Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this work we show that the pain-induced functional impairment model (PIFIR) can be used with cannulated rats as a useful procedure for pharmacokinetic/pharmacodynamic modelling. This model evaluates analgesia by measuring motor impairment of the right limb after intra-articular administration of uric acid. Time of contact with a rotating cylinder is referred to the control limb. We studied the pharmacokinetic and pharmacodynamics of naproxen after six peroral doses to Wistar rats, and we examined the adjuvant action of caffeine with naproxen. Surgery and blood sampling did not produce any difference on functional impairment either in rats without uric acid or in the dysfunction produced by uric acid. The relation between naproxen plasma concentration and the analgesic effect was obtained with few rats. Caffeine alone did not produce any significant modification in functional impairment but the co-administration significantly increased the effect of naproxen. Plasma levels of naproxen did not change when caffeine was co-administered. The PIFIR model with blood sampling is a suitable method for pharmacokinetic/pharmacodynamic relationship studies and is specially useful to characterize drug-drug interactions.
 ...
PMID:Usefulness of the pain-induced functional impairment model to relate plasma levels of analgesics to their efficacy in rats. 767 28

Caffeine is widely consumed in beverages to obtain mild CNS stimulant effects. Long term use produces tolerance to some of the pharmacological effects. Withdrawal of caffeine, even from moderate intake levels, can produce symptoms such as headache, fatigue and anxiety. Caffeine is used therapeutically in combination with ergotamine for migraine headaches and in combination with nonsteroidal anti-inflammatory drugs in analgesic formulations. Caffeine alone is used as a somnolytic, to treat various headache conditions, respiratory depression in neonates, postprandial hypotension and obesity, and to enhance seizure duration in electroconvulsive therapy. In some headache and in pain paradigms, caffeine may produce direct adjuvant analgesic properties, while in other headache conditions (perioperative, postdural puncture) caffeine may be effective by alleviating a manifestation of caffeine withdrawal. Other uses, such as to promote wakefulness, for respiratory stimulation and seizure prolongation, rely on central stimulant properties of caffeine. Effects of caffeine on the vasculature may contribute to the relief of some headaches and in postprandial hypotension. Blockade of methylxanthine-sensitive adenosine receptors is the currently accepted mechanism of action of caffeine.
 ...
PMID:Pharmacological rationale for the clinical use of caffeine. 770 15

Free flaps are used to reconstruct defects that cannot be repaired by traditional methods using local adjacent tissue. Advantages include a single operation, decreased immobility, increased vascular supply to tissues for healing, minimal risk of flap loss, and primary closure of the donor site. Disadvantages are a long operation, two surgical sites, need for surgery if vascular compromise occurs, donor site morbidity, and expense. Preoperative care focuses on readiness for surgery and avoidance of medications (nicotine, caffeine) and situations (cold exposure) that cause vasospasm. Intraoperative nursing care includes positioning, range of motion, and pneumatic compression devices for the long case. The operating microscope requires special care and instruments. After surgery, blood flow to the flap is closely monitored. Laser flow Doppler can be used with data recorded on a flow sheet. Common postoperative problems include temperature instability, pain, blood pressure fluctuations, and oliguria. Dismissal teaching includes avoidance of vasoconstrictive medications and dressing changes.
 ...
PMID:The care and feeding of microvascular flaps: how nurses can help prevent flap loss. 773 91

Opioids, particularly morphine sulfate and fentanyl, continue to be the most commonly used agents for analgesia. Morphine provides greater sedation, and there is less of a problem with rigidity of the chest wall than with fentanyl. Morphine also has a higher level of tolerance than does fentanyl. Table 2 provides considerations for administration of morphine and fentanyl. Sedation for the relief of pain without analgesia is not acceptable. Sedation and analgesia together may be in the baby's best interest. Before any plan of care is implemented, the baby should be evaluated for need based on the amount of current respiratory support versus spontaneous respiration. There is evidence in the research literature that narcotic administration can be safely carried out in the preterm when using intravenous caffeine simultaneously to offset the risk of apnea. Others state that there really is no safe therapeutic window for narcotic administration in the preterm infant, yet the benefits outweigh the respiratory depressant effect. The complication of respiratory depression can be readily dealt with through the administration of neonatal Narcan via the intramuscular, intratracheal, or intravenous routes.
 ...
PMID:Research utilization: pharmacologic management of neonatal pain. 778 25

In this study we examined the effect of partial sciatic nerve ligation (PSNL) on the receptive field size, the baseline firing rate (BFR) and the response of spinal dorsal horn (DH) neurons to mechanical stimulation. In addition, we tested the effect of adenosine agonist, 5'-N-ethylcarboxamide-adenosine (NECA), and the adenosine antagonist caffeine on these parameters. Adult male Sprague-Dawley animals were used. One-third to one-half of the right sciatic nerve was tightly ligated. Unanesthetized animals were tested for their response to mechanical stimulation using Von Frey filaments and a blunt probe. The mean force that produced a paw withdrawal response in the operated animals was significantly less than the force that produced withdrawal in unoperated animals (median: 103.5 vs. 259.7; P < 0.001 for the paw ipsilateral to the ligation). Extracellular recordings were made from nociceptive-specific DH neurons located in laminal I-V of chloral hydrate-anesthetized rats. Recordings were made from 38 neurons in the right and 29 cells in the left DH of unoperated and 40 cells in right and 41 cell in the left DH of operated animals. The BFRs of neurons recorded in the operated animals were not significantly different from those recorded in normal animals. The mean receptive field size (RFS) of neurons (both ipsilateral and contralateral to the ligation) in the operated animals was significantly larger than the RFS of unoperated animals (right side: 180 +/- 2.8 mm2 compared to 66 +/- 2.3 mm2; left side: 93 +/- 31 compared to 65 +/- 21). Twenty-four percent of all neurons in the operated group had bilateral receptive fields; in contrast, only 3% of the neurons in the control animals showed bilateral receptive fields. To examine the effects of adenosine agonist and antagonist, NECA and caffeine were applied next to the recording electrode.(ABSTRACT TRUNCATED AT 250 WORDS)
Pain 1994 Sep
PMID:Partial sciatic nerve ligation results in an enlargement of the receptive field and enhancement of the response of dorsal horn neurons to noxious stimulation by an adenosine agonist. 783 92

The ability of caffeine to potentiate the analgesic effect of aspirin was studied in the pain-induced functional impairment model in the rat. Female Wistar rats received an intra-articular injection of 30% uric acid in the right hind limb, inducing its dysfunction. Once the dysfunction was complete, animals received aspirin oral doses of 0, 0.55, 0.98, and 1.74 mmol/kg with and without 0.17 mmol/kg of caffeine, and the recovery of functionality over time was considered as an expression of analgesia. Blood samples were drawn simultaneously with hind limb functionality determinations, and plasma concentrations of aspirin, salicylic acid, and gentisic acid were measured by high-performance liquid chromatography. Aspirin induced a dose-dependent analgesic effect. Caffeine alone was ineffective. However, caffeine significantly increased the analgesic effect of aspirin at all doses, without modifying aspirin, salicylic acid, or gentisic acid plasma levels. It is concluded that caffeine potentiates the analgesic effect of aspirin by a pharmacodynamic, but not by a pharmacokinetic mechanism.
 ...
PMID:Potentiation by caffeine of the analgesic effect of aspirin in the pain-induced functional impairment model in the rat. 788 76

Six randomized, double-blind, two-period crossover studies, conducted under similar protocols, compared the efficacy of two analgesic combinations containing caffeine with an acetaminophen 1000 mg control and with a placebo in outpatients with episodic tension-type headaches. In four studies, comprising 1900 patients, the caffeine-containing analgesic consisted of a combination of 500 mg acetaminophen, 500 mg aspirin, and 130 mg caffeine (APAP/ASA/CAF). In two studies, comprising 911 patients, the caffeine-containing analgesic consisted of a combination of 1000 mg acetaminophen and 130 mg caffeine (APAP/CAF). Patients self-medicated for moderate or severe headache pain, and with a self-rating record they rated their pain and its relief hourly for 4 hours. In all six studies, the caffeine-containing analgesics were significantly superior both to placebo and to 1000 mg acetaminophen, and acetaminophen was significantly superior to placebo. The significant analgesic adjuvant effect of caffeine was independent of patients' usual caffeine use or their caffeine consumption in the 4 hours before medication. For each treatment, the pooled analgesic responses for the four studies of APAP/ASA/CAF were virtually superimposable on the responses in the two APAP/CAF studies. The combinations produced more stomach discomfort, nervousness, and dizziness than acetaminophen or placebo.
 ...
PMID:Caffeine as an analgesic adjuvant in tension headache. 795 22

Chronic daily headache appears in migraine patients due to chronic consumption of analgesics-ergotamine. This entity was considered intractable without hospital admission. Our aim was to study the response of this headache to an outpatient treatment protocol. The therapeutic protocol included: 1. Oral information to the patient about the role of analgesics in the chronification of the headache; 2. Abrupt withdrawal of analgesics-ergotamine; 3. Administration of naproxen as symptomatic medication, and 4. Prophylactic treatment. After 2.5 months of treatment we evaluated both the frequency and the intensity of pain episodes as well as analgesic consumption. Thirty patients (8.6% of the outpatient consultations) suffered from chronic daily headache secondary to chronic analgesic abuse. Twenty five were females and 5 were males, their mean age +/- SD being 43 +/- 11 years. The mean +/- SD number of units of analgesics-ergotamine taken per week was 28 +/- 12. Three patients exclusively abused analgesics, the remainder either ergotamine, caffeine and various analgesics (18) or caffeine or several analgesics not containing ergotamine (9). In 29 patients the response was positive. Twenty (67%) showed an excellent improvement (> 75%) in frequency and intensity and completely gave up analgesics. The remaining nine (30%) improved moderately (50-75%). Only 3 patients in this group carried on taking analgesics. One patient showed no improvement. Our work confirms the epidemiological magnitude of chronic daily headache and shows that this is a treatable entity on an outpatient basis combining the abrupt withdrawal of analgesics-ergotamine, and their replacement by naproxen, with prophylactic treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Daily chronic headache in patients with migraine induced by abuse of ergotamine-analgesics: response due to a protocol of outpatient treatment]. 810 38

The analgesic activities of paracetamol (100, 178, 316 and 562 mg kg-1), caffeine (10, 18, 32 and 56 mg kg-1) and combinations of these doses were tested on a pain-induced functional impairment model in the rat. Dysfunction of the right hind limb was induced by an intra-articular injection of 30% uric acid in the knee. Drugs were given orally and the recovery of functionality over time was considered as an expression of analgesia. Paracetamol alone induced a dose-dependent analgesic effect whereas caffeine alone did not show any activity at the assayed doses. Combinations of 316 mg kg-1 paracetamol with either 10, 18, 32 or 56 mg kg-1 caffeine yielded analgesic effects significantly greater than that of paracetamol alone. The highest potentiation was observed with a paracetamol-caffeine mixture of 316-32 mg kg-1. Caffeine coadministration, however, did not significantly change paracetamol plasma levels. No potentiation was obtained with other combinations. Paracetamol plasma levels and analgesic effect observed with administration of 316 mg kg-1 paracetamol alone or 316-32 mg kg-1 of paracetamol-caffeine were fitted to the sigmoidal Emax model according to the Hill equation. The curves obtained were parallel, but that of the combination was shifted to the left. It is concluded that caffeine is able to potentiate the analgesic effect of paracetamol by a pharmacodynamic mechanism, but this only occurs at certain dose combinations.
 ...
PMID:Characterization of the analgesic effect of paracetamol and caffeine combinations in the pain-induced functional impairment model in the rat. 810 58

Sumatriptan is a selective 5-HT1-like agonist, which is effective in the treatment of migraine and cluster headache. It has been rigorously assessed in clinical trials involving over 7000 patients who have treated over 35,000 migraine attacks. Both subcutaneous and oral sumatriptan provide a high level of efficacy with 86% of patients obtaining relief after a single 6 mg injection (at 2 h) and 75% after 100 mg oral sumatriptan (4 h), compared with up to 37% in the placebo-treated group (P < 0.001). The onset of effect is rapid, occurring 10 min after injection and 30 min after the tablet. Oral sumatriptan (100 mg) has been evaluated against ergotamine, 2 mg, plus caffeine, 200 mg (as Cafergot); and against aspirin, 900 mg, plus metoclopramide, 10 mg. Headache relief was superior in sumatriptan-treated patients; 66% obtaining relief at 2 h, compared with 48% on Cafergot (P < 0.001). The percentage of patients obtaining complete relief of headache (Grade 0, no pain) was significantly higher with sumatriptan (40%) than with Cafergot (14%) at 2 h. Associated symptoms such as nausea, vomiting and photophobia are effectively relieved by sumatriptan, whereas Cafergot provoked nausea and vomiting in a proportion of patients. Headache relief with sumatriptan was also superior to that seen with aspirin plus metoclopramide. Sumatriptan was as effective in the relief of accompanying nausea and vomiting as aspirin plus metoclopramide. The efficacy of sumatriptan is maintained after repeated long-term use; over a six-month period efficacy was comparable in the first and last attacks, regardless of how many attacks were treated.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Sumatriptan in the acute treatment of migraine. 838 52


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>