Proton Pump Inhibitors (PPI) are very common drugs that are used to treat gastrointestinal conditions associated with excess stomach acid production. Currently there are five PPIs available, omeprazole, lansoprazole, pantoprazole, rabeprazole and esomeprazole.
A meta-analysis1 of 19 studies that directly compared PPIs with each another has assessed if there are any differences between these PPIs in the treatment of gastro-oesophageal reflux disease (GORD).
The analysis concluded that, for equivalent doses, there is no difference between PPIs in the treatment of GORD and therefore choice should be based firstly on cost and secondly on individual patient response.
Action: On the basis of cost the first choice PPI is currently omeprazole. If individual patients fail to respond to an adequate dose of omeprazole, lansoprazole is likely to be a good second choice based on cost and clinician experience of using this drug.
- Klok RM et al. Meta-analysis: comparing the efficacy of proton pump inhibitors in short-term use. Alimentary Pharmacology and Therapeutics 2003;17:1237-45
Diabetes is a relatively common and very serious disease. The treatment of diabetes tends to focus upon the diagnostic measures for the disease, those of blood sugar assessment. Despite this the United Kingdom Prospective Diabetes Study1 (UKPDS) has shown the tight blood sugar control should be a secondary target to tight blood pressure control.
Tight blood pressure control was found to contribute to reductions in deaths from long term complications, strokes and serious deterioration in vision. Tight blood glucose control contributes to a reduction in eye disease and renal damage. It is clear from this that the focus should be upon saving lives not purely preserving renal function and vision.
Another key finding of UKPDS was that in addition to the glucose benefits of Metformin there are additional reductions in the risk of myocardial infarction in comparison to other anti-diabetic agents. Metformin should therefore be the first line anti-diabetic drug in all patients with Type II Diabetes.
NICE appraised the place of the Glitazones in August 2003. This appraisal recommended the use of Glitazones when patients cannot tolerate or are contraindicated to either Metformin or Sulphonyureas. Since this appraisal the evidence supporting the use of Glitazones has grown beyond demonstrated effects in lowering blood sugar. Given that Sulphonylureas tend to cause weight gain as they cause insulin secretion and therefore stimulate appetite, perhaps a more pragmatic approach should now be used when HbA1c remains sub-optimal.
- Metformin for all patients, titrate to maximum tolerated dose
- If BMI < 25 Kg/M2 use a Sulphonylurea (Glicalazide or Glipizide)
- If BMI > 25 Kg/M2 use a Glitazone (Pioglitazone or Rosiglitazone)
- Refer for, or initiate Insulin (Triple therapy is licensed but not recommended for Primary Care. The combination carries extra risks for Heart Failure and Hypoglycaemia and therefore requires close monitoring
Action: Prescribers should aim to control blood pressure in preference to blood glucose in patients with Type II Diabetes.
Treatment of blood glucose should be initially managed with Metformin in all patients with type II Diabetes.
- United Kingdom Prospective Diabetes Study
The MHRA advice regarding the safety of NSAIDs has already been summarised on this site.
The following recommendations apply in relation to the safe prescribing of NSAIDs:
- Review the patient for the overall risks involved with NSAID treatment - this should include an assessment of gastro-intestinal risk, cardio-vascular risk, renal risk as well as pre-treatment assessment of blood pressure and renal function. Where possible use Paracetamol based analgesia as first line with a ladder approach if initial analgesia fails.
- Where the overall risks are low or NSAID treatment is absolutely necessary despite moderate to high risk, the NSAID of lowest risk should be used at the lowest possible dose and for the shortest possible duration.
- This will usually mean that Ibuprofen is the first line NSAID.
- If Ibuprofen therapy fails or is not tolerated, re-assess the patient for an NSAID before trying an alternative. Suitable alternatives would include diclofenac and naproxen.
The safety of NSAIDs is under constant review at the moment following the concerns raised by the withdrawal of some of the newer COX-II Selective NSAIDs. The MHRA review has already been reported on this site.
All interventions made by the NHS, including prescribing drugs, involves an assessment of the risks of the intervention and the likely benefits. The spotlight on NSAID safety has made us all aware of the gastro-intestinal, renal and cardio-vascular risks associated with all NSAIDs.
It is therefore timely to consider a greater use of analgesics that are not NSAIDs. Using a stepped approach to analgesia with Paracetamol as a core component would be a rational approach in all conditions that are not inflammatory for the majority of the time, for example osteoarthritis.
Action: Where analgesia is required for uncomplicated pain, use the following ladder approach before considering NSAIDs or other alternative treatments.
- Paracetamol 500mg tablets, Two four times a day when required
- Co-codamol 8/500mg tablets, Two four times a day when required
- Co-dydramol 10/500mg tablets, Two four times a day when required
- Co-codamol 30/500mg tablets, Two four times a day when required
Note: This approach does not apply to complicated pain, for example Rheumatoid Arthritis, Cancer Pain and Trigeminal Neuralgia
NICE published a Clinical Guideline for Hypertension in August 2004. This guideline was based on the evidence available at the time and was probably dramatically influenced by the ALLHAT Study1.
This Study was conducted in about 42,000 patients and compared active treatments as follows:
- Thiazide Diuretic (Chlorthalidone)
- ACE Inhibitor (Lisinopril)
- Calcium Channel Blocker (Amlodipine)
- Alpha Blocker (Doxazosin)
Based upon the results of this trial there are two key findings that altered (or should alter) daily practice. Firstly, the Doxazosin arm of this study was stopped early as patients in this group were suffering more outcome events than any other arm. It was therefore decided it was unethical to continue this arm of the study and as a consequence of these steps Doxazosin is a fifth line antihypertensive agent.
The ultimate finding of the study was that there is little to choose between the remaining three arms in terms of clinical efficacy in terms of "hard" outcomes like fatal and non-fatal MI. There were differences in blood pressure control between the groups where the Thiazide Diuretic performed well against the other drugs with amlodipine proving better in diastolic pressure only. While the differences are statistically significant, the clinical differences are negligible (0.8 - 2mmHg difference).
This then leaves the only difference for evaluation between the drug arms to be that of cost. As Thiazide Diuretics as the most cost effective option there simply must be the first line treatment for hypertension.
Second line options are added based upon emerging evidence around the risk of diabetes when Beta Blockers are used in conjunction with Thiazide Diuretics. Angiotensin Converting Enzyme Inhibitors (ACEIs) are preferential in those patients who are at higher risk of developing diabetes.
Action: The NICE Guideline is evidence based and should be followed by all clinicians treating Hypertension in Primary Care. For full details of the algorithm, see the Clinical Guideline Quick Reference.
For each of the NICE recommended drug classes the following drugs are recommended:
- Thiazide Diuretic - Bendroflumethiazide 2.5mg
- Beta Blocker - Atenolol 50mg or Bisoprolol 5mg
- ACE Inhibitor - Ramipril or Perindopril (Titrated to maximum tolerated dose)
- Calcium Channel Blocker - Amlodipine (as Mesilate) or Felodipine
ONLY if ACE Inhibitor is not tolerated
- Angiotensin II Receptor Blockers - Candesartan or Irbesartan or Valsartan
- Major Outcomes in High-Risk Hypertensive Patients Randomized to Angiotensin-Converting Enzyme Inhibitor or Calcium Channel Blocker vs Diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group JAMA 2002;288:2981-2997