Case Study

CASE STUDY Background Case studies are based upon the real cases that are quite commonly encountered in the every day practice of medicine and pharmacy. How the cases are presented and what a pharmacist has to play a role is the basic theme of these case studies.

Learning objectives Following are the learning objectives of the case studies: • • • • • • • •

To have the knowledge of the disease and particular condition under consideration What routine tests should be carried out once the patient is brought to the emergency of a hospital To identify the practical implication of CORE, PRIME and FARM in a pharmaceutical care What initial drugs may be prescribed Rationale for the use of different drugs and treatments used How a pharmaceutical care is planned (PWDT) How the drug therapy is monitored How the outcome of the therapy may be evaluated

Hashmi Furqan

UCP, PU

CASE STUDY 01 52 years old Mr. ABC is brought to the hospital emergency following the onset of chest pain approximately two hours earlier while he was replacing some plumbing in a house. He tried several doses of sublingual glyceryl trinitrate (GTN), but his pain had not resolved. He became increasingly breathless and clammy with tight crushing pain across his chest and left shoulder. His past medical history reveals him as a patient of angina. Mr. ABC was noted to be as obese; his past drug history revealed on admission was nifedipine and isosorbide mononitrate (doses unknown at the time of admission). On examination: blood pressure 150 / 110 mmHg with heart rate 112 beats / minute Discussion: Whenever such patient is with the presenting complaints is brought to the emergency patient having typical attack of angina, it is suspected that patient is suffering from myocardial infarction. There are several questions which need to be addressed in dealing such type of patient. SATGE I Questions 1. What routine tests should be carried out to confirm a diagnosis of acute myocardial infarction (AMI)? Mr. ABC was initially prescribed one dose of each of the following drugs: • Morphine 2.5mg I.V • Metoclopramide 10mg I.V • Aspirin 300mg P.O 2. What actions of morphine are particularly useful in AMI? 3. Why is metoclopramide necessary? What alternative anti-emetics could be considered? 4. Why should intramuscular injections generally be avoided in patient suffering with AMI? 5. What is the rationale for aspirin administration during AMI? 6. What other therapies should be considered at this stage? The first step that is usually taken for such type of patients is ECG. ECG revealed ST elevation (2—3mm) in leads V2—V4 which shows an evidence of ischemia in the lateral leads indicating that Mr. ABC has suffered an anterior MI. Having done ECG has revealed a typical case of AMI. The ECG is followed by routine laboratory tests. Blood sample is drawn and sent to laboratory. Laboratory findings • Qualitative troponin (negative) (trop-T test) Hashmi Furqan

UCP, PU

• • • • • • • • • •

Creatine kinase (CK) result not yet available (see discussion portion) Sodium 138mmol/L (135—145mmol/L) Potassium 3.8mmol/L (3.5—5.0mmol/L) Creatinine 104mmol/L (45—120) Urea 6mmol/L (3.3—6.7mmol/L) Glucose 18mmol/L (3—7.8mmol/L) Hb 14.2g (14—18) RBC 6.4 x 1012 /L (4.6—6.5) WBC 6.1 x 109 /L (4—11) Platelets 167 x 109 (150—400)

STAGE II DAY 1 FINDING On basis of analysis of the ECG a decision should be taken to thrombolyse Mr. ABC. • A bolus dose of streptokinase (1 h infusion) / tenecteplace 50mg / alteplase (bolus + 90 min infusion) was administered. • I.V heparin • Sliding scale insulin infusion (high blood sugar as found in the lab report) 7. What is the rationale for thrombolysis in the management of AMI? 8. When should thrombolysis be administered to gain maximal benefit? 9. What are the contra-indications to thrombolysis? 10. What pharmaceutical issues should be considered when choosing a thrombolytic? 11. What monitoring should be undertaken for patients prescribed and administered thrombolytic therapy? 12. What alternative strategies could be employed when thrombolysis is contraindicated? 13. Is I.V heparin indicated for this patient? 14. What other therapies might be considered at this stage? Since Mr. ABC was successfully thrombolysed it should be transferred to coronary care unit for further and better care. On the arrival to CCU Mr. ABC was still breathless although his chest pain was resolved. A repeat ECG is recommended at this stage—showed resolution of ST segment indicating a successful thrombolysis. As the patient is still breathless at this stage, chest X-ray should be requested—the X-ray showed pulmonary edema. At this stage blood gas estimation should be done (pulseoxymetry can also be used). As a result of pulmonary edema the oxygen saturation is usually reduced. So on this basis an oxygen therapy should be initiated. For pulmonary edema furosemide I.V (dose selected on the basis of severity of edema) should be infused over a period of 20 minutes.

Hashmi Furqan

UCP, PU

Blood pressure and heart rate are monitored periodically (usually the ECG monitors showing all parameters are in place as long as patient is kept in CCU). At this stage B.P = 105/65 mmHg and HR 103 beats/min Mr. ABC prescribed with • Morphine 2.5—5 mg I.V (as required) • Metoclopramide 10mg I.V q 8hr (may be PO depending upon patient condition) • GTN 400mcg S/L (when required) • Humidified oxygen at 4L/min • Human insulin 50U in 500ml to run over 24hr s (sliding scale) • Aspirin 75mg PO daily STAGE II DAY 2 FINDINGS Following IV furosemide (three doses) Mr. ABC settled with no further episodes of chest pain and oxygen saturation also improved. A repeat X-ray showed a good response to diuretic therapy with resolution of pulmonary edema. On the ward round a cardiac echo was requested alongside repeat blood tests. B.P = 94/63mmHg

HR = 88 beats / min

Laboratory results • • • • • • • • •

Na 143 mmol/L K 3.1 mmol/L Glucose 4.8 mmol/L Urea 5 mmol/L Creatinine 110 micromol/L Hb 13.2g/dL RBC 5.2 x 1012 /L WBC 6.0 x 109 /L Platelets 172 x 109 /L

(135—145) (3.5—5.0) (3—7.8) (3.3—6.7) (45—120) (14—18) (4.5—6.5) (4—11) (150—400)

Total cholesterol 5.6 mmol/L Triglycerides 4.2 mmol/L On the basis of the above report there are several questions of concern 15. Outline a pharmaceutical care plan for Mr. ABC. 16. Why is his potassium level a cause of concern? What other electrolytes should be monitored closely? 17. Comment on drugs Mr. ABC was taking prior to admission.

Hashmi Furqan

UCP, PU

DAY 2 (PM) Mr. ABC continued to respond well to treatment and was beginning to mobilize (BP = 92/50mmHg and HR = 72 beats/min) Echocardiography report: marked hypokinesia of anteroseptal region of left ventricle Ejection fraction of 35—40%-- indicating compromised ventricular function. Mr. ABC was started Ramipril 1.25mg initially then 2.5mg twice daily plus Pravastatin* 20mg at night. Further questions of concern that may arise: 18. What is the rationale for ACE-I post-MI? 19. Should beta-blocker therapy be considered? 20. What advice should be given for initiation of beta-blockers? 21. Comment on Mr. ABC’s cholesterol. 22. How should the cholesterol be addressed? 23. How should the blood sugar levels be controlled over longer term? DAY 5 Mr. ABC has made a good progress over past three days although he complained about the dry cough. • • • • • •

BP = 95/56mmHg HR 58 beats/min Na 141 mmol/L K 4.2 mmol/L Glucose 5.1 mmol/L Urea 5.3 mmol/L Creatinine 121 micromol/L

On discharge he was stablished on following regimen RX • • • • • •

Aspirin 75mg PO daily Ramipril 2.5mg PO q 12hr Carvedilol 3.125mg PO q 12hr Pravastatin 40mg PO daily at night Human insulin 70/30 8U in morning 10U evening GTN S/L as required

Hashmi Furqan

UCP, PU

24. What lifestyle issues should be discussed? 25. What issues should be highlighted during discharge counseling for this patient?

*Why a statin has been added? Why pravastatin?

No Questions

Answers

1

A 12-lead ECG should be performed & blood sample for measurement of troponin and/or creatine kinase (CK) levels

What routine tests should be carried out to confirm a diagnosis of AMI?

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What actions of diamorphine are particularly useful in AMI?

Morphine has analgesic, anxiolytic and vasodialating effects

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Why is metoclopramide necessary? What alternative anti-emetics could be considered?

Hashmi Furqan

During the acute phase of MI majority of the patients suffer from significant nausea and vomiting. Metoclopramide can easily be administered I.V for rapid onset of action

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12-lead ECG is the key diagnostic tool. Cardiac enzyme measurements are used to determine the presence or absence of myocardial necrosis. CK and CK isozymes are routinely used for the diagnosis of AMI. Other markers include Myoglobin & lactic dehydrogenase. Limitations—CK may be raised after several hours of the onset of MI. CKMB is increased only after significant damage have occurred (cannot detect smaller areas of ischemic damage) Troponin levels are raised within 3—12 hrs after the onset of pain (even on slight damage) Any increase in the level of these biomarkers indicates some degree of myocardial damage. But only ECG changes can help diagnose AMI, also called as STEMI. Repeat CK and Troponin may be used to confirm the working diagnosis and extent of damage in AMI. All of these effects are beneficial in AMI. Analgesia is required to provide immediate relief form chest pain Vasodilatation caused by this drug improves the blood supply to myocardium and contribute to antiischemic effects The anxiolytic effects calm the patient and help in the administration of further therapy Cyclizine 50mg up to three times a day would a suitable alternative; this agent may reduce the blood pressure quite significantly resulting in reduced cardiac output.

UCP, PU

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Why should intramuscular injections generally be avoided in patient suffering with AMI?

What is the rationale for aspirin administration during AMI?

Ck levels can be increased following IM injection, which may confuse the diagnosis of AMI. In addition IV injection allows rapid and predictable onset of action.

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In acute phase the administration of aspirin has been shown to reduce mortality at 5 weeks by approximately 23%

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What other therapies should be considered at this stage?

At this stage the diagnosis in unclear. A number of potential therapies should therefore be under consideration (STAGE-I)

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What is the rationale for thrombolysis in the management of AMI?

Thrombolytic therapy has shown to reduce fiveweek mortality in patients suffering AMI by 18% with benefits being maintained for up to 10 years

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When should thrombolysis be administered to gain maximal benefit?

Hashmi Furqan

Thrombolytic therapy should be administered as soon as possible after the onset of symptoms to gain maximum benefit from the treatment

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A number of non-cardiac problems including cardiac resuscitation, IM injection, diabetes mellitus, skeletal muscle damage and alcoholism can increase CK levels (limiting CK usefulness in MI diagnosis) Troponin release is not entirely specific to MI, it should be cautiously interpreted in the presence of acute renal failure. A study demonstrated that administration of aspirin has reduced mortality & morbidity associated with AMI. A dose of 300mg should be administered immediately regardless of its prior use. Patient is advised to chew the tablet before it is swallowed, which aids early absorption Aspirin also shown to reduce the occlusion and reinfarction Aspirin should be continued indefinitely post-MI at a dose of 75— 150mg / day. Heparin, glycoprotein IIb/IIIa receptor antagonists or thrombolysis with or without I.V beta-blockers my be indicated Patients with ongoing chest pain and ventricular dysfunction may be benefited from I.V GTN. Oxygen should be administered to improve the supply to myocardium and prevent further ischemic damage. Majority of MIs are caused by obstruction of blood flow in coronary arteries due to the formation of blood clot. Thrombolytic therapy is targeted to break the occluded thrombus via fibrinolysis. Thrombolytic therapy limits the infarct size, preserves left ventricular function & reduces deaths. An early treatment has shown to reduce the mortality and survival from AMI. Thrombolytic therapy has significant benefits when administered within 12 hrs of onset of symptoms. Thrombolytic activity within 6 hrs has more benefits than used within 12hrs

UCP, PU

9

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What are indications thrombolysis

contrato

What pharmaceutical issues should be considered when choosing a thrombolytic?

Absolute contraindication—therapy must not be administered Relative contra-indication —the benefits and risks of therapy must be considered for individual patient requiring treatment A number of issues should be considered like comparative efficacy, dose, method of administration and adverse effects

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What monitoring should be undertaken for patients prescribed and administered thrombolytic therapy?

Patients should be monitored closely throughout thrombolytic therapy as they are at risk of hemodynamic instability, reperfusion arrhythmias or other complications. Clinical efficacy of the thrombolysis should be assessed at 90 minutes with repeat ECG.

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12

What alternative strategies could be employed when thrombolysis is contraindicated?

The most effective strategy for managing AMI is primary angioplasty, this has shown to be superior to thrombolytic therapy

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• 13

Is I.V heparin indicated in this patient

Hashmi Furqan

Yes, I.V heparin should be administered at the same time along with other thrombolytic agents & be continued for a minimum period of 48hrs. The use of heparin during thrombolysis is agent dependent.

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Absolute contra-indication—previous hemorrhagic stroke, any cerebrovascular event within the previous year, active internal bleeding Relative contra-indication— uncontrolled hypertension (systolic BP > 180mmHg), anticoagulant therapy or bleeding disorder, recent trauma or major surgery, pregnancy. A number of thrombolytic agents are licensed and can be distinguished from one another on the basis of their pharmacokinetic and pharmacodynamic profiles. The significance of alteplase is that it is free from any allergic potential compared to streptokinase 65% of the total dose is given during the first 30 minutes of 90 minute infusion. Blood pressure monitoring (hypotension may occur), heart rate and rhythm should be monitored ECG carried out after 90 minutes should show resolution of ST-segment indicating a successful thrombolysis Allergic may occur (streptokinase) Complications may be –hemorrhagic stroke, haematuria, epistaxis, haematemesis Full blood count should be done before and after the therapy Patients are at risk for up to 4 days following the administration of thrombolytic therapy. In patients presenting late myocardial damage is likely to be irreversible Standard therapies like heparin, GTN & aspirin may be considered if there is ongoing pain with referral for early angioplasty. I.V beta-blockers may also be used to reduce the occurrence of ischemia related tachyarrythmias The adjunctive use of heparin is necessary to protect against reocclusion. Streptokinase should not be coadministered with heparin due to greater risk of cerebral bleeding and requires transfusions. I.V. dose should be weight adjusted and initiated with a bolus dose

UCP, PU

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What other therapies might be considered at this stage?

Outline pharmaceutical care plan

In view of this patient’s high glucose levels an intensive insulin regimen should be initiated to ensure tight control of blood sugar in order to improve survival Pharmaceutical care plan is made to address the needs of the patient & to handle any drug-related problems that may arise during the treatment

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Why potassium level a cause of concern? What other electrolytes should be monitored closely?

Comment on drugs Mr. ABC was taking prior to admission

Hashmi Furqan

A reduction in serum K may predispose the patient to post-infarction arrhythmias. Serum Mg & Ca should also be monitored & corrected to further protect against arrhythmia. Serum Na, creatinine & urea should be monitored throughout diuretic therapy The drug therapy of Mr. ABC on admission i.e. Nifedipine & isosorbide mononitrate should be reviewed

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Close monitoring of APTT is required. An aggressive blood sugar control approach is required Sliding-scale insulin therapy is recommended for first 24hrs with blood glucose levels raised above 11mmol/L Ensure evidence-based strategies are introduced in a timely manner Drugs initiated at an appropriate time & dose titrations are undertaken Monitor efficacy, drug interactions & adverse effects. Notify relevant staff an advise on alternatives if necessary Ensure nursing staff is administering I.V therapy correctly Ensure secondary preventive therapies are initiated Ensure adequate lifestyle advice is given and the patient is being followed up by appropriate specialist Ensure appropriate information on aims of therapy, doses (post-discharge), duration of treatment and monitoring are provided Counsel the patient on discharge including rationale for therapy, appropriate monitoring, possible side effects & how to deal with them and how therapies should be continued in future Fall in serum K levels is secondary to excessive catecholamine release in response to pain and anxiety caused by AMI. In addition repeated insulin administration and diuretic therapy reduces serum K levels. I.V or oral K-supplements can be used

Nifedipine may increase early mortality post-MI and is not associated with reduction in cardiac events. It should therefore be discontinued Isosorbide mononitrate is an effective anti-anginal therapy, it has not shown to improve outcomes in such patients, more suitable alternatives with secondary benfits may be considered

UCP, PU

18

What is the rationale for ACEI post-MI? How should ACEI therapy be initiated?

A number of reference studies have demonstrated the benefits of use of ACEI post-MI

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Should beta-blocker therapy be considered at this stage?

What advice would you give about the initiation of a betablocker?

Hashmi Furqan

Beta-blockers have been shown to reduce mortality and morbidity post-MI & should therefore be considered for Mr. ABC. Consideration should be made of his concurrent heart failure and reduced ventricular ejection fraction, which may make early use of beta-blockers inappropriate and will also influence the choice of agent and dose regimen chosen

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Beta-blocker therapy should be initiated cautiously starting at low dose with careful monitoring of BP and HR and symptoms of heart failure. The patient’s symptoms may be aggravated during dose adjustment; a diuretic therapy may be required. Occasionally a step-down in beta-blocker dose may be required.

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ACEI therapy should be initiated in all patients post-MI. The greatest benefits from therapy are seen in patients with reduced ventricular ejection fraction, anterior infracts or tachycardia (refer to the echocardiography report) An early initiation of ACEI (within 24hrs) is recommended. ACEI should be initiated at low doses to avoid the problem of first-dose hypotension (Mr. ABC’s BP & HR should be monitored closely) Early use of IV beta-blockers is recommended in most of the case but in case of Mr. ABC its early use is inappropriate because of left ventricular dysfunction (echo cardiography). Beta-blocker therapy may be initiated after few days based upon the evidence that this patient remains clinically stable. Carvedilol may be used (see reference link ). The concomitant use of ACEI and betablockers post-MI is recommended. ACEI therapy should be optimized before the addition of beta blockers Sometimes the concomitant use of both ACEI and beta-blockers may be limited on the basis of consistent low BP. Mr. ABC as found in the echo report has left ventricular dysfunction therefore the references found show that beta-blockers may be used with caution in such patients starting with low dose and that requires monitoring of BP, HR and blood gases as well It is always advisable that beta-blockers should be initiated after a few days followed by the settling of clinical symptoms of the patient.

UCP, PU

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Comment on Mr. ABC’s cholesterol.

How should Mr. ABC’s cholesterol levels be managed?

Mr. ABC has raised cholesterol level which indicates an increased risk of coronary heart disease. Lipid-lowering therapy should be initiated as reducing serum cholesterol has been shown to reduce the risk of death, reinfarction or other cardiovascular events. This patient should be given dietary advice in combination with initiation of a statin.

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23

How should Mr. ABC’s blood sugar levels be controlled over the longer term?

A S/C insulin regimen should be initiated on cessation of his slidingscale I.V. insulin

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Hashmi Furqan

Cholesterol levels should be measured within 24hrs of onset of symptoms, as after 24hrs cholesterol levels have been shown to fall and remain low for approximately three months. In the case of Mr. ABC the cholesterol cannot be measured in fasting state therefore total cholesterol levels can be considered reliable.

The patient is encouraged to reduce his total intake of fat in particular saturated fats. Increase intake of vegetables and fiber. If he smokes, cessation of smoking is encouraged. Statin cause greater reduction in LDL. Reducing cholesterol has reduced the risks of death, reinfarction and other cardiovascular events. The preferred regimen for this patient is the combination of a long acting (basal) insulin with short-acting soluble insulin at meal time to mimic physiologic insulin patterns. Patient assessment, careful selection of insulin dose and administration device and patient education is key to a successful therapy

UCP, PU

REFERENCES • • • • • • • • •

D.K.Scott, J.Dwight, coronary heart diseases, chpt. 20, Clinical Pharmacy & therapeutics 4th ED. Roger Walker Linda J Dodds, Drugs in Use, 3rd ED Russell J Greene, Norman D Harris, Pathology & therapeutics for Pharmacists, Chpt 3, Cardiovascular System. BNF 52, September 2007. David S. Tatro, Drug Interaction Facts 2008, The Authority on Drug Interactions Stockley’s Drug Interaction 6th ED. James E. Tisdale, Drug-induced Cardiovascular Diseases. Kevin M. Swinski, Ischemia and Myocardial Infarction. Brett Cucchiara, MD; Steven Messé, MD Scott E. Kasner, MD, Danger of Treatment Protocols in MI. http://www.rxlist.com/cgi/generic/carvedilol_ids.htm (indicated in left ventricular dysfunction following MI)

Ramipril  Aspirin

Hashmi Furqan

UCP, PU