Tuesday, February 26, 2013


Lactulose is a synthetic, non-digestible sugar used in the treatment of chronic constipation and hepatic encephalopathy, a complication of liver disease. It is a disaccharide (double-sugar) formed from one molecule each of the simple sugars (monosaccharides) fructose and galactose. It is produced commercially by isomerization of lactose.
It is broadly classified as an osmotic laxative.

IUPAC NAME  -   4-O-β-D-Galactopyranosyl-β-D-fructofuranose

Brands - Duphalac, loose

Adult: PO Constipation Initial: 10-20 g (15-30 mL)/day. Max: 45 mL (or 40 g of the reconstituted oral formulation)/day. Hepatic encephalopathy 60-100 g (90-150 mL)/day in 3 divided doses; adjust accordingly. Rectal Hepatic encephalopathy Mix 200 g (300 mL w/ 700 mL water or 0.9% NaCl as a retention enema. Retain enema for 30-60 mins; repeat 4-6 hrly until oral medication can be administered.

Adult: Initially, 10-20 g (15-30 ml) daily as a single dose or in 2 divided doses; gradually adjust according to patient's response. Max dose: 45 ml (or up to 40 g of the reconstituted oral powder formulation)/day.
Child: As 3.35 mg/5 ml solution: 1 mth to 1 yr: 2.5 ml; 1-5 yr: 5 ml; 5-10 yr: 10 ml; 10-18 yr: 15 ml. All doses to be given bid.
Hepatic encephalopathy
Adult: 60-100 g (90-150 ml) daily in 3 divided doses; adjust to produce 2 or 3 soft stools each day.
Hepatic encephalopathy
Adult: Mix 200 g (300 ml) with 700 ml water or 0.9% sodium chloride as a retention enema. Retain enema for 30-60
minutes; repeat every 4-6 hr until oral medication can be administered.

Administration - May be taken with or without food. May be taken w/ meals to reduce GI discomfort. Dilute w/ water, milk, or fruit juice to improve taste.
Contraindications Galactosaemia, intestinal obstruction. Patients on low galactose diet.
Special Precautions Monitor electrolyte imbalance. Lactose intolerance; diabetics

Adverse Drug Reactions - Diarrhoea (dose-related), nausea, vomiting, hypokalaemia, bloating and abdominal cramps.

Potentially Fatal: Dehydration and hypernatraemia on aggressive treatment.
Drug Interactions May prevent release of mesalazine in the colon. Decreased effect with oral neomycin, antacids.

PREGNANCY :  Category B: Either animal-reproduction studies have not demonstrated a foetal risk but there are no controlled studies in pregnant women or animal-reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the 1st trimester (and there is no evidence of a risk in later trimesters).

Storage Oral: Store at 15-30°C (59-86°F). Rectal: Store at 2-30°C (36-86°F).

Mechanism of Action Lactulose promotes peristalsis by producing an osmotic effect in the colon with resultant distention. In hepatic encephalopathy, it reduces absorption of ammonium ions and toxic nitrogenous compounds, resulting in reduced blood ammonia concentrations.
Onset: 48 hr.

Absorption: Not appreciable (oral).

Metabolism: Via colonic flora to lactic acid and acetic acid.
Excretion: Faeces, urine (as unchanged drug).
CIMS Class Laxatives, Purgatives
ATC Classification A06AD11 - lactulose ; Belongs to the class of osmotically acting laxatives.

Lactulose is used in the treatment of chronic constipation. It is safe for people of all ages, except that the dosage may have to be reduced for those in the very small part of the population that are afflicted with galactosemia because most commercially prepared lactulose also contains galactose. For adults, the dosage is that which causes an urgent daily bowel movement that cannot be ignored or resisted. A starting dosage of two tablespoons with breakfast is usually prescribed. But, the dosage can be increased as needed over time to up to three tablespoons with each meal.
Lactulose works by relieving constipation through a number of different methods. Lactulose is made up of sugar molecules and is partly broken down by the bacteria that live in the lower part of the gut. This leads to the contents of the gut becoming more acidic because there are carboxylic acids among its metabolites, which are not absorbed from the lower bowel. That in turn causes water to be retained in the lower bowel. This increases the amount of water in the stools, softening them and making them easier to pass. The added volume of gas and flatulence caused by fermentation of the lactulose adds to the volume of the fecal material, and makes it easier to expel. The slightly acidic condition of the colon caused by the presence of acids causes active peristalsis. The combined effect of all of these processes relieves constipation in a very effective manner.
Lactulose is useful in treating people with chronic constipation due to forgetting or ignoring the need for defecation. The treatment is to start the dosage at a low amount and then gradually increase it over a period of weeks until the urgency is such that a daily bowel movement cannot possibly be ignored. After an efficacious dosage is determined, it is maintained indefinitely or increased over time, as required.
Lactulose is useful in treating people who enjoy abusing laxatives provided that they use lactulose as their only laxative drug, because it has very low toxicity yet produces powerful results.
Lactulose is helpful for treating children who withhold their bowel movements out of fear because, when taken in sufficient quantity and then withheld, it produces a very insistent, irresistible and powerful urge to defecate. For the same reason, it can be used to help children who develop functional constipation out of fear or embarrassment of using the toilet facilities at school. This is because, when dosed with lactulose at breakfast time, there won't be an alternative. Improved compliance can be obtained by masking the lactulose in food or drink at 25% of the prescribed dosage and increasing the dosage one teaspoon (5 ml.) every three days. The standard dosage is one teaspoon (5 ml) for each year of age up to age 16.
Lactulose is also commonly given to elderly people who have diminished mental or physical capacity to have a daily bowel movement. It is the treatment of choice for constipation in rest homes both because of its effectiveness and its lack of side effects.
Lactulose has an overly sweet taste that can be completely masked by mixing it with coffee, tea, fruit juice or desserts. Some commercial preparations come already pre-flavored. It can take 24 to 48 hours to work, but generally produces results within 4 hours if taken on a daily basis. It is best taken at breakfast along with a bowl of bran cereal.
Lactulose is useful for negating the constipating effects of opiates and opioids, as in individuals who are on narcotic pain medication, are opioid dependent, or are receiving Opioid Replacement Therapy such as with methadone or buprenorphine for a previous opioid dependency.
Lactulose is useful for treatment of hemorrhoids because it produces a soft bowel movement without any straining.
Lactulose is considered a prebiotic because it modulates the beneficial bacterial flora of the gut and is considered a digestive aid. Modulation of gut flora presumably works by reducing potential pathogenic bacteria such as Escherichia coli and Staphylococcal species in stool, with increase in non-urease producing Lactobacillus limiting ammonia production. Moreover, lactulose is converted to lactic and acetic acid which results in acidification of colonic contents. The low pH decreases passive non-ionic diffusion of ammonia thus lowering its systemic concentration. Furthermore, with its prebiotic potential, lactulose also encourages growth of probiotic bacteria such as Bifidobacterium species that are known to have health-promoting effects.
For stubborn cases of constipation, lactulose is sometimes combined with polyethylene glycol 3350Da, (sold as Miralax or Dulcolax Balance in the USA without prescription).
If lactulose is taken two or three times a day, especially with polytethylene glycol 3350DA, it can occasionally be explosive. If taken in the morning or at lunch on a regular basis, the action is generally complete by bedtime. However, the evening dosage can be problematic. If given to small children who are in diapers, this is not a problem. However, for older children and adults, there is the ever present danger of voluminous defecation during sleep or being awake for hours on the toilet with a feeling of imminent expulsion. A juvenile or adult diaper with plastic pants along with a chux pad for the bed is recommended. This is especially true if a sleeping pill is taken.
In common with other osmotic laxatives, lactulose can cause electrolytic imbalances in sensitive individuals (see side effects below). However, it tends to do this less because it does not rely on mineral salts to draw fluid into the intestinal tract and also because it relies on nonosmotic modes of action, i.e. it stimulates peristalsis through acidification and gas and increases feeling of urgency through enlarging the volume of the bowel contents.
Lactulose is sold over the counter (without prescription) in most countries in the world. In the United States and Austria, it requires a prescription over unfounded fears that it could be dangerous to diabetics. However, it is an indigestible sugar and has been proved to be safe even for them.

Hepatic encephalopathy

Lactulose is useful in treating the hyperammonemia caused by hepatic encephalopathy, because it helps "draw out" ammonia (NH3) from the body. It is useful for preventing hyperammonemia caused as a side effect of administration of valproic acid.
Lactulose is metabolized in the colon by bacterial flora to short chain fatty acids including the production of the lactic acid and acetic acid. This partially dissociates, acidifying the colonic contents (increasing the H+ concentration in the gut).This favors the formation of the nonabsorbable NH4+ from NH3, trapping NH3 in the colon and effectively reducing plasma NH3 concentrations.
The effectiveness of lactulose in treating hepatic encephalopathy is somewhat controversial.However, lactulose can effectively be used as secondary prophylaxis of hepatic encephalopathy in patients with cirrhosis. Moreover, recent studies showed improved cognitive functions of cirrhotic patients with minimal hepatic encephalopathy treated with lactulose.
Lactulose is not absorbed, does not affect the absorption of spironolactone and may be used by diabetics. It is used in patients with cirrhosis/hepatic encephalopathy to limit the proliferation of ammonia forming gut organisms and increase the clearance of protein load in the gut.
Lactulose for hepatic encephalopathy generally requires oral dosage of at least three tablespoons (45 ml) three or four times a day with episodic diarrhea and constant flatulence almost a certain side effect.

Sunday, February 24, 2013


valathamate is anticholinergic , antispasmodic drug.

Dosage Adult: PO Dysmenorrhoea; GI tract spasm; Post-op pain; Tenesmus; Urinary tract and bile stone colic; Visceral spasms Per tab contains valethamate bromide 10 mg and paracetamol 325 mg: 1 tab 3 times/day. IV/IM Dysmenorrhoea; GI tract spasm; Urinary tract and bile stone colic; Visceral spasms 8-16 mg/day.
Indication & Dosage
Dysmenorrhoea - Adult: Each tablet contains 10 mg valethamate bromide and 325 mg paracetamol. 1 tablet tid.

Postoperative pain -  Adult: Each tablet contains 10 mg valethamate bromide and 325 mg paracetamol. 1 tablet tid.

Visceral spasms - Adult: Each tablet contains 10 mg valethamate bromide and 325 mg paracetamol. 1 tablet tid.

Gastrointestinal tract spasm - Adult: Each tablet contains 10 mg valethamate bromide and 325 mg paracetamol. 1 tablet tid.

Tenesmus - Adult: Each tablet contains 10 mg valethamate bromide and 325 mg paracetamol. 1 tablet tid.

Urinary tract and bile stone colic - Adult: Each tablet contains 10 mg valethamate bromide and 325 mg paracetamol. 1 tablet tid.

Dysmenorrhoea - Adult: 8-16 mg daily, via IM or IV inj.

Visceral spasms - Adult: 8-16 mg daily, via IM or IV inj.

Gastrointestinal tract spasm - Adult: 8-16 mg daily, via IM or IV inj.

Urinary tract and bile stone colic - Adult: 8-16 mg daily, via IM or IV inj.

Contraindications Narrow angle glaucoma, benign prostatic hyperplasia, paralytic ileus, pyloric stenosis, ulcerative colitis, megacolon, tachyarrhythmia. Severe hepatic and renal impairment.

Special Precautions May impair ability to drive or operate machinery at high doses.

Adverse Drug Reactions Dry mouth, blurring of vision, difficulty in swallowing and talking, constipation, urinary retention, mydriasis, arrhythmias.

Drug Interactions Increased antimuscarinic side effects with drugs with antimuscarinic properties e.g. amantadine, antihistamines, phenothiazide antipsychotics, TCAs. Antagonise GI effects of domperidone, metoclopramide. Delayed gastric emptying reduces absorption of other drugs.

Potentially Fatal: Increased antimuscarinic side effects with drugs with antimuscarinic properties e.g. amantadine, antihistamines, phenothiazide antipsychotics, TCAs. Antagonise GI effects of domperidone, metoclopramide. Delayed gastric emptying reduces absorption of other drugs.

Storage Oral: Store below 25°C. Parenteral: Store below 25°C.

Mechanism of Action A quaternary ammonium anticholinergic with peripheral actions close to those of atropine.


It has often been said that medicine is an art based on conjecture and improved by murder. Valethamate bromide is a drug widely used all over India by obstetricians for facilitating cervical dilatation in the first stage of labor.It is sold under many brand names such as Epidosin, Dilaton, Valosin, Valamate, Osdil etc. Even though this drug is available in India for more than a quarter of a century, it is still not listed in the Indian Pharmacopoeia. None of the well established textbooks of pharmacology from North America and the United Kingdom mention the drug, though one popular textbook from India makes a mention.Reliable sources of information like the British National Formulary also do not list it. A Google Scholar search on the term produces ten hits and a PubMed search on the molecule throws up just seven articles with only two clinical trials published in peer reviewed indexed journals. This seems to be the total quantity of information from the web sources. Yet, it is listed in the Tamil Nadu Medical Services Corporation procurement list as the item with the drug code 460.

This raises an interesting question. How and why is this drug so popular when there is so little information of its safety and efficacy? It is obvious that the drug is being used mainly due to three reasons. First, cervical ripening and dilatation is a natural feature of labor and using drugs to hasten the process may be beneficial in crowded labor rooms to facilitate the reduction in time spent in monitoring women in labor rather than any sound medical reason. Second, there are also no “new” drugs for this indication since evaluating drugs in pregnant women has its own share of problems and ethical concerns. Therefore, continuing to use something which was introduced when the criteria for using drugs were less stringent is easy. Third, the promotional pressures from the pharmaceutical companies are relentless. Obstetricians may be duped to believe that they are indeed using a drug which is listed in the Indian Pharmacopoeia (I.P.)

The carton of Epidosin lists three ingredients on it . One is valethamate bromide and the other two are normal saline and water for injection. It is interesting to note that both saline and water have I.P. listed next to their names. What is missed by the undiscerning mind is that there is no I.P next to valethamate bromide. This is perhaps why many practicing obstetricians have failed to question the very basis for the use of this drug. Is it efficacious? There are no studies which prove it, and the meagre data shows that it is ineffective.One study which mentions that valethamate is as effective as drotavarine is an unblinded, underpowered trial which has used inappropriate statistical tests for data analysis, while another study comparing the same drugs says it is less efficacious than drotavarine but has more side effects.


Camylofin is an antimuscarinic.
It is used to treat stomach ache in infants and children. Usually it is given in combination with paracetamol to treat stomach ache, as well as Pyrexia.

isopentyl 2-[2-(diethylamino)ethylamino]-2-phenylacetate

INDICATION & DOSE --- Parenteral
Intestinal colic, Biliary colic, Renal colic, Dysmenorrhoea
Adult: 1mL (25 mg) by IM or IV Inj up to a max of tid

Contraindications -Narrow-angle glaucoma, prostatic hypertrophy, mechanical stenoses.

Special Precautions Camylofin Inj must be administered with care in thyrotoxicosis, obstructive airway disease, during cardiac surgery, elderly or those with fever.

Adverse Drug Reactions - Injection may cause skin rashes, other allergic reactions and infrequently atropine-like side effects.

Drug Interactions - Camylofin Inj should be co-administered with caution in patients taking amantadine, quinidine and tricyclic antidepressants

Mechanism of Action - Camylofin is a smooth muscle relaxant with both anticholinergic action as well as direct smooth muscle action. Anticholinergic action is produced by inhibiting the binding of acetylcholine to muscarinic receptors, but the action is less pronounced. Direct smooth muscle relaxation is achieved by inhibiting phosphodiesterase type IV, which leads to increased cyclic AMP and eventually reduced cytosolic calcium. Thus camylofin has a comprehensive action to relieve smooth muscle spasm.

ATC Classification  - A03AA03 - camylofin ; Belongs to the class of synthetic anticholinergics, esters with tertiary amino group. Used in the treatment of functional bowel disorders.

China - 1 Results
India - 7 Results
ANAFORTAN  [ Khandelwal ]
ANAFORTAN SYR  [ Khandelwal ]  Interaction
ANAFORTAN TAB  [ Khandelwal ]  Interaction
ANAFORTAN-N  [ Khandelwal ]  Interaction
ANASPAS  [ Khandelwal ]  Interaction
SUMO-SPAS  [ Alkem ]  Interaction

Indonesia -

Hong Kong -

Malaysia - 1 Results

Philippines - 1 Results

Singapore - 1 Results

Thailand -

Vietnam - 0 Results

USA - 1 Results

Friday, February 22, 2013



Fondaparinux (trade name Arixtra) is an anticoagulant medication chemically related to low molecular weight heparins. It is marketed by GlaxoSmithKline. A generic version developed by Alchemia is marketed within the US by Dr. Reddy's Laboratories.

Fondaparinux is a synthetic pentasaccharide Factor Xa inhibitor. Apart from the O-methyl group at the reducing end of the molecule, the identity and sequence of the five monomeric sugar units contained in fondaparinux is identical to a sequence of five monomeric sugar units that can be isolated after either chemical or enzymatic cleavage of the polymeric glycosaminoglycans heparin and heparan sulfate (HS). Within heparin and heparan sulfate this monomeric sequence is thought to form the high affinity binding site for the anti-coagulant factor antithrombin III (ATIII). Binding of heparin/HS to ATIII has been shown to increase the anti-coagulant activity of antithrombin III 1000 fold. In contrast to heparin, fondaparinux does not inhibit thrombin.

Fondaparinux is given subcutaneously daily. Clinically, it is used for the prevention of deep vein thrombosis in patients who have had orthopedic surgery as well as for the treatment of deep vein thrombosis and pulmonary embolism.

Comparison to other agents
One potential advantage of fondaparinux over LMWH or unfractionated heparin is that the risk for heparin-induced thrombocytopenia (HIT) is substantially lower. Furthermore, there have been case reports of fondaparinux being used to anticoagulate patients with established HIT as it has no affinity to PF-4. However, its renal excretion precludes its use in patients with renal dysfunction.
Unlike direct factor Xa inhibitors, it mediates its effects indirectly through antithrombin III, but unlike heparin, it is selective for factor Xa.


Fondaparinux is similar to enoxaparin in reducing the risk of ischemic events at nine days, but it substantially reduces major bleeding and improves long term mortality and morbidity.
It has been investigated for use in conjunction with streptokinase.

fondaparinux vs control

patients undergoing either an elective primary total hip replacement (THR) surgery or a revision of a THR 
Abdominal Surgery  
fondaparinux vs no treatment

fondaparinux 2,5 mg daily group during immobilization 
no treatment
Patients with a nonsurgical fracture of the lower extremity immobilised in a below-knee plaster cast 
single blind
fondaparinux vs placebo

fondaparinux subcutaneously at 0.75, 1.5, 2.5, and 3.0 mg for at least 10 calendar days, (with a maximum of 14 days) 
Japanese patients undergoing elective total knee replacement surgery 
Follow-up: 14 days 
double blind
ARTEMIS (Cohen) ,2006
Fondaparinux 2.5 mg once daily for 6–14 days 
High-risk medical patients 
Follow-up: 6-15 days 
double blind
8 countries 
fondaparinux vs placebo (on top intermittent pneumatic comp.)

APOLLO (Turpie) ,2007
fondaparinux 2.5 mg s.c. for 5-9 days, starting 6-8 h postoperatively + intermittent pneumatic compression 
placebo s.c. for 5-9 days, starting 6-8 h postoperatively + intermittent pneumatic compression
Patients aged at least 40 years undergoing abdominal surgery 
Follow-up: 10 days 
double blind
fondaparinux vs control

Sasaki ,2010
fondaparinux 2.5mg daily for 14 days 
usual care
patients undergoing hip fracture surgery 
Follow-up: 14 days 
fondaparinux vs enoxaparin

PENTAMAKS (Bauer) ,2001
fondaparinux 2.5-mg once-daily subcutaneous, starting 6 hours after surgery 
enoxaparin 30mg twice daily (North america recommendation)
elective major knee surgery 
Follow-up: 11 days 
double blind
North america 
PENTHIFRA (Eriksson) ,2001
fondaparinux 2.5-mg once-daily subcutaneous, starting 6 hours after surgery 
enoxaprin 40mg once daily
hip fracture surgery 
Follow-up: 11 days 
double blind
21 countries 
PENTATHLON (Turpie) ,2002
fondaparinux 2.5-mg once-daily subcutaneous, starting 6 hours after surgery 
enoxaparin 30mg twice daily (North america recommendation)
elective hip replacement surgery 
Follow-up: 11 days 
double blind
USA, Canada, Australia 
EPHESUS (Lassen) ,2002
fondaparinux 2.5-mg once-daily subcutaneous, starting 6 hours after surgery 
enoxaprin 40mg once daily
elective hip replacement surgery 
Follow-up: 11 days (6 weeks) 
double blind
16 European countries 
Turpie ,2001
pentasaccharide Org31540/SR90107A subcutaneous once daily at doses 0.75 mg, 1.5 mg, 3.0 mg, 6.0 mg, and 8.0 mg 
enoxaparin 30mg once daily subcutaneous
patients undergoing total hip replacement 
Follow-up: >15 days 
double blind
US, Canada, Autralia 
fondaparinux 2.5mg subcutaneous once-daily for 7+/-2 days 
enoxaparin 40mg s.c. once-daily
chinese patients undergoing major orthopaedic surgery of the lower limbs 
Follow-up: 9 days (49d) 
Fondaparinux 2.5mg once daily subcutaneously for 7 days 
enoxaparin 40mg once daily SC for 7 days
Taiwanese patients undergoing elective knee replacement 
Follow-up: 10 days 
open, blind assessment
fondaparinux 2.5mg qd 
enoxaparin 40mg qd
acute medically ill, non-surgical patients 

once-daily subcutaneous injections of fondaparinux 2·5 mg started 6 h after surgery for 5–9 days 
once-daily subcutaneous injections of dalteparin 5000 units for 5–9 days (2500 units each, given 2 h before surgery and 12 h after the preoperative administration)
patients undergoing major abdominal surgery 
Follow-up: 10 days (30 days) 
double blind
22 countries 
fondaparinux vs nadroparin

subcutaneously, once daily, fondaparinux 2.5 mg for at least 21 Days, up to complete mobilization, with a maximal duration of treatment of 45 days 
daily nadroparin 2850 anti-Xa IU (0.3 mL) for at least 21 Days, up to complete mobilization
patients requiring rigid or semi-rigid immobilization for at least 21 days and up to 45 days because of isolated non-surgical below-knee injury 
Follow-up: 5 weeks