Propoxyphene effects

Levopropoxyphene [2338-37-6] (42), the optical antipode of the dextrorotatory analgetic propoxyphene, is an antitussive without analgetic activity. The 2-naphthalenesulfonate salt has a less unpleasant taste than the hydrochloride salt, and is widely used. Clinical effectiveness has been demonstrated against pathological and artificially induced cough, but the potency is somewhat less than codeine. The compound is reported not to cause addiction. Levopropoxyphene can be prepared (62) by first resolving [ -dimethylamino-CX-methylpropiophenone with dibenzoyl-(+)-tartaric acid. The resolved... 

Few studies have explored the efficacy of opioids specifically for OA. The APS recommends against the use of codeine and propoxyphene for OA because of the high incidence of adverse effects and limited analgesic effectiveness. Oxycodone is the most extensively studied of the agents recommended for OA. However, other narcotic analgesics such as morphine, hydromorphone, methadone, and transdermal fentanyl are also effective. 

Opposite enantiomer may cause different effects (+)-Propoxyphene (2S,3R)... 

There are also known cases of drug enantiomers that possess completely different therapeutic properties. The (+)-2/ ,35 -stereoisomer of propoxyphene (dextropropoxyphene) is marketed as an analgesic agent, whereas its enantiomer ( )-(25, 3/ )-propoxyphene (levopropoxyphene) is available as an effective anti-tussive agent [3]. The enantiomers of some chiral drugs are known to possess essentially identical qualitative and quantitative pharmacological activities, for example, the antihistamine promethazine, which is marketed as a racemate [5]. 

Propoxyphene (Darvon ) is a stronger analgesic but has no antipyretic effects. It is sometimes taken in combination with aspirin and... 

The following are examples of substances that may increase the blood glucose-lowering effect and susceptibility to hypoglycemia oral antidiabetic products, ACE inhibitors, disopyramide, fibrates, fluoxetine, MAO inhibitors, pentoxifylline, propoxyphene, salicylates, and sulfonamide antibiotics. 

The opioids block cough by a mechanism that is not yet understood. No stereoselectivity of the opioids for blockade of the cough reflex has been shown. Thus, the isomers of opioids, such as dextrorphan, are as efficacious as the L-isomers as antitussives. This lack of stereoselectivity prompted the development of the D-isomers of opioids as antitussives since they are devoid of the dependence liability of h-isomers. Drugs with predominantly antitussive effects are described later in this chapter. Certain of the opioids, such as propoxyphene and meperidine, are relatively devoid of antitussive effects. 

Propoxyphene interacts with several drugs. The use of sedatives in combination with propoxyphene can be fatal. In addition, the metabolism of the drug is increased in smokers due to induction of liver enzymes. Thus, smokers may require a higher dose of the drug for pain relief. Propoxyphene enhances the effects of both warfarin and carbamazepine and may increase the toxicity associated with both drugs, such as bleeding and sedation, respectively. 

The patient who uses propoxyphene repeatedly may develop a tolerance to the drug s analgesic effect and physical dependence. 

The risk of tachycardia, hypertension, and cardiotoxicity is increased with coadministration of dronabinol (an antiemetic) and dextroamphetamine. In addition, administration of dextroamphetamine with MAOIs may increase the risk of hypertensive crisis. Al-kalinizing agents can speed absorption (e.g., antacids) or delay urinary excretion (e.g., acetazolamide, thiazide diuretics) of dextroamphetamine, thus potentiating its effects. Gastric or urinary acidifying agents (e.g., ascorbic acid, ammonium chloride) can decrease the effects of dextroamphetamine. Propoxyphene overdose can potentiate amphetamine central nervous system stimulation, potentially resulting in fatal convulsions. 

It is dextro isomer of propoxyphene which is an analgesic and possesses antitussive property. It has low analgesic activity even half of codeine. It is metabolized in Uver. Side effects include vomiting, epigastric distress and sedation. The demethylated metabolite of propoxyphene is cardiotoxic. It is used in the treatment of mild type of pain. 

Propoxyphene is chemically related to methadone but has low analgesic activity. Various studies have reported its potency at levels ranging from no better than placebo to half as potent as codeine that is, 120 mg propoxyphene = 60 mg codeine. Its true potency probably lies somewhere between these extremes, and its analgesic effect is additive to that of an optimal dose of aspirin or acetaminophen. However, its low efficacy makes it unsuitable, even in combination with aspirin, for severe pain. The increasing incidence of deaths associated with its use and misuse has caused it to be scheduled as a controlled substance. Moreover, banning its use in the United States is under consideration. 

Naloxone Narcotic drugs, other opioid derivatives A specific antagonist of opioids 1-2 mg initially by IV, IM, or subcutaneous injection. Larger doses may be needed to reverse the effects of overdose with propoxyphene, codeine, or fentanyl derivatives. Duration of action (2-3 hours) may be significantly shorter than that of the opioid being antagonized. 

Among the compounds that fall within this class are hydrocodone (e.g., Vicodin), oxycodone (e.g., OxyContin—an oral, controlled-release form of the drug), morphine, fentanyl, codeine, and related medications. Morphine and fentanyl are often used to alleviate severe pain, while codeine is used for milder pain. Other examples of opioids prescribed to relieve pain include propoxyphene (Darvon) hydromorphone (Dilaudid) and meperidine (Demerol), which is used less often because of its side effects. In addition to their effective pain-relieving properties, some of these medications can be used to relieve severe diarrhea (for example, Lomotil, also known as diphenoxylate) or severe coughs (codeine). 

Synergism - a potentiation or prolongation which results in much greater than expected effects. This could involve competitive substrates for an enzyme or receptor, decreased excretion, displaced plasma protein binding, etc. The analgesic propoxyphene (Darvon ) slows down the excretion of ethanol and so increases the depressant effects of the alcohol. Recall the example given earlier of the monoamine oxidase inhibitors used as antidepressants and the tyramine-containing foods which could precipitate a hypertensive crisis. 

Propoxyphene (Schedule II) is another opiate prescribed for pain which is much weaker than those mentioned above. Notice the structural similarities to methadone. Its effects last longer than many other drugs in this class which means it can be taken less frequently and the potential of abuse will be lessened. It can also be formulated with aspirin or acetaminophen in order to have a summation effect. 

Lopinavir/Ritonavir (Kaletra) [Anrirelroviral/Protease Inhibitor] Uses HIV Infxn Action Protease inhibitor Dose Adults. Tx naive 2 tab PO daily or 1 tab PO bid Tx experiencedpt 1 tab PO bid (T dose if w/ amprenavir, efavirenz, fosamprenavir, nelfinavir, nevirapine) Peds. 7-15 kg 12/3 mg/kg PO bid 15-40 kg 10/2.5 mg/kg PO bid >40 kg Adult dose w/ food Caution [C, /-] Numerous interactions Contra w/drugs dependent on CYP3A/CYP2D6 (Table VI-8) Disp Tab, soln SE Avoid disulfiram (soln has EtOH), metronidazole GI upset, asthenia, T cholesterol/triglycerides, pancreatitis protease metabolic synd Interactions T Effects Wl clarithromycin, erythromycin T effects OF amiodarone, amprenavir, azole andfungals, bepridil, cisapride, cyclosporine, CCBs, ergot alkaloids, flecainide, flurazepam, HMG-CoA reductase inhibitors, indinavir, lidocaine, meperidine, midazolam, pimozide, propafenone, propoxyphene, quinidine, rifabutin, saquinavir, sildenafil, tacrolimus, terfenadine, triazolam, zolpidem 1 effects Wl barbiturates, carbamazepine, dexamethasone, didanosine, efavirenz, nevirapine, phenytoin, rifabutin, rifampin, St. John s wort 1 effects OF OCPs, warfarin EMS Use andarrhythmics and benzodiazepines... 

T effects OF amiodarone, astemizole, atorvastadn, barbiturates, bepridil, bupropion, cerivastatin, cisapride, clorazepate, clozapine, clarithromycin, desipramine, diazepam, encainide, ergot alkaloids, estazolam, flecainide, flurazepam, indinavir, ketoconazole, lovastatin, meperidine, midazolam, nelfinavir, phenytoin, pimozide, piroxicam, propafenone, propoxyphene, quinidine, rifabutin, saquinavir, sildenafil, simvastatin, SSRIs, TCAs, terfenadine, triazolam, troleandomycin, zolpidem X effects W/ barbiturates, carbamazepine, phenytoin, rifabutin, rifampin, St. John s wort, tobacco X effects OF didanosine, hypnotics, methadone, OCPs, sedatives, theophylline, warfarin EMS T Effects of amiodarone, diazepam, midazolam and BBs, may need X- doses concurrent use of Viagra-type drugs can lead to hypotension X- effects of warfarin concurrent EtOH use can T adverse effects T glucose ODs May cause an extension of adverse SEs symptomatic and supportive Rivasrigmine (Exelon) [Cholinesterase Inhibitor/Anri ... 

Zacny, J.P. and Goldman, R.E., Characterizing the subjective, psychomotor, and physiological effects of oral propoxyphene in non-dmg-abusing volunteers, Drug Alcohol Depend., 73, 133, 2004. 

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