Product Information
Registration Status: ActivePACOFEN TABLET is approved to be sold in Singapore with effective from 1991-07-05. It is marketed by DRUG HOUSES OF AUSTRALIA PTE LTD, with the registration number of SIN06271P.
This product contains Caffeine 30mg,Codeine 8mg, and Paracetamol 500mg in the form of TABLET. It is approved for ORAL use.
This product is manufactured by BEACONS PHARMACEUTICALS PTE. LTD. in SINGAPORE, andSRI KRISHNA PHARMACEUTICALS LTD [Intermediate manufacturer] in INDIA.
It is a Pharmacy Only Medicine that can be obtained from a pharmacist at a retail pharmacy.
Description
A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling.
Indication
For management of fatigue, orthostatic hypotension, and for the short term treatment of apnea of prematurity in infants.
Mechanism of Action
Caffeine stimulates medullary, vagal, vasomotor, and respiratory centers, promoting bradycardia, vasoconstriction, and increased respiratory rate. This action was previously believed to be due primarily to increased intracellular cyclic 3′,5′-adenosine monophosphate (cyclic AMP) following inhibition of phosphodiesterase, the enzyme that degrades cyclic AMP. It is now thought that xanthines such as caffeine act as antagonists at adenosine-receptors within the plasma membrane of virtually every cell. As adenosine acts as an autocoid, inhibiting the release of neurotransmitters from presynaptic sites but augmenting the actions of norepinephrine or angiotensin, antagonism of adenosine receptors promotes neurotransmitter release. This explains the stimulatory effects of caffeine. Blockade of the adenosine A1 receptor in the heart leads to the accelerated, pronounced "pounding" of the heart upon caffeine intake.
Pharmacokinetics
- Absorption
- Readily absorbed after oral or parenteral administration. The peak plasma level for caffeine range from 6-10mg/L and the mean time to reach peak concentration ranged from 30 minutes to 2 hours.
- Distribution
- * 0.8 to 0.9 L/kg [infants] * 0.6 L/kg [adults]
- Metabolism
- Hepatic cytochrome P450 1A2 (CYP 1A2) is involved in caffeine biotransformation. About 80% of a dose of caffeine is metabolized to paraxanthine (1,7-dimethylxanthine), 10% to theobromine (3,7-dimethylxanthine), and 4% to theophylline (1,3-dimethylxanthine).
- Elimination
Toxicity
LD50=127 mg/kg (orally in mice)
Active Ingredient/Synonyms
1-methyltheobromine | 1,3,7-trimethyl-2,6-dioxopurine | 1,3,7-trimethylpurine-2,6-dione | 1,3,7-trimethylxanthine | 3,7-Dihydro-1,3,7-trimethyl-1H-purin-2,6-dion | 7-methyltheophylline | Anhydrous caffeine | Cafeína | Caféine | Caffeinum | Coffein | Coffeinum | Guaranine | Koffein | Mateína | Methyltheobromine | teína | Thein | Theine | Caffeine |
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
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
Acetaminophen, also known as paracetamol, is commonly used for its analgesic and antipyretic effects. Its therapeutic effects are similar to salicylates, but it lacks anti-inflammatory, antiplatelet, and gastric ulcerative effects.
Indication
For temporary relief of fever, minor aches, and pains.
Mechanism of Action
Acetaminophen is thought to act primarily in the CNS, increasing the pain threshold by inhibiting both isoforms of cyclooxygenase, COX-1, COX-2, and COX-3 enzymes involved in prostaglandin (PG) synthesis. Unlike NSAIDs, acetaminophen does not inhibit cyclooxygenase in peripheral tissues and, thus, has no peripheral anti-inflammatory affects. While aspirin acts as an irreversible inhibitor of COX and directly blocks the enzyme's active site, studies have found that acetaminophen indirectly blocks COX, and that this blockade is ineffective in the presence of peroxides. This might explain why acetaminophen is effective in the central nervous system and in endothelial cells but not in platelets and immune cells which have high levels of peroxides. Studies also report data suggesting that acetaminophen selectively blocks a variant of the COX enzyme that is different from the known variants COX-1 and COX-2. This enzyme is now referred to as COX-3. Its exact mechanism of action is still poorly understood, but future research may provide further insight into how it works. The antipyretic properties of acetaminophen are likely due to direct effects on the heat-regulating centres of the hypothalamus resulting in peripheral vasodilation, sweating and hence heat dissipation.
Pharmacokinetics
- Absorption
- Rapid and almost complete
- Distribution
- Metabolism
- Acetaminophen primarily undergoes glucuronidation (45-55% of the dose) in which this process is facilitated by UGT1A1, UGT1A6, UGT1A9, UGT2B15 in the liver or UGT1A10 in the gut. 30-35% of the dose undergoes sulfation. This biotransformation is facilitated by SULT1A1, SULT1A3, SULT1A4, SULT1E1 and SULT2A1. A small percentage of acetaminophen is oxidized by CYP2E1 to form N-acetyl-p-benzo-quinone imine (NAPQI), a toxic metabolite which is then conjugated to glutathione and excreted renally. Studies suggest that CYP3A4 and CYP2E1 are the primary cytochrome P450 isozymes responsible for the generation of toxic metabolites. Accumulation of NAPQI may occur if primary metabolic pathways are saturated.
- Elimination
Toxicity
Oral, mouse: LD50 = 338 mg/kg; Oral, rat: LD50 = 1944 mg/kg. Acetaminophen is metabolized primarily in the liver, where most of it is converted to inactive compounds by conjugation with glucuronic acid and, to a lesser extent, sulfuric acid. Conjugates are then excreted by the kidneys. Only a small portion is excreted in unchanged in urine or oxidized via the hepatic cytochrome P450 enzyme system (CYP2E1). Metabolism via CYP2E1 produces a toxic metabolite, N-acetyl-p-benzoquinoneimine (NAPQI). The toxic effects of acetaminophen are due to NAPQI, not acetaminophen itself nor any of the major metabolites. At therapeutic doses, NAPQI reacts with the sulfhydryl group of glutathione to produce a non-toxic conjugate that is excreted by the kidneys. High doses of acetaminophen may cause glutathione depletion, accumulation of NAPQI and hepatic necrosis. The maximum daily dose of acetaminophen is 4 g. Liver failure has been observed at doses as low as 6 g per day. As such, the maximum daily and single dose of acetaminophen is currently being reviewed in some countries. N-acetyl-cysteine, a precursor of glutathione, may be administered in the event of acetaminophen toxicity.
Active Ingredient/Synonyms
4-(Acetylamino)phenol | 4-acetamidophenol | 4'-hydroxyacetanilide | Acenol | acetaminofén | Acetaminophen | acétaminophène | APAP | N-acetyl-p-aminophenol | p-acetamidophenol | p-acetaminophenol | p-Acetylaminophenol | p-hydroxy-acetanilid | p-hydroxyacetanilide | p-hydroxyphenolacetamide | Paracétamol | Paracetamol | Paracetamolum | Acetaminophen |
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.