Şule Oktay

Prescribing habits of general practitioners in the treatment of childhood respiratory-tract infections

ObjectiveIn the present study, prescribing behavior of general practitioners (GPs) was investigated in the example of childhood upper and lower respiratory-tract infections (URTIs and LRTIs).Study designA face-to-face interview was performed with 352 parents admitted to seven primary health care centers for their children diagnosed with URTI or LRTI. Prescriptions (n=331) written by 25 GPs working at these centers were analyzed regarding legibility, format and suitability of drug choice.ResultsAlmost 60% of parents had self-medicated their children prior to admitting to the doctor. Of the patients, 29 (8.2%) were not examined by the physicians, but were directly prescribed medicine. The physicians did not tell the diagnosis to 25.3% of the patients, did not inform 41.2% of them about the drugs and did not caution 95.7% about the side effects. Further, the physicians did not inform 42.6% of the patients about drug use instructions, did not inform 83.5% about the warnings and did not inform 81.2% about non-drug treatment. Approximately 5% of the individuals remembered the name of the drugs. Only 26.3% of the prescriptions were easily readable, and only five scripts (1.5%) contained all necessary information. The majority of the patients were given antibiotics, penicillin+beta lactamase inhibitors being the first. Paracetamol was the most frequently prescribed analgesic/antipyretic for both indications, followed by nimesulide and ibuprofen.ConclusionsThe present study revealed inappropriate drug use in the treatment of respiratory-tract infections in children at the primary health care level in a district of Istanbul, Turkey. Furthermore, it has been shown that GPs practicing at primary health care centers should be trained to give adequate information about the disease and the treatment to the patients/parents to achieve good compliance and optimal drug therapy for children.

Comparison of rational pharmacotherapy decision-making competence of general practitioners with intern doctors

ObjectiveThe aim of this study was to compare rational pharmacotherapy decision-making competency of interns (final-year medical students) who had received rational pharmacotherapy education (RPE), with their classmates at another medical school and general practitioners (GPs) who had not been exposed to RPE.DesignA written, objective, structured clinical examination (OSCE), consisting of open and structured questions, was given to all participants. The participants were expected to make a treatment plan and prescribe for simple, uncomplicated β-hemolytic streptococcal tonsillitis and mild-to-moderate essential hypertension patients, explain their proposed treatment plans and reasons affecting their drug choice. After the OSCE, a questionnaire to assess knowledge of the rational use of drugs was given to the participants.ResultsFifty RPE(+) interns, 54 RPE(−) interns and 53 GPs participated in the study. Mean scores of RPE(+) interns were higher than those of GPs, which were in turn found to be higher than those of RPE(−) interns for all cases. The RPE(+) interns scored the highest regarding all components of rational pharmacotherapy process for all cases of both indications. However, participants in all groups had higher scores for the structured questions compared with the corresponding open ones for both diseases. Prescription analysis also revealed better results for RPE(+) interns regarding the number of drugs/prescription and treatment costs.ConclusionThe present study demonstrated that the final-year medical students (interns) markedly benefited from undergraduate RPE at the medical school in developing rational prescribing skills compared with their classmates from a medical school with traditional pharmacology education. Interestingly, they got higher scores than not only RPE(−) interns, but also than the GPs participating in this study, indicating the urgent need for continuous medical education programs in this field throughout the country for practicing GPs.

Central muscarinic M2 cholinoceptors involved in cholinergic hypertension

Cholinomimetic agents increase blood pressure and heart rate via central muscarinic cholinoceptors in various species. It was reported that i.c.v. injection of the muscarinic M1 and M3 cholinoceptor selective antagonist, 4-DAMP (4-diphenylacetoxy-N-methyl-piperidine methiodide), inhibited the pressor response to physostigmine, while the M1 selective antagonist, pirenzepine, was ineffective. In the present study, the involvement of muscarinic M2 cholinoceptors in central cholinergic hypertension and tachycardia was investigated. Physostigmine (10-80 micrograms/kg i.v.), a cholinesterase inhibitor, and oxotremorine (20-40 micrograms/kg i.v.), a direct muscarinic cholinoceptor agonist, caused a dose-dependent increase in blood pressure. Additionally, physostigmine induced dose-dependent tachycardiac responses. I.c.v. administration of the muscarinic M2 cholinoceptor antagonists, AF-DX 116 and methoctramine, inhibited both physostigmine (60 micrograms/kg) and oxotremorine (20 micrograms/kg)-induced pressor responses at their lower doses used in this study (100 nmol/rat and 10 nmol/rat, respectively). These findings indicate the partial involvement of postsynaptic muscarinic M2 cholinoceptors. The higher doses of the antagonists (AF-DX 116,300 nmol/rat and methoctramine 30 nmol/rat) potentiated the blood pressure increase due to physostigmine but did not affect that due to oxotremorine. The physostigmine-induced tachycardiac responses were influenced similarly by these antagonists. These results suggest the presence and tonic influence of presynaptic inhibitory muscarinic M2 cholinoceptors.

ROLE OF NEUTROPHILS IN INDOMETHACIN-INDUCED GASTRIC MUCOSAL LESIONS IN RATS

Nonsteroidal anti-inflammatory drugs (NSAIDs) cause clinically important gastric damage by several mechanisms. In order to evaluate the role of neutrophil infiltration in lesion formation, tissue myeloperoxidase activities were assessed in different gastric layers of the stomach both in rats with normal neutrophil levels and in neutropenic rats. Sprague-Dawley rats were treated either with indomethacin (Indo; 25 mg/kg, s.c.) or the vehicle. A group of rats were made neutropenic by administration of methotrexate (MTX; 2.5 mg/kg i.p.) once a day for 3 days. The stomachs were removed for the determination of lesion index, glutathione, lipid peroxide levels, protein oxidation and tissue myeloperoxidase activities. MTX treatment appeared to reduce neutrophil infiltration significantly while producing insignificant effects on eosinophils and macrophages. Indo administration caused multiple gastric lesions and treatment with MTX significantly reduced lesion index. In rats treated with Indo, neither glutathione nor LP levels showed any significant changes but the protein oxidation was significantly higher than that of other groups. The MPO level of gastric mucosa was increased in Indo-treated rats and reversed by MTX pretreatment. The results of the present study indicate that neutrophil infiltration in the gastric mucosa of rats may be involved in the pathogenesis of NSAID-induced gastric mucosal injury, but no correlation was found between lesion formation and protein oxidation in the gastric mucosa.

Reversal of hemorrhagic shock in rats by oxotremorine: the role of muscarinic and nicotinic receptors, and AV3V region.

In an experimental model of hemorrhagic shock resulting in the death of almost all rats within 20-30 min, centrally active cholinomimetic drugs are reported to induce a prompt, sustained and dose-dependent improvement in blood pressure and survival rate claimed to be due to nicotinic, but not muscarinic actions. In the present study, cholinergic receptor agonist, oxotremorine (50 micrograms/kg, i.v.) increased mean arterial pressure (from 22 +/- 1 to 123 +/- 3 mm Hg) and 60 min-survival rate (from 0% to 92%) in rats bled to hypovolemic shock. Atropine (2 mg/kg, i.v.) pretreatment inhibited the pressor effect of oxotremorine significantly, but did not modify its effect on survival rate. On the other hand, pretreatment with mecamylamine (50 micrograms, i.c.v.) almost abolished the reduction in mortality rate, but inhibited the pressor effect of oxotremorine, partially. These results indicate that oxotremorine-induced pressor response and decrease in mortality in rats with severe hemorrhagic shock are primarily mediated via central muscarinic and nicotinic receptors, respectively. AV3V region was previously reported to be involved in pressor and natriuretic effects of i.c.v. carbachol in normotensive rats. In the present study, the electrolytic lesions of AV3V region significantly inhibited oxotremorine-induced increases in both blood pressure and survival rate in rats subjected to hemorrhagic shock. These findings indicate that AV3V region plays a major role in cholinergic cardiovascular control in hypotensive animals as well as normotensives.

Antihypertensive drug utilization at health centres in a district of Istanbul

ObjectiveSince irrational use of antihypertensives has considerable clinical and economical consequences, this study was conducted to evaluate antihypertensive drug utilization in hypertension at seven State Health Centres in Istanbul.MethodA total of 297 hypertensive patients who accepted to␣participate in the study were evaluated by a face-to-face questionnaire and a copy of their prescriptions were collected for prescription analysis.ResultsAngiotensin-converting enzyme (ACE) inhibitors (31.7%), calcium channel blockers (28.8%), diuretics (16.2%), beta blockers (7.5%) and others (15.8%) have been prescribed. There were no statistically significant relation between prescribed antihypertensive drug groups and gender, age, and NSAIDs co-prescribing. The most frequent comorbidity in hypertensive patients was diabetes mellitus (10.4%) and calcium channel blockers (35.5%) have been prescribed to them as a first antihypertensive medication. Average cost per prescription was

Gastric lipid peroxidation, gluathione and calcium channel blockers in the stress-induced ulcer model in rats

42.7±38.1. According to the patients’ self-reporting, the majority of them (85%) were prescribed without a physical examination. The physicians failed to write the prescriptions appropriately; only 5% of the scripts contained all information about the drug(s) and use instructions in full format.ConclusionThe present study indicates that GPs working at primary healthcare centres were rational in terms of antihypertensive drug choice. However, they poorly applied rational pharmacotherapy principles such as (a) writing a “good” prescription which is easily readable by the pharmacist and the patient and that contains full essential information; (b) a medical examination of the patient to assess her/his current clinical condition; and (c) taking care of not prescribing drugs with potential interaction like antihypertensives and NSAIDs together.

Subtypes of muscarinic receptors in rat duodenum: a comparison with rabbit vas deferens, rat atria, guinea-pig ileum and gallbladder by using imperialine.

The antiulcer activity of verapamil and its analogues devapamil and gallopamil was studied. All three drugs reduced cold-restraint stress-induced ulcer development. Gallopamil almost abolished gastric ulcers. Verapamil prevented the increase in gastric lipid peroxidation (LP) due to stress. On the other hand, devapamil and gallopamil increased gastric lipid peroxidation and decreased glutathione levels. This effect may be attributed to the increase in oxygen supply due to possible effective vasodilation at gastric mucosa. The second part of this study revealed that stress-induced gastric ulcers in rats rapidly and spontaneously heal and disappear within 24 h. During recovery, gastric LP decreased and glutathione levels increased within 12 h after the withdrawal of stress, preceded by an initial reduction in glutathione. After 72 h, an unexplained increase in gastric LP and a decrease in glutathione were observed. Treatment with verapamil, devapamil and gallopamil promoted healing, gallopamil being again the most effective. Their effects on gastric LP and glutathione levels are in accordance with the results of pretreatment experiments. In conclusion, devapamil and gallopamil are effective antiulcer agents against stress-induced ulcers, but unlike verapamil, antioxidant activity does not seem likely to be among their mechanisms of action.

The hypotensive effect of cisapride in rat

The specific binding of [3H]QNB to rat duodenum smooth muscle membranes was a saturable process and Scatchard transformation of the saturation curves indicated a linear plot (nH = 1.017+/-0.071). The K(D) and Bmax values were 0.168+/-0.025 nM and 46.7+/-8.6 fmol/mg protein, respectively. Analyses of competition curves using pirenzepine and guanylpirenzepine indicated more than one class of binding site. A minor population of muscarinic binding sites showed high affinity (M1) for both pirenzepine (19.3+/-1.2%; pKi = 8.29+/-0.36) and guanylpirenzepine (29.4+/-2.0%; pKi = 7.28+/-0.11). The antagonistic affinity values of pirenzepine and guanylpirenzepine for the remaining low affinity binding sites, and that of methoctramine indicated the presence of both M2 and M3 subtypes. McN-A-343 produced relaxations in rat duodenum and inhibited twitch contractions of rabbit vas deferens induced by electrical stimulation in a concentration dependent manner. Carbachol (Cch) exerted concentration-dependent negative inotropic effect in rat atria and contractile effects in guinea-pig gallbladder and ileum longitudinal muscle-myenteric plexus preparation. Imperaline displaced the concentration-response curves to McN-A-343 and Cch to the right in parallel, without affecting the maximum responses in all tissues studied. The rank order of the pA2 values was rabbit vas deferens > rat atria > guinea-pig gallbladder = guinea-pig ileum > rat duodenum. The presynaptic muscarinic receptors at the rat duodenum and rabbit vas deferens were concluded to be of M1 and M4 subtypes, respectively.

The role of nitric oxide in the reversal of hemorrhagic shock by oxotremorine

1. Cisapride is a prokinetic agent believed to facilitate acetylcholine release from the myenteric plexus of the gut. The aim of the present study was to investigate the effect of cisapride on blood pressure and the effects of muscarinic receptor antagonists on the cisapride-induced blood pressure changes. 2. Cisapride was given i.v. alone or 10 min after muscarinic receptor antagonists. Cisapride given i.v. produced a significant decrease in blood pressure in a dose-related manner. Atropine, AF-DX 116 and 4-DAMP given 10 min before cisapride injection, partially inhibited the hypotensive response to cisapride. In pithed rat, the effect of cisapride on blood pressure remained unaltered. 3. This study indicates that the action of cisapride is not through central mechanisms and part of cisaprides effect is through the cholinergic system.