Morphine Chlorpromazine

Much of the beneht in solubihty enhancement from salt formation is attributable to the change in solution pH caused by the presence of the counterion. This occurs because the ionization and solubility of acidic drugs (such as barbiturates and non-steroidal anti-inflammatory drugs) increases in basic conditions but decreases in acidic conditions. This behavior is exemplified by derivations of the Henderson-Hasselbalch equations (37.2) and (37.3). The opposite situation occurs for basic drugs such as chlorpromazine, morphine and codeine, which are more soluble in acidic conditions. 

CRF activity in a log-dose response relationship idien assayed in rats treated with chlorpromazine, morphine and Nembutal (CPZ-M-N). 

Hill, H. F., Bell, E. C., and Wilder, A. (1967) Reduction of conditioned suppression Actions of morphine compared with those of amphetamine, pentobarbital, nalorphine, cocaine, LSD-25, and chlorpromazine. Arch. Int. Pharmacodyn., 165 212-225. 

Many drugsbromides, morphine, cocaine, hashish, marijuana, mescaline, scopolamine, di-isopropyl fluorophosphate, ACTH, pervitin, sodium amytal, lysergic acid, reserpine and chlorpromazine are known to have marked effects on the mental processes of the individuals who receive them. These effects are varied and cannot be discussed here. Suffice it to say that some drugs produce symptoms which resemble those observed in mental disease others work in the opposite direction. There can be no doubt that enzyme systems are... 

It is interesting to note that one of the founders of modern psychiatry, Kraepelin, listed only nine substances that were available for the treatment of psychiatric illness in the 1890s. These were opium, morphine, scopolamine, hashish, chloral hydrate, a barbiturate, alcohol, chloroform and various bromides. Later Bleuler, another founder of modern psychiatry, added paraldehyde and sodium barbitone to the list. Thus psychopharmacology is a very recent area of medicine which largely arose from the chance discovery of chlorpromazine by Delay and Deniker in France in 1952, and of imipramine by Kuhn in Switzerland in 1957. 

Fig. 4.3 CSF concentration/free (unbound) plasma concentration ratios for neutral and basic drugs 1, ritropirronium 2, atenolol 3, sulpiride 4, morphine 5, cimetidine 6, meto-prolol 7, atropine 8, tacrine 9, digoxin 10, propranolol 11, carbamazepine 12, ondansetron 13, diazepam 14, imipramine 15, digitonin 16, chlorpromazine and acidic drugs, a, salicylic acid b, ketoprofen c, oxyphenbutazone and d, indomethacin compared to log D.

Morphine and other opioids exhibit intense sedative effects and increased respiratory depression when combined with other sedatives, such as alcohol or barbiturates. Increased sedation and toxicity are observed when morphine is administered in combination with the psychotropic drugs, such as chlorpromazine and monoamine oxidase inhibitors, or the anxiolytics, such as diazepam. 

When the pharmacologic properties of two compounds are compared, one may prove to be more potent and efficacious than the other. For instance, as an analgesic, morphine is more potent and more efficacious than acetylsalicylic acid. On the other hand, two compounds may be equally efficacious but one could be more potent. Haloperidol and chlorpromazine are both efficacious neuroleptics in the management of schizophrenia, but haloperidol is more potent. 

Morphine Sulfate Morphine sulfate precipitates in alkaline media and drugs that are incompatible with it, including aminophylline, sodium salts of barbiturates, and phenytoin. Precipitate was found after 2 horns when morphine sulfate was formulated with acyclovir sodium.70 Incompatibilities also are reported with chlorpromazine hydrochloride injections containing chlorocresol. Admixture of morphine sulfate (1 mg/mL), doxorubicin in doxorubicin hydrochloride... 

Ratio of lethal dose to effective dose for morphine (an opioid, Chapter 14), chlorpromazine (a neuroleptic, Chapter 13), and the anxiolytic, hypnotic drugs, phenobarbital and diazepam. 

Drugs that are known to be substrates of P-gp include antihistamines (e.g. terfenadine), digoxin, ciclosporin, hydrocortisone and other steroids and drugs used in chemotherapy (e.g. paclitaxel, vinblastine). Ciclosporin, in addition to being a substrate of P-gp, is also an inhibitor of P-gp. Drugs known to induce P-gp include morphine, dexamethasone, phenobarbital, rifampin and St John s wort. Inhibitors of P-gp include amiodarone, amitriptyline, atorvastatin, chlorpromazine, ciclosporin, erythromycin, fluphenazine, haloperidol, quinidine, ritonavir and verapamil,... 

Apomorphine (— black), azatadine, benorylate, bisacodyl, buprenorphine, butriptyline, captodiame, chloro-pyrilene, chlorpromazine, clofazimine, codeine, diamorphine, diethylthiambutene, dihydrocodeine, dimeth-indene blue), dimethoxanate, doxorubicin, doxylamine, ethopropazine, ethoxazene, guaiphenesin, guanoxan, hexocyclium methylsulphate, mepyramine, 6-monoacetylmorphine, morphine, nalorphine, nor-morphine, oxprenolol, oxyphenisatin, pecazine, penthienate, perazine, perphenazine, phenoxybenzamine, phenyltoloxamine, pholcodine, pimozide, pipoxolan (-> grey), prochlorperazine, procyclidine, promazine, promethazine, proquamezine, solanidine, thenium, thiopropazate, tricyclamol, trimeprazine, viloxazine... 

Drugs, such as morphine, reserpine, and chlorpromazine, which are used for premedication can also cause an increased secretion of ACTH (El, V2). The stimulatory effects of these drugs can last for many hours. 

Klein applied gas chromatography. 3-0-acetylmorphine results from an incomplete esterification of morphine with acetic anhydride and the amount may be of value for forensic purposes. Because of the very small amounts present in heroin, the compound was derivatized with hepta-fluorobutyric anhydride and gas chromatographed with a Ni electron capture detector on a 3 1 OV-17 on Gas Chrom Q packed column at 230°C using chlorpromazine as an internal standard. The heptafluorobutyric anhydride derivatives were extracted quantitatively from the reaction mixture with light petroleum and were stable for several hours in this solvent. However, it was recommended that upon formation, the analysis should be completed without delay. The analysis was carried out with 1-10 mg heroin samples and the amount of 3-0-acetylmorphine varied from 0.1 to 2 %, acetylcodeine from 3 to 15, morphine and codeine from 0.01 to 0.5. ... 

Full agonists morphine, meperidine, methadone, fentanyl, and heroin Partial agonists buprenorphine, codeine, propoxyphene Mixed agonist-antagonists nalbuphine, pentazocine Antagonists naloxone, naltrexone Phenothiazines chlorpromazine, fluphenazine, thioridazine Others haloperidol, clozapine, risperidone, olanzapine... 

Chlorpromazine increases the respiratory-depressant effects of meperidine, as do tricyclic antidepressants this is not true of diazepam. Concurrent administration of drugs such as promethazine or chlorpromazine also may greatly enhance meperidine-induced sedation without slowing clearance of the drug. Treatment with phenobar-bital or phenytoin increases systemic clearance and decreases oral bioavailability of meperidine this is associated with an elevation of the concentration of normeperidine in plasma. As with morphine, concomitant administration of an amphetamine has been reported to enhance the analgesic effects of meperidine and its congeners while counteracting sedation. 

The effects of morphine-like drugs and chlorpromazine on the synthesis of glycerolipids by homogenates of rat liver Sanderson, Robert F. Dodds, Peter F. Brindley, David N. 

In examining the early inflammatory reaction after the implantation of pellets of plastic sponge in the rat, Saxena measured exudate formation and leucocytic infiltration. The cellular infiltration was significandy decreased by the CNS depressants morphine, pentobarbitone, meprobamate and chlorpromazine hydrochloride promethazine hydrochloride is ineffective. The extent to which this may be a direct metabolic effect of the drugs is not clear since the phagocytic activity of circulating leucocytes is decreased by chlorpromazine . 

Also analyzed acebutolol, acepromazine, acetaminophen, acetazolamide, acetophenazine, albuterol, amitriptyline, amobarbital, amoxapine, antipsrrine, atenolol, atropine, azata-dine, baclofen, benzocaine, bromocriptine, brompheniramine, brotizolam, bupivacaine, buspirone, butabarbital, butalbital, caffeine, carbamazepine, cetirizine, chlorqyclizine, chlordiazepoxide, chlormezanone, chloroquine, chlorpheniramine, chlorpromazine, chlorpropamide, chlorprothixene, chlorthalidone, chlorzoxazone, cimetidine, cisapride, clomipramine, clonazepam, clonidine, clozapine, cocaine, codeine, colchicine, qyclizine, (yclo-benzaprine, dantrolene, desipramine, diazepam, diclofenac, diflunisal, diltiazem, diphenhydramine, diphenidol, dipheno late, dipyridamole, disopyramide, dobutamine, doxapram, doxepin, droperidol, encainide, ethidium bromide, ethopropazine, fenoprofen, fentanyl, flavoxate, fluoxetine, fluphenazine, flurazepam, flurbiprofen, fluvoxamine, fii-rosemide, glutethimide, glyburide, guaifenesin, haloperidol, homatropine, hydralazine, hydrochlorothiazide, hydrocodone, hydromorphone, hydro g chloroquine, hydroxyzine, ibuprofen, imipramine, indomethacin, ketoconazole, ketoprofen, ketorolac, labetalol, le-vorphanol, lidocaine, loratadine, lorazepam, lovastatin, loxapine, mazindol, mefenamic acid, meperidine, mephenytoin, mepivacaine, mesoridazine, metaproterenol, methadone, methdilazine, methocarbamol, methotrexate, methotrimeprazine, methoxamine, methyl-dopa, methylphenidate, metoclopramide, metolazone, metoprolol, metronidazole, midazolam, moclobemide, morphine, nadolol, nalbuphine, naloxone, naphazoline, naproxen, nifedipine, nizatidine, norepinephrine, nortriptyline, oxazepam, oxycodone, oxymetazo-line, paroxetine, pemoline, pentazocine, pentobarbital, pentoxifylline, perphenazine, pheniramine, phenobarbital, phenol, phenolphthalein, phentolamine, phenylbutazone, phenyltoloxamine, phenytoin, pimozide, pindolol, piroxicam, pramoxine, prazepam, prazosin, probenecid, procainamide, procaine, prochlorperazine, procyclidine, promazine, promethazine, propafenone, propantheline, propiomazine, propofol, propranolol, protriptyline, quazepam, quinidine, quinine, racemethorphan, ranitidine, remoxipride, risperidone, salicylic acid, scopolamine, secobarbital, sertraline, sotalol, spironolactone, sulfinpyrazone, sulindac, temazepam, terbutaline, terfenadine, tetracaine, theophylline, thiethyl-perazine, thiopental, thioridazine, thiothixene, timolol, tocainide, tolbutamide, tolmetin, trazodone, triamterene, triazolam, trifluoperazine, triflupromazine, trimeprazine, trimethoprim, trimipramine, verapamil, warfarin, xylometazoline, yohimbine, zopiclone... 

---