BRAND Diagesic-P (Thioridazine HCl/Paracetamol/Caffeine) 3/500/70 mg logo
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BRAND Diagesic-P (Thioridazine HCl/Paracetamol/Caffeine) 3/500/70 mg

Diagesic-P is used for moderate to severe pain. Contains Dextropropoxyphene HCl 32.5mg, paracetamol 325mg. Dextropropoxyphene, manufactured by Eli Lilly and Company, is an analgesic in the opioid category. It is used to treat mild pain and is additionally an anti-tussive and local anesthetic. Dextropropoxyphene is sometimes combined with acetaminophen or acetylsalicylic acid. Trade-names include Darvocet-N, Diagesic and Di-Gesic Darvon with APAP for dextropropoxyphene and paracetamol and Darvon with ASA for dextropropoxyphene and aspirin. The paracetamol combination(s) are known as Capadex or Di-Gesic in Australia, Lentogesic in South Africa, and Di-Antalvic in France. The paracetamol preparation is known as co-proxamol in the UK, but has been withdrawn since 2007 and is no longer available to new patients.

Indications

Analgesia Dextropropoxyphene, like codeine, is a weak opioid, known to cause dependency among recreational users. Codeine is more commonly used; however, as codeine is, in essence, a prodrug that requires in vivo metabolism to the more active opioid morphine for maximum efficacy, it is ineffective for some individuals with the poor metabolizer genotype of the liver Cytochrome P450 enzyme CYP2D6. It is in people with this low-function isoform of the CYP2D6 gene that dextropropoxyphene is particularly useful, as its metabolism does not require CYP2D6. Restless legs syndrome (RLS) Propoxyphene has been found to be helpful in relieving the symptoms of restless legs syndrome (RLS). Opioid withdrawal In pure form, dextropropoxyphene is commonly used to ease the withdrawal symptoms in people addicted to opioids. Being very weak in comparison to the opioids that are commonly abused, dextropropoxyphene can only act as a partial substitute. It does not have much effect on mental cravings; however it can be effective in alleviating physical withdrawal effects, such as muscle cramps.

Contraindications

Allergy to paracetamol or dextropropoxyphene; alcoholism; combination with amphetamine. Not intended for use in patients who are prone to suicide or addiction.

Toxicity

Darvocet overdose is commonly broken into two categories: liver toxicity (from paracetamol poisoning) and dextropropoxyphene overdose. Many users experience toxic effects from the paracetamol (acetaminophen) in pursuit of the endlessly-increasing dose required for pain relief. They suffer acute liver toxicity, which causes severe stomach pains, nausea, and vomiting (all of which are increased by light or stimulation of the sense of sight). An overdose of dextropropoxyphene may lead to various systemic effects. Excessive opioid receptor stimulation is responsible for the CNS depression, respiratory depression, miosis, and gastrointestinal effects seen in propoxyphene poisoning. It may also account for mood/thought altering effects. In addition, both propoxyphene and its metabolite norpropoxyphene, have local anesthetic effects at concentrations about 10 times those necessary for opioid effects. Norpropoxyphene is a more potent local anesthetic than propoxyphene, and they are both more potent than lidocaine. Local anesthetic activity appears to be responsible for the arrhythmias and cardiovascular depression seen in propoxyphene poisoning. Both propoxyphene and norpropoxyphene are potent blockers of cardiac membrane sodium channels and are more potent than lidocaine, quinidine, and procainamide in this respect. As a result, propoxyphene and norpropoxyphene appear to have the characteristics of a Vaughn-Williams Class Ic antiarrhythmic. These direct cardiac effects include decreased heart rate (i.e. cardiovascular depression), decreased contractility, and decreased electrical conductivity (i.e., increased PR, AH, HV, and QRS intervals). These effects appear to be due to their local anesthetic activity and are not reversed by naloxone. Widening of the QRS complex appears to be a result of a quinidine-like effect of propoxyphene, and sodium bicarbonate therapy appears to have a positive direct effect on the QRS dysrhythmia. Seizures may result from either opioid or local anesthetic effects.Pulmonary edema may result from direct pulmonary toxicity, neurogenic/anoxic effects, or cardiovascular depression.


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