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Bellergal edit

 
Bellergal are tablets with yellow, orange and dark green colours.

Bellergal is a combination of belladonna, ergotamine tartrate and phenobarbital, used for the treatment of functional menopause, such as hot flashes and night sweats.[1][2]

Belladonna, including atropine, hyoscyamine, and scopolamine, are antimuscarinic agents.[3] They block acetylcholine from binding to its receptors. It generally reduces the secretion of the body, including mouth, nose, and skin, and causes drowsiness and other anticholinergic effects.[3] Phenobarbital provides sedative and anesthetic effects by depressing the central nervous system.[4] Ergotamine constricts blood vessels in the brain and alleviates headache through stimulating alpha-1, dopamine, and serotonin receptors.[5][6]

Common side effects of Bellergal include drowsiness, flushing, nausea, vomiting, diarrhea, constipation, decreased sweating, visual disturbances, unusual fatigue or weakness, and dry mouth.[7][8] Bellergal has a high potential for potentially serious drug interactions due to strong CYP3A4 inhibition by ergotamine.[9] Ergotamine is a vasoconstrictive CYP3A4 substrate.[10]

Bellergal was widely used during the 1970s and 1980s.[4][9][11]Its limited efficacy on decreasing hot flashes frequency and severity were demonstrated by several randomized controlled trials.[12][13][14] On 6th June 2018, Bellergal was discontinued by Paladin Labs due to its raw material availability and limited efficacy.[15] There are no Bellergal tablets available in the markets now.[2]

Medical uses edit

 
Symptoms of menopause affect different systems in females.

Menopause associated symptoms edit

Bellergal was indicated for hot flashes, perspiration, palpitations, dizzy spells, restlessness, apprehension, fatigue, insomnia, and headache.[1][2][9][11]

Dose and administration edit

Prolong use of bellergal is not recommended due to the risk of ergotism and rare fibrotic complications.[16][17][18] Patients should be made aware of the maximum dosages permitted as well as the initial signs of overdosage, which include hypoesthesia, paresthesia in the fingers and toes, nausea, and vomiting, as well as symptoms of myocardial ischemia and ergotism, such as brain ischemia.

Recommended Daily Dose: edit

The recommended dose of Bellergal is 3-4 tablets daily in oral administration. The maximum dose in one week is 16 tablets. The exact dose depends on symptoms and indications that should be followed the instruction given by doctors or pharmacists.[9]

Pharmacology edit

Belladonna alkaloids, ergotamine tartrate, and phenobarbital are the three main components of Bellergal. These three active components cooperate to alleviate menopausal symptoms.

Bellegral
 
Phenobarbital
 
Ergotamine
 
Hyoscyamine (Belladonna alkaloid)
 
Scopolamine (Belladonna alkaloid)
 
Atropine (Belladonna alkaloid)
Names
IUPAC name
(6aR,9R)-N-[(1S,2S,4R,7S)-7-benzyl-2-hydroxy-4-methyl-5,8-dioxo-3-oxa-6,9-diazatricyclo[7.3.0.02,6]dodecan-4-yl]-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide;2,3-dihydroxybutanedioic acid;5-ethyl-5-phenyl-1,3-diazinane-2,4,6-trione;(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 3-hydroxy-2-phenylpropanoate
Other names
57657-51-9; Bellergal; Bellergal-S; DTXSID30206356; Belladonna alkaloid, ergotamine, phenobarbital drug combination
Identifiers
3D model (JSmol)
ChemSpider
  • InChI=1S/C33H35N5O5.C17H23NO3.C12H12N2O3.C4H6O6/c1-32(35-29(39)21-15-23-22-10-6-11-24-28(22)20(17-34-24)16-25(23)36(2)18-21)31(41)38-26(14-19-8-4-3-5-9-19)30(40)37-13-7-12-27(37)33(38,42)43-32;1-18-13-7-8-14(18)10-15(9-13)21-17(20)16(11-19)12-5-3-2-4-6-12;1-2-12(8-6-4-3-5-7-8)9(15)13-11(17)14-10(12)16;5-1(3(7)8)2(6)4(9)10/h3-6,8-11,15,17,21,25-27,34,42H,7,12-14,16,18H2,1-2H3,(H,35,39);2-6,13-16,19H,7-11H2,1H3;3-7H,2H2,1H3,(H2,13,14,15,16,17);1-2,5-6H,(H,7,8)(H,9,10)/t21-,25-,26+,27+,32-,33+;;;/m1.../s1
    Key: BDGSJEJXSCXBHW-HUUVABQVSA-N
  • CCC1(C(=O)NC(=O)NC1=O)C2=CC=CC=C2.C[C@@]1(C(=O)N2[C@H](C(=O)N3CCC[C@H]3[C@@]2(O1)O)CC4=CC=CC=C4)NC(=O)[C@H]5CN([C@@H]6CC7=CNC8=CC=CC(=C78)C6=C5)C.CN1C2CCC1CC(C2)OC(=O)C(CO)C3=CC=CC=C3.C(C(C(=O)O)O)(C(=O)O)O
Properties
C66H76N8O17
Molar mass 1253.4 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Mechanism of action edit

ERGOTAMINE edit

Ergotamine is a partial agonist (or partial antagonist) that acts on dopamine and serotonin receptors depending on the site of action, and it is a highly potent stimulant to the uterine.[5] Ergotamine alleviates headache by activating serotonin (5-hydroxytryptamine 1D, 5-HT1D) receptors on the blood vessels within the cranium and arterio-venous anastomoses. As a result, blood vessels narrow and the blood flow through the cerebral blood vessels is subsequently decreased.[19] It also agonizes 5-HT1D receptors on sensory nerve endings of the trigeminal nerves, and hence inhibits the release of pro-inflammatory neuropeptide, resulting in the anti-inflammatory effect. [5] It is also a partial agonist that selectively acts on the alpha-1 receptor in the sympathetic nervous system. The stimulation of the alpha-1 receptor activates the phospholipase C that raises the level of IP3 and DAG, increasing calcium levels inside the smooth muscle cells.[20] The smooth muscles surrounding the blood vessels contract, subsequently constricting both arteries and veins.[20] This constriction relieves headaches while also reducing blood flow to the area of a hot flash, lessening its intensity and frequency.

PHENOBARBITAL edit

Phenobarbital is a nonselective central nervous system depressant. Phenobarbital's exact mechanism of action is not completely understood.[9] There are some possible mechanisms of action of Phenobarbital.

Gamma-aminobutyric acid (GABA), a primary inhibitory neurotransmitter in the central nervous system, its synaptic activity may be boosted and/or mimicked by phenobarbital which reduces neuronal excitability.[9][21] Phenobarbital's sedative-hypnotic effects may be brought on by an inhibition of conduction in the reticular formation, which would reduce the number of impulses that reach the cerebral cortex and slow down the activity of the brain. [9][22]

BELLADONNA edit

Belladonna alkaloids, containing atropine, hyoscyamine, and scopolamine, are natural-existing muscarinic receptor antagonists.[3] They compete with acetylcholine at peripheral and central muscarinic receptors and inhibit the muscarinic effect in exocrine glands, smooth muscle, cardiac muscle, and intramural neurons. [3][23] Different organs have different physiological responses to muscarinic receptor blockage. Scopolamine has a larger effect on the eyes, central nervous system, and secretory glands compared to atropine and hyoscyamine. [9] [24] While exerting similar effects to atropine, hyoscyamine has more significant effects on the central and peripheral nervous systems. [9] Higher doses of atropine can cause pupil dilation, an increase in heart rate by blocking vagal nerves on the heart, and the suppression of bowel motility. Lower doses of atropine reduce salivary and bronchial secretion as well as perspiration.[9]

Pharmacokinetics edit

ERGOTAMINE edit

Absorption edit

Ergotamine is poorly absorbed via sublingual administration and is absorbed in the digestive tract slowly and incompletely via oral administration. [25] Its absorption can be enhanced by the co-administration of caffeine.[26] The peak plasma concentration is attained in around 1 hour.

Distribution edit

There is limited information on the distribution of ergotamine in human tissues. Ergotamine has a high affinity to plasma proteins. Around 93-98% of ergotamine binds to plasma protein.[25]

Metabolism edit

The bioavailability is lower than or equal to 5% through oral or rectal administration.[27] The reason is that ergotamine is extensively metabolized by the hepatic first pass.

Elimination edit

90% of ergotamine metabolites are excreted in bile while a trace amount of ergotamine is excreted unchanged through feces and urine (4%). [25] A trace level of ergotamine and its metabolites may be found in saliva and breast milk. [25]

PHENOBARBITAL edit

Absorption edit

Phenobarbital is rapidly and completely absorbed from the digestive tract after oral administration especially it is diluted or taken on an empty stomach. [9] [28] The peak plasma concentration is reached around 6-18 hours.[28] Its bioavailability is 100%.[28]

Distribution edit

Phenobarbital is quickly distributed into all body fluids and tissues, mainly in the liver, brain, and kidney. The volume of distribution is around 0.54 L/kg by intravenous administration.[28]

Metabolism and Elimination edit

Phenobarbital only has a small extent of hepatic metabolism, and 75% of it is excreted unchanged in the urine. [9] Resulting in the long-acting characteristic.

BELLADONNA edit

Absorption edit

Atropine is quickly and efficiently transported to systemic circulation after being adequately absorbed in the digestive system. [29] Hyoscyamine can be fully absorbed through oral administration.[30] Scopolamine has a low bioavailability of around 13%. [31] The peak plasma concentration is attained around 23.5 ± 8.2 minutes. [32]

Distribution edit

Atropine is distributed throughout the whole body while the volume of distribution is around 1.0 to 1.7 L/kg by intravenous administration. There is limited information about the volume of distribution of hyoscyamine and scopolamine in the human body. [33]

Metabolism edit

The major metabolism of atropine is hydrolysis by hepatic enzymes.[29] A little quantity of hyoscyamine is hydrolyzed into tropine and tropic acid, although the majority of it remains unmetabolized.[34] [35] There is limited information about the metabolism of scopolamine in the human body. [33]

Elimination edit

Around 13 to 50% of Atropine is eliminated in the urine as an unaltered parent drug.[29] Most of the hyoscyamine is excreted in the urine unaltered.[34][35] By oral administration, around 2.6% of unaltered scopolamine is excreted through urine.[32]

History and Development edit

 
Rash was discovered in the clinical trials.

Bellergal was widely used during 1970s and 1980s. [4][9][11] Its limited efficacy on decreasing hot flashes frequency and severity were demonstrated by several randomized controlled trials. [12][13][14] After 2 weeks of therapy, bellergal significantly reduced hot flashes.[14][36] The difference between the therapy and placebo, however, vanished after 8 weeks with decreases of 68% and 75%, respectively. Although Bellergal reduced hot flashes compared to placebo, there was a considerable amount of toxicity, with more than 30% of users discontinuing the medication owing to side effects as dry mouth, drowsiness, dizziness, and rash.[36]

There were shortage reports related to phenobarbital from 18th July 2017 to 1st March 2018, disrupting the flow of production process with quality, time and cost control. [37][38]With all the factors considered, on 6th June 2018, Bellergal was discontinued by Paladin Labs due to its raw material availability and limited efficacy; while the remaining supply date was on 1st October 2017. [15]

There are no bellergal tablets available in the markets now.[36] Sandoz in Spain, France and Germany, Novartis in Switzerland, Thailand, Turkey and South Africa and Paladin in Canada discontinued the preparations.[39] Instead, it is replaced by new and similar formulations named as Bellegal-S, manufactured by Novartis in the United States of America.[39] One of the active ingredients is changed to bellafoline (levorotary alkaloids of belladonna).[39]

Contraindications edit

This combination is contraindicated in those with hypersensitivity to the three active ingredients, and in those with narrow-angle glaucoma, hypertension, cardiovascular, liver, kidney, or circulation problems. [9][40][41]People with high temperature, pregnant women, nursing mothers should also avoid this medication. [9][40][41][42][43]

CYP3A4 inhibition

 
Ribbon diagram of human cytochrome P450isozyme 3A4. Heme group visible at center.

Ergotamine is a vasoconstrictive CYP3A4 substrates. The concurrent use of vasoconstricting ergot derivatives and strong CYP3A4 inhibitors, such as HIV protease or reverse transcriptase inhibitors, azole antifungals, or macrolide antibiotics, was associated with ergot toxicity.[9][44][45][46][47][48][49][50][51] The inhibition of CYP3A4 leads to an increase level in serum concentration of Ergot derivatives.[52][53][54] Extreme ischemia, coma or even death is resulted.[9][40][43][55]For this reason, the use with potent CYP3A4 inhibitors should be avoided when prescribing. [56] Moderate CYP3A4 inhibitors such as berotralstat, conivaptan, crizotinib, dilriazem, dronedarone, duvelisib, fedratinib, fluconazole, fosnetupitant, grapefruit juice, imatinib, isavuconazonium sulfate, lefamulin, should also be monitored closely.[57] Cramping, pain and angina were reported.[9][40][43]Patient should be monitored closely for ergot toxicity and the use with this treatment should be done with cautions.[58][59]

Side effects edit

Common side effects Below are some common side effects of taking Bellergal. Symptoms vary among people.[9][40][43]
  • Drowsiness
  • Dizziness
  • Dry mouth
  • Nausea
  • Vomiting
  • Diarrhea
  • Constipation
  • Decreased sweating
Severe side effects If patients have any of these adverse effects, stop taking the medication, speak with their prescribers and get management tips from them as soon as possible.[9][40][43]
  • Confusion
  • Over excitement
  • Low energy and weakness
Rare side effects Some people will encounter rare side effects. If patients experience any symptoms while taking this drug that worry you, speak with their doctor.[9][40][43]
  • Rickets
  • Megaloblastic anemia
  • Mental problems
  • Slow Heartbeat
  • Unstable blood pressure
  • Throat tightness
  • Liver damage and inflammation
  • Accidental falls
  • Visual change
  • Decreased pupil size

References edit

  1. ^ a b PubChem. "Bellergal-S". pubchem.ncbi.nlm.nih.gov. Retrieved 2023-04-10.
  2. ^ a b c Loprinzi, Charles L.; Stearns, Vered; Barton, Debra (2005-12-19). "Centrally active nonhormonal hot flash therapies". The American Journal of Medicine. 118 Suppl 12B: 118–123. doi:10.1016/j.amjmed.2005.09.045. ISSN 1555-7162. PMID 16414336.
  3. ^ a b c d "Belladonna". go.drugbank.com. Retrieved 2023-04-10.
  4. ^ a b c Lewis, Cassaundra B.; Adams, Ninos (2023), "Phenobarbital", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 30335310, retrieved 2023-04-10
  5. ^ a b c "Ergotamine". go.drugbank.com. Retrieved 2023-04-10.
  6. ^ PubChem. "Ergotamine". pubchem.ncbi.nlm.nih.gov. Retrieved 2023-04-10.
  7. ^ "Bellergal Spacetabs - Uses, Side Effects, Interactions - MedBroadcast.com". www.medbroadcast.com. Retrieved 2023-04-10.
  8. ^ "Common and Rare Side Effects for Bellergal-S oral". www.webmd.com. Retrieved 2023-04-10.
  9. ^ a b c d e f g h i j k l m n o p q r s t u "Bellergal® Spacetabs" (PDF). February 13, 2014.{{cite web}}: CS1 maint: date and year (link)
  10. ^ "Ergotamine: Drug information". www.medilib.ir (in Persian). Retrieved 2023-04-10.
  11. ^ a b c Mom, Constantijne H.; Buijs, Ciska; Willemse, Pax H.B.; Mourits, Marian J.E.; de Vries, Elisabeth G.E. (2006). "Hot flushes in breast cancer patients". Critical Reviews in Oncology/Hematology. 57 (1): 63–77. doi:10.1016/j.critrevonc.2005.04.009. ISSN 1040-8428.
  12. ^ a b Christensen, Niels Chr.; Davidsen, Paul Chr.; Secher, Niels J.; Pedersen, Gunnar Thomsen (1975). "Serum Lipids During Oestradiol-Valerate/Norgestrel Treatment of Menopausal Women: Double-blind Study of a Sequential Preparation". Acta Obstetricia et Gynecologica Scandinavica. 54 (3): 213–216. doi:10.3109/00016347509157763. ISSN 0001-6349.
  13. ^ a b Stearns, Vered; Hayes, Daniel F. (2002-04-01). "Approach to menopausal symptoms in women with breast cancer". Current Treatment Options in Oncology. 3 (2): 179–190. doi:10.1007/s11864-002-0064-6. ISSN 1534-6277.
  14. ^ a b c Bergmans, M. G.; Merkus, J. M.; Corbey, R. S.; Schellekens, L. A.; Ubachs, J. M. (1987). "Effect of Bellergal Retard on climacteric complaints: a double-blind, placebo-controlled study". Maturitas. 9 (3): 227–234. doi:10.1016/0378-5122(87)90005-3. ISSN 0378-5122. PMID 3323851.
  15. ^ a b "Discontinuation report BELLERGAL SPACETABS". www.drugshortagescanada.ca. Retrieved 2023-04-10.
  16. ^ Alberti, C (2015). "Drug-induced retroperitoneal fibrosis: short aetiopathogenetic note, from the past times of ergot-derivatives large use to currently applied bio-pharmacology". Giornale di Chirurgia - Journal of Surgery. doi:10.11138/gchir/2015.36.4.187. ISSN 1971-145X. PMC 4732590. PMID 26712075.{{cite journal}}: CS1 maint: PMC format (link)
  17. ^ Liegl, Claudia; McGrath, Michael (2015-02-09). "Ergotism: Case Report and Review of the Literature". International Journal of Angiology. 25 (05): e8–e11. doi:10.1055/s-0034-1376397. ISSN 1061-1711. PMC 5186301. PMID 28031641.{{cite journal}}: CS1 maint: PMC format (link)
  18. ^ "Ergotism - an overview | ScienceDirect Topics". www.sciencedirect.com. Retrieved 2023-04-11.
  19. ^ PubChem. "Ergotamine". pubchem.ncbi.nlm.nih.gov. Retrieved 2023-04-10.
  20. ^ a b Taylor, Bryce N.; Cassagnol, Manouchkathe (2023), "Alpha Adrenergic Receptors", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 30969652, retrieved 2023-04-10
  21. ^ Allen, Mary J.; Sabir, Sarah; Sharma, Sandeep (2023), "GABA Receptor", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 30252380, retrieved 2023-04-10
  22. ^ Condron, Patrick; MSc; February 20, MACLast updated on; 2023. "Phenobarbital Effects | Short-Term, Long-Term, & Side Effects". DrugAbuse.com. Retrieved 2023-04-10. {{cite web}}: |last4= has numeric name (help)CS1 maint: numeric names: authors list (link)
  23. ^ Qureshi, Momina; Ray, Sidhartha D. (2023-01-01), "Belladonna alkaloids", Reference Module in Biomedical Sciences, Elsevier, ISBN 978-0-12-801238-3, retrieved 2023-04-10
  24. ^ "Scopolamine - an overview | ScienceDirect Topics". www.sciencedirect.com. Retrieved 2023-04-10.
  25. ^ a b c d Moore, Joanne (2007-01-01), Enna, S. J.; Bylund, David B. (eds.), "Ergotamine", xPharm: The Comprehensive Pharmacology Reference, New York: Elsevier, pp. 1–6, ISBN 978-0-08-055232-3, retrieved 2023-04-10
  26. ^ Schmidt, R.; Fanchamps, A. (1974-05-01). "Effect of caffeine on intestinal absorption of ergotamine in man". European Journal of Clinical Pharmacology. 7 (3): 213–216. doi:10.1007/BF00560383. ISSN 1432-1041.
  27. ^ Perrin, V. L. (1985-04-01). "Clinical Pharmacokinetics of Ergotamine in Migraine and Cluster Headache". Clinical Pharmacokinetics. 10 (4): 334–352. doi:10.2165/00003088-198510040-00004. ISSN 1179-1926.
  28. ^ a b c d Davies, John A. (2007-01-01), Enna, S. J.; Bylund, David B. (eds.), "Phenobarbital", xPharm: The Comprehensive Pharmacology Reference, New York: Elsevier, pp. 1–5, ISBN 978-0-08-055232-3, retrieved 2023-04-10
  29. ^ a b c "Atropine". go.drugbank.com. Retrieved 2023-04-10.
  30. ^ "Hyoscyamine". go.drugbank.com. Retrieved 2023-04-10.
  31. ^ Renner, Ulf D.; Oertel, Reinhard; Kirch, Wilhelm (2005). "Pharmacokinetics and pharmacodynamics in clinical use of scopolamine". Therapeutic Drug Monitoring. 27 (5): 655–665. doi:10.1097/01.ftd.0000168293.48226.57. ISSN 0163-4356. PMID 16175141.
  32. ^ a b "Scopolamine". go.drugbank.com. Retrieved 2023-04-10.
  33. ^ a b Renner, Ulf D.; Oertel, Reinhard; Kirch, Wilhelm (2005). "Pharmacokinetics and pharmacodynamics in clinical use of scopolamine". Therapeutic Drug Monitoring. 27 (5): 655–665. doi:10.1097/01.ftd.0000168293.48226.57. ISSN 0163-4356. PMID 16175141.
  34. ^ a b "DailyMed - ANASPAZ- hyoscyamine sulfate tablet, orally disintegrating". dailymed.nlm.nih.gov. Retrieved 2023-04-10.
  35. ^ a b Evans, W C; Ghani, A; Treagust, P G (2011-04-12). "Preliminary studies concerning the metabolism of hyoscine and hyoscyamine in the Solanaceae". Journal of Pharmacy and Pharmacology. 26 (Supplement_1): 112P–112P. doi:10.1111/j.2042-7158.1974.tb10143.x. ISSN 2042-7158.
  36. ^ a b c "Bellergal - an overview | ScienceDirect Topics". www.sciencedirect.com. Retrieved 2023-04-11.
  37. ^ "Drug Shortage Report for PHENOBARB". www.drugshortagescanada.ca. Retrieved 2023-04-10.
  38. ^ "Drug Shortage Report for PHENOBARB". www.drugshortagescanada.ca. Retrieved 2023-04-10.
  39. ^ a b c "Shibboleth Authentication Request". login.eproxy.lib.hku.hk. Retrieved 2023-04-10.
  40. ^ a b c d e f g "Contraindications for Bellergal-S oral". www.webmd.com. Retrieved 2023-04-11.
  41. ^ a b "Bellergal Spacetabs - Uses, Side Effects, Interactions - MedBroadcast.com". www.medbroadcast.com. Retrieved 2023-04-11.
  42. ^ "ERGOTAMINE/BELLADONNA/PHENOBARBITAL - ORAL (Bellergal-S) side effects, medical uses, and drug interactions". MedicineNet. Retrieved 2023-04-11.
  43. ^ a b c d e f "Bellergal Spacetabs". Pharmasave. Retrieved 2023-04-11.
  44. ^ Rey, C. P.; Yebra, M.; Borrallo, M.; Vega, A.; Ramos, A.; Montero, M. C. (2003-09-01). "Irreversible Coma, Ergotamine, and Ritonavir". Clinical Infectious Diseases. 37 (5): e72–e73. doi:10.1086/376636. ISSN 1058-4838.
  45. ^ Baldwin, Zachary K.; Ceraldi, Chris C. (2003). "Ergotism associated with HIV antiviral protease inhibitor therapy". Journal of Vascular Surgery. 37 (3): 676–678. doi:10.1067/mva.2003.80. ISSN 0741-5214.
  46. ^ Spiegel, M.; Schmidauer, C.; Kampfl, A.; Sarcletti, M.; Poewe, W. (2001-08-28). "Cerebral ergotism under treatment with ergotamine and ritonavir". Neurology. 57 (4): 743–744. doi:10.1212/wnl.57.4.743. ISSN 0028-3878.
  47. ^ Mortier, Emmanuel; Pouchot, Jacques; Vinceneux, Philippe; Lalande, Martine (2001). "Ergotism related to interaction between nelfinavir and ergotamine". The American Journal of Medicine. 110 (7): 594. doi:10.1016/s0002-9343(01)00655-6. ISSN 0002-9343.
  48. ^ Mohamedi, N.; Mirault, T.; Durivage, A.; Di Primio, M.; Khider, L.; Detriche, G.; El Batti, S.; Sapoval, M.; Messas, E.; Goudot, G. (2021). "Ergotism with acute limb ischemia, provoked by HIV protease inhibitors interaction with ergotamine, rescued by multisite transluminal balloon angioplasty". JMV-Journal de Médecine Vasculaire. 46 (1): 13–21. doi:10.1016/j.jdmv.2020.12.002. ISSN 2542-4513.
  49. ^ Navarro, Jordi; Curran, Adrian; Burgos, Joaquin; Torrella, Ariadna; Ocaña, Inma; Falcó, Vicenç; Crespo, Manuel; Ribera, Esteban (2017). "Acute Leg Ischaemia in an HIV-Infected Patient Receiving Antiretroviral Treatment". Antiviral Therapy. 22 (1): 89–90. doi:10.3851/imp3075. ISSN 1359-6535.
  50. ^ Horowitz, Rivka S. (1996-02-26). "Clinical Ergotism With Lingual Ischemia Induced by Clarithromycin-Ergotamine Interaction". Archives of Internal Medicine. 156 (4): 456. doi:10.1001/archinte.1996.00440040134015. ISSN 0003-9926.
  51. ^ Ausband, Stephen C; Goodman, Peggy E (2001). "An unusual case of clarithromycin associated ergotism". The Journal of Emergency Medicine. 21 (4): 411–413. doi:10.1016/s0736-4679(01)00379-1. ISSN 0736-4679.
  52. ^ Rey, C. P.; Yebra, M.; Borrallo, M.; Vega, A.; Ramos, A.; Montero, M. C. (2003-09-01). "Irreversible Coma, Ergotamine, and Ritonavir". Clinical Infectious Diseases. 37 (5): e72–e73. doi:10.1086/376636. ISSN 1058-4838.
  53. ^ "Ergomar (ergotamine) dosing, indications, interactions, adverse effects, and more". reference.medscape.com. Retrieved 2023-04-11.
  54. ^ Westphal, Jean Frédéric (2000). "Macrolide - induced clinically relevant drug interactions with cytochrome P-450A (CYP) 3A4: an update focused on clarithromycin, azithromycin and dirithromycin: Macrolide-induced metabolic drug interactions". British Journal of Clinical Pharmacology. 50 (4): 285–295. doi:10.1046/j.1365-2125.2000.00261.x. PMC 2015000. PMID 11012550.{{cite journal}}: CS1 maint: PMC format (link)
  55. ^ Saper, Joel R. (1978-06-09). "Migraine: II. Treatment". JAMA. 239 (23): 2480–2484. doi:10.1001/jama.1978.03280500076031. ISSN 0098-7484.
  56. ^ Ashford, Stephen; Breckenridge, Shuling; Nyein, Kyaw (2014-09-02). "Supplementary prescribing for spasticity management". Nurse Prescribing. 12 (9): 457–463. doi:10.12968/npre.2014.12.9.457. ISSN 1479-9189.
  57. ^ "Cytochrome P-450 CYP3A4 Inhibitors (moderate) | DrugBank Online". go.drugbank.com. Retrieved 2023-04-11.
  58. ^ "Homeowners' demand for home insulation". 1978-04-01. {{cite journal}}: Cite journal requires |journal= (help)
  59. ^ Hoekman, John; Ray, Sutapa; Aurora, Sheena K; Shrewsbury, Stephen B (2020). "The Upper Nasal Space—A Novel Delivery Route Ideal for Central Nervous System Drugs". US Neurology. 16 (1): 25. doi:10.17925/usn.2020.16.1.25. ISSN 1758-4000.
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