Product Information
Registration Status: ActiveCODIPRONT CAPSULE is approved to be sold in Singapore with effective from 2007-07-30. It is marketed by RX PHARMA PTE LTD, with the registration number of SIN13319P.
This product contains Codeine 30mg, and Phenyltoloxamine 10mg in the form of CAPSULE, EXTENDED-RELEASE. It is approved for ORAL use.
This product is manufactured by CTS Chemical Industries Ltd in ISRAEL.
It is a Pharmacy Only Medicine that can be obtained from a pharmacist at a retail pharmacy.
Description
An opioid analgesic related to morphine but with less potent analgesic properties and mild sedative effects. It also acts centrally to suppress cough.
Indication
For treatment and management of pain (systemic). It is also used as an antidiarrheal and as a cough suppressant.
Mechanism of Action
Opiate receptors are coupled with G-protein receptors and function as both positive and negative regulators of synaptic transmission via G-proteins that activate effector proteins. Binding of the opiate stimulates the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine and noradrenaline is inhibited. Opioids also inhibit the release of vasopressin, somatostatin, insulin and glucagon. Codeine's analgesic activity is, most likely, due to its conversion to morphine. Opioids close N-type voltage-operated calcium channels (OP2-receptor agonist) and open calcium-dependent inwardly rectifying potassium channels (OP3 and OP1 receptor agonist). This results in hyperpolarization and reduced neuronal excitability.
Pharmacokinetics
- Absorption
- Well absorbed following oral administration with a bioavailability of approximately 90%. Maximum plasma concentration occurs 60 minutes post-administration. Food does not effect the rate or extent of absorption of codeine.
- Distribution
- Apparent volume of distribution = 3-6 L/kg
- Metabolism
- Hepatic. Codeine is a prodrug, itself inactive, but demethylated to the active morphine by the liver enzyme CYP2D6 to morphine. 70-80% of the dose undergoes glucuronidation to form codeine-6-glucuronide. This process is mediated by UDP-glucuronosyltransferase UGT2B7 and UGT2B4. 5-10% of the dose undergoes O-demethylation to morphine and 10% undergoes N-demethylation to form norcodeine. CYP2D6 mediates the biotransformation to morphine. CYP3A4 is the enzyme that mediates the conversion to norcodiene. Morphine and norcodeine are further metabolized and undergo glucuronidation. The glucuronide metabolites of morphine are morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G). Both morphine and morphine-6-glucuronide are active and have analgesic activity. Norcodiene and M3G do not have any analgesic properties.
- Elimination
Toxicity
Respiratory depression, sedation and miosis and common symptoms of overdose. Other symptoms include nausea, vomiting, skeletal muscle flaccidity, bradycardia, hypotension, and cool, clammy skin. Apnea and death may ensue.
Active Ingredient/Synonyms
(−)-Codeine | (5alpha,6alpha)-7,8-Didehydro-4,5-epoxy-3-methoxy-17-methylmorphinan-6-ol | (5α,6α)-7,8-didehydro-4,5-epoxy-3-methoxy-17-methylmorphinan-6-ol | 3-Methylmorphin | 3-methylmorphine | 7,8-didehydro-4,5alpha-epoxy-3-methoxy-17-methylmorphinan-6alpha-ol | 7,8-didehydro-4,5α-epoxy-3-methoxy-17-methylmorphinan-6α-ol | Codein | Codeína | Codéine | Codeine anhydrous | Codeine polistirex | Codeinum | L-Codeine | Methylmorphine | morphine 3-methyl ether | Morphine monomethyl ether | morphine monomethyl ether | morphine-3-methyl ether | O(3)-methylmorphine | Codeine |
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.
Description
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 [A32705]. Nevertheless, phenyltoloxamine is used to a fairly limited extent in contemporary medicine, with only very few products involving it as an active ingredient.
Indication
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 [L2499]; 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 [L2495].
Mechanism of Action
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 [L2508]. 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 [L2508]. Moreover, lowering calcium ion concentration leads to increased mast cell stability which reduces further histamine release [L2508]. 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 [L2508]. 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 [L2508]. Furthermore, although some studies propose that phenyltoloxamine may possess some intrinsic antispasmodic and distinct local anesthetic properties [A32713], 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 [A32708, A32709], there are also studies that observed no potentiating effects associated with phenyltoloxamine use either [A32712].
Pharmacokinetics
- Absorption
- 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 [A32705].
- Distribution
- 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 [A32705].
- Metabolism
- Readily accessible data regarding the metabolism 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 [A32705].
- Elimination
Clearance
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 [A32705].
Toxicity
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 [A32705].
Active Ingredient/Synonyms
Feniltoloxamina | Phenyltoloxaminum | Phenyltoloxamine |
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.