A review of rapid-onset opioids for breakthrough pain in patients with cancer

2014 ◽  
Vol 10 (3) ◽  
pp. 207 ◽  
Author(s):  
Steven M. Simon, RPh, MD ◽  
Lee S. Schwartzberg, MD, FACP
Keyword(s):  
Breakthrough Pain ◽  
Immediate Release ◽  
Rapid Onset ◽  
Systemic Circulation ◽  
Abrupt Onset ◽  
Onset Of Action ◽  
Duration Of Action ◽  
Patients With Cancer ◽  
Duration Of Effect ◽  
Effective Pain Relief

Pain management in patients with cancer remains suboptimal. Breakthrough pain (BTP) is characterized by abrupt onset of severe pain in a background of otherwise stable managed pain and presents a substantial burden to patients, as it disrupts activities and quality of life. Rapid-onset opioids (ROOs), with an appropriate onset and duration of effect, provide new options for effective and well-tolerated management of BTP. All currently available ROOs are various formulations of transmucosal immediate-release fentanyl (TIRF) and, although they were originally developed and approved for use in children before painful procedures, are only approved for use in opioid-tolerant adult patients with cancer and BTP. The formulation options include oral lozenge, buccal tablet, buccal film, sublingual tablet, nasal spray, and a sublingual spray; each has practical considerations that vary with the product and route of administration. All have the common advantage of rapid entry into the systemic circulation via transmucosal absorption, avoiding hepatic and intestinal first-pass metabolism and allowing a rapid onset of action that rivals intravenous injections. Rapid onset and short duration of action allow good patient control of analgesia. The pharmacokinetic and analgesic properties of ROOs may allow reduction of the total opioid burden and associated adverse effects, while still providing effective pain relief. The shared TIRF risk evaluation and mitigation strategy program implemented in March 2012 has simplified enrollment and administration of these products to help mitigate the risks of abuse and misuse and to help ensure safe use in patients with cancer suffering from BTP.

Intranasal Fentanyl for Breakthrough Pain Control

2012 ◽  
Vol 4 ◽  
pp. CMT.S7298 ◽  
Author(s):  
Claudia F. Clavijo ◽  
Rachael Rzasa Lynn ◽  
Uwe Christians ◽  
Jeffrey L. Galinkin
Keyword(s):  
Short Duration ◽  
Breakthrough Pain ◽  
Immediate Release ◽  
Rapid Onset ◽  
Time Profile ◽  
Economic Consequences ◽  
Onset Of Action ◽  
Oral Medications ◽  
Pharmacokinetic Properties ◽  
High Bioavailability

Breakthrough pain (BTP) is experienced by approximately 65% of children and adults with chronic pain. Undiagnosed or untreated BTP produces negative emotional, physical, and economic consequences. BTP episodes have a rapid onset and short duration. Short acting oral opioids are the cornerstone of BTP management. Oral medications available to treat BTP episodes like immediate-release morphine or oxycodone have a delayed onset of action so that there is a mismatch between the episode of BTP and the effect of the oral opioids. Novel fentanyl delivery systems for BTP offer pharmacokinetic properties that match the time profile of BTP. Among the transmucosal routes, intranasal fentanyl has gained popularity due to its high bioavailability, rapid onset of action, high potency, short duration, and ease of administration. Its efficacy and safety have been demonstrated in adults who are opioid tolerant. Although children with chronic cancer pain also experience BTP, there is paucity of data on the use of intranasal fentanyl for BTP in this age group.

Pharmacokinetic peculiarities of drugs used in the form of rapidly dispersible tablets (oral delivery system)

2020 ◽  
pp. 7-24
Author(s):  
Zhanna Kozlova ◽  
Ivan Krasnyuk ◽  
Yuliya Lebedeva ◽  
Ekaterina Odintsova
Keyword(s):  
Oral Mucosa ◽  
Oral Delivery ◽  
Chemical Properties ◽  
Rapid Onset ◽  
Systemic Circulation ◽  
Systemic Delivery ◽  
Onset Of Action ◽  
Mucosal Drug Delivery ◽  
Physical And Chemical ◽  
Pass Metabolism

Oral mucosal drug delivery is an alternative method of systemic delivery with several advantages over both injectable and enteral methods. Drugs that are absorbed through the oral mucosa directly enter the systemic circulation, passing through the gastrointestinal tract and first-pass metabolism in the liver due to oral mucosa being highly vascularised. This results in rapid onset of action for some drugs because of a more comfortable and convenient way of delivery than the intravenous one. But not all drugs can be administered through the oral mucosa due to characteristics of the oral mucosa and physical and chemical properties of the drug.

scholarly journals Nasal Delivery of Acute Medications for Migraine: The Upper Versus Lower Nasal Space

2021 ◽  
Vol 10 (11) ◽  
pp. 2468
Author(s):  
Vincent Martin ◽  
John Hoekman ◽  
Sheena K. Aurora ◽  
Stephen B. Shrewsbury
Keyword(s):  
Acute Treatment ◽  
Drug Efficacy ◽  
Hepatic Metabolism ◽  
Rapid Onset ◽  
Systemic Circulation ◽  
Nasal Delivery ◽  
Attractive Alternative ◽  
Gi Tract ◽  
Onset Of Action ◽  
First Pass

The acute treatment of migraine requires effective drugs that are well tolerated and provide rapid and consistent pain relief. Oral tablets are the most commonly used acute treatment for migraine; however, their effectiveness is limited by the rate of gastrointestinal (GI) tract absorption and first-pass hepatic metabolism, and they may not be ideal for patients experiencing GI motility issues. Nasal delivery is an attractive alternative route as it may circumvent GI tract absorption, avoid first-pass metabolism in the liver, and potentially reduce the frequency of GI adverse events. The large surface area and high vascularity within the nose may permit rapid absorption of therapeutics into the systemic circulation, allowing for rapid onset of action. However, the site of drug deposition (upper versus lower nasal cavity) may influence drug pharmacokinetics. Most approved nasal migraine therapies target the lower nasal space where the epithelium is less permeable, and they may be quickly cleared away due to increased ciliary function or dripping from the nose or swallowing, resulting in variable absorption and limited bioavailability. Together with its abundant vascularization, relative mucosal thickness stability, and low clearance rates, the upper nasal space harnesses the benefits of nasal delivery to potentially maximize drug efficacy.

scholarly journals Clinical Evaluation of Etidocaine in Continuous Caudal Analgesia for Pelvic Floor Repair and Post-Operative Pain Relief

1976 ◽  
Vol 4 (3) ◽  
pp. 239-244 ◽  
Author(s):  
L. T. Seow ◽  
H. H. Chiu ◽  
C. Y. Tye
Keyword(s):  
Pelvic Floor ◽  
Muscle Relaxation ◽  
Rapid Onset ◽  
Onset Of Action ◽  
Double Blind ◽  
Duration Of Action ◽  
Pelvic Floor Repair ◽  
Post Operative Pain ◽  
Caudal Anaesthesia ◽  
Caudal Analgesia

A randomized double-blind trial compared 1·0% etidocaine and 1·5% lignocaine (both with 1/200,000 adrenaline), for caudal anaesthesia for pelvic floor repair. Etidocaine was highly effective for the surgical procedure, with rapid onset of action, adequate muscle relaxation and longer duration of action. Its use for post-operative analgesia may be hindered by the concomitant immobilization of the legs. The problem of tachyphylaxis with etidocaine needs further investigation.

Sedation at the end of life

2015 ◽  
Author(s):  
Eric L. Krakauer
Keyword(s):  
Informed Consent ◽  
Neuropsychiatric Symptoms ◽  
Terminally Ill ◽  
Rapid Onset ◽  
Palliative Sedation ◽  
Anaesthetic Induction ◽  
Onset Of Action ◽  
Duration Of Action ◽  
Agitated Delirium ◽  
Induction Agents

Palliative sedation is a well-accepted therapy that should be considered in the rare situations when a terminally ill patient whose overriding goal is comfort experiences severe suffering that is refractory to all available standard palliative interventions. Typically, such suffering is caused by physical or neuropsychiatric symptoms such as pain, dyspnoea, vomiting, seizures, agitated delirium, anxiety, or depression. The level of sedation should be proportional to an individual patient’s suffering and should be just deep enough to provide the desired relief. In some cases, sedation to unconsciousness is necessary. The intention of palliative sedation should be only to relieve suffering, never to hasten death. Informed consent must be obtained, and clinicians should demonstrate their intentions by documenting the regimen used and the patient’s response. Ideal medications have a rapid onset of action and a short duration of action that facilitate titration to the desired effect. The best agents are barbiturates such as pentobarbital and anaesthetic induction agents such as propofol.

An Evaluation of Andursil – A New Antacid

1977 ◽  
Vol 5 (6) ◽  
pp. 99-104 ◽  
Author(s):  
G Beaumont ◽  
G I J Rigby ◽  
J Seldrup
Keyword(s):  
General Practitioner ◽  
Rapid Onset ◽  
Onset Of Action ◽  
Duration Of Effect ◽  
The Ideal

A number of characteristics of an ideal antacid are proposed. A new antacid formulation, Andursil, has been assessed both by in vitro and in vivo methods. Andursil has been found to compare favourably in its properties, with the profile of the ideal antacid. In a multicentre general practitioner trial it was found to be effective in relieving the symptoms of dyspepsia, to have a rapid onset of action and a satisfactory duration of effect, to be palatable and to be relatively free from undesirable effects.

scholarly journals Fentanyl Buccal Tablet for the Treatment of Breakthrough Pain: Pharmacokinetics of Buccal Mucosa Delivery and Clinical Efficacy

2010 ◽  
Vol 4 ◽  
pp. PMC.S3928 ◽  
Author(s):  
Mona Darwish ◽  
Ehab Hamed ◽  
John Messina
Keyword(s):  
Clinical Efficacy ◽  
Breakthrough Pain ◽  
Systemic Exposure ◽  
Pharmacokinetic Profile ◽  
Tolerability Profile ◽  
Onset Of Action ◽  
Patients With Cancer ◽  
Fentanyl Buccal Tablet ◽  
Buccal Tablet ◽  
Buccal Absorption

The treatment of breakthrough pain (BTP), a transitory exacerbation of pain that occurs on a background of otherwise-controlled, persistent pain, requires an opioid formulation and/or method of administration that can provide rapid and extensive systemic exposure. Fentanyl buccal tablet (FBT; FENTORA®, Cephalon, Inc.) employs OraVescent® drug delivery technology, which enhances the rate and extent of fentanyl absorption. OraVescent technology enhances the oral dissolution and buccal absorption of fentanyl, which facilitates rapid uptake of fentanyl into the bloodstream, reducing gastrointestinal absorption and minimizing extensive first-pass metabolism. The resulting pharmacokinetic profile of FBT is characterized by greater bioavailability and a higher early systemic exposure compared with the earlier oral transmucosal fentanyl citrate formulation. In clinical studies of opioid-tolerant patients with cancer-related and noncancer-related BTP, FBT has provided consistent and clinically relevant improvements in pain intensity and pain relief relative to placebo, with a safety and tolerability profile that is generally typical of that observed with other potent opioids. The pharmacokinetic properties of FBT allow for meaningful clinical efficacy, with an onset of action that closely matches the onset of BTP.

scholarly journals Clinical Pharmacology of Midazolam in Neonates and Children: Effect of Disease—A Review

2014 ◽  
Vol 2014 ◽  
pp. 1-20 ◽  
Author(s):  
Gian Maria Pacifici
Keyword(s):  
Clinical Pharmacology ◽  
Intranasal Administration ◽  
Rapid Onset ◽  
Volume Of Distribution ◽  
Multiple Organ ◽  
Onset Of Action ◽  
Antiepileptic Agent ◽  
Antiepileptic Therapy ◽  
Duration Of Effect ◽  
Ecmo Therapy

Midazolam is a benzodiazepine with rapid onset of action and short duration of effect. In healthy neonates the half-life (t1/2) and the clearance (Cl) are 3.3-fold longer and 3.7-fold smaller, respectively, than in adults. The volume of distribution (Vd) is 1.1 L/kg both in neonates and adults. Midazolam is hydroxylated by CYP3A4 and CYP3A5; the activities of these enzymes surge in the liver in the first weeks of life and thus the metabolic rate of midazolam is lower in neonates than in adults. Midazolam acts as a sedative, as an antiepileptic, for those infants who are refractory to standard antiepileptic therapy, and as an anaesthetic. Information of midazolam as an anaesthetic in infants are very little. Midazolam is usually administered intravenously; when minimal sedation is required, intranasal administration of midazolam is employed. Disease affects the pharmacokinetics of midazolam in neonates; multiple organ failure reduces the Cl of midazolam and mechanical ventilation prolongs thet1/2of this drug. ECMO therapy increasest1/2, Cl, and Vd of midazolam several times. The adverse effects of midazolam in neonates are scarce: pain, tenderness, and thrombophlebitis may occur. Respiratory depression and hypotension appear in a limited percentage of infants following intravenous infusion of midazolam. In conclusion, midazolam is a safe and effective drug which is employed as a sedative, as antiepileptic agent, for infants who are refractory to standard antiepileptic therapy, and as an anaesthetic.

An analgesiometry system for use in rabbits with some preliminary data on the effects of buprenorphine and lofentanil

1988 ◽  
Vol 22 (3) ◽  
pp. 217-222 ◽  
Author(s):  
R. Wootton ◽  
G. Crosst ◽  
S. Wood ◽  
C. D. Westt
Keyword(s):  
Preliminary Data ◽  
Low Cost ◽  
Heating System ◽  
Rectal Administration ◽  
Rapid Onset ◽  
Onset Of Action ◽  
Duration Of Action ◽  
Long Acting

A low cost infrared skin heating system has been designed to measure the efficacy of analgesics in rabbits. Following construction of a prototype, it was used to assess the effect of buprenorphine given subcutaneously and per rectum. Buprenorphine administered subcutaneously has a rapid onset of action, but its duration (8-10 h) appears slightly shorter than has been suggested previously; rectal administration appears to prolong its effect. Preliminary data show that lofentanil has a longer duration of action than buprenorphine and it may prove, therefore, to be a valuable long-acting analgesic in the rabbit.

ORG 9487 Neuromuscular Block at the Adductor Pollicis and the Laryngeal Adductor Muscles in Humans 

1997 ◽  
Vol 86 (6) ◽  
pp. 1300-1305 ◽  
Author(s):  
Bertrand Debaene ◽  
Thomas Lieutaud ◽  
Valerie Billard ◽  
Claude Meistelman
Keyword(s):  
Neuromuscular Block ◽  
Onset Time ◽  
Rapid Onset ◽  
Adductor Pollicis ◽  
Vocal Cords ◽  
Onset Of Action ◽  
Duration Of Action ◽  
Adductor Pollicis Muscle ◽  
Org 9487 ◽  
Adductor Muscles

Background ORG 9487 is a new steroidal nondepolarizing muscle relaxant with a rapid onset of action. This study was designed to determine the neuromuscular blocking profile of ORG 9487 at the adductor muscles of the larynx and the adductor pollicis. Methods In 30 adults, anesthesia was induced with propofol (2-5 mg/kg) and fentanyl (2-3 microg/kg). After train-of-four stimulation, the block of the laryngeal adductor muscles was evaluated by measuring the pressure changes in the cuff of the tracheal tube placed between the vocal cords, and the force of the contraction of the adductor pollicis was measured with a force transducer. Patients were randomly allocated to receive ORG 9487 at intravenous bolus doses of 0.75, 1.5 or 2 mg/kg (n = 10 in each group). Results Time to peak effect was significantly shorter at the vocal cords than at the adductor pollicis muscle (P < 0.001). Onset time at the vocal cords was 62 +/- 16 s, 62 +/- 13 s, and 52 +/- 14 s (mean +/- SD) after doses of 0.75, 1.5, and 2 mg/kg, respectively (not significant). Onset time at the adductor pollicis muscle was 126 +/- 33 s, 96 +/- 20 s, and 82 +/- 21 s after 0.75, 1.5, and 2 mg/kg doses, respectively (P < 0.001). Maximum block was significantly less intense at the vocal cords than at the adductor pollicis muscle (69 +/- 15% vs. 94 +/- 4% after 0.75 mg/kg; 86 +/- 7% vs. 97 +/- 4% after 1.5 mg/kg; and 91 +/- 5% vs. 99 +/- 1% after 2 mg/kg). After 1.5 mg/kg duration to 25%, recovery was 3.7 +/- 2.2 min versus 10.2 +/- 2.5 min at the vocal cords and the adductor pollicis muscle, respectively, and 75% recovery occurred at 9.7 +/- 3.7 min at the vocal cords and at 18.3 +/- 5.2 min at the adductor pollicis muscle. Conclusions ORG 9487 has a rapid onset of action at the laryngeal adductor and the adductor pollicis muscles. Onset and duration of action are faster at the vocal cords than at the adductor pollicis muscle. However, the maximum block obtained at the laryngeal muscles was less than at the adductor pollicis, regardless of the dose of ORG 9487.

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