Sunday, July 25, 2010

Antihypertensives in Renally Impaired Patients

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.

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.

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

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

2. Add
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.

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.

TPN in Genery Surgery

Total parenteral nutrition (TPN) is an interesting aspect of pharmacy indeed. It is one of those areas whereby there is no overlap with the doctors (but with the dietitians! hehe) and pharmacists' roles are indispensable. My short stint at TPN unit was mind-opening indeed; not only does the TPN pharmacist needs to be well-versed with the clinical part and be skilful in compounding, he/she is also involved in stock procurement &control and his/her knowledge in aseptic room design is important.

Prior to the commencement of TPN, patient assessment is done to find out if he/she requires nutrition support. This can be done using the ESPEN guidelines for nutrition screening 2002.

If the patient requires a nutrition plan, the next step will be to decide if oral, enteral or parenteral means of nutrition support is suitable.

1st choice in postoperative artificial nutrition: enteral feeding or a combination of enteral & supplementary parenteral feeding. This is because
enteral nutrients maintain GI mucosal structure & function,is less costly and less invasive.

Indications for Postoperative Parenteral Nutrition:

Undernourished pt in whom enteral nutrition is not feasible/not tolerable

Patient with postoperative complications impairing gastrointestinal function who are unable to receive adequate amounts of oral/enteral feeding for at least 7 day

Patient is undernourished if ≥1 criteria present:

Weight loss >10-15% within 6 months

BMI < style="line-height: 115%;">

Serum albumin <>(with no evidence of hepatic or renal dysfunction)

Contraindications for Enteral Nutrition:

  • Intestinal obstruction
  • Malabsorption
  • Multiple fistulas with high output
  • Intestinal ischaemia
  • Severe shock with impaired splanchnic perfusion
  • Fulminant sepsis

25 kcal/kg ideal body weight gives an approximate estimate of daily energy expenditure & requirements

Severe stress: may require 30kcal/kg ideal body weight

In patient unable to be fed via enteral route after surgery, a full range of vitamins & trace elements should be supplemented on a daily basis.

Weaning from PN is not necessary.

It has been recommended that PN is tapered prior to discontinuation to prevent hypoglycaemia.

However it has been shown that even after prolonged PN, the beta-cells remain sensitive to changes in glucose levels & adaptation of glucose levels and insulin secretion occurs very quickly.

In some other institutions, the non-protein calories to nitrogen (NPC: N) ratio is used in TPN compounding.

NPC/N = Non-protein calories (kcal)/nitrogen (g)


1g N= 6.25 g protein

1g dextrose = 4kcal

1g protein = 4 kcal

1g lipid = 9kcal

The calculations below are what I was taught in my uni days by an experienced TPN pharmacist.

1. Decide NPC:N ratio for patient (e.g. 100: 1 for severely stressed patients)

2.Estimate total protein requirement. (1.5 g/kg/day; 1.5 x 50kg =75 g protein= 75/6.25=12g N)

If 12g N is to be given, 12 x 100 = 1200 kcal non-protein calorie is required for reach a NPC: N of 100.

3.Non-protein calories (dextrose & lipid) = 1200 kcal

1200 kcal --> 600 kcal dextrose, 600 kcal lipid

4. Dextrose = 600kcal/4kcal= 150 g

Lipid = 600kcal/9kcal = 67g

Desirable NPC:N ratios

80:1 the most severely stressed patients

100:1 severely stressed patients

150:1 unstressed patient

Increasing the amount of amino acids administered is particularly effective under surgically stressed conditions due to the increase in amino acid requirements.

The optimal NPC/N ratio is estimated to be about 100 (50 g as amino acids), when the IV solution is administered at the anticipated daily dose in clinical use (1000 kcal/day)

  • Test solutions with NPC/N ratio 50, 100, 150 or 200 were administered parenterally at a rate of 120 kcal/kg/day for 5 days to normal rats
  • Protein synthesis rate in the liver increased with a decrease in the NPC/N ratio
  • NPC/N: 50, the levels of serum urea nitrogen and serum branched chain amino acids were high, implying an excessive accumulation of amino acids.

How is the TPN practice in your hospital?


  1. Holcombe BJ. Adult parenteral nutrition. In Yong LL, Koda-Kimble MA (editors). Applied therapyeutics-the clinical use of drugs. Pennsylvania: Lippincott Williams & Wilkins;1995. p. 35-1—35-15.
  2. ESPEN guidelines on parenteral nutrition: surgery. Clin nutr 2009; 28: 376-386.
  3. Kondrup J, Allison SP, Elia M, Plauth M. ESPEN guidelines for nutrition screening 2002. Clin nutr 2003; 22 (4): 415-421.
  4. California State University Northridge. Parenteral nutrition total [Online]. 2000 September 7 [accessed 2010 July 14]; Available from: URL:
  5. Nakayama M., Motoki T, Kuwahata T and Onodera R. The optimal nitrogen proportion to non-protein calories in normal rats receiving hypocaloric parenteral nutrition. Nutrition Research 2002; 22: 1091–1099.