Cinchocaine + Hydrocortisone + Framycetin + Esculin

Uses

This is used for the treatment of-

• Internal and external haemorrhoids
• Haemorrhoids post-partum
• Anal pruritus, peri-anal eczema, anal fissures and proctitis
• Post-haemorrhoidectomy application to relieve pain and discomfort

Cinchocaine + Hydrocortisone + Framycetin + Esculin is also used to associated treatment for these conditions: Hemorrhoids, Pruritis of the skin, Pruritus Ani, Skin IrritationAnal Fissures, Anal Fistulas, Hemorrhoids, Proctitis, Pruritus Ani, CryptitisAcute Crusting Rhinitis, Conjunctivitis, Corneal Abrasions, Infection, Skin Infections, Bacterial, Stye, Ulcerative keratitis, Acute rhino-sinusitis, Bacterial blepharitis, Nasal carriage of staphylococciAcute Gouty Arthritis, Acute Otitis Externa, Adrenal Insufficiency, Allergic Rhinitis (AR), Allergic corneal marginal ulcers, Anal Fissures, Ankylosing Spondylitis (AS), Anterior Segment Inflammation, Aspiration Pneumonitis, Asthma, Atopic Dermatitis (AD), Berylliosis, Bullous dermatitis herpetiformis, Chorioretinitis, Choroiditis, Congenital Adrenal Hyperplasia (CAH), Congenital Hypoplastic Anemia, Corneal Inflammation, Crohn's Disease (CD), Dermatitis, Dermatitis exfoliative generalised, Dermatitis, Contact, Dermatomyositis, Dermatosis, Drug hypersensitivity reaction, Epicondylitis, Erythroblastopenia, Hemorrhoids, Herpes Labialis, Hypercalcemia of Malignancy, Idiopathic Thrombocytopenic Purpura, Infection of the Fenestration Cavity, Infection of the Mastoidectomy Cavity, Iridocyclitis, Iritis, Itching caused by Hemorrhoids, Itching of the Anus, Leukemia, Acute, Leukemias, Loeffler's syndrome, Lymphomas NEC, Malignant Lymphomas, Mycosis Fungoides (MF), Ophthalmia, Sympathetic, Optic Neuritis, Pain caused by Hemorrhoids, Pemphigus, Post-traumatic Osteoarthritis, Primary adrenocortical insufficiency, Proctitis, Proteinuria, Psoriatic Arthritis, Rectal inflammations NEC, Rheumatic heart disease, unspecified, Rheumatoid Arthritis, Rheumatoid Arthritis, Juvenile, Seasonal Allergic Conjunctivitis, Secondary adrenocortical insufficiency, Secondary thrombocytopenia, Serum Sickness, Severe Seborrheic Dermatitis, Skin Diseases, Stevens-Johnson Syndrome, Synovitis, Systemic Lupus Erythematosus (SLE), Trichinosis, Tuberculous Meningitis, Ulcerative Colitis, Acquired immune hemolytic anemia, Acute Bursitis, Acute Tenosynovitis, Acute rheumatic carditis, Cryptitis, Disseminated Pulmonary Tuberculosis, Fulminating Pulmonary Tuberculosis, Itching skin, Non-suppurative Thyroiditis, Severe Erythema multiforme, Severe Psoriasis, Subacute Bursitis, Superficial infection of the external auditory canal with inflammation, Symptomatic Sarcoidosis, Systemic Dermatomyositis, Varicella-zoster virus acute retinal necrosis, Palliative

How Cinchocaine + Hydrocortisone + Framycetin + Esculin works

Local anesthetics block both the initiation and conduction of nerve impulses by decreasing the neuronal membrane's permeability to sodium ions through sodium channel inhibition. This reversibly stabilizes the membrane and inhibits depolarization, resulting in the failure of a propagated action potential and subsequent conduction blockade.

The main activities of Esculine focus on capillary protection, as it improves capillary permeability and fragility. It is reported to inhibit catabolic enzymes such as hyaluronidase and collagenase, thus preserving the integrity of the perivascular connective tissue. Esculine also showed good antioxidant properties, protecting triglycerides against auto-oxidation at high temperatures . The antioxidant property might as well explain some of the anti-inflammatory activity of the product, making it a suitable product for after sun treatments, for example.

Framycetin binds to specific 30S-subunit proteins and 16S rRNA, four nucleotides of 16S rRNA and a single amino acid of protein S12. This interferes with decoding site in the vicinity of nucleotide 1400 in 16S rRNA of 30S subunit. This region interacts with the wobble base in the anticodon of tRNA. This leads to interference with the initiation complex, misreading of mRNA so incorrect amino acids are inserted into the polypeptide leading to nonfunctional or toxic peptides and the breakup of polysomes into nonfunctional monosomes.

The short term effects of corticosteroids are decreased vasodilation and permeability of capillaries, as well as decreased leukocyte migration to sites of inflammation.[A187463] Corticosteroids binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple downstream effects over hours to days.[A187463]

Glucocorticoids inhibit neutrophil apoptosis and demargination; they inhibit phospholipase A2, which decreases the formation of arachidonic acid derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote anti-inflammatory genes like interleukin-10.[A187463]

Lower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive.[A187463] High doses of glucocorticoids for an extended period bind to the mineralocorticoid receptor, raising sodium levels and decreasing potassium levels.[A187463]

Dosage

Cinchocaine + Hydrocortisone + Framycetin + Esculin dosage

Ointment: Apply the ointment in a small quantity with the finger, on the painful or pruritic area, morning and evening and after each stool. For deep application, insert the cannula or applicator to full extent and squeeze tube gently from lower end whilst withdrawing.

Suppository: A suppository is inserted morning and evening, and after each stool.

Side Effects

Long-term continuous treatment with topical corticosteroids should be avoided as far as possible as this may cause atrophic changes in the skin leading to thinning, loss of elasticity, dilatation of superficial blood vessels, telangiectasia and ecchymoses. These changes are particularly likely to occur when occlusive dressings are used. Systemic absorption of topically applied corticosteroids may occur, particularly under the following conditions: when large quantities are used or when application is made to wide areas of the body, or to damaged skin; when potent topical corticosteroids are used, and when the occlusive dressing technique is applied. Depression of the hypothalamic-pituitary-adrenal axis with consequent suppression of the adrenal gland may occur. These effects are most likely to be severe in children. Growth may be retarded and a Cushingoid state may be produced. Benign intracranial hypertension has been rarely reported.

Toxicity

Subcutaneous LD₅₀ in rat is 27 mg/kg. Symptoms of overdose include convulsions, hypoxia, acidosis, bradycardia, arrhythmias and cardiac arrest.

Organism : Mouse Test type : LD50 Route: Intraperitoneal Reported dose: 1900mg/kg No reported effects known other than LD50

Data regarding acute overdoses of glucocorticoids are rare. Chronic high doses of glucocorticoids can lead to the development of cataract, glaucoma, hypertension, water retention, hyperlipidemia, peptic ulcer, pancreatitis, myopathy, osteoporosis, mood changes, psychosis, dermal atrophy, allergy, acne, hypertrichosis, immune suppression, decreased resistance to infection, moon face, hyperglycemia, hypocalcemia, hypophosphatemia, metabolic acidosis, growth suppression, and secondary adrenal insufficiency. Overdose may be treated by adjusting the dose or stopping the corticosteroid as well as initiating symptomatic and supportive treatment.

Precaution

Discontinue use if sensitization occurs. Other specific measures against infections, allergy, and other causal factors must not be neglected. The possibility, however rare, that prolonged use of this preparation might produce systemic corticosteroid effects, should be borne in mind. Patients should be advised to inform subsequent physicians of the previous use of hydrocortisone.

Interaction

Co-admin of gramicidin with framycetin reduces the risk of selecting resistant bacteria.

Drug interaction of hydrocortisone has been reported with amphotericin B, potassium-depleting agents, macrolide antibiotics, warfarin, antidiabetics, isoniazid, digitalis glycosides, estrogens, barbiturates, phenytoin, carbamazepine, ketoconazole, aspirin etc.

Volume of Distribution

Total hydrocortisone has a volume of distribution of 39.82L, while the free fraction has a volume of distribution of 474.38L.

Elimination Route

In general, ionized forms (salts) of local anesthetics are not readily absorbed through intact skin. However, both nonionized (bases) and ionized forms of local anesthetics are readily absorbed through traumatized or abraded skin into the systemic circulation.

Rarely, absorbed into the blood stream if used as a combination with other ingredients in suppository form. But, Applying cream or ointment form to open wound or skin may lead this drug to absorb and circulate into blood stream.

Oral hydrocortisone at a dose of 0.2-0.3mg/kg/day reached a mean C_max of 32.69nmol/L with a mean AUC of 90.63h*nmol/L A 0.4-0.6mg/kg/day dose reached a mean C_max of 70.81nmol/L with a mean AUC of 199.11h*nmol/L. However, the pharmacokinetics of hydrocortisone can vary by 10 times from patient to patient.

Topical hydrocortisone cream is 4-19% bioavailable[8546995] with a T_max of 24h.

Hydrocortisone retention enemas are have a bioavailability of 0.810 for slow absorbers and 0.502 in rapid absorbers. Slow absorbers take up hydrocortisone at a rate of 0.361±0.255/h while fast absorbers take up hydrocortisone at a rate of 1.05±0.255/h.

A 20mg IV dose of hydrocortisone has an AUC of 1163±277ng*h/mL.

Half Life

Absorption half life about 1 hour and elimination half life about 20 hours

Total hydrocortisone via the oral route has a half life of 2.15h while the free fraction has a half life of 1.39h. A 20mg IV dose of hydrocortisone has a terminal half life of 1.9±0.4h.

Clearance

Total hydrocortisone by the oral route has a mean clearance of 12.85L/h, while the free fraction has a mean clearance of 235.78L/h. A 20mg IV dose of hydrocortisone has a clearance of 18.2±4.2L/h.

Elimination Route

Corticosteroids are eliminated predominantly in the urine.[A187436] However, data regarding the exact proportion is not readily available.

Pregnancy & Breastfeeding use

The safe use of topical corticosteroids during pregnancy has not been fully established. Therefore, during pregnancy, they should not be used unnecessarily on extended areas, in large amounts or for prolonged periods of time.

Contraindication

Known hypersensitivity to any of the four ingredients. Corticosteroids have been shown to be teratogenic in animals following dermal application. As these agents are absorbed percutaneously, teratogenicity following topical application cannot be excluded. Therefore this product should not be used during pregnancy. Topical corticosteroid preparations are contraindicated in the treatment of herpes simplex, vaccinia or varicella, or tuberculous infection of the anal region.

Special Warning

Use in elderly patients: Clinical studies were not done in patients’ aged 65 and above. In general dose selection for an elderly patients should be cautious, usually starting at the low end of the dosing range.

Storage Condition

Store at a cool and dry place, protected from light. Store below 25° C. Do not freeze.

Innovators Monograph

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