CASE # 4.
A 62 years old business man presented to A & E department of Hospital with Central Chest Pain. He was partially relieved by Sublingual GTN. On examination he was tachyarrythemic with B.P. 155/95 mm of Hg. His past medical history revealed that he experienced Angina. His attacks become more frequent over last few weeks & symptoms were partially relieved by Sublingual GTN. He also had Type 2 diabetes. BSR 11 mmol/L. He is hypercholesterolimea. Fasting cholesterol was 7.2 mmol/L. He was treated in hospital for five days & Angina was relieved.
He was prescribed follow up therapy as:
Rx
Aspirin 75 mg 1 tab p.o. /day
Ranitidine 150 mg 1 tab b.i.d
Isosorbide MN 40 mg 1 tab O.D
Atenolol 100 mg 1 tab p.o. O.D
Simvastatin 20mg 1 tab p.o H.S
Ramipril 2.5 mg 1 tab. O.D.
Metformin 850 mg 1 tab b.i.d
Clopidogrel 75 mg 1 tab p.o. /day
GTN s/l 0.5 mg SOS
1. What tests should be performed to evaluate his past 3 month sugar fluctuations?
2. What are the aims of treatment of Angina
3. How long he should be kept on anti-platelet therapy?
4. What point should you like to discuss with patient?
5. Write rationale of use of each drug?
6. Find the interactions and manage them.
1. TESTS FOR PAST 3 MONTHS SUGAR FLUCTUATIONS:
1. HbA1c is a test that measures the amount of glycosylated hemoglobin in your blood. Glycosylated hemoglobin is a molecule in red blood cells that attaches to glucose (blood sugar). You have more glycosylated hemoglobin if you have more glucose in your blood.
The test gives a good estimate of how well diabetes is being managed over the last 2 or 3 months. Alternative Names are: Glycosylated hemoglobin; Hemoglobin – glycosylated; A1C; GHb; Glycohemoglobin; Diabetic control index .It is used to measures your blood sugar control over several months. In general, the higher your HbA1c, the higher the risk that you will develop problems such as eye disease, kidney disease, nerve damage, heart disease, and stroke. This is especially true if your HbA1c remains high for a long period of time. HbA1c is normal if it is 5% or less. Normal ranges may vary slightly depending on the laboratory used. Abnormal results mean that your blood glucose levels have not been well-regulated over a period of weeks to months. If your HbA1c is above 7%, it means your diabetes is poorly controlled.
High values mean you are at greater risk of diabetic complications. If you can bring your level down, you decrease your chances of long-term complications.
Patient should try to keep your level below 7%.
2. AIMS OF TREATMENT OF ANGINA:
The main aims of treatment are:
i. to ease pain quickly if it occurs,
ii. to prevent angina pains as much as possible,
iii. to limit further atheroma or plaques (deposits of fatty substances) from forming in the coronary arteries. This prevents or delays the worsening of the condition,
iv. to reduce the risk of having a heart attack.
3. ANTIPLATELET THERAPY DURATION:
• Clopidogrel, in combination with low dose aspirin is licensed for acute coronary syndrome without ST – segment elevation.
• In this situation, the combination is given for at least 1 month but usually no longer than 9-12 months.
• However long use of Clopidogrel with aspirin increases the risk of bleeding and the evidence of benefits of such use is not compelling.
• Clopidogrel is restricted for use in confirmed Acute coronary Syndrome (without ST-segment elevation).
4. DISCUSSION WITH PATIENT:
• The patient is HYPERLIPIDAEMIC (Hypercholesterolaemic) so lipid lowering strategies are discussed with the patient as:
a. To reduce the total fat intake e.g. Dairy products. Fish and poultry should be substituted.
b. Low fat skimmed milk should be substituted for full fat varieties.
c. Pastries and cakes should be avoided.
d. Saturated fats should be replaced with unsaturated oils.
e. Reduce total cholesterol intake. Eggs and prawns are rich source of Cholesterol but they don’t contribute to body’s cholesterol pool.
f. Increased intake of fibrous foods such as vegetables, pulses etc.
g. Avoid alcohol and achieve ideal body weight.
• The patient is advised to take Simvastatin for long term therapy, so he should be advised to measure the LFT’s periodically.
• The patient is Type 2 Diabetic, Hyperlipidaemic and having cardiovascular disorders so he should be thoroughly examined during hospitalization and afterwards to reduce following risk factors.
a. Macrovascular complications (Stroke, MI, Amputation of foot for gangrene, Insulin resistance, priteinuria)
b. Microvascular complications include disease process at:
i. Retina
ii. Renal Glomerulus.
iii. Nerve sheets. (All contribute to Diabetic retinopathy, nephropathy and neuropathy)
c. The patient should be advised for a regular checkup during therapy.
d. Regular checks may include:
i. Biochemical assessment, body weight, B.P.
ii. Measure plasma liquids, visual activity, state of retina, urine tests, RFT’s, LFT’s etc.
• The patient is advised to take Antiplatelet Drug combination (Aspirin, Clopidogrel) for long term therapy, so he should be awared of the risk of bleeding and the evidence of benefits of such use is not compelling.
• The patient should be informed any potential interaction occurring in his prescription.
5. RATIONALE OF DRUGS USE:
1. ASPIRIN:(75mg)
2The U.S. Preventive Services Task Force (USPSTF) strongly recommends that clinicians discuss aspirin chemoprevention with adults who are at increased risk for coronary heart disease (CHD). Discussions with patients should address both the potential benefits and harms of aspirin therapy.
Rationale: The USPSTF found good evidence that aspirin decreases the incidence of coronary heart disease in adults who are at increased risk for heart disease. They also found good evidence that aspirin increases the incidence of gastrointestinal bleeding and fair evidence that aspirin increases the incidence of hemorrhagic strokes. The USPSTF concluded that the balance of benefits and harms is most favorable in patients at high risk of CHD (5-year risk of greater than or equal to 3 percent) but is also influenced by patient preferences.
2. RANITIDINE (150mg)
Rationale: The use of Ranitidine is that it should be used for 7 days in case of Gastric irritation as 300 mg/day. It should only be used in adults.
3. ISOSORBIDE MONONITRATE (40mg)
Rationale: Isosorbide mononitrate is used to prevent chest pain in patients with a heart condition known as angina. This medication is normally taken twice a day. The first dose should be taken in the morning and second dose should be taken 7 hours later. This medication works by dilating blood vessels throughout the body. This can cause dizziness and lightheadedness when standing quickly and during the first days of therapy. This medication can cause headache – which also indicates the drug is working. These headaches are relieved with aspirin or acetaminophen. For this drug to be most effective it should be taken as prescribed, separating doses by 7 hours. Missed doses should not be doubled up
4. ATENOLOL (100mg)
• The initial dose of Atenolol is 50 mg given as one tablet a day. If an optimal response is not achieved within one week, the dosage should be increased to ATENOLOL 100 mg given as one tablet a day. Some patients may require a dosage of 200 mg once a day for optimal effect
• Twenty-four hour control with once daily dosing is achieved by giving doses larger than necessary to achieve an immediate maximum effect. The maximum early effect on exercise tolerance occurs with doses of 50 to 100 mg, but at these doses the effect at 24 hours is attenuated, averaging about 50% to 75% of that observed with once a day oral doses of 200 mg
• If withdrawal of ATENOLOL therapy is planned, it should be achieved gradually and patients should be carefully observed and advised to limit physical activity to a minimum.
5. SIMVASTATIN (20mg)
• For patients at high risk for a CHD event due to existing CHD, diabetes, peripheral vessel disease, history of stroke or other cerebrovascular disease, the recommended starting dose is 40 mg/day. Lipid determinations should be performed after 4 weeks of therapy and periodically thereafter.
• All patients starting therapy with SIMVASTATIN should be advised of the risk of myopathy and told to report promptly any unexplained muscle pain, tenderness or weakness.
• It is recommended that liver function tests be performed before the initiation of SIMVASTATIN, and thereafter when clinically indicated
6. RAMIPRIL (2.5mg)
• For patients with hypertension and renal impairment, the recommended initial dose is 1.25 mg RAMIPRIL once daily. Dosage may be titrated upward until blood pressure is controlled or to a maximum total daily dose of 5 mg.
• Angioedema: Angioedema, including laryngeal edema, can occur with treatment with ACE inhibitors, especially following the first dose. Patients should be so advised and told to report immediately any signs or symptoms suggesting angioedema (swelling of face, eyes, lips, or tongue, or difficulty in breathing) and to take no more drug until they have consulted with the prescribing physician
• Symptomatic Hypotension: Patients should be cautioned that lightheadedness can occur, especially during the first days of therapy, and it should be reported
• Hyperkalemia: Patients should be told not to use salt substitutes containing potassium without consulting their physician
• Neutropenia: Patients should be told to promptly report any indication of infection (e.g., sore throat, fever), which could be a sign of neutropenia
7. METFORMIN (850mg)
• The usual starting dose of Metformin hydrochloride is 500 mg twice a day or 850 mg once a day, given with meals. Dosage increases should be made in increments of 500 mg weekly or 850 mg every 2 weeks, up to a total of 2000 mg per day, given in divided doses.
8. CLOPIDEOGERAL (75mg)
• For patients with non-ST-segment elevation acute coronary syndrome (unstable angina/non-Q-wave MI), Clopidogrel should be initiated with a single 300-mg loading dose and then continued at 75 mg once daily. Aspirin (75 mg-325 mg once daily) should be initiated and continued in combination with Clopidogrel.
• Patients should be told that it may take them longer than usual to stop bleeding, that they may bruise and/or bleed more easily when they take Plavix or Plavix combined with aspirin, and that they should report any unusual bleeding to their physician. Patients should inform physicians and dentists that they are taking Plavix and/or any other product known to affect bleeding before any surgery is scheduled and before any new drug is taken.
9. GTN (0.5)mg)
• One tablet should be dissolved under the tongue or in the buccal pouch at the first sign of an acute anginal attack. The dose may be repeated approximately every 5 minutes, until relief is obtained. If the pain persists after a total of 3 tablets in a 15-minute period, prompt medical attention is recommended. Nitrostat may be used prophylactically 5 to 10 minutes prior to engaging in activities which might precipitate an acute attack.
• If possible, patients should sit down when taking Nitrostat tablets. This eliminates the possibility of falling due to lightheadedness or dizziness.
• Nitroglycerin should be kept in the original glass container, tightly capped.
• Headaches can sometimes accompany treatment with nitroglycerin. In patients who get these headaches, the headaches may be a marker of the activity of the drug.
6. INTERACTIONS
a. CLOPIDOGREL + ASPIRIN
Mechanism:
Although the mechanism is poorly understood, it is believed that when aspirin and clopidogrel are used together in some people, the risk of severe bleeding is increased. Platelets are cells in the blood that are partly responsible for forming blood clots that stop bleeding from injuries or other types of damage to the blood vessels. Clopidogrel and aspirin are both known to decrease the platelets? ability to clot. So, when taken together, clopidogrel and aspirin can increase the risk of excessive or otherwise dangerous bleeding.
Advice:
Doctor may want you to have more frequent blood tests to make sure that your blood is clotting properly. If you are currently taking clopidogrel and have recently suffered from a stroke or heart attack, you should avoid taking aspirin unless otherwise directed by your doctor or pharmacist.
Significance:
This interaction is well-documented and is considered major in severity.
b. METFORMIN + RANITIDINE:
Mechanism:
Ranitidine is a cationic drug and theoretically could decrease the excretion of metformin by competing for renal tubular transport. Although this interaction has not been specifically reported for ranitidine, cimetidine (also a cationic drug) has been reported to interact with metformin in this manner. Increased metformin levels may increase the risk of lactic acidosis. TYPE:
Moderate Type.
MANAGEMENT:
If ranitidine and metformin must be used together, particularly slow and cautious titration of metformin dosage is recommended. The maximal dose of metformin probably also should be reduced until further information about this interaction is available. Patients should be advised to monitor their blood glucose and to promptly notify their physician if they experience possible signs of lactic acidosis such as malaise, myalgia, respiratory distress, hyperventilation, slow or irregular heartbeat, somnolence, abdominal upset, or other unusual symptoms.
c. METFORMIN + RAMIPRIL:
Mechanism:
Limited data suggest that ACE inhibitors may potentiate the hypoglycemic effects of oral antidiabetic drugs, including metformin. The mechanism is unknown. Symptomatic and sometimes severe hypoglycemia has
occurred. TYPE:
Moderate Type.
MANAGEMENT:
Close monitoring for the development of hypoglycemia is recommended if ACE inhibitors are coadministered with metformin, particularly in patients with advanced age and/or renal impairment. Dosage adjustments may be required if an interaction is suspected. Patients should be apprised of the signs and symptoms of hypoglycemia (e.g., headache, dizziness, drowsiness, nausea, hunger, tremor, weakness, sweating, palpitations), how to treat it, and to contact their physician if it occurs. Patients should be observed for loss of glycemic control when ACE inhibitors are withdrawn.
d. ISOSORBIDE MONONITRATE + RAMIPRIL:
Mechanism:
Angiotensin converting enzyme (ACE) inhibitors may enhance the vasodilatory and hypotensive effects of nitroglycerin. Data have also shown that captopril can prevent nitrate tolerance. ACE inhibitors can decrease systemic vascular resistance and cardiac work, further enhancing the effectiveness of nitroglycerin. TYPE:
Moderate Type.
MANAGEMENT:
In general, this combination is used to clinical advantage; however, some manufacturers recommend that nitrates and other vasodilators should be discontinued before starting ACE inhibitors or resumed at a reduced dose. Blood pressure monitoring is advisable.
