what is the influence of anti cholinergics and of prokinetic agents on the oral availability of drugs
Answers
Answer:
Drugs may affect gastrointestinal motility and, therefore, absorption of other concomitantly administered drugs. Gastrointestinal prokinetic agents increase the rate of gastric emptying and also upper intestinal motility. These effects would be expected to increase the initial rate of absorption of orally administered drugs, but reduce total bioavailability of the agents. Metoclopramide has been shown to increase the rate of absorption of several classes of drug, reflected by reduced time taken to achieve maximal plasma concentration (tmax) and increased maximal plasma concentration (Cmax). However, the effect of these agents on the area under the plasma concentration-time curve from zero to infinity (AUC0-infinity), when measured, is not consistent. Cisapride and domperidone appear to have similar effects, but there are relatively less data available regarding these products. Opioids may delay gastric emptying considerably, an effect which will often have significant clinical and therapeutic implications. Most of the data confirming this observation concern oral analgesics, but the effect should be considered when prescribing any oral medication. Drugs with anticholinergic or sympathomimetic activity are likely to have a similar effect and this is confirmed, in the main, by the limited data available. Although many effects reported in the literature are of limited clinical importance, they may be significant when prescribing a drug with a narrow therapeutic index, especially if it is absorbed poorly.
Answer:
Prokinetic agents are often employed to reverse an inhibition of physiological GI motility that has occurred as the result of disease or iatrogenic effects, such as in diabetic gastroparesis or following the use of opioid analgesia. However, prokinetic agents can also be employed in the absence of such deficits but where an increase of baseline motility can be demonstrated to generate benefit, such as in GERD. In several disease states patient symptoms result from a reduction in motility in the GI tract. For example, in type 1 diabetes, a retardation in gastric emptying, which appears to result from a neuropathy affecting the myenteric plexus in the proximal GI tract, can be demonstrated in up to 50% of patients. In a subset of these patients, this results in a significant symptom burden, most commonly manifest as nausea, vomiting, and early satiety, and in these patients the use of prokinetic agents can improve symptoms. Similarly, reduced motility in the distal GI tract, from either iatrogenic or idiopathic causes, can result in constipation, which can become chronic and present a significant problem to patients. In both circumstances, prokinetic agents have been shown to be beneficial to patients by improving their bowel habit and other symptoms. Prokinetic agents also appear to have a significant impact in the treatment of postoperative ileus. During surgery a combination of opioid analgesia and anesthetic use, incision of the peritoneum, and handling of the intestines results in a temporary cessation of GI motility, most probably through a combination of pharmacologic, physiologic, and inflammatory events. This can generate significant postoperative problems with symptoms such as bloating inhibiting resumption of feeding and delaying patient discharge from hospital. A number of less common conditions have been described in which GI motility is profoundly inhibited, such as systemic sclerosis and intestinal pseudo-obstruction. The value of prokinetic agents in these conditions is more controversial but these data serve to illustrate that one needs to consider the pathology that underlines the patient's condition before one can select a prokinetic agent with an appropriate mechanism of action to treat them. For example, 5HT4 receptor agonists increase GI motility through the stimulation of cholinergic neurotransmission. In disease states where there is loss of acetylcholine-containing neurons, the prokinetic activity of agents such as cisapride will be attenuated.
Historically, the most common usage of prokinetic agents was in the treatment of GERD. Before the withdrawal of the prokinetic agent cisapride (2) in 2000, over half of all uses were for the treatment of GERD. However, in only a small proportion of GERD patients has a delay in gastric emptying ever been demonstrated and a relationship between degree of delay and severity of reflux has not been found.