CYP450 polymorphisms and clinical pharmacogenetics of ibuprofen after lower third molar extraction.

PURPOSE: This study hypothesized that drugs accumulate in the bloodstream of poor-metabolizing patients and may have more adverse effects and different pain perceptions and aimed to investigate the influence of CYP450 polymorphisms on acute postoperative pain, swelling, and trismus controlled by ibuprofen (600 mg) in 200 volunteers after dental extraction. In addition, surgical outcomes can determine pain, edema, and trismus and indicate inflammatory reactions after oral surgeries. METHODS: Genetic sequencing was performed to identify CYP450 polymorphisms and the surgical parameters evaluated: pre and postoperative swelling, trismus, and temperature; self-reported postoperative pain with visual analog scale (VAS); rescue medication consumed; and severity of adverse reactions. RESULTS: A multiple linear regression model with independent variables [single nucleotide polymorphisms (SNPs), BMI (body mass index), duration, and difficulty of surgery] and dependent variables [postoperative pain by sum of pain intensity difference (SPID), trismus, and swelling] was used for analysis. The duration of surgery was a predictor for pain at 8 h and 96 h after surgery, and BMI was a predictor for both swelling and trismus on the 2nd postoperative day. When evaluating CYP2C8 and C9 genotyped SNPs, it was observed that normal metabolizers showed higher pain levels than the intermediate/poor metabolizers on the postoperative periods as compared with time 0 h. In another analysis, the poor metabolizers for CYP2C8 and C9 presented lower levels of postoperative pain after 8 h and used rescue medication earlier than normal metabolizers. CONCLUSION: Ibuprofen 600 mg was very effective in controlling inflammatory pain after lower third molar surgeries, without relevant adverse reactions; although in a very subtle way, patients with poor metabolism had higher levels of pain in the first hours, and no longer after 8 h, and used pain relief medication earlier. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov ID (NCT03169127), on March 16th, 2017.

Passive Cigarette Smoking Impact on Blood Pressure Response to Epinephrine and Felypressin in 1K1C Hypertensive Rats Treated or not with Atenolol.

BACKGROUND: Cigarette smoking is usually associated with hypertension and may modify vasoconstrictor response. OBJECTIVE: The present study aimed to analyze and compare the interaction of passive cigarette smoking and hypertension on epinephrine and felypressin blood pressure effects after intravascular injection. METHOD: 45-day male Wistar rats had the main left renal artery partially constricted and the right kidney removed (1K1C model). Rats were placed in the chamber for exposition to passive cigarette smoking (10 cigarettes) during 10 min (6 days a week). Hypertensive rats received atenolol (90 mg/kg/day) by gavage for two weeks. Hypotensive and hypertensive response, response duration and heart rate were recorded from direct blood pressure values. The significance level was 5%. RESULTS: Passive cigarette smoking increased maximal hypertensive response to epinephrine in normotensive and 1K1C-atenolol treated rats and to felypressin only in 1K1C-atenolol treated rats; it also reduced epinephrine hypotensive response. Epinephrine increased heart rate in normotensive and hypertensive passive smokers or non-smoker rats. Comparing the two vasoconstrictors, epinephrine showed greater hypertensive response in normotensive smokers, 1K1C-atenolol treated smokers and non-smokers. However, in normotensive-nonsmoker rats, felypressin showed a greater and longer hypertensive effect. CONCLUSIONS: Our results suggest that passive cigarette smoking may reduce epinephrine vasodilation and increase hypertensive response when compared to felypressin. Therefore, felypressin may be safe for hypertensive patients to avoid tachycardia and atenolol interaction, but for normotensive and non-smoker patients, epinephrine may be safer than felypressin.

Epinephrine concentration (1:100,000 or 1:200,000) does not affect the clinical efficacy of 4% articaine for lower third molar removal: a double-blind, randomized, crossover study.

PURPOSE: This study compared the use of 4% articaine in association with 1:100,000 (10 mug/mL; A100) or 1:200,000 (5 mug/mL; A200) epinephrine in lower third molar removal. PATIENTS AND METHODS: Fifty healthy volunteers underwent removal of symmetrically positioned lower third molars, in 2 separate appointments, under local anesthesia with either A100 or A200, in a double-blind, randomized, and crossed manner. Latency, duration of postoperative analgesia, duration of anesthetic action on soft tissues, intraoperative bleeding, and hemodynamic parameters were evaluated. RESULTS: A100 and A200 presented very similar latency (1.64 +/- 0.08 and 1.58 +/- 0.08 minutes, respectively; P > .05). Identical volumes of both anesthetic solutions were used: 2.7 mL = 108 mg of articaine plus 27 mug (A100) or 13.5 mug (A200) of epinephrine. The 2 solutions provided similar duration of postoperative analgesia regardless of bone removal (around 200 minutes; P > .05). The 2 solutions also had a similar duration of anesthetic action on soft tissues (around 250 minutes; P > .05). The surgeon's rating of intraoperative bleeding was considered very close to minimal. Transient changes in hemodynamic parameters were observed, but these were neither clinically significant nor attributable to the type of anesthetic used (P > .05). CONCLUSIONS: An epinephrine concentration of 1:100,000 or 1:200,000 in 4% articaine solution does not affect the clinical efficacy of this local anesthetic. It is possible to successfully use the 4% articaine formulation with a lower concentration of epinephrine (1:200,000 or 5 mug/mL) for lower third molar extraction with or without bone removal.

Passive Cigarette Smoking Impact on Blood Pressure Response to Epinephrine and Felypressin in 1K1C Hypertensive Rats Treated or not with Atenolol / Impacto do Tabagismo Passivo na Resposta Pressórica à Epinefrina e Felipressina em Ratos Hipertensos 1K1C Tratados ou não com Atenolol

Abstract Background: Cigarette smoking is usually associated with hypertension and may modify vasoconstrictor response. Objective: The present study aimed to analyze and compare the interaction of passive cigarette smoking and hypertension on epinephrine and felypressin blood pressure effects after intravascular injection. Method: 45-day male Wistar rats had the main left renal artery partially constricted and the right kidney removed (1K1C model). Rats were placed in the chamber for exposition to passive cigarette smoking (10 cigarettes) during 10 min (6 days a week). Hypertensive rats received atenolol (90 mg/kg/day) by gavage for two weeks. Hypotensive and hypertensive response, response duration and heart rate were recorded from direct blood pressure values. The significance level was 5%. Results: Passive cigarette smoking increased maximal hypertensive response to epinephrine in normotensive and 1K1C-atenolol treated rats and to felypressin only in 1K1C-atenolol treated rats; it also reduced epinephrine hypotensive response. Epinephrine increased heart rate in normotensive and hypertensive passive smokers or non-smoker rats. Comparing the two vasoconstrictors, epinephrine showed greater hypertensive response in normotensive smokers, 1K1C-atenolol treated smokers and non-smokers. However, in normotensive-nonsmoker rats, felypressin showed a greater and longer hypertensive effect. Conclusions: Our results suggest that passive cigarette smoking may reduce epinephrine vasodilation and increase hypertensive response when compared to felypressin. Therefore, felypressin may be safe for hypertensive patients to avoid tachycardia and atenolol interaction, but for normotensive and non-smoker patients, epinephrine may be safer than felypressin.

Resumo Fundamento: O tabagismo geralmente está associado à hipertensão e pode modificar a resposta vasoconstritora. Objetivo: O presente estudo teve como objetivo analisar e comparar a interação do tabagismo passivo e hipertensão sobre os efeitos da epinefrina e felipressina na pressão arterial após injeção intravascular. Métodos: Ratos Wistar machos de 45 dias tiveram a artéria renal principal esquerda parcialmente obstruída e o rim direito removido (modelo 1K1C). Os ratos foram colocados na câmara para exposição ao tabagismo passivo (10 cigarros) durante 10 minutos (6 dias por semana). Ratos hipertensos receberam atenolol (90 mg/kg/dia) por gavagem durante duas semanas. A resposta hipotensora e hipertensiva, a duração da resposta e a frequência cardíaca foram registradas a partir da medida dos valores diretos da pressão arterial. O nível de significância foi de 5%. Resultados: O tabagismo passivo aumentou a resposta hipertensiva máxima à epinefrina em ratos normotensos e ratos 1K1C tratados com atenolol e à felipressina apenas em ratos 1K1C tratados com atenolol; também reduziu a resposta hipotensiva à epinefrina. A epinefrina aumentou a frequência cardíaca em ratos fumantes passivos ou não-fumantes, normotensos e hipertensos. Comparando os dois vasoconstritores, a epinefrina apresentou maior resposta hipertensiva em fumantes normotensos, ratos 1K1C fumantes e não fumantes tratados com atenolol. No entanto, em ratos normotensos e não fumantes, a felipressina apresentou um efeito hipertensivo maior e mais prolongado. Conclusões: Nossos resultados sugerem que o tabagismo passivo pode reduzir a vasodilatação da epinefrina e aumentar a resposta hipertensiva quando comparado à felipressina. Portanto, a felipressina pode ser segura para pacientes hipertensos, com o objetivo de evitar a interação entre taquicardia e atenolol, mas para pacientes normotensos e não-fumantes, a epinefrina pode ser mais segura que a felipressina.

Are antibiotics necessary after lower third molar removal?

OBJECTIVE: Patients (n = 110) free of antibiotics, operated on by 3 surgeons ranging in clinical experiences, were evaluated for infection. STUDY DESIGN: In the preoperative period and during the second and seventh postoperative days, the following parameters were analyzed: pain, infection, swelling, trismus, body temperature, C-reactive protein levels (CRP), and salivary neutrophil counts (SNC). During surgery, the following parameters were analyzed: systolic, diastolic, and mean arterial pressure; oximetry; heart rate; anesthesia quality; local anesthetic amount; bleeding; surgery difficulty; and surgery duration. RESULTS: There were some differences in the surgery duration, local anesthetic amount, anesthesia quality, bleeding, pain experienced, trismus, CRP, and SNC, and no changes in hemodynamic parameters, rescue analgesic medication, wound healing, swelling, body temperature, confirmed case of dry socket, or any other type of local infection. Particularly, no systemic infections were found after lower third molar removal (LTMR). CONCLUSIONS: This study suggests that antibiotic prescriptions are unnecessary after LTMR when preoperative infections are absent.

Sublingual ketorolac and sublingual piroxicam are equally effective for postoperative pain, trismus, and swelling management in lower third molar removal.

OBJECTIVE: Lower third molar removal provides a clinical model for studying analgesic drugs. The present study's aim was to compare the clinical efficacy of sublingual ketorolac and sublingual piroxicam in managing pain, trismus and swelling after lower third molar extraction in adult volunteers. STUDY DESIGN: In this double-blinded, randomized, crossover investigation, 47 volunteers received for 4 days ketorolac sublingually (10 mg 4 times daily) and piroxicam sublingually (20 mg once daily) during 2 separate appointments after lower third molar extraction of symmetrically positioned lower third molars. A surgeon evaluated objective parameters (surgery duration, mouth opening, rescue analgesic medication, and facial swelling) and volunteers documented subjective parameters (postoperative pain and global evaluation), comparing postoperative results for a total of 7 days after surgery. The means of the objective and subjective parameters were compared for statistical significance (P < .05). RESULTS: Volunteers reported low pain scores during the postoperative period when treated with either sublingual ketorolac or piroxicam. Also, volunteers ingested similar amounts of analgesic rescue medication (paracetamol) when they received either drug sublingually (P > .05). Additionally, values for mouth openings measured just before surgery and immediately after suture removal 7 days later were similar among volunteers (P > .05), and the type of nonsteroidal antiinflammatory drug (NSAID) used in this study showed no significant differences between swellings on the second or seventh days after surgery (P > .05). CONCLUSIONS: Pain, trismus, and swelling after lower third molar extraction, independent of surgical difficulty, were successfully controlled by sublingual ketorolac (10 mg 4 times daily) or sublingual piroxicam (20 mg once daily), and no significant differences were observed between the NSAIDs evaluated.

A comparison of the clinical anesthetic efficacy of 4% articaine and 0.5% bupivacaine (both with 1:200,000 epinephrine) for lower third molar removal.

OBJECTIVE: This study compared the clinical efficacy of 4% articaine (A200) and 0.5% bupivacaine (B200), both with 1:200,000 epinephrine, for lower third molar removal. STUDY DESIGN: Fifty patients underwent removal of symmetrically positioned lower third molars, in 2 separate appointments, under local anesthesia either with A200 or B200, in a double-blind, randomized, and crossover manner. Time to onset, duration of postoperative analgesia, duration of anesthetic action on soft tissues, intraoperative bleeding, and hemodynamic parameters were evaluated. RESULTS: A statistically significant difference between the time to onset of A200 (1.66 +/- 0.13 minutes) and B200 (2.51 +/- 0.21 minutes) was found (P < .05). There was no statistically significant difference in the duration of analgesia, whether the patient was subjected to osteotomy or not, regardless of the local anesthetic used (3 to 4 hours; P > .05). However, when patients received B200 they experienced a statistically significant longer period of anesthesia on the soft tissues as compared with when they had received A200 (around 5 hours and 4 hours, respectively, P < .05). The surgeon's rating of intraoperative bleeding was considered very close to minimal for both anesthetics. In the surgeries with osteotomy, the comparison between A200 and B200 showed statistically significant differences in the diastolic (64 mm Hg and 68 mm Hg, respectively, P = .001) and mean arterial pressure (86 mm Hg and 89 mm Hg, respectively, P = .031) when data from all the surgical phases were pooled. Additionally, the mouth opening at the suture removal was statistically different for A200 and B200 solutions (91.90% +/- 3.00% and 88.57% +/- 2.38% of the preoperative measure, respectively) when surgeries required bone removal (P < .05). CONCLUSIONS: In comparison with 0.5% bupivacaine, 4% articaine (both with 1:200,000 epinephrine) provided a shorter time to onset and comparable hemostasis and postoperative pain control with a shorter duration of soft tissue anesthesia in lower third molar removal.

The changing pattern of analgesic and anti-inflammatory drug use in cleft lip and palate repair.

OBJECTIVE: This work aimed at performing a retrospective and comparative investigation of pharmacological therapeutic approach for pain and inflammation control for cleft lip and/or palate repair. STUDY DESIGN: Medical charts from 2000 patients who underwent surgical procedures at the Hospital for Rehabilitation of Craniofacial Anomalies, University of São Paulo (HRAC-USP), Brazil, were assessed to obtain information regarding type of cleft, surgical procedure, and analgesic and anti-inflammatory drugs prescribed. The first 1000 consecutive surgeries performed in 1992 and 2002 were assessed. RESULTS: Different analgesic and anti-inflammatory agents-nonsteroidal anti-inflammatory drugs (NSAIDS), steroids, and opioids-were given to patients perioperatively and postoperatively. NSAIDS were given to almost all patients (97.03% in 1992 and 99.88% in 2002, P > .05). Steroid administration increased in 2002 (8.66% versus 17.71%, P < .05). Opioids were administered only in 2002 (50.31%, P < .05). CONCLUSION: NSAIDS, steroids, and opioids were used for pain and inflammation control in cleft lip and palate repair at HRAC-USP. A change in the pattern of analgesic and anti-inflammatory drug use was observed when comparing 1992 and 2002. More potent compounds, such as opioids, were used in 2002 in a significant percentage of all the surgical procedures.

Articaine and mepivacaine efficacy in postoperative analgesia for lower third molar removal: a double-blind, randomized, crossover study.

OBJECTIVE: Comparison of the clinical efficacy of 4% articaine in relation to 2% mepivacaine, both with 1:100,000 epinephrine, in the prevention of postoperative pain after lower third molar removal. STUDY DESIGN: Twenty patients underwent removal of bilateral lower third molars under local anesthesia (articaine or mepivacaine) in 2 separate appointments, in a double-blind, randomized, and crossed manner. Objective and subjective parameters were recorded for paired comparison of postoperative courses. RESULTS: Duration of analgesia provided by articaine and mepivacaine was 198.00 +/- 25.86, and 125.40 +/- 13.96 min, respectively (P = .02), whereas the duration of anesthesia was 273.80 +/- 15.94 and 216.85 +/- 20.15 min, respectively (P = .06). Both solutions exerted no important effects upon arterial pressure, heart rate, or oxygen saturation (P > .05). CONCLUSIONS: Articaine provides a longer period of analgesic effect and a tendency for a longer period of anesthesia as compared to mepivacaine. The presence of a vasoconstrictor agent in local anesthetic solutions does not seem to influence hemodynamic parameters during lower third molar removal in healthy subjects.

Dosis letales del sulfato de quinina y de quinidina en el ratón: influencia del sexo / Lethal doses of quinine sulfate and quinidine in mice: sex influence

La influencia del sexo sobre la letalidad del sulfato de quinina y de quinidina en el ratón se estudió mediante 2 series experimentales; cálculo de las dosis letales según el método de Litchfield y Wilcoxon y observación de la mortalidad producida por la administración de una dosis única prefijada de cada droga. Los resultados de la primera serie se procesaron tal como describe el método referido (límites, linealidad, paralelismo, potencia relativa), en tanto que en la segunda serie se utilizó la prueba de probabilidad exacta de Fisher. Con ambas drogas se obtuvieron valores de dosis letales semejantes entre sí según el sexo, pero se observó una diferencia significativa entre hembras y machos. Se concluyó que el ratón hembra fue mucho más sensible al efecto letal de las drogas estudiadas. Se analizan algunos factores que pudieron influir sobre los valores de dosis efectivas de estas drogas

Comparación de la potencia de drogas conveniencia de expresar la dosificación en molaridad / Comparison of durg potency. Convinience of expressing the dosification in moles

Se comparó la potencia del diclorhidrato de histamina en relación con su sal de fostatocido mediante el método de Litchfield y Wilcoxon de determinación de dosis letales en el ratón, y el método de "los cuatro puntos" en tiras de fleon aislado de cobayo. Se encontr'o que tanto in vivo como in vitro la potencia relativa difiri'o significativamente, al efectuar los c'alculos tomando las dosis o concentraciones en unidades que no reflejan la masa activa de la droga (g ó mg/kg y g ó mg/L), pero no hubo diferencias significativa cuando dichas dosificaciones se expresaron en moles/kg o moles/L según el tipo de experimento. Se concluyó que para obtener la verdadera relación de potencia entre drogas la comparación debe realizarse mol a mol tanto in vivo como in vitro, siendo lo más adecuado utilizar las dosis o concentraciones moleculares de las drogas que se comparan