Amlodipine versus Felodipine

A student wanted to know why some doctors prescribed Amlodipine while others prescribed Felodipine as the calcium channel blocker for treating hypertension. This is what I found in the published literature:

Amlodipine seems to be more effective than felodipine when these drugs are compared in the same dose, with regard to the effect on BP measured in the clinic 24 hours after dosing, and to ambulatory BP during the night. The longer elimination half-life of amlodipine as compared to felodipine is the probable reason for this finding. (1998) (reference). 

However another side to the story is this: Felodipine decreased BP sooner than amlodipine. Amlodipine and felodipine are similar antihypertensive agents and have comparable BP profiles during the day and night following 8 weeks of therapy in patients with mild to moderate hypertension.  (2001) (reference).

Current advice from NICE recommends calcium channel blockers as potential first line agents in older patients (over 55 years) or black patients of any age and as potential second line adjunctive agent in younger non-black patients. No specific calcium channel blocker is recommended.  The choice of calcium channel blocker may depend on local recommendations, with the least expensive one being preferred. For patients with both hypertension and angina, amlodipine or felodipine are suitable choices. (2012) (reference).

A patient with pernicious anemia

A young man with anemia had paresthesiae of his feet and difficulty in walking. Investigations revealed that he had a macrocytic anemia due to Vitamin B12 deficiency. 

Pernicious anemia is due to Vit B12 deficiency. This is a macrocytic anemia with a megaloblastic reaction in the bone marrow. Patients with pernicious anemia can also have pancytopenia because of defective cell formation in the bone marrow. Neurological disorders involving the spinal cord, peripheral nerves and sometimes the brain are what gives this anemia the adjective 'pernicious' which means dangerous. The neurological complications of Vit B12 deficiency can occur without the anemia and anemia can be present without the neurological complications.

Pernicious anemia is often associated with gastric atrophy and hypochlorhydria which leads to poor iron absorption and associated iron deficiency. Gastric atrophy increases the risk of gastric adenocarcinoma in patients with pernicious anemia.

Autoantibodies directed against the gastric parietal cells and the intrinsic factor produced by these parietal cells are the usual cause of pernicious anemia. These patients are therefore at increased risk of other autoimmune diseases involving the thyroid, pancreas and adrenal glands.

Serum LDH levels are useful in diagnosis because they are elevated in patients with haemolytic anemia. Once the diagnosis is made, treatment is started with either cyanocobalamin or hydroxocobalamin. These are given as injections subcutaneously or intramuscularly until the desired response is achieved. Maintenance doses of Vit B12 need only be given once a month because the body requires very low amounts of Vit B12 per day (1ug per day). It may also be possible for maintenance doses of Vit B12 to be given orally in high daily doses because, even without intrinsic factor, about 1 percent of Vit B12 is absorbed from the gut.

People at risk of pernicious anemia are those who do not consume either meat or milk because the natural source of Vit B12 is from these two dietary products.

Data published by the Institute of Medical Research in 1994 (article) gives us an idea of the prevalence of Vitamin B12 deficiency in Malaysia. In the year 1993 to 1994 it was around 8.2 percent (based on a sample of around 9000 patients who were suspected to have Vit B12 deficiency). 

Macrocytic anemia can also be due to folic acid deficiency. Folic acid deficiency can cause cognitive changes, depression, dementia and rarely the spinal cord and peripheral nerve damage of Vitamin B12 deficiency. Both folic acid and Vitamin B12 are therefore important vitamins for the blood and nervous system (article). 

A patient with rheumatoid arthritis on methotrexate

A patient with rheumatoid arthritis was prescribed Tab Methotrexate 5mg per week and Tab Folic acid 5mg per day. I know that methotrexate blocks the conversion of folic acid to folinic acid and hence can inhibit the action of certain important enzymes in the body.  

I asked myself two questions: 

1. Is folic acid really necessary when prescribing low dose long term methotrexate? 
2. Will folic acid reduce the efficacy of methotrexate? 

A Medscape article provided the answers. Low dose methotrexate refers to the use of less than 20mg of methotrexate per week. Studies have shown that folic acid supplementation has a beneficial effect in reducing the side effects of methotrexate like stomatitis, gastrointestinal upsets, liver dysfunction and bone marrow suppression. Folinic acid too has the same benefit but it is more expensive. It is not entirely clear whether folic acid supplementation will reduce the efficacy of methotrexate in rheumatoid arthritis but it probably will not. The beneficial effect of low dose methotrexate in rheumatoid arthritis appears not to be related to its inhibition of folic acid metabolism. 

A cardiovascular benefit in providing supplementation with folic acid is also present. Methotrexate tends to increase homocysteine levels (a cardiovascular risk factor) in the blood. This will be prevented by folic acid. 

A patient with pericardial effusion and an endocrine problem

An elderly man with diabetes and chronic renal failure was diagnosed with a pericardial effusion a few months ago. He underwent pericardial aspiration and analysis of the pericardial fluid at another hospital before coming to us. The cardiologist in that hospital felt that the pericardial effusion was due to his renal failure. This patient presented to us because of a feeling of extreme tiredness and a history of hypoglycemic episodes. We initially attributed his tiredness to his hypoglycemic episodes. He was on oral Glibeclamide for diabetes and we stopped that drug. When his blood reports showed a severe degree of hyponatremia and his physical examination showed pigmentation of the palms, palate and lips, we considered another diagnosis.

Discussion

The pigmentation over the skin and mucosa along with the hyponatremia and hypoglycemia are suggestive of adrenal insufficiency or Addison's disease. Since this patient has chronic renal failure and is on a long acting sulphonylurea - Glibenclamide - the hypoglycemic episodes can also be blamed on the inappropriate use of glibenclamide. The suspicion of Addison's disease can be tested by doing a random plasma cortisol level. If the random plasma cortisol value is more than 25mcg/dL in a patient whose serum albumin is normal, Addison's disease is unlikely. Confirmation of diagnosis of Addison's disease can be done by doing the ACTH stimulation tests to see if the adrenal cortex responds appropriately by producing glucocorticoids and mineralocorticoids to an injection of ACTH. Treatment of Adrenal insufficiency for this patient can be initiated with a higher than usual replacement doses of hydrocortisone (for example, 100mg three times a day for one day followed by 50mg three times a day for one day and tapering thereafter). Maintenance doses of hydrocortisone for Addison's disease is usually between 15 and 20mg per day: a larger portion of hydrocortisone (10 -15mg) is given in the morning and a smaller portion (5 -10mg) is given in the late afternoon. When hydrocortisone is given at night, it may cause insomnia and that is why it is preferable to give the evening dose in the late afternoon. One thing to remember is that the adrenal gland produces both glucocorticoids and mineralocorticoids and replacement for both is needed. However, since hydrocortisone has a slight degree of mineralocorticoid activity, it is not necessary to add a separate mineralocorticoid drug (fludrocortisone) if more than 100mg per day of hydrocortisone is being given. When maintenance doses of hydrocortisone are being used, fludrocortisone is needed.

The following facts are nice to know:

1. Cortisol is the name of the glucocorticoid produced by the adrenal gland. This is the same as hydrocortisone.

2. Cortisone is the inactive form of cortisol. When given as a tablet, it is converted to cortisol in the body.

3. Prednisolone is the active form of prednisone. This is a synthetic glucocorticoid. Prednisolone is preferred over prednisone in patients with liver disease.

4. All glucocorticoid hormones have anti-inflammatory activity. These are graded as:

5mg of prednisolone being equivalent to 20mg of hydrocortisone / 25mg cortisone / 0.75mg dexamethasone /4mg methylprednisolone.