Botulinum toxins: Pharmacology, immunology, and current developments
Anthony V. Benedetto in Botulinum Toxins in Clinical Aesthetic Practice, 2017
The most common BoNT products in clinical use are onabotulinumtoxinA (Allergan), abobotulinumtoxinA (Ipsen), incobotulinumtoxinA (Merz), and rimabotulinumtoxinB (Solstice). BoNTs are most often injected into overactive skeletal muscles that vary depending on the condition to be treated and the patient's individual presentation. The clinical onset of action following intramuscular injection is generally reported to be within 3–7 days, with a peak effect in approximately 2–4 weeks. However, when injected into small muscles for the treatment of glabellar lines, the onset of clinical effects have been reported within 24 hours.63,64 The duration of beneficial effects of each treatment is approximately 3–5 months following intramuscular injection,65 although some differences have been noted.66 The duration of BoNT-B is somewhat shorter than that of type A, and has been reported as 6–12 weeks in the management of facial lines.67 Most patients respond to BoNT-A for many years without decrements in safety, responsiveness, or quality of life, and without increased doses.68,69
Drug-induced bronchospasm
Philippe Camus, Edward C Rosenow in Drug-induced and Iatrogenic Respiratory Disease, 2010
In the acute setting of an anaphylaxis and anaphylactoid reaction, small doses of intramuscular adrenaline is the most important therapeutic agent.68 The usual doses for intramuscular injection are from 50 to 250 μg for children up to 12 years and 500 μg for adolescents and adults – given as solution diluted as 1 in 1000 (1 mg/mL). Intravenous administration is potentially hazardous and runs the risk of provoking a hypertensive crisis, tachyarrhythmias, myocardial infarction, or pulmonary oedema.69 Supplementary treatment includes supine posture, intravenous fluids, oxygen, parenteral antihistamines, and corticosteroids. Bronchospasm usually is reversible with adrenaline, and β2-agonists are beneficial.
Trigeminal autonomic cephalgias I – cluster headache: diagnosis and treatment
Stephen D. Silberstein, Richard B. Upton, Peter J. Goadsby in Headache in Clinical Practice, 2018
Dihydroergotamine (DHE), available in injectable and intranasal forms, is effective in relieving acute attacks of cluster headache. Parenteral DHE (1mg intramuscularly)87 and intranasal DHE88 are effective for some, but not all, patients. Intravenous injection gives more rapid relief than intramuscular injection, with benefit in less than 10 minutes. Andersson and Jespersen88 conducted a double-blind comparative trial of DHE nasal spray (lmg). DHE did not change the duration or frequency of the attacks, but it did decrease pain intensity. Since DHE as a nasal spray has a 40% bioavailability, administration of a higher dose may be more effective for the treatment of cluster headache.
Improvement of solubility, dissolution and stability profile of artemether solid dispersions and self emulsified solid dispersions by solvent evaporation method
Published in Pharmaceutical Development and Technology, 2018
Muhammad Tayyab Ansari, Muhammad Sohail Arshad, Altaf Hussain, Zeeshan Ahmad
Over the years various treatments have been proposed for the eradication of malaria. These include various drug types such as sulfonamides and cinchona alkaloids. However, the emergence of malarial resistance toward conventional treatments has led to persistent risk of infection5. The more recent anti-malarial agent “artemether,” belongs to the Artemisinins family and is an active constituent of Chinese herbs known as qinghao, also termed Artemisia annua. Artemether is metabolized into de-methylated derivative dihydroartemisinin in the liver. Both artemether and its metabolite possess a 1,2,4-trioxane ring, which is an active pharmacophore responsible for anti-malarial properties6 and exhibits efficient schizontocidal action against P. falciparum7,8. However, the poor water solubility of artemether poses obstacles in the development of oral formulations. Although this issue is partly resolved when administered as an intramuscular injection, the development of oral formulations is much preferred, providing greater patient compliance and economical benefits. Solubility enhancement approaches such as solid dispersions (SDs) in water soluble polymers, SESDs, micronization and complex formation with cyclodextrins are expected to yield novel strategies and therapeutic effects9,10.
An evaluation of long-acting cabotegravir + rilpivirine for the treatment of virologically suppressed adults living with HIV
Published in Expert Opinion on Pharmacotherapy, 2022
Hamdi Qazzaz, Christopher Parganas, Theodore James Cory
Long-acting injectable products may have advantages as compared to traditional antiretroviral therapy strategies. The non-inferiority clinical trials including LATTE, LATTE-2 and ATLAS, coupled with high patient satisfaction scores, suggests that these approaches are safe, efficacious, and well tolerated. A potential niche of therapy for CAB+RPV is in patients that may benefit from an extended dosing interval product. Patients with adherence concerns, such as those who work long hours or who struggle with remembering to take daily medications would be significantly impacted by long-acting formulations. In addition, patients who experienced side effects from oral medications would also benefit from therapy that bypasses first pass metabolism or presystemic circulation. The intramuscular injection has a significant advantage in this subpopulation due to controlled administration at the clinician level. The benefits allow for increased dosing schedules for patients and allow for structured and atypical dosing schedules to fit the needs of patients who cannot be maintained on a fixed oral dosing regimen.
Fatal and life-threatening ADRs associated with paliperidone palmitate: an observational study in the French pharmacovigilance database
Published in Clinical Toxicology, 2021
D. Boels, J. Mahé, A. Olry, A. Citterio-Quentin, J. Moragny, P. Jolliet
On the basis of PK modeling data, because of their extremely low water solubility (log p≈8), PP particles in the suspension slowly dissolve into the local fluids at the injection site, and they gradually enter systemic circulation after hydrolysis. Several PK studies suggest that the rate-limiting factor is PP dissolution at the injection site. The median peak concentration and AUC can vary noticeably between injection site: in one study, after second administration, PP exposure was approximately 45% higher for deltoid injection than for gluteal injection, and approximately 25% higher after fourth administration [6,28]. In our series, injection site was not reported. This observed variation between injection sites can be explained by the distribution of muscle and adipose tissue, which condition plasma paliperidone uptake. True intramuscular injection is more likely for deltoid injection sites. The hypovascularity of subcutaneous adipose tissue relative to muscle tissue may result in a slower plasma uptake of paliperidone. Furthermore, the hydrolyzing capacities of each tissue probably differ, and this may affect paliperidone pharmacokinetics (i.e., Cmax, tmax, and AUC). There is still a lack of consensus on the bioequivalence of the two administration sites: doubt remains as to the risk (especially of supratherapeutic concentrations) posed by site switching [29]. Further investigation of this question may be warranted.
Related Knowledge Centers
- Deltoid Muscle
- First Pass Effect
- Muscle
- Vastus Lateralis Muscle
- Blood Vessel
- Injection
- Route of Administration
- Subcutaneous Administration
- Intradermal Injection
- Gluteal Muscles