Thursday, January 25, 2018

Lactulose in Diabetes

Lactulose
  • consists of the monosaccharides fructose and galactose
  • In the colon, lactulose is broken down primarily to lactic acid, and also to small amounts of formic and acetic acids, by the action of via evolved-beta galactosidase from colonic bacteria, which results in an increase in osmotic pressure and slight acidification of the colonic contents.
  • This in turn causes an increase in stool water content and softens the stool.
  • In treating heptic diseases (hepatic encephalopathy) it is thought that lactulose draws out ammonia from the body in the same way that it draws out water into the colon.
Affect on Sugar level
  • The interaction of lactulose and diabetes is categorised as ‘moderate’
  • Product information states that there is a possibility of affected glycaemic control
  • Lactulose may contain more than 5 g lactose/galactose/epilactose depending upon the dose taken. This should be taken into account in patients with diabetes mellitus. [15 ml of Lactulose contain 42.7 KJ (10.2 kcals) = 0.21 BU]
Glycaemic Index
  • In terms of glycaemic Index, comparatively lactose (45) and galactose (25) has lower index compared to glucose (100).
  • However do keep in mind that GI value represents the type of carbohydrate in a food but says nothing about the amount of carbohydrate typically eaten. Thus, a higher consumption of lower index food is still able to increase the sugar level
Studies: Galactose
  • Following galactose ingestion, there was a modest transient increase in peripheral glucose and insulin concentrations. This was associated with a modest increase in the glucose Ra (rate of glucose appearance)
  • conversion of galactose to glucose in the liver may have been greater than suggested by the increase in glucose appearance in the circulation due to substitution for other gluconeogenic substrates
  • Oral galactose is a relatively potent insulin secretagogue, and the insulin response is also additive to that following glucose ingestion
Studies: Lactose
  • decrease in the glucagon area response observed with 25 g galactose + 25 g glucose or 50 g lactose was less than that with ingestion of 25 g glucose alone. The latter suggests inhibition of the glucagon response to glucose by the added galactose
Studies : Lactulose
  • In a study to test the effects of a preparation containing fibre and lactulose in the form of biscuits on glucose and insulin levels in obesity, they found a contradicting trend that glucose and insulin in response to breakfast and to lunch were blunted by dietary fibre and lactulose, without any trend towards post-meal hypoglycaemia
  • However, there is also a single case report that reported a case of a patient with diet-controlled diabetes and cirrhosis who experienced a marked deterioration in glycemic control, requiring insulin use, when he began using a different brand of lactulose syrup. The hyperglycemia resolved and insulin was discontinued after use of the original brand of lactulose syrup was resumed
Recommendations
  • Most references suggest of being cautious to the addition of lactulose. However this is not a contraindication
  • While may affect the sugar level, most likely it will not affect levels significantly to the extent of impacting diabetes control
  • Based on guidelines and data from published literature, food and dietary change with exercise and lifestyle change should be the first step in management. For patients recalcitrant to these changes, laxatives should be the next step of treatment. Treatment should begin with bulking agents such as psyllium, bran or methylcellulose followed by osmotic laxatives if response is poor
References:
  1. https://www.drugs.com/disease-interactions/lactulose.html
  2. https://www.ncbi.nlm.nih.gov/pubmed/11172481
  3. http://www.metabolismjournal.com/article/0026-0495(93)90151-D/pdf
  4. https://www.medicines.org.uk/emc/medicine/25597
  5. https://beta.nhs.uk/medicines/lactulose/
  6. https://www.ncbi.nlm.nih.gov/pubmed/9145450
  7. https://www.ncbi.nlm.nih.gov/pubmed/7716610
  8. https://www.ncbi.nlm.nih.gov/pubmed/27987136

Thursday, January 18, 2018

Comparison of oral antifungals



Availability in Hospital Keningau
  • Cap Fluconazole 50mg & 200mg
  • Tab Griseofulvin 125mg
  • Cap Itraconazole 100mg
  • Tab Ketoconazole 200mg 
  • Suspension Nystatin 100 000 units/ml
Comparison of Oral Antifungals
Antifungal
Indication (FUKKM)           
Pharmacokinetics
Ketoconazole
200mg
(B)
  • Pityriasis Versicolor
  • Systemic Mycoses (other skin mycosis)
  • Nail infection
  • Absorption can be increased by administration with a cola beverage (requires acidic condition)
  • Half life elimination is biphasic (initial 2 hours and terminal 8 hours)
Fluconazole 50mg

Fluconazole 100mg
(A)
  • Oropharyngeal candidiasis, atrophic oral candidiasis
  • Tinea Pedis, corporis, cruris, versicolor and dermal candidiasis
  • Invasive candida & cryptocococcal infections (includes meningitis)
  • Prevention of relapse cryptococcal meningitis in AIDS after completion of primary therapy
  • Prevention of fungal infections in immunocompromised patients
  • Oral bioavailability > 90%
  • The long serum half-life (approximately 24 hours) allows once-daily dosing
  • Good penetration into CSF
  • Absorption is not affected by the presence of food or gastric pH.
Itraconazole 100mg
(A/KK)
  • Dermatomycosis including pityriasis versicolor
  • Oral candidiasis
  • Palmar tinea manus and plantar tinea pedis
  • Fingernail onychomycosis
  • Toenail onychomycosis
  • Vulvovaginal candidiasis
  • Capsule bioavailability of approximately 55%
  • Relatively long half-life, approaching 25 to 50 hours thus allows OD dosing
  • Absorption increased by concurrent ingestion of cola or cranberry juice
Voriconazole 200mg

Voriconazole 50mg
(A*)
  • Treatment of immunocompromised patients with progressive, possibly life-threatening infections such as invasive aspergillosis, fluconazole-resistant serious invasive candidiasis, candidiasis of the oesophagus, serious fungal infections caused by Scedosporium species and Fusarium species
  • Prevention of breakthrough fungal infections in febrile high risk neutropenic patients

  • Oral biovailability >90% in adult and may vary with <12 year old
  • Ability to penetrate CSF



Syr. Nystatin
500 000
(B)
  • Prevention and treatment of candidiasis of the skin and mucous membranes
  • Protection against candidas overgrowth during antimicrobial /corticosteroid therapy and as selective decontamination regimens
  • Poorly absorbed
  • Excreted unchanged at feces 
  • Should be swished about the mouth and retained in the mouth for as long as possible (several minutes) before swallowing.
Griseofulvin
(B)
  • Dermatophyte infection of the skin, scalp, hair and nails, where topical therapy has failed or inappropriate
  • Absorption is almost complete (ultramicrosize)
  • Half life elimination is 9-24 hours
Flucytosine 500mg
(A*)
  • Only for the treatment of fungal meningitis
  • Ability to penetrate CSF
  • Bioavailability 78%-89% (decreased in neonates

Spectrum of activity



Imidazole (Ketoconazole)
  • Ketoconazole causes more gastrointestinal disturbances compared to other azoles.
  • Has been largely replaced by other triazoles due to favourable pharmacokinetic and safety profile
  • Should not be used as first-line treatment for any fungal infection.
  • It should be used for the treatment of endemic mycoses (eg, histoplasmosis, blastomycosis) only when alternative antifungal therapies are not available or tolerated.
  • Contraindicated in acute or chronic liver disease.
Triazole (Itraconazole, Fluconazole, Voriconazole)
  • The drugs in this class offer activity against many fungal pathogens without the serious nephrotoxic effects observed with amphotericin B 
  • Due to its inotropic effects, itraconazole’s labeling includes a black box warning in patients with heart failure, particularly in patients receiving a total daily oral dose of 400 mg
Pyrimidine (Flucytosine)
  • Flucytosine has limited clinical indication and is used primarily in combination with Amphotericin B as combination therapy for cryptococcal meningitis and selected life threatening Candida syndromes                 
References
  • Uptodate
  • https://mycology.adelaide.edu.au/docs/antifungals.pdf 
  • https://www.uspharmacist.com/article/the-fungus-among-us-an-antifungal-review 
  • Lexicomp 
  • FUKKM