DIPHENHYDRAMINE EXPECTORANT

Ammonium Chloride
Diphenhydramine
Sodium Citrate

Source of information: Drugbank (External Link). Last updated on: 3rd July 18
*Trade Name used in the content below may not be the same as the HSA-registered product.

Active Ingredient / Synonyms

Ammonium chloride | Ammonium chloride |

Description

Ammonium chloride is an inorganic compound with the formula NH4Cl and a white crystalline salt that is highly soluble in water. Solutions of ammonium chloride are mildly acidic.

Indication

1. Expectorant in cough syrups. 2. The ammonium ion (NH4+) in the body plays an important role in the maintenance of acid-base balance. The kidney uses ammonium (NH4+) in place of sodium (Na+) to combine with fixed anions in maintaining acid-base balance, especially as a homeostatic compensatory mechanism in metabolic acidosis. The therapeutic effects of Ammonium Chloride depend upon the ability of the kidney to utilize ammonia in the excretion of an excess of fixed anions and the conversion of ammonia to urea by the liver, thereby liberating hydrogen (H+) and chloride (Cl–) ions into the extracellular fluid. Ammonium Chloride Injection, USP, after dilution in isotonic sodium chloride injection, may be indicated in the treatment of patients with: (1) hypochloremic states and (2) metabolic alkalosis.

Mechanism of Action

1. Increases acidity by increasing the amount of hydrogen ion concentrations. 2. Ammonium chloride is used as an expectorant in cough medicine. Its expectorant action is caused by irritative action on the bronchial mucosa, which causes the production of excess respiratory tract fluid and make it easier to cough it up.

Pharmacodynamics

Systemic acidifier. In liver ammonium chloride is converted into urea with the liberation of hydrogen ions ( which lowers the pH) and chloride.

Pharmacokinetics

Absorption:

Completely absorbed within 3–6 h. In healthy persons, absorption of ammonium chloride given by mouth was practically complete. Only 1 to 3% of the dose was recovered in the feces.

Distribution:

Data not found.

Metabolism:

Ammonium ion is converted to urea in the liver; chloride ion replaces bicarbonate.

Elimination:

Excretion: Urine

Half-life

Unknown

Clearance

Data not found.

Toxicity

LD50 "Rat" after oral administration is: 1650 mg/kg. Overdosage of Ammonium Chloride has resulted in a serious degree of metabolic acidosis, disorientation, confusion and coma. If metabolic acidosis occur following overdosage, the administration of an alkalinizing solution such as sodium bicarbonate or sodium lactate will serve to correct the acidosis. Patients administering Ammonium chloride should be watched to the signs of ammonia toxicity including (pallor, sweating, irregular breathing, bradycardia, cardiac arrhythmias, local and general twitching, tonic convulsions and coma). It should be used with caution in patients with high total CO2 and buffer base secondary to primary respiratory acidosis. Intravenous administration should be slow to avoid local irritation and toxic effects.

Source of information: Drugbank (External Link). Last updated on: 3rd July 18
*Trade Name used in the content below may not be the same as the HSA-registered product.

Active Ingredient / Synonyms

(O-Benzhydryl(dimethylamino)ethanol) 8-chlorotheophyllinate | 8-chloro-1,3-Dimethyl-3,7-dihydro-1H-purine-2,6-dione - 2-(diphenylmethoxy)-N,N-dimethylethanamine (1:1) | Benzhydryl-beta-dimethylaminoethylether 8-chlorotheophylline | beta-Dimethylaminoethyl benzhydryl ether 1,3-dimethyl-8-chloroxanthine | Dimenhidrinato | Dimenhydrinatum | Diphenhydramine 8-chlorotheophyllinate | Diphenhydramine 8-chlorotheophylline | Diphenhydramine theoclate | Diphenhydrinate | N,N-Dimethyl-2-diphenylmethoxyethylamine 8-chlorotheophyllinate | O-Benzhydryldimethylaminoethanol 8-chlorotheophyllinate | Dimenhydrinate |

Description

Dimenhydrinate, also known as Dramamine or Gravol, is an over-the-counter drug used to prevent nausea, vomiting, and dizziness caused by motion sickness. Dimenhydrinate is a combination drug composed of [DB01075] and [DB14132] in a salt form, with 53%-55.5% of diphenhydramine, and not less than 44%-47% of 8-chlorotheophylline, calculated on the dried basis. The antiemetic properties of dimenhydrinate are primarily thought to be produced by diphenhydramine's antagonism of H1 histamine receptors in the vestibular system [A1540] while the excitatory effects are thought to be produced by 8-chlorotheophylline's adenosine receptor blockade [A33889]. The addition of 8-chlorotheophylline was initially intended to counteract the sedative effects of diphenhydramine. When used in large doses, dimenhydrinate has been shown to cause a "high" characterized by hallucinations, excitement, incoordination, and disorientation [A1539].

Indication

Dimenhydrinate is indicated for the prevention and treatment of nausea, vomiting, or vertigo of motion sickness.

Mechanism of Action

The mechanism by which some antihistamines exert their antiemetic, anti-motion sickness, and anti-vertigo effects is not precisely known but may be related to their central anticholinergic actions. They diminish vestibular stimulation and depress labyrinthine function. An action on the medullary chemoreceptive trigger zone may also be involved in the antiemetic effect. Dimenhydrinate is a competitive antagonist at the histamine H1 receptor, which is widely distributed in the human brain. Dimenhydrinate's anti-emetic effect is probably due to H1 antagonism in the vestibular system in the brain.

Pharmacodynamics

Dimenhydrinate is an antiemetics drug combination that contains diphenhydramine and theophylline. It is not effective in the treatment of nausea associated with cancer chemotherapy. Dimenhydrinate directly inhibits the stimulation of certain nerves in the brain and inner ear to suppress nausea, vomiting, dizziness, and vertigo. Diphenhydramine and dimenhydinate both reduce vestibular neuronal excitation due to angular or linear acceleration motions.

Pharmacokinetics

Absorption:

Well absorbed after oral administration.

Distribution:

Not Available

Metabolism:

Hepatic (cytochrome P-450 system).

Elimination:

Not Available

Half-life

1 to 4 hours

Clearance

Not Available

Toxicity

Symptoms of overdose include delerium, hallucinations, and excitment. Patients may be violent and confused.

Source of information: Drugbank (External Link). Last updated on: 3rd July 18
*Trade Name used in the content below may not be the same as the HSA-registered product.

Active Ingredient / Synonyms

Sodium citrate anhydrous | Sodium citrate, anhydrous | trisodium citrate anhydrous | Trisodium citrate, anhydrous | Sodium Citrate |

Description

Sodium citrate is the sodium salt of citric acid. It is white, crystalline powder or white, granular crystals, slightly deliquescent in moist air, freely soluble in water, practically insoluble in alcohol. Like citric acid, it has a sour taste. From the medical point of view, it is used as alkalinizing agent. It works by neutralizing excess acid in the blood and urine. It has been indicated for the treatment of metabolic acidosis.

Indication

Used as an anticoagulant during plasmophoresis as well as a neutralizing agent in the treatment of upset stomach and acidic urine [FDA Label] [L788] [L789].

Mechanism of Action

Citrate chelates free calcium ions preventing them from forming a complex with tissue factor and coagulation factor VIIa to promote the activation of coagulation factor X [A19410] [A19411]. This inhibits the extrinsic initiation of the coagulation cascade. Citrate may also exert an anticoagulant effect via a so far unknown mechanism as restoration of calcium concentration does not fully reverse the effect of citrate [A19410]. Citrate is a weak base and so reacts with hydrochloric acid in the stomach to raise the pH. It it further metabolized to bicarbonate which then acts as a systemic alkalizing agent, raising the pH of the blood and urine [L790]. It also acts as a diuretic and increases the urinary excretion of calcium.

Pharmacodynamics

Citrate prevents activation of the clotting cascade by chelating calcium ions. Citrate neutralizes acid in the stomach and urine, raising the pH [L790].

Pharmacokinetics

Absorption:

Tmax of 98-130min [A19414].

Distribution:

19-39L [A19414].

Metabolism:

Citrate is metabolized to bicarbonate in the liver and plays a role as an intermediate in the citric acid cycle [A19419] [L795].

Elimination:

Largely eliminated through hepatic metabolism with very little cleared by the kidneys [A19414] [A19415].

Half-life

18-54 min [A19414]

Clearance

Total clearance of 313-1107mL/min [A19414].

Toxicity

Overdose toxicity is mainly due to alkalosis as well as tetany or depressed heart function due to lack of free calcium [L790].

References

  1. Health Science Authority of Singapore - Reclassified POM
  2. Drugbank

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Approval Information

DIPHENHYDRAMINE EXPECTORANT was registered with Health Science Authority of Singapore by DRUG HOUSES OF AUSTRALIA PTE LTD. It is marketed with the registration number of SIN00004P with effective from 1987-10-16.

This product contains 125mg/5ml of Ammonium Chloride, 10mg/5ml of Diphenhydramine, and 50mg/5ml of Sodium Citrate in the form of SOLUTION.

The medicine was manufactured by DRUG HOUSES OF AUSTRALIA PTE LTD in SINGAPORE

It is a Pharmacy Only Medicine which can be obtained from a pharmacist at a retail pharmacy.

Anatomical Therapeutic Chemical (ATC) Classification

ATC Code: R05FB01

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407TRIMAXAZOLE TABLETSulfamethoxazole|TrimethoprimPOMBEACONS PHARMACEUTICALS PTE LTDActive
435APO-SULFATRIM TABLETSulfamethoxazole|TrimethoprimPOMPHARMAFORTE SINGAPORE PTE LTDActive
508APO-SULFATRIM PEDIATRIC TABLETSulfamethoxazole|TrimethoprimPOMPHARMAFORTE SINGAPORE PTE LTDActive
526B.S. SUSPENSIONSulfamethoxazole|TrimethoprimPOMAPEX PHARMA MARKETING PTE LTDActive
583CO-TRIMEXAZOLE SUSPENSIONSulfamethoxazole|TrimethoprimPOMBEACONS PHARMACEUTICALS PTE LTDActive
676BANEOCIN OINTMENTBacitracin|NeomycinPOMNOVARTIS (SINGAPORE) PTE LTDActive
678BANEOCIN POWDERBacitracin|NeomycinPOMNOVARTIS (SINGAPORE) PTE LTDActive