine (less potent opioid) → Requires a higher milligram dose for the same level of pain relief

Clinical relevance

Higher potency does not mean greater efficacy; some potent drugs have serious side effects
Potency affects dosing considerations, risk of toxicity, and client response

(Ernstmeyer & Christman, 2023)

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Common Medications Requiring Blood Level Monitoring

Lithium (bipolar disorder)

Therapeutic range 0.6 - 1.2 mEq/L, toxic > 1.5 mEq/L

Digoxin (heart failure)

Therapeutic range 0.5 - 2.0 ng/ml, toxic > 2.5 ng/ml

Vancomycin (antibiotic)

Trough level 10 - 20 mcg/mL, peak level not routinely measured

Theophylline (asthma, COPD)

Therapeutic range 10 - 20 mcg/mL, toxic > 20 mcg/mL

(Ernstmeyer & Christman, 2023)

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Critical Thinking Question

A client is prescribed digoxin for heart failure. The nurse is monitoring the client's digoxin levels and notes that the most recent level is 2.8 ng/mL.

What actions should the nurse take based on this information?

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Factors Affecting Therapeutic Levels 1

Liver function

Impaired liver function can lead to drug accumulation and toxicity

Kidney function

Impaired renal function can lead to drug accumulation and toxicity

Age

Elderly clients may have reduced drug clearance and require lower doses

(Ernstmeyer & Christman, 2023)

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Factors Affecting Therapeutic Levels 2

Hydration status

Dehydration can lead to increased drug concentrations

Genetic variations in metabolism

Some clients may be poor or rapid metabolizers of certain drugs

(Ernstmeyer & Christman, 2023)

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Genetic Variability in Drug Metabolism 1

Some drugs (e.g., clopidogrel, codeine, warfarin) require genetic testing due to variations in metabolism
Differences in CYP450 enzyme metabolism affect drug efficacy and toxicity
Poor metabolizers

Reduced enzyme activity, higher risk of toxicity at standard doses

(Ernstmeyer & Christman, 2023)

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Genetic Variability in Drug Metabolism 2

Rapid metabolizers

Increased enzyme activity, may require higher doses for therapeutic effect

Example

Codeine is metabolized by CYP2D6 to its active form, morphine
Poor metabolizers may not achieve adequate pain relief
Rapid metabolizers may experience opioid toxicity at standard doses

(Ernstmeyer & Christman, 2023)

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Nursing Considerations for Medications Requiring Blood Level Monitoring

Monitor renal function (creatinine, GFR), hydration status, and electrolyte levels (potassium, sodium)
Assess for signs and symptoms of toxicity

Example: nausea, vomiting, diarrhea, dizziness, confusion

Collaborate with pharmacists and providers to adjust doses based on lab results and clinical status

(Ernstmeyer & Christman, 2023)

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Critical Thinking Question

A client is admitted to the hospital with a severe infection and is started on intravenous vancomycin. The client's vancomycin trough level is 8 mcg/mL. The nurse notes that the client's serum creatinine has increased from 1.0 mg/dL to 1.8 mg/dL since starting vancomycin therapy.

What should the nurse consider, and what actions should be taken?

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Explanation:

In this scenario, the client's vancomycin trough level is subtherapeutic (goal trough range: 10-20 mcg/mL), and the increased serum creatinine indicates a decline in renal function. Vancomycin is eliminated primarily by the kidneys, and impaired renal function can lead to drug accumulation and toxicity. The nurse should consider the following:

The subtherapeutic vancomycin level may not effectively treat the infection, but increasing the dose without addressing the renal function may lead to toxicity.

The decline in renal function may be due to vancomycin-induced nephrotoxicity or other factors such as sepsis or dehydration.

The nurse should take the following actions:

Notify the provider about the subtherapeutic vancomycin level and the increase in serum creatinine.

Assess the client's hydration status and monitor urine output.

Collaborate with the provider and pharmacist to adjust the vancomycin dose based on the client's renal function and vancomycin levels.

Monitor the client's renal function (serum creatinine, BUN) and vancomycin levels closely.

Assess the client for signs and symptoms of vancomycin toxicity, such as red man syndrome, ototoxicity, and further decline in renal function.

Educate the client and family about the importance of monitoring vancomycin levels and renal function during therapy.

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Side Effects vs. Adverse Effects 1

Side effects

Unintended but generally anticipated effects other than the intended effect
Example: nausea, vomiting, diarrhea, drowsiness

Adverse effects

Relatively unpredictable, severe, and harmful effects that require discontinuation of the medication

(Ernstmeyer & Christman, 2023)

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Side Effects vs. Adverse Effects 2

Example

An adverse effect to Ciprofloxacin is tendon rupture

Adverse effects should be reported to the pharmacy and tracked as a client safety concern

(Ernstmeyer & Christman, 2023)

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The Nurse's Role in Evaluating Medications: Assessment

Pre-administration assessment

Review client history
Renal/liver function
Drug interactions

Assess for contraindications and precautions
Obtain baseline vital signs and lab values

(Ernstmeyer & Christman, 2023)

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The Nurse's Role in Evaluating Medications: Monitoring

Check therapeutic drug levels according to the recommended schedule
Assess for signs and symptoms of toxicity

Example: nausea, arrhythmias in case of digoxin toxicity

Monitor for side effects and adverse reactions

(Ernstmeyer & Christman, 2023)

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The Nurse's Role in Evaluating Medications: Evaluation

Evaluate the effectiveness of the medication in treating the underlying condition
Assess for any changes in the client’s clinical status or lab values
Determine if the medication dose needs to be adjusted or discontinued

(Ernstmeyer & Christman, 2023)

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The Nurse's Role in Evaluating Medications: Intervention

Stop medication if drug levels are too high and notify the provider
Administer medications to manage side effects

Example: antiemetics for nausea

Implement interventions to prevent or manage adverse effects

Example: fall precautions for clients experiencing dizziness

(Ernstmeyer & Christman, 2023)

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The Nurse's Role in Evaluating Medications: Education

Explain the purpose of the medication and how it works
Educate clients on the importance of adhering to the prescribed dosing schedule
Teach clients how to recognize and report signs of toxicity

Example: Blurred vision in case of digoxin toxicity

Provide information on lifestyle modifications that can enhance the effectiveness of the medication

Example: Diet, exercise

(Ernstmeyer & Christman, 2023)

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The Nurse's Role in Evaluating Medications: Collaboration

Coordinate with pharmacists and providers to adjust doses based on lab results and clinical status
Participate in interdisciplinary rounds to discuss the client’s response to medication therapy
Communicate any concerns or changes in the client’s condition to the healthcare team

(Ernstmeyer & Christman, 2023)

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References

Ernstmeyer, K. & Christman, E. (2023). Open RN Nursing Pharmacology. Open RN. https://wtcs.pressbooks.pub/pharmacology2e/

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