/library/oar/handle/123456789/33088 2026-05-30T18:44:44Z /library/oar/handle/123456789/33957 Title: A comparison of the effects of paracetamol and a corticosteroid against a non-steroidal anti-inflammatory drug on the sequelae following the surgical removal of mandibular third molars Abstract: The reduction of postoperative discomfort from oral surgical procedures is an area of great concern to all practicing dental surgeons, as well as their patients. Pain, swelling and trismus (limitation of opening) are the common sequelae after surgical removal of impacted mandibular third molars, and a wide variety of therapeutic measures have been used to reduce the incidence ofthese sequelae. The factors contributing to the postoperative pain, oedema, and trismus (a form of loss of function) are complex, but many of the contributing factors are related to the inflammation following tissue trauma. These may, therefore, be reduced in intensity or severity by pharmacologically controlling the extent of the inflammatory process. In most cases, unless contraindicated, non-steroidal anti-inflammatory drugs (NSAIDs) have been used to prevent postoperative pain, while corticosteroids appear to have maximal effect in controlling oedema, but have minimal analgesic effects. In this double-blind randomised controlled clinical trial, a combination of oral paracetamol Ig and oral dexamethasone lmg four times daily, was evaluated against oral diclofenac sodium 50mg three times daily, for the control of postoperative pain, swelling and trismus following the surgical removal of mandibular third molars under local anaesthesia. The purpose for such a study was to find an alternative drug regimen for the control of the common postoperative sequelae of oral surgery, especially for those patients in whom the usual drug regimens (e.g. NSAIDs) are contraindicated. Postoperative pain was recorded 8-hourly by the patients using a visual analogue scale pain chart for 7 days, while facial swelling and trismus were assessed by the investigator on the second, fourth and seventh postoperative days. Facial swelling was determined using a measuring tape, while trismus was evaluated by measuring maximal interincisal opening. ANOVA for repeated measures analysis indicated that the patients in the paracetamol and dexamethasone group experienced an overall mean reduction of 36% in pain (p<0.05), of 76% in facial swelling (p>0.001) and of 56% in trismus (p>0.001) as compared to the patients in the diclofenac sodium control group. Levene's test for equality of variances showed that the inter-patient variation with respect to pain, swelling and trismus in the paracetamol and dexamethasone group, was also significantly less than that in the diclofenac sodium group (p<0.05). Pearson bivariate correlation tests show that the reduction in swelling and trismus (p<0.05) are significantly correlated in both groups. None of the patients reported any adverse drug reactions. It could therefore be concluded that in the absence of contraindications, a combination of oral paracetamol Ig and oral dexamethasone lmg four times daily, was significantly superior to oral diclofenac sodium 50mg three times daily, in safely reducing the postoperative pain, swelling and trismus following the surgical removal of mandibular third molars under local anaesthesia in otherwise healthy patients. Also, a more predictable and consistent patient response could be expected with paracetamol and dexamethasone combination therapy than with the diclofenac sodium. This may be especially beneficial for those patients in whom the usual drug regimens (e.g. NSAIDs) are contraindicated. The use of paracetamol and dexamethasone• combination therapy following this kind of oral surgical procedure, may also obviate the need for the common hospital practice to admit patients overnight in order to allow parenteral administration of opioid analgesia if necessary, thus reducing healthcare costs and avoiding opioid-associated adverse effects. Description: M.SC.PHARMACOLOGY 2004-01-01T00:00:00Z /library/oar/handle/123456789/33111 Title: The therapeutics of novel antiepileptic drugs in paediatric patients in Malta Abstract: Therapeutic drug monitoring is important for drugs that exhibit inter-individual variability in pharmacokinetics, and where drug-drug interactions, concurrent disease or age alters the kinetics of that drug. This is of particular importance in a chronic neurological condition such as epilepsy. In this study, the value of therapeutic drug monitoring for lamotrigine, a novel anti epileptic drug, was investigated in a group of paediatric patients. Plasma lamotrigine levels in 20 paediatric patients (mean ± S.D., age 8.85 ± 3.47 years and weight, 32.22 ± 20.81 kg) were measured using a novel validated high performance liquid chromatography (HPLC) technique that gave a retention time for lamotrigine and internal standard of 1.258 min and 2.30 min respectively. The method proved to be linear, precise and reproducible over the plasma concentration range of 0.08 - 20 mg/L. Plasma lamotrigine levels at steady state (mean ± S.D.) in epileptic patients were thus measured using this novel analysis. The levels thus estimated were 10.1 ± 4.95 mg/L in lamotrigine monotherapy group. In valproate co-medication group; carbamazepine co-medication group; clonazepam co-medication group; and valproate and clonazepam co-medication group, these were 8.11 ± 5.48, 1.89 ± 1.55, 8.33 ± 0.91 and 8.86 ± .98 mg/L respectively. A statistically significant difference (P < 0.05) was obtained between valproate co-medication group and carbamazepine co-medication group, between valproate co-medication group and clonazepam co-medication group, and between valproate co-medication group and valproate, clonazepam co-medication group. The pharmacokinetic parameters in the four groups (lamotrigine alone, valproate co-medication group, carbamazepine co-medication group, and clonazepam co-medication group) were estimated in this study using non-compartmental pharmacokinetic equations. The only significant difference (P < 0.05) was obtained between the four groups in the case of estimated volume of distribution, predicated minimum plasma concentration, estimated area under the curve and average plasma concentration. The data was also analysed using a modification of a one compartment first order absorption model with an Adapt® population simulation programme. Overall, the results thus obtained from the studies in this research, indicate the important need to streamline pharmacokinetic data for the use of anti epileptic drugs in children. Most physicians use ad hoc reasoning in the design of therapeutics and dosage regimens for these drugs in children. Our studies have shown that there are too many variables that could influence the plasma drug concentrations obtained. There is still a lack of satisfactory models and software packages that will allow accurate predictions of drug levels with these drugs in these populations. Description: M.PHIL. 2004-01-01T00:00:00Z