Phenytoin
|
|
| Systematic (IUPAC) name |
|
5,5-diphenylimidazolidine-2,4-dione
|
| Clinical data |
| Pronunciation |
; |
| Trade names |
Originally Dilantin, many names worldwide[1] |
| AHFS/Drugs.com |
monograph |
| MedlinePlus |
a682022 |
Pregnancy
category |
- AU: D
- US: D (Evidence of risk)
|
Routes of
administration |
Oral, parenteral |
| Legal status |
| Legal status |
- AU: S4 (Prescription only)
- CA: ℞-only
- UK: POM (Prescription only)
- US: ℞-only
|
| Pharmacokinetic data |
| Bioavailability |
70-100% oral, 24.4% for rectal administration |
| Protein binding |
95%[2] |
| Metabolism |
liver |
| Onset of action |
10 to 30 min (IV)[3] |
| Biological half-life |
10–22 hours[2] |
| Duration of action |
24 hr[3] |
| Excretion |
Primarily through the bile, urinary |
| Identifiers |
| CAS Number |
57-41-0 Y |
| ATC code |
N03AB02 (WHO) |
| PubChem |
CID 1775 |
| IUPHAR/BPS |
2624 |
| DrugBank |
DB00252 Y |
| ChemSpider |
1710 Y |
| UNII |
6158TKW0C5 Y |
| KEGG |
D00512 Y |
| ChEBI |
CHEBI:8107 N |
| ChEMBL |
CHEMBL16 N |
| Chemical data |
| Formula |
C15H12N2O2 |
| Molar mass |
252.268 g/mol |
SMILES
-
O=C2NC(=O)NC2(c1ccccc1)c3ccccc3
|
InChI
-
InChI=1S/C15H12N2O2/c18-13-15(17-14(19)16-13,11-7-3-1-4-8-11)12-9-5-2-6-10-12/h1-10H,(H2,16,17,18,19) N
-
Key:CXOFVDLJLONNDW-UHFFFAOYSA-N N
|
| NY (what is this?) (verify) |
Phenytoin, sold under the brand name Dilantin among others,[1] is an anti-seizure medication. It is useful for the prevention of tonic-clonic seizures, partial seizures, but not absence seizures. The intravenous form is used for status epilepticus that does not improve with benzodiazepines. It may also be used for certain heart arrhythmias or neuropathic pain. It can be taken intravenously or by mouth.[2] The intravenous form generally begins working within 30 minutes and is effective for 24 hours.[3] Blood levels can be measured to determine the proper dose.[2]
Common side effects include nausea, stomach pain, loss of appetite, poor coordination, increased hair growth, and enlargement of the gums. Potentially serious side effects include sleepiness, self harm, liver problems, bone marrow suppression, low blood pressure, and toxic epidermal necrolysis. There is evidence that use during pregnancy results in abnormalities in the baby. It appears to be okay during breastfeeding. Alcohol may interfere with the medication's effects.[2]
Phenytoin was first made in 1908 and found useful in seizures in 1936.[4] It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.[5] Phenytoin is available as a generic medication and usually not too expensive.[6] Wholesale it costs between 0.003 and 0.15 USD per dose.[7] A month of treatment is about 30 USD in the United States.[2]
Contents
- 1 Medical uses
- 1.1 Seizures
- 1.2 Other
- 1.3 Special considerations
- 2 Side effects
- 2.1 Heart and blood vessels
- 2.2 Neurological
- 2.3 Blood
- 2.4 Pregnancy
- 2.5 Cancer
- 2.6 Mouth
- 2.7 Skin
- 2.8 Immune system
- 2.9 Psychological
- 2.10 Bones
- 3 Interactions
- 4 Mechanism of action
- 5 Pharmacokinetics
- 6 History
- 7 Society and culture
- 8 See also
- 9 References
- 10 External links
Medical uses
Information in this section adapted from Lexi-Comp[8]
Seizures
- Tonic-clonic seizures - Mainly used in the prophylactic management of tonic-clonic seizures with complex symptomatology (psychomotor seizures). A period of 5–10 days may be required to achieve anticonvulsant effects.
- Focal seizures - Mainly used to protect against the development of focal seizures with complex symptomatology (psychomotor and temporal lobe seizures). Also effective in controlling partial seizures with autonomic symptoms.
- Absence seizures - Not used in treatment of pure absence seizures due to risk for increasing frequency of seizures. However, can be used in combination with other anticonvulsants during combined absence and tonic-clonic seizures.
- Seizures during surgery - Used as prevention and treatment of seizures occurring during and after neurosurgery.
- Status epilepticus - Considered after failed treatment using a benzodiazepine due to slow onset of action.
Other
- Abnormal heart rhythms- may be used in the treatment of ventricular tachycardia and sudden episodes of atrial tachycardia after other antiarrhythmic medications or cardioversion has failed. It is a class 1b antiarrhythmic.[9]
- Digoxin toxicity- IV formulation is drug of choice for arrhythmias caused by cardiac glycoside toxicity.
- Trigeminal neuralgia - Second choice drug to carbamazepine.[10]
- Wound healing- Tentative evidence suggests that topical phenytoin is useful in wound healing in people with chronic skin wounds.[11][12] A meta-analysis also supported the use of phenytoin in managing various ulcers.[13]
Special considerations
- Monitoring plasma concentrations: Narrow therapeutic index. Anticonvulsant effect: 10–20 µg/mL; Antiarrhythmic effect: 10–20 µg/mL
- Avoid giving intramuscular formulation unless necessary due to skin cell death and local tissue destruction.
- Elderly- May show earlier signs of toxicity.
- Obese- Use ideal body weight for dosing calculations.
- Pregnancy- Pregnancy Category D due to risk of fetal hydantoin syndrome and fetal bleeding. However, optimal seizure control is very important during pregnancy so drug may be continued if benefits outweigh the risks. Due to decreased drug concentrations during pregnancy, dose of phenytoin may need to be increased if only option for seizure control.
- Breast feeding- The manufacturer does not recommend breast feeding because low concentrations of phenytoin are excreted in breast milk.[14]
- Liver disease- Do not use oral loading dose. Consider using decreased maintenance dose.
- Kidney disease- Do not use oral loading dose. Can begin with standard maintenance dose and adjust as needed.
- IV use is contraindicated in patients with sinus bradycardia, SA block, second- or third-degree AV block, Stokes-Adams syndrome, or have known hypersensitivity to phenytoin or any ingredient in the respective formulation or to other hydantoins.
Side effects
Common side effects include nausea, stomach pain, loss of appetite, poor coordination, increased hair growth, and enlargement of the gums. Potentially serious side effects include sleepiness, self harm, liver problems, bone marrow suppression, low blood pressure, and toxic epidermal necrolysis. There is evidence that use during pregnancy results in abnormalities in the baby. It appears to be okay during breastfeeding. Alcohol may interfere with the medication's effects.[2]
Heart and blood vessels
Severe low blood pressure and abnormal heart rhythms can be seen with rapid infusion of IV phenytoin. IV infusion should not exceed 50 mg/min in adults or 1–3 mg/kg/min (or 50 mg/min, whichever is slower) in children. Heart monitoring should occur during and after IV infusion. Due to these risks, oral phenytoin should be used if possible.[15]
Neurological
At therapeutic doses, phenytoin may produce nystagmus on lateral gaze. At toxic doses, patients experience vertical nystagmus, double vision, sedation, slurred speech, cerebellar ataxia, and tremor.[16] If phenytoin is stopped abruptly, this may result in increased seizure frequency, including status epilepticus.[15]
Phenytoin may accumulate in the cerebral cortex over long periods of time which can cause atrophy of the cerebellum. The degree of atrophy is related to the duration of phenytoin treatment and is not related to dosage of the medication.[17]
Abrupt discontinuation of phenytoin can precipitate status epilepticus.[14]
Blood
It has been suggested that phenytoin causes a reduction in folic acid levels, predisposing patients to megaloblastic anemia. Folate is presented in foods as polyglutamate, which is then converted into monoglutamates by intestinal conjugase. Phenytoin acts by inhibiting this enzyme, thereby causing folate deficiency.[18] Other side effects may include: agranulocytosis, aplastic anemia, decreased white blood cell count,[citation needed] and a low platelet count.[19]
Pregnancy
Phenytoin is a known teratogen. The syndrome consists of craniofacial anomalies (broad nasal bridge, cleft lip and palate, smaller than normal head) and a mild form of mental retardation (average IQ=71).[20] This syndrome resembles the well-described Fetal Alcohol Syndrome[21] and has also been called the "fetal hydantoin syndrome". Some recommend avoiding polytherapy and maintaining the minimal dose possible during pregnancy, but acknowledge that current data do not provide clear answers.[22] Data now being collected by the Epilepsy and Antiepileptic Drug Pregnancy Registry may one day answer this question definitively.
Cancer
There is no good evidence that phenytoin is a human carcinogen.[23][24]
Mouth
Phenytoin has been associated with drug-induced gingival enlargement (overgrowth of the gums), probably due to above-mentioned folate deficiency; indeed, evidence from a randomized controlled trial suggests that folic acid supplementation can prevent gingival enlargement in children who take phenytoin.[25] Plasma concentrations needed to induce gingival lesions have not been clearly defined. Effects consist of the following: bleeding upon probing, increased gingival exudate, pronounced gingival inflammatory response to plaque levels, associated in some instances with bone loss but without tooth detachment.
Skin
Hypertrichosis, Stevens-Johnson syndrome, purple glove syndrome, rash, exfoliative dermatitis, itching, excessive hairiness, and coarsening of facial features can be seen in those taking phentyoin.
Phenytoin therapy has been linked to the life-threatening skin reactions Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). These conditions are significantly more common in patients with a particular HLA-B allele, HLA-B*1502.[26] This allele occurs almost exclusively in patients with ancestry across broad areas of Asia, including South Asian Indians.
Phenytoin is primarily metabolized to its inactive form by the enzyme CYP2C9. Variations within the CYP2C9 gene that result in decreased enzymatic activity have been associated with increased phenytoin concentrations, as well as reports of drug toxicities due to these increased concentrations.[27] The U.S. Food and Drug Administration (FDA) notes on the phenytoin drug label that since strong evidence exists linking HLA-B*1502 with the risk of developing SJS or TEN in patients taking carbamazepine, consideration should be given to avoiding phenytoin as an alternative to carbamazepine in patients carrying this allele.[28]
Immune system
Phenytoin has been known to cause drug-induced lupus.[29]
Phenytoin is also associated with induction of reversible IgA deficiency.[30]
Psychological
Phenytoin may increase risk of suicidal thoughts or behavior. People on phenytoin should be monitored for any changes in mood, the development or worsening depression, and/or any thoughts or behavior of suicide.[14]
Bones
Chronic phenytoin use has been associated with decreased bone density and increased bone fractures. Phenytoin induces metabolizing enzymes in the liver. This leads to increased metabolism of vitamin D, thus decreased vitamin D levels. Vitamin D deficiency, as well as low calcium and phospate in the blood cause decreased bone mineral density.[14]
Interactions
Phenytoin is an inducer of the CYP3A4 and CYP2C19 families of the P450 enzyme responsible for the liver's degradation of various drugs.[31]
A 1981 study by the National Institutes of Health showed that antacids administered concomitantly with phenytoin "altered not only the extent of absorption but also appeared to alter the rate of absorption. Antacids administered in a peptic ulcer regimen may decrease the AUC of a single dose of phenytoin. Patients should be cautioned against concomitant use of antacids and phenytoin."[32]
Warfarin (Coumadin) and trimethoprim increase serum phenytoin levels and prolong the serum half-life of phenytoin by inhibiting its metabolism. Consider using other options if possible.[33]
Mechanism of action
The mechanism of action of phenytoin sodium. Sodium channels are: 1) Closed 2) Open 3) Inactive (phenytoin effect)
Phenytoin is believed to protect against seizures by causing voltage-dependent block of voltage gated sodium channels.[34] This blocks sustained high frequency repetitive firing of action potentials. This is accomplished by reducing the amplitude of sodium-dependent action potentials through enhancing steady state inactivation. Sodium channels exist in three main conformations: the resting state, the open state, and the inactive state.
Phenytoin binds preferentially to the inactive form of the sodium channel. Because it takes time for the bound drug to dissociate from the inactive channel, there is a time dependent block of the channel. Since the fraction of inactive channels is increased by membrane depolarization as well as by repetitive firing, the binding to the inactive state by phenytoin sodium can produce voltage-dependent, use-dependent and time-dependent block of sodium-dependent action potentials.[35]
The primary site of action appears to be the motor cortex where spread of seizure activity is inhibited.[36] Possibly by promoting sodium efflux from neurons, phenytoin tends to stabilize the threshold against hyperexcitability caused by excessive stimulation or environmental changes capable of reducing membrane sodium gradient. This includes the reduction of post-tetanic potentiation at synapses which prevents cortical seizure foci from detonating adjacent cortical areas. Phenytoin reduces the maximal activity of brain stem centers responsible for the tonic phase of generalized tonic-clonic seizures.[15]
Pharmacokinetics
Phenytoin elimination kinetics show mixed-order behaviour at therapeutic concentrations. A small increase in dose may lead to a large increase in drug concentration as elimination becomes saturated. The time to reach steady state is often longer than 2 weeks.[37][38][39][40]
History
Phenytoin (diphenylhydantoin) was first synthesized by German chemist Heinrich Biltz in 1908.[41] Biltz sold his discovery to Parke-Davis, which did not find an immediate use for it. In 1938, outside scientists including H. Houston Merritt and Tracy Putnam discovered phenytoin's usefulness for controlling seizures, without the sedative effects associated with phenobarbital.
According to Goodman and Gilman's Pharmacological Basis of Therapeutics,
- In contrast to the earlier accidental discovery of the antiseizure properties of bromide and phenobarbital, phenytoin was the product of a search among nonsedative structural relatives of phenobarbital for agents capable of suppressing electroshock convulsions in laboratory animals.[42]
It was approved by the USA Food and Drug Administration in 1953 for use in seizures.
Jack Dreyfus, founder of the Dreyfus Fund, became a major proponent of phenytoin as a means to control nervousness and depression when he received a prescription for Dilantin in 1966. He is believed to have supplied large amounts of the drug to Richard Nixon throughout the late 1960s and early 1970s. Dreyfus' experience with phenytoin is outlined in his book, A Remarkable Medicine Has Been Overlooked.[43] Despite more than $70 million in personal financing, his push to see phenytoin evaluated for alternative uses has had little lasting effect on the medical community. This was partially because Parke-Davis was reluctant to invest in a drug nearing the end of its patent life, and partially due to mixed results from various studies.
In 2008, the drug was put on the FDA's Potential Signals of Serious Risks List to be further evaluated for approval. The list identifies medications that the FDA has identified a potential safety issue, but does not mean that FDA has identified a causal relationship between the drug and the listed risk. To address this concern, the Warnings and Precautions section of the labeling for Dilantin injection was updated to include additional information about purple glove syndrome in November 2011.[44]
Society and culture
Cost
Phenytoin is available as a generic medication and usually not too expensive.[6] Wholesale it costs between 0.003 and 0.15 USD per dose.[7] A month of treatment is about 30 USD in the United States.[2]
Since September 2012, the marketing licence in the UK has been held by Flynn Pharma Ltd, of Dublin, Ireland, and the product, although identical, has been called Phenytoin Sodium xxmg Flynn Hard Capsules. (The xxmg in the name refers to the strength - for example 'Phenytoin sodium 25 mg Flynn Hard Capsules').[45] The capsules are still made by Pfizer's Goedecke subsidiary's plant in Freiburg, Germany and they still have Epanutin printed on them.[46] After Pfizer's sale of the UK marketing licence to Flynn Pharma, the price of a 28-pack of 25 mg phenytoin sodium capsules marked Epanutin rose from 66p (about $0.88) to £15.74 (about $25.06). Capsules of other strengths also went up in price by the same factor - 2384%[47] costing the UK's National Health Service an extra £43 million (about $68.44 million) a year.[48] The companies were referred to the Competition and Markets Authority who found that they had exploited their dominant position in the market to charge “excessive and unfair” prices.[49]
Trade names
Phenytoin is marketed under many trade names worldwide.[1] Dilantin should not be confused with Dolantin (the tradename for meperidine).
See also
- Fosphenytoin
- Ethotoin
- Mephenytoin
References
- ^ a b c Drugs.com International trade names for phenytoin Page accessed Feb 27, 2016
- ^ a b c d e f g h "Phenytoin". The American Society of Health-System Pharmacists. Retrieved Aug 22, 2015.
- ^ a b c Marx, John A. (2010). Rosen's emergency medicine : concepts and clinical practice (7 ed.). Philadelphia: Mosby/Elsevier. p. 1352. ISBN 9780323054720.
- ^ Aicardi, Jean (2008). Epilepsy : a comprehensive textbook (2nd ed.). Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. p. 1431. ISBN 9780781757775.
- ^ "WHO Model List of Essential Medicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.
- ^ a b Hamilton, Richard J. (2013). Tarascon pocket pharmacopoeia. (14 ed.). Burlington, MA.: Jones & Bartlett Learning. p. 294. ISBN 9781449673635.
- ^ a b "Phenytoin". International Drug Price Indicator Guide. Retrieved 23 August 2015.
- ^ "Phenytoin". Lexi-Comp Online. Retrieved 18 April 2014.
- ^ McEvoy, GK (2004). "AHFS drug information 2004". American Society of Health-System Pharmacists: 2117–2120.
- ^ Pharmacology and pharmacotheraputics 22ed edition pg:129 By R S Satoskar
- ^ Shaw, J; Hughes, CM; Lagan, KM; Bell, PM (Nov 2007). "The clinical effect of topical phenytoin on wound healing: a systematic review.". The British journal of dermatology 157 (5): 997–1004. doi:10.1111/j.1365-2133.2007.08160.x. PMID 17854378.
- ^ Bhatia, A; Prakash, S (Jul 15, 2004). "Topical phenytoin for wound healing.". Dermatology online journal 10 (1): 5. PMID 15347487.
- ^ Thangaraju, Pugazhenthan; Tamilselvan, T; Venkatesan, S; Eswaran, T; singh, H; Giri, VC; showkath Ali, MK (Jul 16, 2015). "Topical Phenytoin for Managing Various Ulcers:A meta-analysis.". Sudan Medical Monitor 10: 63–67.
- ^ a b c d Phenytoin [package insert]. New York, NY: Pfizer Inc.; 2013. Accessed November 2, 2014.
- ^ a b c "FDA drug label" (PDF). FDA. Retrieved 18 April 2014.
- ^ "Dilantin Toxicity".
- ^ De Marco, Felipe A; et al. (July 2003). "Cerebellar Volume and Long-Term Use of Phenytoin". European Journal of Epilepsy 12 (5): 312–315. doi:10.1016/s1059-1311(02)00267-4. PMID 12810345. Retrieved 20 April 2014.
- ^ Carl GF, Smith ML (1992). "Phenytoin-folate interactions: differing effects of the sodium salt and the free acid of phenytoin". Epilepsia 33 (2): 372–375. doi:10.1111/j.1528-1157.1992.tb02330.x. PMID 1547769.
- ^ http://www.netdoctor.co.uk/diseases/facts/aplasticanaemia.htm
- ^ Beckmann CR, et al. (2002). Obstetrics and Gynecology (4th ed.). Baltimore: Lippincott Williams & Wilkins.
- ^ CDC. (2004). Fetal Alcohol Syndrome: Guidelines for Referral and Diagnosis. Can be downloaded at http://www.cdc.gov/fas/faspub.htm.
- ^ Adab N, Tudur SC, Vinten J, Williamson P, Winterbottom J (2004). Adab, Naghme, ed. "Common Antiepileptic Drugs in Pregnancy in Women with Epilepsy". Cochrane Database of Systematic Reviews 2004 (3): CD004848. doi:10.1002/14651858.CD004848. PMID 15266543.
- ^ Report on Carcinogens, Eleventh Edition (PB2005-104914, 2004) p III-216.
- ^ Maeda T, Sano N, Togei K, Shibata M, Izumi K, Otsuka H (1988). "Lack of carcinogenicity of phenytoin in (C57BL/6 x C3H)F1 mice". Journal of Toxicology and Environmental Health 24 (1): 111–119. doi:10.1080/15287398809531144. PMID 3373561.
- ^ Arya R, Gulati S, Kabra M, Sahu JK, Kalra V (2011). "Folic acid supplementation prevents phenytoin-induced gingival overgrowth in children". Neurology 76 (15): 1338–1343. doi:10.1212/WNL.0b013e3182152844. PMC 3090066. PMID 21482950.
- ^ Man CB, Kwan P, Baum L, et al. (2007). "Association between HLA-B*1502 allele and antiepileptic drug-induced cutaneous reactions in Han Chinese". Epilepsia 48 (5): 1015–1018. doi:10.1111/j.1528-1167.2007.01022.x. PMID 17509004.
- ^ Caudle, KE; Rettie, AE; Whirl-Carrillo, M; Smith, LH; Mintzer, S; Lee, MT; Klein, TE; Callaghan, JT (November 2014). "Clinical pharmacogenetics implementation consortium guidelines for CYP2C9 and HLA-B genotypes and phenytoin dosing.". Clinical pharmacology and therapeutics 96 (5): 542–8. doi:10.1038/clpt.2014.159. PMID 25099164.
- ^ "DILANTIN- phenytoin sodium capsule, extended release". http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8848de76-8d74-4620-bcc7-a86a596e5dd9.
- ^ Scheinfeld N (2003). "Phenytoin in Cutaneous Medicine: Its Uses, Mechanisms and Side Effects". Dermatology Online Journal 9 (3): 6. PMID 12952753.
- ^ Gilhus NE, Aarli JA (1981). "The reversibility of phenytoin-induced IgA deficiency". Journal of Neurology 226 (1): 53–61. doi:10.1007/BF00313318. PMID 6181216.
- ^ Cuttle, L; et al. (August 2000). "Phenytoin metabolism by human cytochrome P450: involvement of P450 3A and 2C forms in secondary metabolism and drug-protein adduct formation". Drug Metabolism and Disposition 28 (8): 945–950. PMID 10901705. Retrieved 20 April 2014.
- ^ Carter, BL; et al. (1981). "Effect of antacids on phenytoin availability". Therapeutic Drug Monitoring 3 (4): 333–340. doi:10.1097/00007691-198104000-00003. PMID 7336470. Retrieved 20 April 2014.
- ^ "Lexi-Comp Online Interaction Lookup". Lexi-Comp.
- ^ Rogawski MA, Löscher W (Jul 2004). "The neurobiology of antiepileptic drugs". Nat Rev Neurosci 5 (7): 553–564. doi:10.1038/nrn1430. PMID 15208697.
- ^ lippincots modern pharmacology with clinical applications pg no:377 5th Edition
- ^ Dilantin. (2015). In MIMS. Retrieved from https://www.mims.com/Hongkong/drug/info/Dilantin/?type=full#Actions
- ^ http://ebooks.cambridge.org/chapter.jsf?bid=CBO9781139103992&cid=CBO9781139103992A081
- ^ Chapter 67 - Antiepileptic drug pharmacokinetics and therapeutic drug monitoring pp. 358-366 By Philip N. Patsalos View chapter as PDF Antiepileptic drug pharmacokinetics and therapeutic drug monitoring By Philip N. Patsalos
- ^ http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/9993
- ^ DONAHUE, S; FLOCKHART, D; ABERNETHY, D (December 1999). "Ticlopidine inhibits phenytoin clearance". Clinical Pharmacology & Therapeutics 66 (6): 563–568. doi:10.1053/cp.1999.v66.103277001.
- ^ Biltz H (1908). "Über die Konstitution der Einwirkungsprodukte von substituierten Harnstoffen auf Benzil und über einige neue Methoden zur Darstellung der 5,5-Diphenyl-hydantoine" [Constitution of the Products of the Interaction of Substituted Carbamides on Benzil and Certain New Methods for the Preparation of 5,5-Diphenylhydantoin]. Chemische Berichte (in German) 41 (1): 1379–1393. doi:10.1002/cber.190804101255.
- ^ Goodman and Gilman's Pharmacological Basis of Therapeutics (10th ed.). New York: McGraw-Hill. 2001.
- ^ Dreyfus J (1998). A Remarkable Medicine Has Been Overlooked: Including an Autobiography and the Clinical Section of the Broad Range of Use of Phenytoin. Continuum International Publishing Group. ISBN 0-8264-1069-3.
- ^ "AERS data". FDA. Retrieved 18 April 2014.
- ^ Phenytoin Sodium Flynn Hard Capsules...Marketing authorisation holder, Flynn Pharma patient information leaflet at the electronic Medicines Compendium, 24 April 2014.Accessed 13 May 2014.
- ^ Healthcare Professionals Advised That Epanutin Capsules Are Only To Be Available Under The Generic Name, MediGuard, Durham, NC, 2 October 2012.Accessed 13 May 2014.
- ^ Pharma firm hikes cost of epilepsy drug 24 times, Stephen Adams, Medical Correspondent, Daily Telegraph, London, 12 October 2012.Accessed 13 May 2014.
- ^ Price of anti-epilepsy drug rockets, Mark Gould, Pulse, London, 21 November 2012.Accessed 13 May 2014.
- ^ White, Michael (12 August 2015). "Pharma market abuse isn't picked up fast enough". Health Service Journal. Retrieved 6 October 2015.
External links
- Medicines for Epilepsy: Dilantin Epilepsy Foundation.
- Remarkable Medicine, a website about the Dreyfus Foundation's work to expand the indications for phenytoin
- Phenytoin Pharmacokinetics (not a public link)
- [1] English Translation of 1908 German article on phenytoin synthesis by Heinrich Biltz
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Anticonvulsants (N03)
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| GABAergics |
| GABAAR PAMs |
- Barbiturates: Barbexaclone
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- #WHO-EM
- ‡Withdrawn from market
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- †Phase III
- §Never to phase III
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Antiarrhythmic agents (C01B)
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| Channel blockers |
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class I
(Na+ channel blockers)
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class Ia (Phase 0→ and Phase 3→)
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- Ajmaline
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class Ib (Phase 3←)
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class Ic (Phase 0→)
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|
class IV
(Phase 4→, Ca2+ channel blockers)
|
|
|
|
Receptor agonists
and antagonists |
|
class II
(Phase 4→, β blockers)
|
- Nadolol
- Pindolol
- Propranolol
- cardioselective (Acebutolol
- Atenolol
- Esmolol
- Metoprolol)
|
|
|
A1 agonist
|
- Adenosine
- Benzodiazepines
- Barbiturates
|
|
|
M2
|
- muscarinic antagonist: Atropine
- Disopyramide
- Quinidine
muscarinic agonist: Digoxin
|
|
|
α receptors
|
- Amiodarone
- Bretylium
- Quinidine
- Verapamil
|
|
|
| Ion transporters |
|
|
- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
|
|
|
GABAA receptor positive allosteric modulators
|
|
| Alcohols |
- Brometone
- Butanol
- Chloralodol
- Chlorobutanol (cloretone)
- Ethanol (drinking alcohol)
- Ethchlorvynol
- Isobutanol
- Isopropanol
- Menthol
- Methanol
- Methylpentynol
- Pentanol
- Petrichloral
- Propanol
- tert-Butanol (2M2P)
- tert-Pentanol (2M2B)
- Tribromoethanol
- Trichloroethanol
- Triclofos
- Trifluoroethanol
|
|
| Barbiturates |
- (-)-DMBB
- Allobarbital
- Alphenal
- Amobarbital
- Aprobarbital
- Barbexaclone
- Barbital
- Benzobarbital
- Benzylbutylbarbiturate
- Brallobarbital
- Brophebarbital
- Butabarbital/Secbutabarbital
- Butalbital
- Buthalital
- Butobarbital
- Butallylonal
- Carbubarb
- CP-1414S
- Crotylbarbital
- Cyclobarbital
- Cyclopentobarbital
- Difebarbamate
- Enallylpropymal
- Ethallobarbital
- Eterobarb
- Febarbamate
- Heptabarb
- Heptobarbital
- Hexethal
- Hexobarbital
- Metharbital
- Methitural
- Methohexital
- Methylphenobarbital
- Narcobarbital
- Nealbarbital
- Pentobarbital
- Phenallymal
- Phenobarbital
- Phetharbital
- Primidone
- Probarbital
- Propallylonal
- Propylbarbital
- Proxibarbital
- Reposal
- Secobarbital
- Sigmodal
- Spirobarbital
- Talbutal
- Tetrabamate
- Tetrabarbital
- Thialbarbital
- Thiamylal
- Thiobarbital
- Thiobutabarbital
- Thiopental
- Thiotetrabarbital
- Valofane
- Vinbarbital
- Vinylbital
|
|
| Benzodiazepines |
|
|
| Carbamates |
- Carisbamate
- Carisoprodol
- Clocental
- Cyclarbamate
- Difebarbamate
- Emylcamate
- Ethinamate
- Febarbamate
- Felbamate
- Hexapropymate
- Lorbamate
- Mebutamate
- Meprobamate
- Nisobamate
- Pentabamate
- Phenprobamate
- Procymate
- Styramate
- Tetrabamate
- Tybamate
|
|
| Flavonoids |
- 6-Methylapigenin
- Ampelopsin (dihydromyricetin)
- Apigenin
- Baicalein
- Baicalin
- Catechin
- EGC
- EGCG
- Hispidulin
- Linarin
- Luteolin
- Rc-OMe
- Skullcap constituents (e.g., baicalin)
- Wogonin
|
|
| Imidazoles |
- Etomidate
- Metomidate
- Propoxate
|
|
| Kava constituents |
- 10-Methoxyyangonin
- 11-Methoxyyangonin
- 11-Hydroxyyangonin
- Desmethoxyyangonin
- 11-Methoxy-12-hydroxydehydrokavain
- 7,8-Dihydroyangonin
- Kavain
- 5-Hydroxykavain
- 5,6-Dihydroyangonin
- 7,8-Dihydrokavain
- 5,6,7,8-Tetrahydroyangonin
- 5,6-Dehydromethysticin
- Methysticin
- 7,8-Dihydromethysticin
- Yangonin
|
|
| Monoureides |
- Acecarbromal
- Apronal (apronalide)
- Bromisoval
- Carbromal
- Capuride
- Ectylurea
|
|
| Neuroactive steroids |
- Acebrochol
- Allopregnanolone
- Alfadolone
- Alfaxalone
- 3α-Androstanediol
- Androstenol
- Androsterone
- Cholesterol
- DHDOC
- 3α-DHP
- 5α-DHP
- 5β-DHP
- Etiocholanolone
- Ganaxolone
- Hydroxydione
- Minaxolone
- Org 20599
- Org 21465
- Pregnanolone (eltanolone)
- Progesterone
- Renanolone
- SAGE-217
- SAGE-689
- THDOC
|
|
| Nonbenzodiazepines |
- β-Carbolines: Abecarnil
- Gedocarnil
- Harmane
- SL-651,498
- ZK-93423; Cyclopyrrolones: Eszopiclone
- Pagoclone
- Pazinaclone
- Suproclone
- Suriclone
- Zopiclone; Imidazopyridines: Alpidem
- DS-1
- Necopidem
- Saripidem
- Zolpidem; Pyrazolopyrimidines: Divaplon
- Fasiplon
- Indiplon
- Lorediplon
- Ocinaplon
- Panadiplon
- Taniplon
- Zaleplon; Others: Adipiplon
- CGS-8216
- CGS-9896
- CGS-13767
- CGS-20625
- CL-218,872
- CP-615,003
- CTP-354
- ELB-139
- GBLD-345
- JM-1232
- L-838,417
- Lirequinil (Ro41-3696)
- NS-2664
- NS-2710
- NS-11394
- Pipequaline
- ROD-188
- RWJ-51204
- SB-205,384
- SX-3228
- TGSC01AA
- TP-003
- TPA-023
- TP-13
- U-89843A
- U-90042
- Viqualine
- Y-23684
|
|
| Phenols |
- Fospropofol
- Propofol
- Thymol
|
|
| Piperidinediones |
- Glutethimide
- Methyprylon
- Piperidione
- Pyrithyldione
|
|
| Pyrazolopyridines |
- Cartazolate
- Etazolate
- ICI-190,622
- Tracazolate
|
|
| Quinazolinones |
- Afloqualone
- Cloroqualone
- Diproqualone
- Etaqualone
- Mebroqualone
- Mecloqualone
- Methaqualone
- Methylmethaqualone
- Nitromethaqualone
- SL-164
|
|
| Volatiles/gases |
- Acetone
- Acetophenone
- Acetylglycinamide chloral hydrate
- Aliflurane
- Benzene
- Butane
- Butylene
- Centalun
- Chloral
- Chloral betaine
- Chloral hydrate
- Chloroform
- Cryofluorane
- Desflurane
- Dichloralphenazone
- Dichloromethane
- Diethyl ether
- Enflurane
- Ethyl chloride
- Ethylene
- Fluroxene
- Gasoline
- Halopropane
- Halothane
- Isoflurane
- Kerosine
- Methoxyflurane
- Methoxypropane
- Nitric oxide
- Nitrogen
- Nitrous oxide
- Norflurane
- Paraldehyde
- Propane
- Propylene
- Roflurane
- Sevoflurane
- Synthane
- Teflurane
- Toluene
- Trichloroethane (methyl chloroform)
- Trichloroethylene
- Vinyl ether
|
|
| Others/unsorted |
- 3-Hydroxybutanal
- α-EMTBL
- AA-29504
- Avermectins (e.g., ivermectin)
- Bromide compounds (e.g., lithium bromide, potassium bromide, sodium bromide)
- Carbamazepine
- Chloralose
- Chlormezanone
- Clomethiazole
- DEABL
- Dihydroergolines (e.g., dihydroergocryptine, dihydroergosine, dihydroergotamine, ergoloid (dihydroergotoxine))
- DS2
- Efavirenz
- Etazepine
- Etifoxine
- Fenamates (e.g., flufenamic acid, mefenamic acid, niflumic acid, tolfenamic acid)
- Fluoxetine
- Flupirtine
- Hopantenic acid
- Lanthanum
- Lavender oil
- Lignans (e.g., 4-O-methylhonokiol, honokiol, magnolol, obovatol)
- Loreclezole
- Menthyl isovalerate (validolum)
- Monastrol
- Niacin
- Nicotinamide (niacinamide)
- Org 25,435
- Phenytoin
- Propanidid
- Retigabine (ezogabine)
- Safranal
- SAGE-547
- Seproxetine
- Stiripentol
- Sulfonylalkanes (e.g., sulfonmethane (sulfonal), tetronal, trional)
- Terpenoids (e.g., borneol)
- Topiramate
- Valerian constituents (e.g., isovaleric acid, isovaleramide, valerenic acid, valerenol)
- Unsorted benzodiazepine site PAMs: MRK-409 (MK-0343)
- TCS-1105
- TCS-1205
|
|
|
See also: GABAergics
|
|
|
Estrogenics
|
|
Receptor
(ligands) |
|
ER (α, β)
|
|
Agonists
|
- (R)-DPN
- (S)-DPN
- (R,R)-THC
- (S,S)-THC
- 2,8-DHHHC
- 3α-Androstanediol
- 3β-Androstanediol
- 3α-Hydroxytibolone
- 3β-Hydroxytibolone
- 7-Oxo-DHEA
- 7α-Hydroxy-DHEA
- 7β-Hydroxyepiandrosterone
- 8β-VE2
- 16α-Hydroxy-DHEA
- 16α-Hydroxyestrone
- 16α-IE2
- 16α-LE2 (Cpd1471)
- Δ4-Androstenedione
- Δ5-Androstenediol
- 17α-Estradiol (alfatradiol)
- 17β-Estradiol (estradiol)
- Alestramustine
- Almestrone
- Anabolic steroids (prodrugs; e.g., testosterone, metandienone (methandrostenolone), others)
- Anethole
- Anol
- Atrimustine
- Benzestrol
- Bifluranol
- Bisdehydrodoisynolic acid
- Carbestrol
- Chalconoids (e.g., isoliquiritigenin, phloretin, phlorizin (phloridzin), wedelolactone)
- Cloxestradiol
- Conjugated equine estrogens (e.g., sodium equilin sulfate, sodium equilenin sulfate)
- Coumestans (e.g., coumestrol, psoralidin)
- DHEA
- DHEA-S
- Deoxymiroestrol
- Dianethole
- Dianol
- Diarylpropionitrile
- Dieldrin
- Dienestrol
- Dienestrol acetate
- Diethylstilbestrol
- Diethylstilbestrol dipropionate
- Diosgenin
- Doisynoestrol (fenocycline)
- Doisynolic acid
- DY-131 (GSK-9089)
- Endosulfan
- Epiestriol
- Epimestrol
- ERB-196 (WAY-202196)
- Esterified estrogens (e.g., estrone sulfate, equilin sulfate, equilenin sulfate)
- Estetrol
- Estradiol benzoate
- Estradiol butyrylacetate
- Estradiol cypionate
- Estradiol dienanthate
- Estradiol dipropionate
- Estradiol diundecylate
- Estradiol diundecylenate
- Estradiol enanthate
- Estradiol furoate
- Estradiol hemihydrate
- Estradiol hemisuccinate
- Estradiol hexahydrobenzoate
- Estradiol monopropionate
- Estradiol palmitate
- Estradiol pivalate
- Estradiol propoxyphenylpropionate
- Estradiol stearate
- Estradiol succinate
- Estradiol undecylate
- Estradiol valerate
- Estramustine
- Estramustine phosphate
- Estrapronicate
- Estrazinol
- Estriol
- Estriol succinate
- Estriol tripropionate
- Estrobin (DBE)
- Estrofurate
- Estromustine
- Estrone
- Estrone acetate
- Estrone cyanate
- Estrone sulfate
- Estrone tetraacetylglucoside
- Estropipate
- Estropronicate
- Etamestrol (eptamestrol)
- Ethinyl estradiol
- Ethinyl estradiol 3-isopropylsulfonate
- Etynodiol diacetate
- Fenarimol
- Fenestrel
- FERb 033
- Flavonoids (incl. 7,8-DHF, 8-prenylnaringenin, apigenin, baicalein, baicalin, calycosin, catechin, daidzein, daidzin, ECG, EGCG, epicatechin, equol, formononetin, glabrene, glabridin, genistein, genistin, glycitein, kaempferol, liquiritigenin, mirificin, myricetin, naringenin, pinocembrin, prunetin, puerarin, quercetin, tectoridin, tectorigenin)
- Fosfestrol
- Furostilbestrol
- GSK-4716
- Hexestrol
- Hexestrol diacetate
- Hexestrol dicaprylate
- Hexestrol diphosphate
- Hexestrol dipropionate
- Hydroxyestrone diacetate
- Lavender oil
- Lignans (e.g., enterodiol, enterolactone)
- Mestranol
- Metalloestrogens (e.g., cadmium)
- Methallenestril
- Methestrol
- Methestrol dipropionate
- Methiocarb
- Methylestradiol
- Miroestrol
- Moxestrol
- Nilestriol
- Noretynodrel
- Orestrate
- Paroxypropione
- Phytosterols (e.g., β-sitosterol, campesterol, stigmasterol)
- Polyestradiol phosphate
- Prinaberel (ERB-041, WAY-202041)
- Propylpyrazoletriol
- Promestriene
- Resorcylic acid lactones (e.g., zearalanone, zearalenol, zearalenone, zeranal (zearalanol))
- Quadrosilan
- Quinestradol
- Quinestrol
- SKF-82,958
- Stilbenoids (e.g., resveratrol)
- Synthetic xenoestrogens (e.g., alkylphenols, bisphenols (e.g., BPA, BPF, BPS), DDT, parabens, PBBs, PHBA, phthalates, PCBs)
- WAY-166818
- WAY-200070
|
|
|
Mixed (SERMs)
|
- 2-Hydroxyestrone
- 27-Hydroxycholesterol
- Acolbifene
- Afimoxifene
- Anordrin
- Anordriol
- Arzoxifene
- Bazedoxifene
- Broparestrol
- Chlorotrianisene
- Clomifene
- Clomifenoxide
- Cyclofenil
- Droloxifene
- Enclomifene
- Endoxifen
- Ethamoxytriphetol (MER-25)
- Femarelle
- Fispemifene
- GW5638
- Idoxifene
- Lasofoxifene
- Levormeloxifene
- Menerba
- Mepitiostane
- Miproxifene
- Nafoxidine
- Nitromifene
- Ormeloxifene
- Ospemifene
- Panomifene
- Phenytoin
- Pipendoxifene
- Raloxifene
- SS1010
- Sivifene
- Tamoxifen
- TAS-108
- Tesmilifene
- Tibolone
- Toremifene
- Trioxifene
- Y-134
- Zindoxifene
- Zuclomifene
|
|
|
Antagonists
|
- (R,R)-THC
- Fulvestrant
- ICI-164384
- Methylpiperidinopyrazole
- MIBE
- PHTPP
- Prochloraz
- RU-58668
- SS1020
- XCT-790
- ZK-164015
- ZK-191703
|
|
|
|
GPER
|
|
Agonists
|
- 7β-Hydroxyepiandrosterone
- Afimoxifene (4-hydroxytamoxifen)
- Atrazine
- Bisphenol A
- Daidzein
- DDT (p,p'-DDT, o',p'-DDE)
- Equol
- Estradiol
- Fulvestrant (ICI-182,780)
- G-1
- Genistein
- GPER-L1
- GPER-L2
- Hydroxytyrosol
- Kepone
- Niacin
- Nicotinamide
- Nonylphenol
- Oleuropein
- PCB (2,2',5'-PCB-4-OH)
- Propylpyrazoletriol
- Quercetin
- Raloxifene
- Resveratrol
- Tamoxifen
- Tectoridin
- Zearalenone
|
|
|
Antagonists
|
|
|
|
|
| Enzyme |
|
Modulators
|
- See here instead (modulators of 20,22-desmolase, 17α-hydroxylase/17,20-lyase, 3β-HSD, 17β-HSD, 5α-reductase, aromatase, and 27-hydroxylase).
|
|
|
| Others |
|
Precursors
|
- Cholesterol
- 22R-Hydroxycholesterol
- 20α,22R-Dihydroxycholesterol
- Pregnenolone
- Pregnenolone sulfate
- 17-Hydroxypregnenolone
- Progesterone
- 17-Hydroxyprogesterone
- 11-Deoxycortisol (cortodoxone)
- DHEA
- DHEA sulfate
- 16-Hydroxy-DHEA sulfate
- Δ5-Androstenediol
- Δ4-Androstenedione
- 16-Hydroxyandrostenedione
- Testosterone
|
|
|
Indirect
|
- Antigonadotropins (e.g., androgens, estrogens, progestogens, prolactin)
- Calcitriol (vitamin D)
- GnRH agonists (e,g, GnRH, leuprorelin)
- GnRH antagonists (e.g., cetrorelix)
- Gonadotropins (e.g., FSH, hCG, LH)
- Kisspeptin
- Plasma proteins (ABP, albumin, SHBG)
|
|
|
|
See also: Androgenics • Glucocorticoids • Mineralocorticoids • Progestogenics
|
|
|
Steroid hormone metabolism modulators
|
|
| 20,22-Desmolase |
- Inhibitors: 22-ABC
- 3,3′-Dimethoxybenzidine
- 3-Methoxybenzidine
- Aminoglutethimide
- Canrenone
- Cyanoketone
- Danazol
- Etomidate
- Ketoconazole
- Mitotane
- Spironolactone
- Trilostane
|
|
17α-Hydroxylase,
17,20-Lyase |
- Inhibitors: 22-ABC
- 22-Oxime
- Abiraterone
- Abiraterone acetate
- Bifonazole
- Canrenone
- CFG-920
- Clotrimazole
- Cyanoketone
- Cyproterone acetate
- Danazol
- Econazole
- Galeterone
- Gestrinone
- Isoconazole
- Ketoconazole
- L-39
- Liarozole
- LY-207,320
- MDL-27,302
- Miconazole
- Mifepristone
- Orteronel
- Pioglitazone
- Prochloraz
- Rosiglitazone
- Spironolactone
- Stanozolol
- SU-10,603
- TGF-β
- Tioconazole
- Troglitazone
- VN/87-1
- VT-464
- YM116
|
|
| 3α-HSD |
- Inhibitors: Coumestrol
- Daidzein
- Genistein
- Indomethacin
- Medroxyprogesterone acetate
- Inducers: Fluoxetine
- Fluvoxamine
- Mirtazapine
- Paroxetine
- Sertraline
- Venlafaxine
|
|
| 3β-HSD |
- Inhibitors: 4-MA
- Abiraterone
- Abiraterone acetate
- Azastene
- Cyanoketone
- Cyproterone acetate
- Danazol
- Epostane
- Genistein
- Gestrinone
- Metyrapone
- Norethisterone
- Oxymetholone
- Pioglitazone
- Rosiglitazone
- Trilostane
- Troglitazone
|
|
| 11β-HSD |
- Inhibitors: 18α-Glycyrrhizic acid
- ABT-384
- Acetoxolone
- Carbenoxolone
- Enoxolone (glycyrrhetinic acid)
- Epigallocatechin gallate
- Glycyrrhizin (glycyrrhizic acid)
|
|
| 21-Hydroxylase |
- Inhibitors: Aminoglutethimide
- Amphenone B
- Bifonazole
- Canrenone
- Clotrimazole
- Diazepam
- Econazole
- Genistein
- Isoconazole
- Ketoconazole
- Metyrapone
- Miconazole
- Midazolam
- Spironolactone
- Tioconazole
|
|
| 11β-Hydroxylase |
- Inhibitors: Abiraterone
- Abiraterone acetate
- Aminoglutethimide
- Canrenone
- Etomidate
- Fadrozole
- FETO
- Ketoconazole
- Metomidate
- Metyrapone
- Mitotane
- Potassium canrenoate
- Spironolactone
- Trilostane
|
|
| 18-Hydroxylase |
- Inhibitors: Aminoglutethimide
- Canrenone
- FAD286
- Fadrozole
- Ketoconazole
- LCI699
- Metyrapone
- Mespirenone
- Potassium canrenoate
- Spironolactone
|
|
| 17β-HSD |
- Inhibitors: Danazol
- Simvastatin
|
|
| 5α-Reductase |
- Inhibitors: 22-Oxime
- Alfatradiol
- Azelaic acid
- β-Sitosterol
- Bexlosteride
- Chlormadinone acetate
- Cl-4AS-1
- Dutasteride
- Epitestosterone
- Epristeride
- Fatty acids (α-linolenic acid, linoleic acid, γ-linolenic acid, monolinolein, oleic acid)
- Finasteride
- Ganoderic acid
- Izonsteride
- L-39
- Lapisteride
- Saw palmetto
- TFM-4AS-1
- Turosteride
- Vitamin B6
- Zinc
|
|
| Aromatase |
- Inhibitors: 4-AT
- 4-Cyclohexylaniline
- 4-Hydroxytestosterone
- 5α-DHNET
- Abyssinone II
- Aminoglutethimide
- Anastrozole
- Ascorbic acid (vitamin C)
- Atamestane
- ATD
- Bifonazole
- CGP-45,688
- CGS-47,645
- Chalconoids (e.g., isoliquiritigenin)
- Corynesidone A
- Clotrimazole
- DHT
- Difeconazole
- Econazole
- Ellagitannins
- Endosulfan
- Exemestane
- Fadrozole
- Fatty acids (e.g., conjugated linoleic acid, linoleic acid, linolenic acid, palmitic acid)
- Fenarimol
- Finrozole
- Flavonoids (e.g., 7-hydroxyflavone, 7-hydroxyflavanone, 7,8-DHF, acacetin, apigenin, baicalein, biochanin A, chrysin, EGCG, gossypetin, hesperetin, liquiritigenin, myricetin, naringenin, pinocembrin, rotenone, quercetin, sakuranetin, tectochrysin)
- Formestane
- Imazalil
- Isoconazole
- Ketoconazole
- Letrozole
- Liarozole
- Melatonin
- MEN-11066
- Miconazole
- Minamestane
- Nimorazole
- NKS01
- Norendoxifen
- ORG-33,201
- Penconazole
- Phenytoin
- Prochloraz
- PGE2 (dinoprostone)
- Plomestane
- Prochloraz
- Propioconazole
- Pyridoglutethimide
- Quinolinoids (e.g., berberine, casimiroin, triptoquinone A, XHN22, XHN26, XHN27)
- Resorcylic acid lactones (e.g., zearalenone)
- Rogletimide
- Stilbenoids (e.g., resveratrol)
- Talarozole
- Terpenoids (e.g., dehydroabietic acid, (–)-dehydrololiolide, retinol (vitamin A), Δ9-THC, tretinoin)
- Testolactone
- Tioconazole
- Triadimefon
- Triadimenol
- Troglitazone
- Valproic acid
- Vorozole
- Xanthones (e.g., garcinone D, garcinone E, α-mangostin, γ-mangostin, monodictyochrome A, monodictyochrome B)
- YM-511
- Zinc
- Inducers: Atrazine
- Flavonoids (e.g., genistein, quercetin)
|
|
| 27-Hydroxylase |
- Inhibitors: Anastrozole
- Bicalutamide
- Dexmedetomidine
- Fadrozole
- Posaconazole
- Ravuconazole
|
|
|
See also: Androgenics • Estrogenics • Glucocorticoidics • Mineralocorticoidics • Progestogenics
|
|