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Cardiac decompensation following verapamil ther- apy in infants with supraventricular tachycardia order tenormin 100mg without a prescription. Acute conversion of paroxysmal supraventricular tachycardia with intravenous diltiazem buy tenormin 100mg cheap. The addition of these agents reduces early acute rejection events and may improve long-term graft and patient outcomes tenormin 50 mg line. The most controversial issue is whether corticos- teroids should be routinely added to form a “triple therapy. Finally, there is no agreement on whether intravenous anti- body induction therapy should be routinely used. A summary of the options for induction and maintenance therapy is shown in Table 8-1. It should be noted that there have been no large-scale randomized controlled tri- als of any immunosuppressive therapy in pediatric thoracic transplantation. Corticosteroids (Methylprednisolone and Prednisone) Indication Corticosteroids have broad immunosuppressive and anti-inflammatory effects. Many pediatric heart transplant centers are using steroid-avoidance regimens or early steroid withdrawal to avoid the many side effects and complications associated with long-term steroid use in children. High-dose steroids remain the standard therapy for treatment of acute rejection episodes. Mechanism of Action Corticosteroids decrease inflammation through the suppression of the migration of polymorphonuclear leukocytes and the reversal of increased 8. Corticosteroids prevent immune activation by inhibiting antigen presentation, cytokine production, and proliferation of lymphocytes. Some centers use moderate-dose oral steroids for less severe episodes of acute rejection (e. Maintenance Therapy Those centers that use long-term maintenance therapy typically use prednisone in doses of 0. Webber prednisone indefinitely, whereas others wean to discontinuation in the first few months if the rejection history is benign. Increasing evidence suggests that complete steroid avoidance beyond the intraoperative period is possible in many children, especially infants. Pharmacokinetics The peak and duration are dependent on the route of administration of the drug. Oral: peak effect occurs within 1 to 2 hours, and the duration is 30 to 36 hours Intramuscular: peak effect is 4 to 8 days, and the duration is 1 to 4 weeks Corticosteroids are metabolized in the liver to inactive glucuronide and sulfate metabolites. Monitoring Parameters Blood pressure, weight, height, serum electrolytes, and glucose should be monitored. Phenytoin, phenobarbital, and rifampin increase clearance of methylpred- nisolone; potassium-depleting diuretics (furosemide) enhance potassium depletion. Permanent diabetes mellitus may be precipitated when corticosteroids are used in combination with cyclosporine or tacrolimus. Cyclosporine was the most commonly used agent 5 years ago, but, currently, almost half of pediatric heart transplant recipients are receiving tacrolimus. Cyclosporine and tacrolimus have not been compared in large randomized tri- als in children after transplantation of thoracic organs. One small (26 children), single-center randomized trial in pediatric heart transplantation has been per- formed but was not powered to identify differences between immunosuppres- sive regimens. In the presence of intracellular calcium and calmodulin, the cyclosporine-cyclo- philin complex binds to an active site on calcineurin. Webber Dosing The oral dosage for cyclosporine is approximately three times the I. The bioavailability of Sandimmune® capsules and the oral solution are equivalent, and the bioavailability of the oral solution is approximately 30% of the I. Currently, almost all children receive microemulsion formulations, which have more predictable bioavailability. The bioavailability of Neoral® capsules and the oral solution are equivalent, 43% in children, ranging from 30 to 68%. Cyclosporine is metabolized to a lesser extent by the gastroin- testinal tract and kidneys, and clearance is affected by age. The half-life of cyclosporine is 7 to 19 hours in children and 19 to 40 hours in adults. Metabolites are excreted primarily through the bile into feces; approximately 6% of cyclosporine is eliminated in the urine, with 0. Sandim- mune® oral solution may be diluted with milk, chocolate milk, or orange juice. Mix cyclosporine in a glass con- tainer and rinse the container with more diluent to ensure that the total dose is taken. However, many transplant cent- ers administer cyclosporine as divided doses (2–3 doses/day) or as a 24-hour continuous infusion. Patients should be under continuous observation for at least the first 30 minutes of the infusion, and should be monitored frequently thereafter. Pediatric Heart Transplantation 195 Monitoring Parameters Blood/serum drug concentration (trough), renal and hepatic function, serum electrolytes, lipid profile, blood pressure, and heart rate should be monitored. Reference Range The reference range of target serum trough concentrations depends on the time after transplantation. Typically, it is 300ng/mL in the first few weeks, 200ng/ mL over subsequent months, and 100 to 150ng/mL during long-term follow- up. Trough levels should be obtained 12 hours after oral dose (chronic usage), 12 hours after intermittent I. When central venous administration is used, peripheral venipuncture, capillary pin prick, or a double-lumen catheter should be used to draw blood samples for therapeutic drug monitoring. Drug-Drug Interactions Acyclovir, aminoglycosides, diclofenac, amphotericin B, erythromycin, and metoclopramide increase cyclosporine absorption. Ketoconazole, fluconazole, erythromycin, diltiazem, verapamil, and meth- ylprednisolone increase cyclosporine concentration by inhibiting hepatic metabolism. Phenytoin, phenobarbital, carbamazepine, primidone, rifampin, trimetho- prim, and nafcillin decrease cyclosporine concentration by increasing hepatic metabolism. Prednisolone, digoxin, and lovastatin may undergo reduced clearance when used with cyclosporine.
House of Commons Home Affairs Select Committee The government’s drugs policy: is it working? Jaffe J & O’Keeffe C (2003) From morphine clinics to buprenorphine; regulating opioid antagonist treatment of addiction in the United States generic 100mg tenormin with mastercard. Haasen C order 100mg tenormin, Verthein U & Degkwitz P (2007) Heroin-assisted treatment for opioid dependence: randomised controlled trial discount tenormin 50mg overnight delivery. National Institute for Health and Clinical Excellence (2007) Methadone and buprenorphine for the management of opioid dependence. Her Majesty’s Government (2010) Drug strategy 2010: reducing demand, restricting supply, building recovery: supporting people to live a drug free life. Robins L (1993) Vietnam veterans rapid recovery from heroin addiction: a fluke, or normal expectation? Recovery Orientated Drug Treatment Group, National Treatment Agency for Substance Misuse (2012) Medications in recovery. Hubbard R, Marsden M, Rachel J et al (1989) Drug abuse treatment: a national study of effectiveness. Bell J, Dru A, Fischer B et al (2002) Substitution therapy for heroin addiction Substance Use and Misuse 37: 1145-74. Romelsjö A, Engdahl B, Stenbacka M et al (2010) Were the changes to Sweden’s maintenance treatment policy 2000-06 related to changes in opiate-related mortality and morbidity? De Maeyer J, Vanderplasschen W & Broekaert E (2010) Quality of life among opiate-dependent individuals: a review of the literature. Moffatt S, Weatherburn D & Donnelly N (2005) What caused the recent drop in property crime? Rosenbaum M (1985) A matter of style: variation among methadone clinics in the control of clients. General Accounting Office (1990) Methadone maintenance: some treatment programs are not effective; greater federal oversight needed. Report to the chairman, Select Committee on Narcotic Abuse and Control, House of Representatives. De Maeyer J, Vanderplasschen W, Camfield L et al (2011) A good quality of life under the influence of methadone: a qualitative study among opiate-dependent individuals. Bell J, Chan J & Kuk A (1995) Investigating the effect of treatment philosophy on outcome of methadone maintenance. Bell J, Butler B, Lawrance A et al (2009) Comparing overdose mortality associated with methadone and buprenorphine treatment. Bell J, Shanahan M, Mutch C et al (2007) A randomised trial of effectiveness and cost effectiveness of observed versus unobserved administration of buprenorphine-naloxone for heroin dependence. Barau K, Thirion X, Micallef J et al (2001) Comparison of methadone and high dosage buprenorphine users in French care centres. Auriacombe M, Fatséas M, Dubernet J et al (2004) French field experience with buprenorphine. Amato L, Minozzi S, Davoli M et al (2011) Psychosocial combined with agonist maintenance treatments versus agonist maintenance treatments alone for treatment of opioid dependence. Gossop M, Stewart D, Browne N et al (2003) Methadone treatment for opiate dependent patients in general practice and specialist clinic settings: outcomes at 2-year follow-up. Taylor D, Paton C & Kapur S (2009) The Maudsley prescribing guidelines in psychiatry (10e). National Institute for Health and Clinical Excellence (2011) Alcohol dependence and harmful alcohol use. Minozzi S, Amato L, Vecchi S et al (2011) Oral naltrexone maintenance treatment for opioid dependence. Volume 1: A study of effectiveness and financing of public and private drug treatment systems. Strang J, Manning V, Mayet S et al (2007) Does prescribing for opiate addiction change after national guidelines? Methadone and buprenorphine prescribing to opiate addicts by general practitioners and hospital doctors in England 1995-2005. Marsden J, Eastwood B, Bradbury C et al (2009) Effectiveness of community treatments for heroin and crack cocaine addiction in England: a prospective, in-treatment cohort study. Bell J, Trinh L, Butler B et al (2009) Comparing retention in treatment and mortality in people after initial entry to methadone and buprenorphine treatment. Bell J, Butler B, Lawrance A et al (2009) Comparing overdose mortality associated with methadone and buprenorphine treatment. Strang J, Griffiths P, Powis B et al (1999) Which drugs cause overdose among opiate misusers? Zador D & Sunjic S (2000) Deaths in methadone maintenance treatment in New South Wales, Australia 1990-1995. Williams A, Reed K, Groshkova T et al (2010) Training family members and carers of opiate users in overdose management and naloxone administration: a randomised trial. Strang J, Darke S, Hall W et al (1996) Heroin overdose: the case for take-home naloxone? Neale J, Tompkins C & Sheard L (2008) Barriers to accessing generic health and social care services: a qualitative study of injecting drug users. Barnaby B, Drummond C, McCloud A et al (2003) Substance misuse in psychiatric inpatients: comparison of a screening questionnaire survey with case notes. Kouimtsidis C, Reynolds M, Hunt M et al (2003) Substance use in the general hospital. Ryrie I & Ford C (2001) The primary care treatment of drug users: is shared care really the best approach? McCambridge J & Strang J (2004) The efficacy of single-session motivational interviewing in reducing drug consumption and perceptions of drug-related risk and harm among young people: results from a multi-site cluster randomized trial. Marijuana Treatment Project Research Group (2004) Brief treatments for cannabis dependence: findings from a randomized multisite trial. National Institute for Health and Clinical Excellence (2007) Drug misuse: opioid detoxification. Bell J (2010) The global diversion of pharmaceutical drugs: opiate treatment and the diversion of pharmaceutical opiates: a clinician’s perspective. Blackwell J (1988) The saboteurs of Britain’s opiate policy: overprescribing physicians or American-style ‘junkies’? National Institute for Health and Clinical Excellence (2011) Anxiety: management of anxiety (panic disorder, with or without agoraphobia, and generalised anxiety disorder) in adults in primary, secondary and community care. Sikdar S (1998) Physical dependence on zopiclone: prescribing this drug to addicts may give rise to iatrogenic drug misuse.
When sink conditions occur 100 mg tenormin for sale, it ensures that a large concentration gradient is maintained throughout the absorption phase buy 100mg tenormin with amex, thereby enhancing the driving-force for absorption tenormin 50mg on-line. In active absorption, carriers may transport substrates against a concentration gradient, in an energy- consuming process. This form of transport may occur through “dynamic pores”, consisting of proteins or protein systems which span the plasma membrane. Alternatively, the proteins may be located on the apical surface of the membrane and active absorption is associated with a series of steps: 1 The substrate forms a complex with the carrier in the membrane surface. The major substances that are believed to be actively transported across membranes are sodium and calcium ions. Absorption of many molecules occurs by co- transport, a variation of active transport in which absorption into the cell against the concentration gradient is linked to the secretion of a cellular ion such as sodium down its concentration gradient. This process is important for the absorption of glucose and amino acids in the small intestine. The small intestine contains a wide variety of transporters (amino acid transporters, oligopeptide transporters, glucose transporters, lactic acid transporters etc. On the basolateral membrane, the presence of amino acid and oligopeptide transporters has been demonstrated. Active transport mechanisms for di- and tri-peptides have also been demonstrated in the nasal and buccal epithelia. Facilitated diffusion involves carrier-mediated transport down a concentration gradient. The existence of the carrier molecules means that diffusion down the concentration gradient is much greater than would be expected on the basis of the physicochemical properties of the drug. A much larger number of substances are believed to be transported by facilitated diffusion than active transport, including vitamins such as thiamine, nicotinic acid, riboflavin and vitamin B6, various sugars and amino acids. Both processes exhibit classical saturation kinetics, since there are only a finite number of carrier molecules. Thus unlike passive absorption (paracellular or transcellular), where the rate of transport is directly proportional to the drug concentration (Figure 1. At higher concentrations, the carrier mechanism becomes saturated and the rate of absorption remains constant (Figure 1. If a drug is sufficiently similar to a substance naturally transported by a carrier-mediated system, the drug may also be transported by the same system. For example, the drugs levodopa, methyldopa and 15 penicillamine are all absorbed via various amino acid transporters. Serine and threonine derivatives of nitrogen mustard, which have been investigated for antitumor activity, are also absorbed by a carrier- mediated process. Digitalis and other cardioselective glycosides also demonstrate behavior not compatible with simple partition theory, which suggests the involvement of carrier-mediated transport. Considerable attention is being focused on the identification of the structural requirements necessary for the binding and transport via the di- and tri-peptide transporters present in the gastrointestinal tract, in order to exploit this route for the oral delivery of peptides. Critical structural features that have been found to influence transport include stereoisomerism, side-chain length and net charge. Several drugs including a pGlu-L-dopa prodrug, as well as angiotensin-converting enzyme inhibitors and various thrombin inhibitors, have all demonstrated success in targeting endogenous transporters and enhancing transport across the intestinal mucosa. Endocytic processes All the above transport mechanisms are only applicable to the absorption of small molecules, less than approximately 500 Da. There is evidence that larger molecules can be absorbed with low efficiency due to endocytosis. Endocytosis is defined as the internalization of plasma membrane with concomitant engulfment of extracellular material and extracellular fluid. Pinocytosis is a non-specific process that goes on continually in all cell types, in which the plasma membrane invaginates and forms an inward channel, into which extracellular fluid flows (Figure 1. Solutes dissolved in the extracellular fluid, including large (soluble) macromolecules, may flow with the extracellular fluid into the invaginations and become internalized. Alternatively, uptake may involve: • adsorptive pinocytosis, in which macromolecules bind to non-specific membrane receptors, prior to pinocytosis; • receptor-mediated pinocytosis, in which macromolecules bind to specific membrane receptors, prior to pinocytosis. The pinocytic vesicles (endosomes) migrate inwardly and fuse with lysosomes, which contain many lyosomal enzymes, to form secondary lyosomes. The ligand is degraded by the lysosomal enzymes, the degraded products are released and the membrane is recycled back to the plasma membrane. Alternatively, the secondary lysosomes can fuse with the cell membrane, leading to exocytosis of their contents, and the membranes are recycled back to the plasma membrane. Thus pinocytosis offers a pathway through which large macromolecules, which are otherwise incapable of passing through the membrane, may be taken up by cells. In some cases, following uptake of a drug via receptor-mediated pinocytosis, the endosomes carrying the drug actually bypass the lysosomes and migrate toward the basolateral membrane, resulting in the release of the undegraded drug into the extracellular space bounded by the basolateral membrane. This process, known as transcytosis, represents a potentially useful and important pathway for the absorption of high molecular weight drugs such as peptides and proteins. Indeed, some peptides and proteins are known to enter intestinal mucosal cells through pinocytosis; furthermore, a few peptides and proteins (including immunoglobulin G, nerve growth factor and epidermal growth factor) have been reported to reach blood vessels in the lamina propria and the portal venous circulation. This process may be facilitated by serum proteins knows as opsonins, which cover the particulate and promote adsorption and ingestion. The extent and pattern of opsonization depends highly on antigen surface characteristics such as charge and hydrophilicity. When digestion is complete, the lysosomal membrane may rupture, discharging its contents into the cytoplasm. Fixed macrophages are found lining certain blood and lymph-filled spaces, such as the sinusoids of the liver (these cells are commonly referred to as Kuppfer cells), bone marrow and spleen. For the purpose of completeness, the process of phagocytosis has been described briefly here. The process of phagocytosis is of particular relevance when particulate delivery systems, such as microspheres, liposomes and other advanced delivery systems (described in Chapter 5), are used. Phagocytic processes are also finding applications in oral drug delivery and targeting. Specialized epithelial cells known as M cells, which overly lymphoid sections of the gastrointestinal tract, may be involved in the phagocytic uptake of macromolecules and microparticles from the gut (see Section 6.