C-hist-sr
C-hist-sr Uses, Dosage, Side Effects, Food Interaction and all others data.
Chlorpheniramine is an alkylamine antihistamine. It is one of the most potent H1 blocking agents and is generally effective in relatively low doses. Chlorpheniramine is not so prone to produce drowsiness, readily absorbed from the gastro-intestinal tract, metabolised in the liver and excreted usually mainly as metabolised in the urine.
In allergic reactions an allergen interacts with and cross-links surface IgE antibodies on mast cells and basophils. Once the mast cell-antibody-antigen complex is formed, a complex series of events occurs that eventually leads to cell-degranulation and the release of histamine (and other chemical mediators) from the mast cell or basophil. Once released, histamine can react with local or widespread tissues through histamine receptors. Histamine, acting on H1-receptors, produces pruritis, vasodilatation, hypotension, flushing, headache, tachycardia, and bronchoconstriction. Histamine also increases vascular permeability and potentiates pain. Chlorpheniramine, is a histamine H1 antagonist (or more correctly, an inverse histamine agonist) of the alkylamine class. It competes with histamine for the normal H1-receptor sites on effector cells of the gastrointestinal tract, blood vessels and respiratory tract. It provides effective, temporary relief of sneezing, watery and itchy eyes, and runny nose due to hay fever and other upper respiratory allergies.
Phenylephrine is an alpha-1 adrenergic receptor agonist used to treat hypotension, dilate the pupil, and induce local vasoconstriction. The action of phenylephrine, or neo-synephrine, was first described in literature in the 1930s.
Phenylephrine was granted FDA approval in 1939.
Phenylephrine is an alpha-1 adrenergic agonist that raises blood pressure, dilates the pupils, and causes local vasoconstriction. Ophthalmic formulations of phenylephrine act for 3-8 hours while intravenous solutions have an effective half life of 5 minutes and an elimination half life of 2.5 hours. Patients taking ophthalmic formulations of phenylephrine should be counselled about the risk of arrhythmia, hypertension, and rebound miosis. Patients taking an intravenous formulation should be counselled regarding the risk of bradycardia, allergic reactions, extravasation causing necrosis or tissue sloughing, and the concomitant use of oxytocic drugs.
Phenyltoloxamine is an antihistamine drug with sedative and analgesic effects. It is a H1 receptor blocker and a member of the ethanolamine class of antihistaminergic drugs. It is available in combination products that also contain other analgesics and antitussives such as acetaminophen. Phenyltoloxamine citrate is the more common salt form that acts as an active ingredient in pharmaceutical products and promotes hay fever relief via reversing the effects of histamine. Phenyltoloxamine acts as an adjuvant analgesic, which augments the analgesic effect of acetaminophen. It also potentiates the effects of other drugs, such as codeine and codeine derivatives.
Although phenyltoloxamine's ability to potentiate the effects of analgesics may be explained in part by its chemical nature as a first-generation H1 antihistamine that is capable of crossing the blood-brain barrier and causing tranquilizing effects at CNS histamine receptors, many of the drug's specific pharmacokinetics are not readily available - perhaps also because many early (phenyltoloxamine was involved in studies as early as the 1950s) first-generation antihistamines were not optimally investigated . Nevertheless, phenyltoloxamine is used to a fairly limited extent in contemporary medicine, with only very few products involving it as an active ingredient.
As a member of the first generation H1 antihistamines, it is known that phenyltoloxamine - like virtually all first generation H1 antihistamines - has a propensity for crossing the blood-brain barrier and acting on H1 histamine receptors there to interfere with neurotransmission . The most common results of this kind of first generation H1 antihistamine CNS neurotransmission interference are adverse effects like drowsiness, sedation, somnolence, and fatigue . Given these effects, under specific circumstances like a patient experiencing a pain or a cough that may be preoccupying all of their waking energy and attention, it is perhaps possible that the sedative and tranquilizing characteristics of phenyltoloxamine may be the factors that contribute to its apparent adjunctive analgesic and antitussive actions .
| Trade Name | C-hist-sr |
| Generic | Chlorpheniramine + phenylephrine + phenyltoloxamine |
| Weight | 2.5mg + 5mg + 7.5mg/5ml, 4mg + 20mg + 40mg |
| Type | Oral liquid, oral tablet, extended release |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Indicated mainly in allergic conditions including urticaria, sensitivity reactions, angioneurotic oedema, seasonal hay fever, vasomotor rhinitis, cough, common cold, motion sickness.
Phenylephrine is an alpha-1 adrenergic agonist used in the management of hypotension, generally in the surgical setting associated with the use of anesthetics.
Phenylephrine injections are indicated to treat hypotension caused by shock or anesthesia, an ophthalmic formulation is indicated to dilate pupils and induce vasoconstriction, an intranasal formulation is used to treat congestion, and a topical formulation is used to treat hemorrhoids. Off-label uses include situations that require local blood flow restriction such as the treatment of priapism.
Phenyltoloxamine is a medication used to treat minor aches and pains.
The primary therapeutic use for which phenyltoloxamine is currently indicated is as an adjuvant therapy in various combination products containing an analgesic(s) (either narcotic or non-narcotic), where it is expected to potentiate the pain relieving, anti-tussive, etc. effect(s) of the analgesic component of the product.
In that regard, some of these aforementioned combination products are typically indicated for the temporary relief of minor aches and pains like headache, muscular aches, backaches, minor arthritis pain, common cold, toothaches, menstrual cramps, etc ; or perhaps for the treatment of exhausting or non-productive cough, associated with cold or with upper respiratory allergic condition that does not respond to non-narcotic antitussives .
C-hist-sr is also used to associated treatment for these conditions: Allergic Contact Dermatitis, Allergic Reaction, Allergic Rhinitis (AR), Allergic cough, Allergies, Allergies caused by Serum, Allergy to House Dust, Allergy to vaccine, Angioneurotic Edema, Asthma, Bronchial Asthma, Bronchitis, Common Cold, Conjunctival congestion, Conjunctivitis, Conjunctivitis allergic, Cough, Cough caused by Common Cold, Coughing caused by Flu caused by Influenza, Drug Allergy, Eye allergy, Fever, Flu caused by Influenza, Food Allergy, Headache, Headache caused by Allergies, Itching of the nose, Itching of the throat, Migraine, Nasal Congestion, Nasal Congestion caused by Common Cold, Pollen Allergy, Productive cough, Pruritus, Rash, Rhinorrhoea, Seasonal Allergic Conjunctivitis, Sinus Congestion, Sinusitis, Sneezing, Transfusion Reactions, Upper Respiratory Tract Infection, Upper respiratory tract hypersensitivity reaction, site unspecified, Urticaria, Vasomotor Rhinitis, Acute Rhinitis, Allergic purpura, Conjunctival hyperemia, Dry cough, Excess mucus or phlegm, Itchy throat, Mild bacterial upper respiratory tract infections, Ocular hyperemia, Throat inflammation, Upper airway congestion, Upper respiratory symptoms, Watery eyes, Watery itchy eyes, Airway secretion clearance therapyAllergic Rhinitis (AR), Anorectal discomfort, Cold, Common Cold, Common Cold/Flu, Congestion of the Conjunctivas, Conjunctivitis allergic, Cough, Cough caused by Common Cold, Eye allergy, Eye redness, Fever, Flu caused by Influenza, Headache, Headache caused by Allergies, Headache caused by Common Cold, Headache caused by Pollen Allergy, Hemorrhoids, Hypotension, Irritative cough, Itching of the nose, Itching of the throat, Laryngotracheitis, Nasal Congestion, Nose discomfort, Ocular Inflammation, Ocular Irritation, Paroxysmal Supraventricular Tachycardia, Pollen Allergy, Respiratory tract congestion, Respiratory tract irritation, Rhinopharyngitis, Rhinorrhoea, Seasonal Allergies, Shock, Cardiogenic, Sinus Congestion, Sinus pressure, Sinusitis, Sneezing, Sore Throat, Tracheobronchitis, Upper respiratory tract hypersensitivity reaction, site unspecified, Vasomotor Rhinitis, Aching caused by Flu caused by Influenza, Bronchial congestion, Itchy throat, Minor aches and pains, Watery itchy eyes, Airway secretion clearance therapy, Antihistamine, Dilatation of the pupil, Vasoconstrictor in regional analgesia therapyBronchitis, Cough, Minor aches and pains, Airway secretion clearance therapy
How C-hist-sr works
Chlorpheniramine binds to the histamine H1 receptor. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on by histamine.
Phenylephrine is an alpha-1 adrenergic agonist that mediates vasoconstriction and mydriasis depending on the route and location of administration. Systemic exposure to phenylephrine also leads to agonism of alpha-1 adrenergic receptors, raising systolic and diastolic pressure as well as peripheral vascular resistance. Increased blood pressure stimulates the vagus nerve, causing reflex bradycardia.
As a first-generation H1 antihistamine, phenyltoloxamine interferes with the agonist activity of histamine at the H1 receptor and are ostensibly used to attenuate inflammatory processes as a means to treat conditions like allergic rhinitis, allergic conjunctivitis, and urticaria . Reduction of the activity of the NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells) immune response transcription factor via the phospholipase C and phosphatidylinositol (PIP2) signaling pathways also serves to decrease antigen presentation and the expression of pro-inflammatory cytokines, cell adhesion molecules, and chemotactic factors . Moreover, lowering calcium ion concentration leads to increased mast cell stability which reduces further histamine release .
Additionally, first-generation antihistamines like phenyltoloxamine readily cross the blood-brain barrier and cause sedation and other adverse central nervous system (CNS) effects, like nervousness and insomnia . By comparison, second-generation antihistamines are more selective for H1 receptors in the peripheral nervous system and do not cross the blood-brain barrier, resulting in fewer adverse drug effects overall .
Furthermore, although some studies propose that phenyltoloxamine may possess some intrinsic antispasmodic and distinct local anesthetic properties , the specific mechanisms of action for these effects have not been formalized. Also, even though the combination of phenyltoloxamine's ability to cross the blood-brain barrier and cause various tranquilizing effects may explain to some extent how it may be able to potentiate analgesic effects , there are also studies that observed no potentiating effects associated with phenyltoloxamine use either .
Dosage
C-hist-sr dosage
Adults: 4 mg 3-4 times daily.
Children:
- Up to 1( one) year: 1 mg twice daily
- 1-5 years: 1 mg 3-4 times daily
- 6-12 years: 2 mg 3-4 times daily or as directed by the physician
Side Effects
Drowsiness, dizziness, headache, psychomotor impairment, urinary retention, dry mouth, blurred vision and gastro intestinal disturbances, paradoxical stimulation may rarely occur, especially in high dosage or in children.
Toxicity
Oral LD50 (rat): 306 mg/kg; Oral LD50 (mice): 130 mg/kg; Oral LD50 (guinea pig): 198 mg/kg [Registry of Toxic Effects of Chemical Substances. Ed. D. Sweet, US Dept. of Health & Human Services: Cincinatti, 2010.] Also a mild reproductive toxin to women of childbearing age.
Patients experiencing and overdose may present with headache, hypertension, reflex bradycardia, tingling limbs, cardiac arrhythmias, and a feeling of fullness in the head. Overdose may be treated by supportive care and discontinuing phenylephrine, chronotropic medications, and vasodilators. Subcutaneous phentolamine may be used to treat tissue extravasation.
Toxicity after overdose may involve CNS effects like extreme drowsiness, lethargy, confusion, delirium, and coma in adults; paradoxical excitation, irritability, hyperactivity, insomnia, hallucinations, seizures, and respiratory depression or arrest in infants and young children, CNS adverse effects predominate o er cardiac adverse effects; death may occur within hours after ingestion of drug in untreated patients; rhabdomyolysis has also been reported .
Precaution
Chlorpheniramine may produce mild sedation and it is advised that patients under continuous treatment should avoid operating machinery. Not recommended during pregnancy & lactation.
Interaction
Alcohol, CNS depressants, anticholinergic drugs, MAOIs.
Volume of Distribution
The volume of distribution of phenylephrine is 340L.
Readily accessible data regarding the volume of distribution of phenyltoloxamine is not available. In fact, many first-generation H1 antihistamines have never had their pharmacokinetics (ie. absorption, distribution, metabolism, and elimination) optimally investigated .
Elimination Route
Well absorbed in the gastrointestinal tract.
Phenylephrine is 38% orally bioavailable. Clinically significant systemic absorption of ophthalmic formulations is possible, especially at higher strengths and when the cornea is damaged.
Readily accessible data regarding the absorption of phenyltoloxamine is not available. In fact, many first-generation H1 antihistamines have never had their pharmacokinetics (ie. absorption, distribution, metabolism, and elimination) optimally investigated .
Half Life
21-27 hours
Intravenous phenylephrine has an effective half life of 5 minutes and an elimination half life of 2.5 hours.
Readily accessible data regarding the half-life of phenyltoloxamine is not available. In fact, many first-generation H1 antihistamines have never had their pharmacokinetics (ie. absorption, distribution, metabolism, and elimination) optimally investigated .
Clearance
Phenylephrine has an average clearance of 2100mL/min.
Readily accessible data regarding the clearance of phenyltoloxamine is not available. In fact, many first-generation H1 antihistamines have never had their pharmacokinetics (ie. absorption, distribution, metabolism, and elimination) optimally investigated .
Elimination Route
86% of a dose of phenylephrine is recovered in the urine with 16% as the unmetabolized drug, 57% as the inactive meta-hydroxymendelic acid, and 8% as inactive sulfate conjugates.
Readily accessible data regarding the primary route of elimination of phenyltoloxamine is not available. In fact, many first-generation H1 antihistamines have never had their pharmacokinetics (ie. absorption, distribution, metabolism, and elimination) optimally investigated .
Pregnancy & Breastfeeding use
Pregnancy Category B. Either animal-reproduction studies have not demonstrated a foetal risk but there are no controlled studies in pregnant women or animal-reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the 1st trimester (and there is no evidence of a risk in later trimesters).
Contraindication
There is no definite contraindication to therapy. It should be used with caution in epilepsy, prostatic hypertrophy, glaucoma and hepatic disease. The ability to drive or operate machinery may be impaired.
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