ratio-Calmydone
ratio-Calmydone Uses, Dosage, Side Effects, Food Interaction and all others data.
Doxylamine is a first-generation antihistamine. It can be used by itself as a short-term sedative and in combination with other drugs to provide night-time allergy and cold relief. Doxylamine is also used in combination with the analgesics paracetamol (acetaminophen) and codeine as an analgesic/calmative preparation, and is prescribed in combination with vitamin B6 (pyridoxine) to prevent morning sickness in pregnant women.
Doxylamine is an antihistamine derived from monoethanolamine possessing antimuscarinic and pronounced sedative effects.
Doxylamine is an antihistamine commonly used as a sleep aid. This drug is also used to relieve symptoms of hay fever (allergic rhinitis), hives (rash or itching), and other allergic reactions. Doxylamine is a member of the ethanolamine class of antihistamines and has anti-allergy power far superior to virtually every other antihistamine on the market, with the exception of diphenhydramine (Benadryl). It is also the most powerful over-the-counter sedative available in the United States, and more sedating than many prescription hypnotics. In a study, it was found to be superior to even the barbiturate, phenobarbital for use as a sedative. Doxylamine is also a potent anticholinergic.
Etafedrine (INN) or ethylephedrine is a long-acting bronchodilator and has been an ingredient combined with other drugs in the brand names Nethaprin and Dalmacol . It was previously available as both the free base and as the hydrochloride salt manufactured by Sanofi-Aventis (now Sanofi) has been discontinued .
Ethylephedrine is be formed by alkylating ephedrine with ethyl iodide. The hydrochloride is be prepared by passing hydrogen chloride through a solution of ethylephedrine in diethyl ether .
This belongs to the family of medications called decongestants. It acts by narrowing blood vessels in the nasal passages, helping to relieve nasal congestion .
Hydrocodone is a synthetic opioid derivative of codeine. It is commonly used in combination with acetaminophen to control moderate to severe pain. Historically, hydrocodone has been used as a cough suppressant although this has largely been replaced by dextromethorphan in current cough and cold formulations. Hydrocodone's more potent metabolite, hydromorphone has also found wide use as an analgesic and is frequently used in cases of severe pain. The FDA first approved Hydrocodone for use as part of the cough suppressant syrup Hycodan in March of 1943.
Hydrocodone inhibits pain signaling in both the spinal cord and brain . Its actions in the brain also produce euphoria, respiratory depression, and sedation.
| Trade Name | ratio-Calmydone |
| Generic | etafedrine + doxylamine + hydrocodone |
| Type | |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | Canada, United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Doxylamine is used for Hypersensitivity reactions, Insomnia
Etafedrine is a beta-2 adrenoceptor agonist used to treat a cough associated with inflamed mucosa.
Conditions characterized by bronchial congestion and bronchospasm when an expectorant or bronchodilator action is required, such as acute bronchitis, acute episodes of chronic bronchitis and bronchial asthma , .
Hydrocodone is an opioid agonist used as an analgesic and antitussive agent.
Hydrocodone is indicated for the management of acute pain, sometimes in combination with acetaminophen or ibuprofen, as well as the symptomatic treatment of the common cold and allergic rhinitis in combination with decongestants, antihistamines, and expectorants.
ratio-Calmydone is also used to associated treatment for these conditions: Common Cold, Flu Symptoms, Insomnia, Mild Allergic Rhinitis, Nausea, VomitingAsthma, Bronchospasm, Chronic Bronchitis, Bronchial congestionCough, Cough caused by Allergic Rhinitis, Cough caused by Common Cold, Nasal Congestion caused by Allergic Rhinitis, Nasal Congestion caused by Common Cold, Pain, Acute, Pain, Chronic, Rhinitis caused by Common Cold, Severe Pain, Moderate Pain, Upper respiratory symptoms caused by Allergic Rhinitis, Upper respiratory symptoms caused by Common Cold
How ratio-Calmydone works
Like other antihistamines, doxylamine acts by competitively inhibiting histamine at H1 receptors. It also has substantial sedative and anticholinergic effects.
A sympathomimetic agent, etafedrine acts on the sympathetic receptors of the bronchial tree, relieving spasm in a manner similar to that of ephedrine .
Etafedrine acts as a selective β adrenoreceptor agonist, thereby mediating its bronchodilator effects without increasing norepinephrine release . This is distinctly different from ephedrine and tyramine which trigger the release of epinephrine or norepinephrine.
N-ethylation of ephedrine suppresses the indirect sympathomimetic activity and markedly enhances the efficacy on beta 2- adrenoceptors .
Hydrocodone binds to the mu opioid receptor (MOR) with the highest affinity followed by the delta opioid receptors (DOR). Hydrocodone's agonist effect at the MOR is considered to contribute the most to its analgesic effects. Both MOR and DOR are Gi/o coupled and and produces its signal through activation of inward rectifier potassium (GIRK) channels, inhibition of voltage gated calcium channel opening, and decreased adenylyl cyclase activity. In the dorsal horn of the spinal cord, activation of pre-synaptic MOR on primary afferents the inhibition of calcium channel opening and increased activity of GIRK channels hyperpolarizes the neuron and prevents release of neurotransmitters. Post-synaptic MOR can also prevent activation of neurons by glutamate through the aforementioned mechanisms.
Hydrocodone can also produce several actions in the brain similarly to other opioids. Activation of MOR in the periaquaductal gray (PAG) inhibits the GABAergic tone on medulo-spinal neurons. This allows these neurons, which project to the dorsal horn of the spinal cord, to suppress pain signalling in secondary afferents by activating inhibitory interneurons. MOR can also inhibit GABAergic neurons in the ventral tegmental area, removing the inhibitory tone on dopaminergic neurons in the nucleus accumbens and contributing to the activation of the brain's reward and addiction pathway. The inhibitory action or MOR likely contributes to respiratory depression, sedation, and suppression of the cough reflex.
Activation of DOR may contribute to analgesia through the above mechanisms but has not been well studied.
Dosage
ratio-Calmydone dosage
Hypersensitivity reactionn: 25 mg every 4-6 hr. Max: 150 mg daily.
Insomnia: 25 mg given 30 minutes before retiring at night.
Should be taken with food. Take with food or milk.
Side Effects
Acute dystonic reactions and long-lasting impaired consciousness in child. CNS depression including slight drowsiness to deep sleep, lassitude, dizziness, incoordination. Headache, psychomotor impairment and antimuscarinic effects. Rarely rashes and hypersensitivity reactions, blood disorders, convulsions, sweating, myalgia, extrapyramidal effects, tremor, confusion, tinnitus, hypotension, hair loss.
Toxicity
Signs of overdose include wheezing, tightness in the chest, fever, itching, bad cough, blue skin color, fits, swelling of face, lips, tongue, or throat.
This drug is a sympathomimetic, and therefore has the following adverse effects (in parallel with ephedrine) : tremor, fear, anxiety, confusion, irritability, insomnia, and psychotic states. Paranoid psychosis, delusions, and hallucinations may also follow overdose .
The adverse effects of ephedrine and similar drugs are believed to be related to coronary artery constriction, vasospasm, shortening of cardiac refractory periods allowing re-entrant cardiac arrhythmias, hypertension-induced subarachnoid hemorrhage, cerebral artery vasoconstriction as well as sympathomimetic-induced platelet activation .
Overdosage with hydrocodone presents as opioid intoxication including respiratory depression, somnolence, coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, pulmonary edema, bradycardia, hypotension, partial or complete airway obstruction, atypical snoring, and death.
In case of oversdosage the foremost priority is the maintenance of a patent and protected airway with the provision of assisted ventilation if necessary. Supportive measures such as IV fluids, supplemental oxygen, and vasopressors may be used to manage circulatory shock. Advanced life support may be necessary in the case of cardiac arrest or arrhythmias. Opioid antagonists such as naloxone may be used to reverse the respiratory and circulatory effects of hydrocodone. Emergency monitoring is still required after naloxone administration as the opioid effects may reappear. Additionally, if used in an opioid tolerant patient, naloxone may produce opioid withdrawal symptoms.
Precaution
May impair ability to drive and operate machinery. Angle-closure galucoma, urinary retention, prostatic hypertrophy or pyloroduodenal obstruction; epilepsy; hepatic impairment. Elderly. Lactation.
Interaction
Enhance effects of CNS depressants eg alcohol, barbiturates, hypnotics, opioid analgesics, anxiolytic sedatives and antipsychotics. Atropine, TCAs, MAOIs. Can mask signs of ototoxicity caused by aminoglycosides.
Volume of Distribution
Similar to ephedrine, at about 3L/kg .
The apparent volume of distribution ranges widely in published literature. The official FDA labeling reports a value of 402 L. Pharmacokinetic studies report values from 210-714 L with higher values associated with higher doses or single dose studies and lower values associated with lower doses and multiple dose studies. Hydrocodone has been observed in human breast milk at levels equivalent to 1.6% of the maternal dosage. Only 12 of the 30 women studied had detectable concentrations of hydromorphone at mean levels of 0.3 mcg/kg/day.
Elimination Route
Readily absorbed via the gastrointestinal tract.
Similar to its parent drug, ephedrine, it is readily and completely absorbed from the gastrointestinal tract; plasma peak concentrations are reached an hour after ingestion .
A single oral dose of 24 mg produced an average peak plasma concentration of 0.10 mg/L .
The absolute bioavailability of hydrocodone has not been characterized due to lack of an IV formulation. The liquid formulations of hydrocodone have a Tmax of 0.83-1.33 h. The extended release tablet formulations have a Tmax of 14-16 h. The Cmax remains dose proportional over the range of 2.5-10 mg in liquid formulations and 20-120 mg in extended release formulations. Administration with food increases Cmax by about 27% while Tmax and AUC remain the same. Administration with 40% ethanol has been observed to increase Cmax 2-fold with an approximate 20% increase in AUC with no change in Tmax. 20% alcohol produces no significant effect.
Half Life
10 hours
It has a plasma half-life ranging from 3 to 6 hours depending on urinary pH .
The half-life of elimination reported for hydrocodone is 7-9 h.
Clearance
Official FDA labeling reports an apparent clearance of 83 L/h. Pharmacokinetic studies report values ranging from 24.5-58.8 L/h largely dependent on CYP2D6 metabolizer status.
Elimination Route
Excreted mainly in the urine .
Most hydrocodone appears to be eliminated via a non-renal route as renal clearance is substantially lower than total apparent clearance. Hepatic metabolism may account for a portion of this, however the slight increase in serum concentration and AUC seen in hepatic impairment indicates a different primary route of elimination.
Pregnancy & Breastfeeding use
Category A: Controlled studies in women fail to demonstrate a risk to the fetus in the 1st trimester (and there is no evidence of a risk in later trimesters), and the possibility of fetal harm remains remote.
Contraindication
Severe liver disease; avoid alcohol; premature infants or full-term neonates.
Storage Condition
Store at 15-30°C.
Innovators Monograph
You find simplified version here ratio-Calmydone
