Chief Complaint

"Doc, the drugs aren't working for my chest pain”!

HPIJack Palmer is a 72-year-old man with coronary artery disease. He is an avid golfer and prefers to walk the course, but this is becoming progressively more difficult for him due to frequent angina. He has had two coronary artery bypass operations in the past. A coronary angiogram performed 1 month ago revealed significant disease in the RCA proximal to his graft but this was considered high risk for angioplasty. His dose of isosorbide mononitrate was increased at that time from 60 to 120 mg once daily. This had no effect on his angina. He is still using about 30 nitroglycerin tablets a week, and these do relieve his chest pain. He reports that most often the chest discomfort comes on with activity, such as walking up slight inclines on the golf course. The discomfort is located in the center of his chest and rated as a 3–4/10 on average. He reports that the chest discomfort slowly fades as he slows his activity. He also complains of occasional lightheadedness with a pulse around 50 bpm and SBP near 100 mm Hg.

PMH . Acute anterior wall MI with CABG in 1976

. Posterior lateral MI in 1990 and PTCA to the circumflex at that time

. Redo CABG in 1998

. Ischemic cardiomyopathy

. Heart failure with an ejection fraction of 40%

. Dyslipidemia

. COPD (mild)

. Chronic low back pain

. Depression

FHNoncontributory for premature coronary artery disease

SHRetired dairy farmer, lives with wife, drinks occasionally, previous smoker—quit in 1998

MedsCarvedilol 6.25 mg twice daily

Digoxin 0.25 mg once daily

Lisinopril 5 mg once daily

Furosemide 40 mg once daily

Aspirin 325 mg once daily

Isosorbide mononitrate, extended release 120 mg once daily

MedsDiltiazem, extended-release 240 mg once daily

St. John's wort 300 mg three times daily

Celecoxib 200 mg once daily

Simvastatin 40 mg once daily

Nitroglycerin 0.4 mg SL PRN

NKDA

ROSNo fever, chills, or night sweats. No recent viral illnesses. No shortness of breath; occasional cough with cold weather. No nausea, vomiting, diarrhea, constipation, melena, or hematochezia. No dysuria or hematuria. No myalgias or arthralgias.

Gen

Pleasant, cooperative man in no acute distress

VS

BP 105/68, P 50, RR 22, T 36.4°C, Ht 5'11″, Wt 93 kg, waist circumference 43 in

Skin

Intact, no rashes or ulcers

HEENT

PERRL; EOMI; oropharynx is clear

Neck

Supple, no masses; no JVD, lymphadenopathy, or thyromegaly

Lungs

Bilateral air entry is clear. No wheezes.

CV

RRR, S1, S2 normal; no murmurs or gallops; PMI palpated at left fifth ICS, MCL

Abd

Soft, NT/ND; bowel sounds normoactive

Genit/Rect

Heme (–) stool

Ext

No CCE; pulses 2+ throughout

Neuro

A & O x 3, CN II–XII intact; speech is fluent; no motor or sensory deficit; no facial asymmetry; tongue midline

Na 137 mEq/L

K 4.8 mEq/L

Cl 103 mEq/L

CO2 21 mEq/L

BUN 24 mg/dL

SCr 1.2 mg/dL

Glu 98 mg/dL

Hgb 11.8 g/dL

Hct 35.1%

Plt 187 x 103/mm3

 

WBC 7.9 x 103/mm3

 

MCV 77 m3 MCV 77 m3

MCV 77cm3

MCHC 29 g/dL

Chol 202 mg/dLLDL 125 mg/dL

HDL 38 mg/dL

Trig 215 mg/dL

MCV 77 m3 MCV 77 m3

Fasting lipid profile:

Digoxin serum concentration: 1.8 mg/ml

Sinus rhythm, first-degree AVB, 50 bpm, old AWMI, no ST–T wave changes noted, QT/QTc 406/431

Assessment

A 72-year-old man with poorly controlled angina on multiple medications who is a poor candidate for angioplasty

Clinical Pearl

The COURAGE trial made major headlines in 2007 by showing that coronary stenting with optimal medical therapy is no better at preventing future coronary events than optimal medical therapy alone in patients with stable coronary disease, potentially saving the US health care system $5 billion a year.14

Problem Identification

1.a. What drug-related problems appear to be present in this patient?

•Angina pectoris, poorly controlled on current drug therapy

•Dyslipidemia, poorly controlled •More safe drug is recommended instead of Diltiazem

because of his mild HF •Unsafe drug is been using Celecoxib due to increase risk

of CVD •Safety dosage regimen issues ( digoxin ,aspirin ) •Metabolic syndrome (abdominal obesity, elevated

triglyceride and low HDL-C )

1.b. Could any of these problems potentially be caused or exacerbated by his current therapy?

•Medical management of angina must take into considerationthe patient’s hemodynamic status and left ventricular function.

Although CCB and BB are both reasonable antianginal drugs, they are likely the cause of his relatively low heart rate and blood pressure and associated lightheadedness.

According to the American Heart Association (AHA)/AmericanCollege of Cardiology (ACC) guidelines, he should remain on aβ-blocker such as carvedilol, if possible, to slow progression ofsystolic heart failure but diltiazem is a poor choice in a patientwith left ventricular dysfunction as it is known to depress myocardialcontractility.

•According to a recent statement by the AHA, selective COX-2 inhibitors such as celecoxib increase the risk of myocardial infarction, stroke, heart failure, and hypertension .

Questions

2 .What are the goals of pharmacotherapy for IHD in this case?

Short term :Stabilize chest pain and discomfort and reduce and stabilize angina symptoms Prevent ischemia and subsequent infarctionImprove exercise tolerance and quality of life Long term :Prevent primary or secondary CV event MI HF Stabilize the pattern of chest painDecrease overall CV morbidity and mortality

Desired Outcome

3.a. Does this patient possess any modifiable risk factors for IHD?

Therapeutic Alternatives

• He has poorly controlled dyslipidemia. His LDL-C and triglycerides are too high, and his HDL-C is too low. Hypercholesterolemia is a significant cardiovascular risk factor, and risk is directly related to the degree of

cholesterol elevation. (target LDL <100 mg/dL; <70 mg/dL in patients with CHD and multiple risk factors is reasonable ) Additional goals include HDL-C greater than 40 mg/dL and triglycerides less than 150 mg/dL. Because his triglycerides are in the range of 200–499 mg/dL, a secondary target is non-HDL cholesterol <130 mg/dL.

• Alcohol ingestion in small to moderate amounts (<40 g/day of

pure ethanol) reduces the risk of coronary heart disease; however,

consumption of large amounts (>50 g/day) or binge drinking ofalcohol is associated with increased mortality from stroke,

cancer,vehicular accidents, and cirrhosis

• Body mass index is associated with an increased mortality ratio compared with individuals of normal body weight, and the objective for patients with IHD is to maintain or reduce to a normal body weight

• This patient meets the criteria for the definition of metabolic syndrome on the basis of abdominal obesity, elevated triglycerides,and low HDL-C.

ATP III1 identified 6 components of the metabolic syndrome that relate to CVD:

.11 )Abdominal obesity It presents clinically as increased waist circumference. Waist circumference ≥40 in (102 cm) in men and ≥35 in (88 cm) in women

2 )Atherogenic dyslipidemia raised triglycerides and low concentrations of HDL cholesterol. HDL-C <40 mg/dL in men and <50 mg/dL in women Triglycerides ≥150 mg/dL

3) Raised blood pressure ≥130/85 mm Hg

4) Insulin resistance ± glucose intolerance

5) Proinflammatory state recognized clinically by elevations of C-reactive protein (CRP), is commonly present in persons with metabolic syndrome. 

6) Prothrombotic statecharacterized by increased plasma plasminogen activator inhibitor (PAI)-1 and fibrinogen, also associates with the metabolic syndrome.

• He is currently taking celecoxib for low back pain, which may put him at risk for cardiovascular events.

All NSAIDs are associated with an increased risk of serious (and potentially fatal ) adverse cardiovascular thrombotic events, including MI and stroke

Risk may be increased with duration of use or pre existing cardiovascular risk factors or disease

3.b. What pharmacotherapeutic options are available for treating this patient's IHD? Discuss the agents in each class with respect to their relative utility in his care.

We use nitroglycerine to relieve acute symptom

Pharmacotherapy to prevent recurrent ischemic symptom-Beta blocker -Calcium channel blocker -Long acting nitrate -Ranolazine

Pharmacotherapy to prevent acute coronary syndromes and death

( vasoprotictive agent )-Antiplatlet agent-Statin-ACE inhibitors and ARB -Control of risk factors

Nitrate Nitrate therapy should be first step in managing acute attack for patient

with chronic stable angina or for prophylaxis of symptoms.its leading to reductions in preload and afterload reduction of myocardial oxygen demand ,Nitrate –free interval (10-12 hours/day) is recommended to avoid tolerance development .

Nitroglycerin (NTG) : Nitroglycerin concentrations are affected by the route of administration, with the highest concentrations usually obtained with intravenous

administration, the lowest seen with lower oral doses

Isosorbide dinitrate (ISDN): Chewable, oral, and transdermal products are acceptable for the long-term prophylaxis of angina, its given 1 tablet three to four time daily.

Isosorbide mononitrate (ISMN): is available in two types of oral formulations:

Regular release tablet : initial 5-20 mg BID with the 2 doses given 7 hours apart (eg. 8AM and 3PM )to decrease tolerance development

Extended release tablet : initial 30-60 mg given once daily in the morning ;titrate upword as needed maximum daily dose : 240 mg

Calcium channel blockers (CCBs) Calcium channel antagonists have the potential advantage of improving

coronary blood flow through coronary artery vasodilation as well as decreasing MVO2. Calcium antagonists may provide better skeletal muscle oxygenation, resulting in decreased fatigue and better exercise tolerance.

Patients with conduction abnormalities and moderate to severe LV dysfunction (ejection fraction <35%) should not be treated with verapamil and Diltiazem whereas amlodipine may be safely used in many of these patients.

We must consider that this patient has a relatively low heart rate and moderate LV dysfunction. Therefore, use of a negative inotrope such as diltiazem is inadvisable.

B-blockers β-blockers may be preferable because of less-frequent dosing and

other properties inherent in β-blockade (e.g., potential cardioprotective effects, antiarrhythmic effects, lack of tolerance, and antihypertensive effects), as well as their antianginal effects and documented protective effects in post- MI patients.

Decreased heart rate, decreased contractility, and a slight to moderate

decrease in blood pressure with β-adrenergic receptor antagonismreduce MVO2

Carvedilol is a nonselective beta-adrenergic blocking agent with a1 blocking activity

This patient has mild COPD but seems to be tolerating his carvedilol well at present.

Ranolazine Ranolazine exerts antianginal and anti-ischemic effects

without changing hemodynamic parameters (HR & BP)

Ranolazine doesn’t relieve acute angina attack.Has been shown to prolong QT interval

We need to avoid grapefruit –contaning product or dose adjusment of ranolazine may be required

St John’s wort may decrease the serum concentration of ranolazine

With moderate CYP3A inhibitors (e.g., diltiazem, verapamil, erythromycin), the ranolazine dose should be limited to 500 mg twice daily.

Antiplatelet

ACE inhibitors

Statins

Optimal Plan

4 .Given the patient information provided, construct a complete pharmacotherapeutic plan for optimizing management of his IHD.

Outcome Evaluation

5. When the patient returns to the clinic in 2 weeks for a follow-up visit, how will you evaluate the response to his new antianginal regimen for efficacy and adverse effects?

Efficacy:We need to ask him :about the number and severity of anginal attacks

and what provoke his anginal pain .and for how long its

remain

Does sublingual NTG relieve the pain? Have any attacks

occurred at rest which is a sign of unstable angina and would require hospital admission?

Adverse effects: We need to Check vital signs.: heart rate and

blood pressureWe would ask if he had any of these symptoms

dizziness, lightheadedness, headache, andfacial flushing. Because we want to give him amlodipine

instead of diltiazem we need to check if he had any edema

We need to be careful about sign of bleeding

Questions Patient Education

6 .What information will you communicate to the patient about his antianginal regimen to help him experience the greatest benefit and fewest adverse effects?

Nitroglcerin SL 1 )Used at start of angina if the pain not

released you can take another one after 5 mint and if the pain also not released you can take another one after 5 mint and if the pain is not reliesed after 5 mint you must to go to emergency beceuse of MI ( acute condition )

2 ) Stor them away of heat and moisture and light

Aspirine 1 )aspirin is give you some protection against

recurrence MI or occurring of stroke2 )if you feel any pain in your stomach or you

see blood in the stool you must to tell your doctor

Metoprolol XL1 )you must to check your pulse daily because this

drug reduce the HR

2 ) you may feel dizziness or fatigue

Celecoxib

We stop using this drug because it increase the risk of

MI and stroke

ISMNThis drug have high tolerance but you take it once daily so no tolerance will occur

Amlodipine

We replace diltiazm by this drug because your HR is low and this drug has less effect on HR than diltiazm but may feel some dizziness and fatigue

Ranalozine

We give you this drug to improve your ischemic condition and this drug has also less effect on BP and HR so this good in your case because your pulse is low and your BP also low

May have some nausea and constipation and headache