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Parkinson's Disease

The stomach is the gateway

Absorption and Metabolism of L‐Dopa by the  Stomach

Department of Medicine, Division of Clinical Pharmacology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.A.

European Journal of Clinical Investigation (Impact Factor: 3.37). 09/1971; 1(5):313 – 320. DOI: 10.1111/j.1365-2362.1971.tb00637.x

ABSTRACT The absorption and gastric metabolism of L-dopa (L-dihydroxyphenylalanine) were studied in 14 Parkinsonian patients. Patients were given p. o. 25 μCi (500 mg) 14C L-dopa labelled at the β-carbon mixed with 2 g polyethylene glycol as a dilution marker. Absorption was evaluated by determining the gastric rate of absorption, gastric clearance, serum levels, and urinary excretion of 14C. L-dopa and its metabolites in the gastric juice and serum were fractionated by column chromatography. Patients with gastric juice pH of 1.2-2.1 had a gastric rate of absorption of 62.6±4.7 mg/h with a gastric clearance of 31.7.4.1 ml/h. The gastric emptying time was 228±96min. 17.2–26.4% of total radioactivity in the gastric juice were dopa metabolites. Patients with gastric pH of 6.9-7.2 had a very rapid emptying time (an average of 22 min.) with no gastric absorption. The amount of metabolites in their gastric juice was insignificant. Gastric absorption and emptying time were reduced in patients when the gastric pH was raised to 3.5-4.5 with antacids. Serum peak concentrations were higher and more rapidly achieved in patients with high gastric pH than in those with low pH.The most rapidly achieved and highest serum peak levels were observed in patients with partial gastrectomy and in those who were given the drug by duodenal infusion. It appears that direct absorption of L-dopa by the stomach may be limited by gastric metabolism of the drug, a possibility supported by the study in vitro of human stomach tissue obtained at surgery. The inverse relationship between the gastric emptying time and serum levels suggests that the intestine is the major site of L-dopa absorption. Thus factors that prolong gastric emptying time may lower serum levels of L-dopa by delaying access of the drug to the site of absorption and by increasing metabolism before absorption.

August 12, 2014 Posted by | Anatomy-gut, Medication, Research | Leave a Comment

Parkinson’s disease and Acid reflux

Parkinson’s disease and Acid reflux.

July 9, 2014 Posted by | Anatomy-gut | Leave a Comment

The Gut

 

Management of illness through oral medication is the usual route of drug delivery. The limiting efficiency is the individual.

Significant to all is gastric emptying time, delayed or rapid, the result is fluctuations in response with each dose of medication taken.

 

 

 GASTROINTESTINAL TRACT

The stomach is divided into 3 regions:

 

  • fundus, reservoir for undigested material
  • body
  • antrum is for mixing motions and is a pump for gastric emptying.

 

 

 

 EXIT OF MEDICATION

  • To get out of the stomach a pill has to pass through the pyloric valve into the small intestine and its size needs to be 1 to 2 mm.

 

 

STOMACH  PH

  • Empty stomach 1.5 to 2.0
  • Fed stomach is 2.0 to 6.0.

 

A large volume of water with medication raises the PH of stomach contents to 6.0 to 9.0.

 

Some drugs  have a better chance of dissolving in fed state than in a fasting state.

 

STOMACH  EMPTYING

 

The rate of your stomach emptying depends on the density volume and calories consumed.

Nutritive density of meals helps determine gastric emptying time.

It doesn’t matter for this part of the process whether the meal has high protein, fat, or carbohydrate it. It is the calorific load that is significant.

FACTS

  • Increase in acidity and caloric value slows down gastric emptying time.

 

  • Biological factors such as age, body mass index (BMI), posture and disease status influence gastric emptying.

 

  • In elderly persons, gastric emptying is slowed down.
  • Generally females have slower gastric emptying rates than males.

 

  • Stress increases gastric emptying rates

 

  • Depression slows it down.

 

  •  Fluids taken at body temperature leave the stomach faster than colder or warmer fluids.

 

  • Studies have revealed that gastric emptying of some pills in the fed state can also be influenced by size. Small-size tablets leave the stomach earlier in the digestive process than larger ones.

 

CONCLUSION

Drug absorption in the gastrointestinal tract is a highly

variable procedure.

Delivery systems are emerging as an effective means

of enhancing the bioavailability by improving the controlled release of many drugs.

The increasing sophistication of new delivery technology will

ensure the development of an increased number of drugs that have at present absorption window, low bioavailability.

 

June 30, 2014 Posted by | Anatomy-gut | Leave a Comment

Gut pathology in Parkinsons Disease

The function of the gut and pathology of evidence is gaining credibility.

Braak’s staging scheme is that the areas of the nervous system littered with Lewy bodies at the earliest stages of disease could account for the non-motor symptoms. The staging system, , “has drawn attention to the damage in other transmitter systems—in other words, apart from and before the nigrostriatal system. In addition, it can serve as a framework for relating the pathology in other parts of the nervous system (gastrointestinal tract, spinal cord, and so on) to that in the brain.”

The focus on the substantia nigra faces challenge, most PD patients have additional, non-motor symptoms, and PD is coming to be understood as a much broader disease.

Chronic constipation, loss of smell, and REM sleep disorders often occur before the motor

problems (O’Sullivan et al., 2008 and ARF related news story). A large epidemiological

study, the Honolulu-Asia Aging Study, showed that men who reported less frequent

bowel movements had a significantly higher risk of developing PD within the next 24

years (Abbott et al., 2001; Abbott et al., 2003).

One of the attractive features of Braak’s staging scheme is that the areas of the nervous system littered with Lewy bodies at the earliest stages of disease could account for these non-motor symptoms. The staging system, wrote Braak in an e-mail “has drawn attention to the damage in other transmitter systems—in other words, apart from and before the nigrostriatal system. In addition, it can serve as a framework for relating the pathology in other parts of the nervous system (gastrointestinal tract, spinal cord, and so on) to that in the brain.”

Read on————–

http://www.alzforum.org/new/pdf/ParkinsonsSeries.pdf

January 13, 2012 Posted by | Anatomy-gut | | Leave a Comment