Laxatives (purgatives, aperients)

The causes of constipation can vary:

1. Inadequate intake of dietary fiber
2. Less fluid intake
3. Lack of exercise, sedentary lifestyle
4. Changes in life or routine
5. Misconception about normal frequency, amount or consistency of stools
6. Side effects of medications (narcotics, antispasmodics, antiparkinsonism drugs, antidepressants, diuretics, etc.)
7. Diseases like irritable bowel syndrome, hypothyroidism, colorectal cancer, etc.

Laxative or Purgative abuse:

Some individuals are obsessed with using purgatives regularly. Laxative abuse occurs when a person attempts to get rid of unwanted calories, lose weight, feel thin, or feel empty through the repeated misuse of laxatives. This may be the reflection of psychological problem.

Others use a purgative casually, obtain thorough bowel evacuation, and by the time the colon fills up for a proper motion (2-3 days) they get convinced that they are constipated and start taking the drug regularly. Chronic use of purgatives give rise to the risk of laxative dependence, i.e., the inability to do without them. Once the purgative habit forms, it is difficult to break.

Health consequences of laxative/purgative abuse:

1. Constipation and laxative dependency
2. Flairing of intestinal pathology, rupture of inflamed appendix
3. Fluid and electrolyte imbalance, specially hypokalemia
4. Steatorrhoea, malabsorption syndrome
5. Lazy colon, Irritable bowel syndrome
6. Renal failure
7. Liver damage
8. Protein losing enteropathy
9. Spastic colitis
10. Severe dehydration

How laxative habituation occurs?

Normally:
When the sigmoid colon and rectum are filled, the natural defecation reflex empties the large bowel (intestine) up to and including the descending colon.

When laxative is taken:
A large bowel irritant purgative (sennae, phenolpthalein, bisacodyl, picosulfate) clears out the entire colon leading to requirement of a longer period for the next natural defecation to occur. Fearing constipation, the user becomes impatient and again resorts to the laxative, which then produces the desired effect as a result of emptying out the upper colonic segments. Therefore, a “compensatory pause” following cessation of laxative use must not give cause for concern.

Development of laxative abuse cylce:
When the colon empties prematurely, there will be an enteral loss of NaCl, KCl and water. To compensate this depletion of NaCl and water, the body responds with an increased release of aldosterone which stimulates their reabsorption in the kidney. The enteral and renal K+ (potassium) loss add up to a K+ depletion of the body, evidenced by hypokalemia accompanied by a reduction in intestinal peristalsis (bowel atonia). The affected individual infers “constipation,” again partakes of the purgative, and the vicious circle is closed.

No laxatives should be used unless suggested by a healthcare provider. Tapering off laxatives is necessary to prevent problems.

In 2012, war broke out. Soon the war was fought all over the world. This time the enemy were not human neither aliens. They were invisible , tiny but lethal. The war was between doctors and bacteria.
Doctors used every weapon they had – antibiotics but the bacteria had become too resistant.

“Once upon a time, penicillin was discovered and it could cure almost every disease. The germs retreated but soon they were back for the revenge with weapons like Penicillinase- Methicillin and Vancomycin Resistance. They researched on genetics and modified themselves against antibiotics.
Soon doctors had few useful weapons, but cost was always an issue”

By April 2013, VRSA had become widespread infecting entire world including the doctors. Most of the infected died.

Watch this short animation which is almost self explanatory:

Are we prepared for it?

Unfractioned Heparin- is derived from  porcine intestinal mucosa or bovine lung tissue. UFH catalyzises that inactivation of thrombin and factor Xa by inhibiting Anti-thrombin III.  At usual dose it prolongs TT and aPTT and has a minimal effect on PT/INR.

Benefits of UFH-

1. 1. The effect of UFH normalizes within hours of discontinuation
2. 2. It is reversible with Protamine Sulphate.
3. 3. Can be titrated according to aPTT.
4. 4. Dosing is not typically affected by Renal function.

Dosage-

1. DVT prophylaxis- 5000 U SC  Q8-Q12hrly ( aPTT monitoring not necessary)

2. Therapeutic anticoagulation

a. Weight based Heparin dosing-

Bolus- 80 U/kg

Infusion- 18U/kg/hr.

ADJUSTMENTS

aPTT target level may vary depending upon the Hospital standards.

aPTT to be sent 6 hrly after any bolus or dose change.

b. For Acute STEMI patients-

60U/kg bolus ( usually 5000U bolus) followed by 12U/kg/hr(  usu. 1000U/kg/hr)

Dose-adjusted UFH may be administered SC q8hrly ( 12000U UFH) or Q12hr ( 16000U UFH) à  aPTT after 6 hrs.

2. Low-Molecular Heparin-

Produced by chemical and enzymatic cleavage of UFH.  LMW inactivates factor Xa to greater extent. It minimally prolongs aPTT.

Caution required in patients with deranged RFT, obesity, pregnancy—facter Xa assay may be needed.

These are only partially reversible with Protamine.

Lepirudin ( Refludan, recombinant hirudin) – direct thrombin inhibitor that is used for treatment of HIT.( Heparin Induced Thrombocytopenia )

By Dr Sujit Shrestha ( Reference – various sources including Washington manual, internet)

Further Reading:
Isoenzymes and their Diagnostic Importance