Cyproheptadine

Last updated

Cyproheptadine
Cyproheptadine.svg
Cyproheptadine-Spartan-PM3-3D-balls.png
Clinical data
Pronunciation /ˌsaɪproʊˈhɛptədiːn/ [1]
Trade names Periactin, others
AHFS/Drugs.com Monograph
MedlinePlus a682541
License data
Pregnancy
category
  • AU:A
Routes of
administration 		Oral
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding 96 to 99%
Metabolism Liver, [2] [3] mostly CYP3A4 mediated.
Elimination half-life 8.6 hours [4]
Excretion Faecal (2–20%; of which, 34% as unchanged drug) and renal (40%; none as unchanged drug) [2] [3]
Identifiers
  • 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-methylpiperidine
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.004.482 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C21H21N
Molar mass 287.406 g·mol−1
3D model (JSmol)
  • c43\C(=C1/CCN(C)CC1)c2ccccc2\C=C/c3cccc4
  • InChI=1S/C21H21N/c1-22-14-12-18(13-15-22)21-19-8-4-2-6-16(19)10-11-17-7-3-5-9-20(17)21/h2-11H,12-15H2,1H3 Yes check.svgY
  • Key:JJCFRYNCJDLXIK-UHFFFAOYSA-N Yes check.svgY
   (verify)

Cyproheptadine, sold under the brand name Periactin among others, is a first-generation antihistamine with additional anticholinergic, antiserotonergic, and local anesthetic properties.

Contents

It was patented in 1959 and came into medical use in 1961. [5] In 2021, it was the 280th most commonly prescribed medication in the United States, with more than 800,000 prescriptions. [6] [7]

Medical uses

Periactin (cyproheptadine) 4 mg tablets Periactin.jpg
Periactin (cyproheptadine) 4 mg tablets
Cyproheptadine's 3D molecular structure represented as space-filling model Cyproheptadine3Dan.gif
Cyproheptadine's 3D molecular structure represented as space-filling model

Cyproheptadine is used to treat allergic reactions (specifically hay fever). [8] The evidence for its use for this purpose indicates its effectiveness but second generation antihistamines such as ketotifen and loratadine have shown equal results with fewer side effects. [9]

It is also used as a preventive treatment against migraine. In a 2013 study the frequency of migraine was dramatically reduced in patients within 7 to 10 days after starting treatment. The average frequency of migraine attacks in these patients before administration was 8.7 times per month, this was decreased to 3.1 times per month at 3 months after the start of treatment. [9] [10] This use is on the label in the UK and some other countries.

It is also used off-label in the treatment of cyclical vomiting syndrome in infants; the only evidence for this use comes from retrospective studies. [11]

Cyproheptadine is sometimes used off-label to improve akathisia in people on antipsychotic medications. [12]

It is used off-label to treat various dermatological conditions, including psychogenic itch, [13] drug-induced hyperhidrosis (excessive sweating), [14] and prevention of blister formation for some people with epidermolysis bullosa simplex. [15]

One of the effects of the drug is increased appetite and weight gain, which has led to its use (off-label in the USA) for this purpose in children who are wasting as well as people with cystic fibrosis. [16] [17] [18] [19]

It is also used off-label in the management of moderate to severe cases of serotonin syndrome, a complex of symptoms associated with the use of serotonergic drugs, such as selective serotonin reuptake inhibitors (and monoamine oxidase inhibitors), and in cases of high levels of serotonin in the blood resulting from a serotonin-producing carcinoid tumor. [20] [21]

Cyproheptadine has sedative effects and can be used to treat insomnia similarly to other centrally-acting antihistamines. [22] [23] [24] [25] The recommended dose for this use is 4 to 8 mg. [23]

Adverse effects

Adverse effects include: [2] [3]

Overdose

Gastric decontamination measures such as activated charcoal are sometimes recommended in cases of overdose. The symptoms are usually indicative of CNS depression (or conversely CNS stimulation in some) and excess anticholinergic side effects. The LD50 in mice is 123 mg/kg and 295 mg/kg in rats. [2] [3]

Pharmacology

Pharmacodynamics

Cyproheptadine [27]
SiteKi (nM) [lower-alpha 1] Action [lower-alpha 2] SpeciesRef.
H1 0.06↓Human
H2 NDND
H3 >10,000Human
H4 202Human
M1 12↓Human
M2 7↓Human
M3 12↓Human
M4 8↓Human
M5 11.8↓Human
5-HT1A 59↓Human
5-HT2A 1.67↓Human
5-HT2B 1.54↓Human
5-HT2C 2.23↓Human
5-HT3 228Mouse
5-HT6 142Human
5-HT7 123Human
D1 117Human
D2 112↓Human
D3 8Human
SERT Tooltip Serotonin transporter4,100Rat
NET Tooltip Norepinephrine transporter290Rat
DAT Tooltip Dopamine transporterNDND
  1. ↑ The smaller the equilibrium constant, the more strongly the drug binds to the site.
  2. ↑
    • ↑ Agonist
    • ↓ Antagonist

Cyproheptadine is a very potent antihistamine or inverse agonist of the H1 receptor. At higher concentrations, it also has anticholinergic, antiserotonergic, and antidopaminergic activities. Of the serotonin receptors, it is an especially potent antagonist of the 5-HT2 receptors. This is thought to underlie its effectiveness in the treatment of serotonin syndrome. [28] However, it is possible that blockade of 5-HT1 receptors may also contribute to its effectiveness in serotonin syndrome. [29] Cyproheptadine has been reported to block 85% of 5-HT2 receptors in the human brain at a dose of 4 mg three times per day (12 mg/day total) and to block 95% of 5-HT2 receptors in the human brain at a dose of 6 mg three times per day (18 mg/day total) as measured with positron emission tomography (PET). [30] The dose of cyproheptadine recommended to ensure blockade of the 5-HT2 receptors for serotonin syndrome is 20 to 30 mg. [28] Besides its activity at neurotransmitter targets, cyproheptadine has been reported to possess weak antiandrogenic activity. [31]

Pharmacokinetics

Cyproheptadine is well-absorbed following oral ingestion, with peak plasma levels occurring after 1 to 3 hours. [32] Its terminal half-life when taken orally is approximately 8 hours. [4]

Chemistry

Cyproheptadine is a tricyclic benzocycloheptene and is closely related to pizotifen and ketotifen as well as to tricyclic antidepressants.

Research

Cyproheptadine was studied in one small trial as an adjunct in people with schizophrenia whose condition was stable and were on other medication; while attention and verbal fluency appeared to be improved, the study was too small to draw generalizations from. [33] It has also been studied as an adjuvant in two other trials in people with schizophrenia, around fifty people overall, and did not appear to have an effect. [34]

There have been some trials to see if cyproheptadine could reduce sexual dysfunction caused by SSRI and antipsychotic medications. [35]

Cyproheptadine has been studied for the treatment of post-traumatic stress disorder. [34]

Veterinary use

Cyproheptadine is used in cats as an appetite stimulant [36] [37] : 1371  and as an adjunct in the treatment of asthma. [38] Possible adverse effects include excitement and aggressive behavior. [39] The elimination half-life of cyproheptadine in cats is 12 hours. [38]

Cyproheptadine is a second line treatment for pituitary pars intermedia dysfunction in horses. [40] [41]

Related Research Articles

<span class="mw-page-title-main">Serotonin syndrome</span> Symptoms caused by an excess of serotonin in the central nervous system

Serotonin syndrome (SS) is a group of symptoms that may occur with the use of certain serotonergic medications or drugs. The symptoms can range from mild to severe, and are potentially fatal. Symptoms in mild cases include high blood pressure and a fast heart rate; usually without a fever. Symptoms in moderate cases include high body temperature, agitation, increased reflexes, tremor, sweating, dilated pupils, and diarrhea. In severe cases, body temperature can increase to greater than 41.1 °C (106.0 °F). Complications may include seizures and extensive muscle breakdown.

<span class="mw-page-title-main">Tricyclic antidepressant</span> Class of medications

Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants. TCAs were discovered in the early 1950s and were marketed later in the decade. They are named after their chemical structure, which contains three rings of atoms. Tetracyclic antidepressants (TeCAs), which contain four rings of atoms, are a closely related group of antidepressant compounds.

<span class="mw-page-title-main">Chlorpromazine</span> Antipsychotic medication

Chlorpromazine (CPZ), marketed under the brand names Thorazine and Largactil among others, is an antipsychotic medication. It is primarily used to treat psychotic disorders such as schizophrenia. Other uses include the treatment of bipolar disorder, severe behavioral problems in children including those with attention deficit hyperactivity disorder, nausea and vomiting, anxiety before surgery, and hiccups that do not improve following other measures. It can be given orally, by intramuscular injection, or intravenously.

<span class="mw-page-title-main">Haloperidol</span> Typical antipsychotic medication

Haloperidol, sold under the brand name Haldol among others, is a typical antipsychotic medication. Haloperidol is used in the treatment of schizophrenia, tics in Tourette syndrome, mania in bipolar disorder, delirium, agitation, acute psychosis, and hallucinations from alcohol withdrawal. It may be used by mouth or injection into a muscle or a vein. Haloperidol typically works within 30 to 60 minutes. A long-acting formulation may be used as an injection every four weeks by people with schizophrenia or related illnesses, who either forget or refuse to take the medication by mouth.

<span class="mw-page-title-main">Quetiapine</span> Atypical antipsychotic medication

Quetiapine, sold under the brand name Seroquel among others, is an atypical antipsychotic medication used for the treatment of schizophrenia, bipolar disorder, and major depressive disorder. Despite being widely used as a sleep aid due to its sedating effect, the benefits of such use may not outweigh its undesirable side effects. It is taken orally.

<span class="mw-page-title-main">Mirtazapine</span> Antidepressant medication

Mirtazapine, sold under the brand name Remeron among others, is an atypical tetracyclic antidepressant, and as such is used primarily to treat depression. Its effects may take up to four weeks but can also manifest as early as one to two weeks. It is often used in cases of depression complicated by anxiety or insomnia. The effectiveness of mirtazapine is comparable to other commonly prescribed antidepressants. It is taken by mouth.

<span class="mw-page-title-main">Dopamine antagonist</span> Drug which blocks dopamine receptors

A dopamine antagonist, also known as an anti-dopaminergic and a dopamine receptor antagonist (DRA), is a type of drug which blocks dopamine receptors by receptor antagonism. Most antipsychotics are dopamine antagonists, and as such they have found use in treating schizophrenia, bipolar disorder, and stimulant psychosis. Several other dopamine antagonists are antiemetics used in the treatment of nausea and vomiting.

<span class="mw-page-title-main">Doxepin</span> Medication to treat depressive disorder, anxiety disorders, chronic hives, and trouble sleeping

Doxepin is a medication belonging to the tricyclic antidepressant (TCA) class of drugs used to treat major depressive disorder, anxiety disorders, chronic hives, and insomnia. For hives it is a less preferred alternative to antihistamines. It has a mild to moderate benefit for sleeping problems. It is used as a cream for itchiness due to atopic dermatitis or lichen simplex chronicus.

<span class="mw-page-title-main">Trimipramine</span> Antidepressant

Trimipramine, sold under the brand name Surmontil among others, is a tricyclic antidepressant (TCA) which is used to treat depression. It has also been used for its sedative, anxiolytic, and weak antipsychotic effects in the treatment of insomnia, anxiety disorders, and psychosis, respectively. The drug is described as an atypical or "second-generation" TCA because, unlike other TCAs, it seems to be a fairly weak monoamine reuptake inhibitor. Similarly to other TCAs, however, trimipramine does have antihistamine, antiserotonergic, antiadrenergic, antidopaminergic, and anticholinergic activities.

<span class="mw-page-title-main">Chlorprothixene</span> Typical antipsychotic medication

Chlorprothixene, sold under the brand name Truxal among others, is a typical antipsychotic of the thioxanthene group.

<span class="mw-page-title-main">Dosulepin</span> Antidepressant

Dosulepin, also known as dothiepin and sold under the brand name Prothiaden among others, is a tricyclic antidepressant (TCA) which is used in the treatment of depression. Dosulepin was once the most frequently prescribed antidepressant in the United Kingdom, but it is no longer widely used due to its relatively high toxicity in overdose without therapeutic advantages over other TCAs. It acts as a serotonin–norepinephrine reuptake inhibitor (SNRI) and also has other activities including antihistamine, antiadrenergic, antiserotonergic, anticholinergic, and sodium channel-blocking effects.

<span class="mw-page-title-main">Amisulpride</span> Atypical antipsychotic and antiemetic medication

Amisulpride is an antiemetic and antipsychotic medication used at lower doses intravenously to prevent and treat postoperative nausea and vomiting; and at higher doses by mouth to treat schizophrenia and acute psychotic episodes. It is sold under the brand names Barhemsys and Solian, Socian, Deniban and others. At very low doses it is also used to treat dysthymia.

<span class="mw-page-title-main">Sulpiride</span> Atypical antipsychotic

Sulpiride, sold under the brand name Dogmatil among others, is an atypical antipsychotic medication of the benzamide class which is used mainly in the treatment of psychosis associated with schizophrenia and major depressive disorder, and is sometimes used in low dosage to treat anxiety and mild depression. Sulpiride is commonly used in Asia, Central America, Europe, South Africa and South America. Levosulpiride is its purified levo-isomer and is sold in India for similar purposes. It is not approved in the United States, Canada, or Australia. The drug is chemically and clinically similar to amisulpride.

Extrapyramidal symptoms (EPS) are symptoms that are archetypically associated with the extrapyramidal system of the brain's cerebral cortex. When such symptoms are caused by medications or other drugs, they are also known as extrapyramidal side effects (EPSE). The symptoms can be acute (short-term) or chronic (long-term). They include movement dysfunction such as dystonia, akathisia, parkinsonism characteristic symptoms such as rigidity, bradykinesia, tremor, and tardive dyskinesia. Extrapyramidal symptoms are a reason why subjects drop out of clinical trials of antipsychotics; of the 213 (14.6%) subjects that dropped out of one of the largest clinical trials of antipsychotics, 58 (27.2%) of those discontinuations were due to EPS.

<span class="mw-page-title-main">Pizotifen</span> Drug used to reduce frequency of headaches

Pizotifen (INN) or pizotyline (USAN), trade name Sandomigran, is a benzocycloheptene-based drug used as a medicine, primarily as a preventive to reduce the frequency of recurrent migraine headaches.

<span class="mw-page-title-main">Serotonin receptor agonist</span> Neurotransmission-modulating substance

A serotonin receptor agonist is an agonist of one or more serotonin receptors. They activate serotonin receptors in a manner similar to that of serotonin, a neurotransmitter and hormone and the endogenous ligand of the serotonin receptors.

<span class="mw-page-title-main">Iloperidone</span> Atypical antipsychotic medication

Iloperidone, commonly known as Fanapt and previously known as Zomaril, is an atypical antipsychotic for the treatment of schizophrenia.

<span class="mw-page-title-main">Zuclopenthixol</span> Typical antipsychotic medication

Zuclopenthixol, also known as zuclopentixol, is a medication used to treat schizophrenia and other psychoses. It is classed, pharmacologically, as a typical antipsychotic. Chemically it is a thioxanthene. It is the cis-isomer of clopenthixol. Clopenthixol was introduced in 1961, while zuclopenthixol was introduced in 1978.

A serotonin antagonist, or serotonin receptor antagonist, is a drug used to inhibit the action of serotonin and serotonergic drugs at serotonin (5-HT) receptors.

<span class="mw-page-title-main">Lurasidone</span> Atypical antipsychotic medication

Lurasidone, sold under the brand name Latuda among others, is an antipsychotic medication used to treat schizophrenia and bipolar disorder. It is taken by mouth.

References

  1. ↑ "Cyproheptadine". Dictionary.com Unabridged (Online). n.d.
  2. 1 2 3 4 "Cyproheptadine Hydrochloride tablet [Boscogen, Inc.]" (PDF). DailyMed. U.S. National Library of Medicine. November 2010. Retrieved 26 October 2013.
  3. 1 2 3 4 "Product Information: Periactin (cyproheptadine hydrochloride)" (PDF). Aspen Pharmacare Australia. Aspen Pharmacare Australia Pty Ltd. 17 November 2011. Archived from the original (PDF) on 29 October 2013. Retrieved 26 October 2013.
  4. 1 2 Gunja N, Collins M, Graudins A (2004). "A comparison of the pharmacokinetics of oral and sublingual cyproheptadine". Journal of Toxicology. Clinical Toxicology. 42 (1): 79–83. doi:10.1081/clt-120028749. PMID   15083941. S2CID   20196551.
  5. ↑ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 547. ISBN   9783527607495.
  6. ↑ "The Top 300 of 2021". ClinCalc. Archived from the original on 15 January 2024. Retrieved 14 January 2024.
  7. ↑ "Cyproheptadine - Drug Usage Statistics". ClinCalc. Retrieved 14 January 2024.
  8. ↑ "Cyproheptadine". MedlinePlus Drug Information. U.S. National Library of Medicine.
  9. 1 2 De Bruyne P, Christiaens T, Boussery K, Mehuys E, Van Winckel M (January 2017). "Are antihistamines effective in children? A review of the evidence". Archives of Disease in Childhood. 102 (1): 56–60. doi:10.1136/archdischild-2015-310416. PMID   27335428. S2CID   21185048.
  10. ↑ Saito Y, Yamanaka G, Shimomura H, Shiraishi K, Nakazawa T, Kato F, et al. (May 2017). "Reconsideration of the diagnosis and treatment of childhood migraine: A practical review of clinical experiences". Brain & Development. 39 (5): 386–394. doi:10.1016/j.braindev.2016.11.011. PMID   27993427. S2CID   34703034.
  11. ↑ Salvatore S, Barberi S, Borrelli O, Castellazzi A, Di Mauro D, Di Mauro G, et al. (July 2016). "Pharmacological interventions on early functional gastrointestinal disorders". Italian Journal of Pediatrics. 42 (1): 68. doi: 10.1186/s13052-016-0272-5 . PMC   4947301 . PMID   27423188.
  12. ↑ Taylor DM, Paton C, Kapur S (2015). The Maudsley Prescribing Guidelines in Psychiatry. John Wiley & Sons. p. 85. ISBN   978-1-118-75457-3.
  13. ↑ Szepietowski JC, Reszke R (2016). "Psychogenic Itch Management". Current Problems in Dermatology. 50: 124–132. doi:10.1159/000446055. ISBN   978-3-318-05888-8. PMID   27578081.
  14. ↑ Ashton AK, Weinstein WL (May 2002). "Cyproheptadine for drug-induced sweating". The American Journal of Psychiatry. 159 (5): 874–875. doi:10.1176/appi.ajp.159.5.874-a. PMID   11986151.
  15. ↑ So JY, Teng J (1993). "Epidermolysis Bullosa Simplex". In Adam MP, Everman DB, Mirzaa GM, Pagon RA, Wallace SE, Bean LJ, Gripp KW, Amemiya A (eds.). GeneReviews. University of Washington, Seattle. PMID   20301543.
  16. ↑ "Ciproheptadina, estimulante del apetito" [Cyproheptadine, appetite stimulant]. vademecum.es (in Spanish).
  17. ↑ "Bioplex NF". Archived from the original on 18 April 2018. Retrieved 18 April 2018.
  18. ↑ Harrison ME, Norris ML, Robinson A, Spettigue W, Morrissey M, Isserlin L (June 2019). "Use of cyproheptadine to stimulate appetite and body weight gain: A systematic review". Appetite. 137: 62–72. doi:10.1016/j.appet.2019.02.012. PMID   30825493. S2CID   72333631.
  19. ↑ Kim SY, Yun JM, Lee JW, Cho YG, Cho KH, Park YG, Cho B (October 2021). "Efficacy and Tolerability of Cyproheptadine in Poor Appetite: A Multicenter, Randomized, Double-blind, Placebo-controlled Study". Clinical Therapeutics. 43 (10): 1757–1772. doi:10.1016/j.clinthera.2021.08.001. PMID   34509304. S2CID   237493456.
  20. ↑ Rossi S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN   978-0-9805790-9-3.
  21. ↑ Iqbal MM, Basil MJ, Kaplan J, Iqbal MT (November 2012). "Overview of serotonin syndrome". Annals of Clinical Psychiatry. 24 (4): 310–318. PMID   23145389.
  22. ↑ Badr B, Naguy A (October 2022). "Cyproheptadine: a psychopharmacological treasure trove?". CNS Spectrums. 27 (5): 533–535. doi: 10.1017/S1092852921000250 . PMID   33632345.
  23. 1 2 Ekambaram V, Owens J (January 2021). "Medications Used for Pediatric Insomnia". Child and Adolescent Psychiatric Clinics of North America. 30 (1): 85–99. doi:10.1016/j.chc.2020.09.001. PMID   33223070. S2CID   227131545.
  24. ↑ Rombaut NE (1995). Antihistamines and Sedation: Methods and Measures (Thesis). OCLC   59660401. ProQuest   301570569.
  25. ↑ Wanderer AA, St Pierre JP, Ellis EF (October 1977). "Primary acquired cold urticaria. Double-blind comparative study of treatment with cyproheptadine, chlorpheniramine, and placebo". Archives of Dermatology. 113 (10): 1375–1377. doi:10.1001/archderm.113.10.1375. PMID   334082.
  26. ↑ Chertoff J, Alam S, Clark V (July 2014). "Cyproheptadine-Induced Acute Liver Failure". ACG Case Reports Journal. 1 (4): 212–213. doi:10.14309/crj.2014.56. PMC   4286888 . PMID   25580444.
  27. ↑ Roth BL, Driscol J. "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 14 August 2017.
  28. 1 2 Gillman PK (1999). "The serotonin syndrome and its treatment". Journal of Psychopharmacology. 13 (1): 100–109. doi:10.1177/026988119901300111. PMID   10221364. S2CID   17640246.
  29. ↑ Sporer KA (August 1995). "The serotonin syndrome. Implicated drugs, pathophysiology and management". Drug Safety. 13 (2): 94–104. doi:10.2165/00002018-199513020-00004. PMID   7576268. S2CID   19809259.
  30. ↑ Kapur S, Zipursky RB, Jones C, Wilson AA, DaSilva JD, Houle S (June 1997). "Cyproheptadine: a potent in vivo serotonin antagonist". The American Journal of Psychiatry. 154 (6): 884a–884. doi:10.1176/ajp.154.6.884a. PMID   9167527.
  31. ↑ Pucci E, Petraglia F (December 1997). "Treatment of androgen excess in females: yesterday, today and tomorrow". Gynecological Endocrinology. 11 (6): 411–433. doi:10.3109/09513599709152569. PMID   9476091.
  32. ↑ Murray L, Daly F, McCoubrie DM, Cadogan M (15 January 2011). Toxicology Handbook. Elsevier Australia. p. 388. ISBN   978-0-7295-3939-5 . Retrieved 27 November 2011.
  33. ↑ Buoli M, Altamura AC (March 2015). "May non-antipsychotic drugs improve cognition of schizophrenia patients?". Pharmacopsychiatry. 48 (2): 41–50. doi:10.1055/s-0034-1396801. PMID   25584772. S2CID   19202816.
  34. 1 2 Dabaghzadeh F, Khalili H, Ghaeli P, Dashti-Khavidaki S (December 2012). "Potential benefits of cyproheptadine in HIV-positive patients under treatment with antiretroviral drugs including efavirenz". Expert Opinion on Pharmacotherapy. 13 (18): 2613–2624. doi:10.1517/14656566.2012.742887. PMID   23140169. S2CID   25769557.
  35. ↑ Nunes LV, Moreira HC, Razzouk D, Nunes SO, Mari J (2012). "Strategies for the treatment of antipsychotic-induced sexual dysfunction and/or hyperprolactinemia among patients of the schizophrenia spectrum: a review". Journal of Sex & Marital Therapy. 38 (3): 281–301. doi:10.1080/0092623X.2011.606883. PMID   22533871. S2CID   23406005.
  36. ↑ Agnew W, Korman R (September 2014). "Pharmacological appetite stimulation: rational choices in the inappetent cat". Journal of Feline Medicine and Surgery. 16 (9): 749–756. doi:10.1177/1098612X14545273. PMID   25146662. S2CID   37126352.
  37. ↑ Gupta RC, ed. (2012). Veterinary Toxicology : Basic and Clinical Principles (2 ed.). Amsterdam Boston: Academic Press. pp. xii+1438. ISBN   978-0-12-385926-6. OCLC   794491298.
  38. 1 2 Dowling PM (8 February 2005). "Systemic Therapy of Airway Disease: Cyproheptadine". In Kahn CM, Line S, Aiello SE (eds.). The Merck Veterinary Manual (9th ed.). John Wiley & Sons. ISBN   978-0-911910-50-6. Retrieved on 26 October 2008.
  39. ↑ Dowling PM (8 February 2005). "Drugs Affecting Appetite". In Kahn CM, Line S, Aiello SE (eds.). The Merck Veterinary Manual (9th ed.). John Wiley & Sons. ISBN   978-0-911910-50-6. Retrieved on 26 October 2008.
  40. ↑ Durham AE (April 2017). "Therapeutics for Equine Endocrine Disorders". The Veterinary Clinics of North America. Equine Practice. 33 (1): 127–139. doi:10.1016/j.cveq.2016.11.003. PMID   28190613.
  41. ↑ Kritchevsky JE (July 2019). "Hirsutism Associated with Adenomas of the Pars Intermedia". Merck Vet Manual. Retrieved 24 April 2011.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.