Scenario in a Klinik Kesihatan

I have a patient discharged from a hospital to our clinic, and he is on life-long tiotropium bromide Handihaler (Spiriva) and Symbicort Turbohaler for chronic pulmonary obstructive disease (COPD). As these medicines are not in the formulary our pejabat kesihatan daerah (district health office), the hospital is to supply us with those medicines.


When I called up the hospital, I was told that my clinic has to find an alternative since the hospital in low on budget and will no longer supply those medicines to my patient. So this prompted my mini search (or rather, refreshing of) COPD guidelines.Tiotropium bromide (List A*) [Spiriva] is a long-acting anticholinergics (duration: 24 hours) used for the long term maintanance treatment of bronchospasm and dyspnoea associated with COPD. It is usually added to standard therapy (e.g. inhaled steroids, theophylline) and the dose is 18mcg od.

Symbicort Turbohaler (List A) contains budesonide (a glucocorticosteroid) 160mcg and formoterol (long-acting beta2-agonist, duration: 12+ hours) 4.5 mcg; the dose is 1-2puff bd,max 4puff bd.

My clinic only has MDI salbutamol, MDI budesonide and MDI Berodual. MDI Berodual contains ipratropium bromide (a short-acting anticholinergics; duration: 6-8 hours) 20 mcg/dose and fenoterol hydrobromide (short-acting beta2-agonist); duration: 4-6 hours)50 mcg/dose.

According to the GOLD guidelines, an inhaled glucococorticosteroid combined with a long-acting beta2 bronchodilator is more effective than individual components in reducing exacerbations and improving lung function and health status.

Regular treatment with long-acting bronchodilators is more effective and convenient than treatment with short-acting bronchodilators.

GOLD guidelines: Therapy at each stage of COPD

Guidelines according to NICE

Since my patient is on a long-acting bronchodilator and inhaled steroids, his stage of COPD must have necessitated the use of these medicines, and that the short-acting bronchodilator and short-acting anticholinergics in my clinic are not sufficient for his condition. These are conveyed to the hospital and arrangement is made for them to supply us with those medicines currently, after which my budget-strained clinic has to exchange similar-valued medicines with tiotropium and Symbicort Turbohaler from the hospital for my patient's life-long supply of medicines. I believe that patient's care should not be compromised even when he is under follow-up in a clinic !

Antihypertensives in Renally Impaired Patients

Beta-blockers
Patients with renal disease respond well to beta-blockers. The choice of drug would be a cardioselective, hepatically excreted drug like metoprolol. However, atenolol, which is renally excreted, can eb given safely if introduced at low doses.


ACE inhibitors
ACE inhibitors are often useful since hypertension can be caused by activation of the renin-angiotensin system. However, renal function should be closely monintored in pre-dialysis pateitns when these drugs are introduced as they are contraindicated in patients with renal artery stenosis.

Do note that in conditions of decreased renal perfusion, the desirable effects will be efferent arteriolar vasocontriction to increase intraglomerular hydrostatic pressure and maintain ultrafiltrate production. Another effect will be afferent arteriolar vasodilatation to improve blood flow to the glomerulus. ACE inhibitors are efferent arteriolar vasodilators, hence they can increase the rate of decline of renal function. However, this can be used to advantage in patients with diabetes, where a reduction in hyperfiltration can delay the progression of diabetic nephropathy.

ACE inhibitors are renally excreted (ramipril is also partially hepatically excreted) and the half-life of these drugs is increased in renally impaired patients, hence they should be used with caution. Also, they can cause an increase in potassium levels.


Angiotensin II Receptor Blockers (ARBs)
ARBs can be beneficial in patients with chronic kidney disease since they block the effects of angiotensin II (a vasoconstrictor), causing vasodilation. As with ACEi, renal function should be closely monitored. They can also be useful when used in combination with an ACEi.


Calcium Channels Blockers (CCBs)
CCBs can be used safely in patients with chronic renal failure. However, one of the side effects of this group, especially of nifedipine, is ankle swelling and unresponsive to diuretics, which can be mistaken for fluid overland.

Ankle swelling is less of a problem with longer-acting agents, such as amlodipine.


Vasodilators
These include doxazocin, prazosin, hydralazine and minoxidil, all of which are hepatically metabolised. They are usually added when other drugs are ineffective. Minoxidil is best given with a beta-blocker and a diuretic, since it can cause tachycardia and fluid retention.


Summary
If BP > 130/80 mmHg: (proceed to next step if BP still not at goal)

1. Start ACEi or ARB
Check serum creatinine & potassium in 1 week; if SrCr or K increases by > 30%, discontinue
agent.

2. Add diuretics
CrCL > or = 30 mL/min: thiazide diuretic
Cr CL <>calcium channel blocker
May consider adding low-dose beta blocker instead of CCB if patient has angina, heart failure
or arrhythmia necessitating their use.

4. Baseline pulse > or = 84: low-dose beta blocker OR alpha/beta blocker (if not already in use)
Baseline pulse < style="color: rgb(51, 51, 255);">subgroup of CCB (e.g. a dihydropyridine if a
non-dihydropyridine is in use)
Note: the use of beta blcoker and a non-dihydropyridine CCB should be avoided in the
elderly and those with conduction abnormalities.

5. Add long-acting alpha blocker, central alpha agonist, OR vasodilator.
Note: Central alpha agonists (i.e. clonidine) should not be used with beta blockers due to the
high likelihood of severe bradycardia.


References:
1. Wells BG, Dipiro JT, Schwinghammer TL and Hamilton CW. Pharmacotherapy handbook. USA: The McGraw-Hills Company; 2006.

2. Morlidge C. Managing chronic renal disease. The Pharmaceutical Journal 2001; 266: 655-657.