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A patient is to be given 100 mg of gentamicin intravenously over 1 hour every 8 hours purchase accutane 5 mg with visa acne 6 weeks postpartum. For the patient in the question above purchase genuine accutane skin care shiseido, what will the peak plasma concentration be after 20 doses? For the patient in the previous question, calculate the trough plasma concentration after 20 doses. Because the time interval would be relatively short, there would not be as much time for plasma concentrations to decline. A larger volume of distribution will result in the same amount of drug distributing in a greater volume, which would result in a lower peak-to-trough variation. When clearance decreases, plasma concentrations will increase because drug is administered at the same rate (dose and dosing interval) but is being removed at a lower rate. At five half-lives, approximately 97% of the steady-state concentration has been reached. The changes in the infusion rate will directly affect plasma concentrations, if other factors remain constant. If volume of distribution increased, the steady-state plasma concentration would decrease. The steady-state concentration is directly proportional to the drug infusion rate. If K (the elimination rate constant) increased, the steady-state plasma concentration would decrease. To double the steady-state plasma concentration from 10 to 20 mg/L, the infusion rate should be doubled to 50 mg/hour. The loading dose is determined by multiplying the desired concentration (15 mg/L) by the volume of distribution: Css(desired) × V = 15 mg/L × 40 L = 600 mg. By 20 doses, steady state would have been reached, and the equation below would be used: B, C, D. The trough concentration is calculated from the peak value as follows: -K(t -τ) Ctrough = Cpeak × e -0. Explain how changing the dosing interval (τ) influences the time to reach steady state when multiple doses are administered. If clearance is reduced to 25% of the initial rate and all other factors (such as dose, dosing interval, and volume of distribution) remain constant, how will steady-state plasma concentrations change? The following pharmacokinetic parameters are estimated for this patient: Cl = 15 mL/minute,t V = 31. If the infusion is stopped after steady state is reached, what would the concentration be 24 hours later? A loading dose of 1000 mg is infused over 30 minutes and a continuous infusion is begun when the loading infusion is stopped. What will the plasma concentration be 12 hours after beginning the constant infusion? What is the following portion of the multiple-dose equation called, and why is it called that? Explain why, for most drugs, the increase in drug plasma concentrations resulting from a single dose will be the same magnitude whether it is the first or the tenth dose. Calculate alpha (α), beta (β), and intercepts A and B for a drug conforming to a two-compartment model. Calculate Vc, Varea (also known as Vβ), and Vss (using both methods) for a two-compartment model. In this lesson, we briefly discuss multicompartment models and present a few applications. Multicompartment models are not used as frequently as the one-compartment model in therapeutic drug monitoring, partly because they are more difficult to construct and apply. Generally, multicompartment models are applied when the natural log of plasma drug concentration versus time curve is not a straight line after an intravenous dose or when the plasma concentration -Kt versus time profile cannot be characterized by a single exponential function (i. When the natural log of plasma drug concentration versus time curve is not a straight line, a multicompartment model must be constructed to describe the change in concentration over time (Figure 6-1). Of the multicompartment models, the two-compartment model is most frequently used. This model usually consists of a central compartment of the well-perfused tissues and a peripheral compartment of less well-perfused tissues (such as muscle and fat). Figure 6-2 shows a diagram of the two- compartment model after an intravenous bolus dose, where: X0 = dose of drug administered Xc = amount of drug in central compartment Xp = amount of drug in peripheral compartment K12 = rate constant for transfer of drug from the central compartment to the peripheral compartment. A natural log of plasma drug concentration versus time curve for a two-compartment model shows a curvilinear profilea curved portion followed by a straight line. The phases of the curve may represent rapid distribution to organs with high blood flow (central compartment) and slower distribution to organs with less blood flow (peripheral compartment). After the intravenous injection of a drug that follows a two-compartment model, the drug concentrations in all fluids and tissues associated with the central compartment decline more rapidly in the distribution phase than during the post-distribution phase. After some time, a pseudoequilibrium is attained between the central compartment and the tissues and fluids of the peripheral compartment; the plasma drug concentration versus time profile is then characterized as a linear process when plotted on semilog paper (i. If plasma concentrations are measured after this phase is completed, the central compartment can be ignored and a one-compartment model adequately represents the plasma concentrations observed. If plasma concentrations of vancomycin are determined within the first few hours after a dose is given, the nonlinear (multiexponential) decline of vancomycin concentrations must be considered when calculating half- life and other parameters. Clinical Correlate Digoxin is a drug that, when administered as a short intravenous infusion, is best described by a two-compartment model. After the drug is infused, the distribution phase is apparent for 4-6 hours (Figure 6-4). Digoxin distributes extensively into muscle tissue (the peripheral compartment) and out of plasma (the central compartment). After the initial distribution phase, a pseudoequilibrium in distribution is achieved between the central and peripheral compartments. Because the site of digoxin effect is in muscle (specifically, the myocardium), the plasma concentrations observed after completion of the distribution phase more accurately reflect concentrations in the tissue and pharmacodynamic response. For patients receiving digoxin, blood should be drawn for plasma concentration determination after completion of the distribution phase; thus, trough digoxin concentrations are usually used clinically when monitoring digoxin therapy. Vancomycin is another drug that follows a two-compartment model with an initial 2- to 4-hour α- distribution phase followed by a linear terminal elimination phase. As described later in the vancomycin cases (see Lesson 13) peak vancomycin concentrations must be drawn approximately 2 hours after the end of a vancomycin infusion to avoid obtaining a peak concentration during the initial distribution phase (see Figure 13-3). Four stages of drug distribution and elimination after rapid intravenous injection. Point I: The injection has just been completed, and drug density in the central compartment is highest. The density of drug in the peripheral compartment has not yet reached that of the central compartment. Drug distribution in both directions continues to take place, but the ratio of drug quantities in the central and peripheral compartments remains constant.

Psychotropic drugs but also antconvulsants and centrally actng anthypertensives may impede intellectual functons and motor coordinaton buy discount accutane 10 mg on line skin care 15 days before marriage. The antmuscarinic efects of some antdepressants and neuroleptc drugs may be responsible for agitaton generic accutane 5mg mastercard acne vulgaris cause, confusion, and delirium in elderly. If drug therapy is absolutely necessary, the dosage should be ttrated to a clearly defned clinical or biochemical therapeutc goal startng from a low inital dose. Storage The term used to describe the safe keeping of all fnished drugs and pharmaceutcals awaitng dispatch. The term is also applied for safe stores in hospitals and dispensaries under the specifed conditons, so as to maintain their quality and potency. Dosage Form Refers to the gross physical form in which a drug is adminis- tered to or used by a patent. Drug Product A dosage form containing one or more actve therapeutc ingredients along with other substance included during manu- facturing process. Finished Product A medicinal product which has completed all stages of manu- facture including packaging. Strength The concentraton of the drug substance (for example weight/ weight, weight/volume or unit dose/volume basis) and the potency i. Stability Degree of resistance to chemical and physical changes, the efcacy of the preparaton must remain constant or change only within the limit specifed by ofcial compendia. Expiraton Date The date placed on the immediate container label of a drug product that designates the date through which the product is expected to remain within specifcatons. Storage Procedure and Instructons Drugs must be stored under conditons which minimize dete- rioraton, contaminaton or damage. They must be stored under conditons compatble with their recommended storage requirements of temperature and humidity and where neces- sary to comply with legal requirements, under secured or segregated conditons. Appropriate storage conditons are: Temperature or humidity controlled environment must be equipped with suitable indicators, recorders and/or failure warning devices which must be checked at appropriate inter- vals and the results are coded. Temperature should be measured at diferent levels in the warehouse and if necessary storage of sensitve drugs should be restricted to locatons in the warehouse where they will be protected from extreme conditons. Temperatures of the refrigerators, deep freezers, and Relatve Humidity in humidity control area as well as general areas of storage at room temperature should be recorded on a daily basis. Storage conditons not related to temperature are indicated in following terms: Drug storage should be regularly checked for cleanliness and good order and for misplaced/deteriorated/out dated stock. Drugs with expired shelf life should be destroyed unless an extension of shelf life is granted following the sats- factory results or re-analysis. Some categories of supplies require special storage condi- tons which include vaccines, narcotcs, and combustbles e. Narcotcs and other controlled substances should be kept in secure locking rooms with only one entrance. Inspecton for Deterioraton Pharmacists should be aware that deterioraton of drug product may happen even before their expiraton. Hence inspecton should include frequent product examinaton to detect signs of product deterioraton which difer according to dosage form. The Pharmacists in the Stores should prepare an exhaustve list of following deterioraton/spoilage indicators and keep them. Liquid Dosage Forms Slight gradual discolouraton, Swirly precipitaton, Whickering: pin hole at ampoule tp that leaks soluton which precipitate or crystalline solid mater, clouding, fading of colour, Cake sedimentaton (suspension), Creaming and cracking (emul- sion), Discolouraton. Semisolid Dosage Forms Ointments creams, gels and suppositories -Change in consist- ency and feel to touch, Phase separaton, Discolouraton, Surface crystal growth 3. Solid Dosage Forms Surface chipping or pitng (plain tablets), Deformaton (capsules), Increased hardness, Discolouraton, Colour fading (coloured tablets), Chipping of coat (coated tablets). Most vitamins, hormones enzymes are highly sensitve to oxidaton and photo decompositon. The integrity of packaging of dosage form is one of the impor- tant tasks of inspecton for pharmacist as these protect the drug in a tailored fashion. Afer each inspecton, products showing any signs of instability should be subjected to sample analysis to ensure quality. Aerosols Aerosols should be stored in a clean separate area away from heat and sunlight because the container contents are under pressure, flled containers must be checked for weight loss over the expiraton datng period, for contents under pres- sure. The label should display “Do not expose to heat or store at a temperature above 40⁰C, keep out of reach of children”. Creams Creams can be destroyed under extreme temperature fuctua- tons hence they should be stored at temperature above 10oC and not exceeding 30⁰C. If the creams are opened and diluted they should not be kept for more than 14 days to avoid micro- bial contaminaton. Ophthalmic Solutons and Drops They should be stored according to the conditons specifed on the label. Afer opening they should not be used for more than one month at home and not more than 15 days in hospitals. Suppositories Suppositories should be protected from heat and preferably stored in the refrigerator. Polyethylene glycol supposito- ries and suppositories enclosed in solid shell are less prone to distorton at temperature slightly above body tempera- ture. Glycerinated gelatn suppositories should be protected from heat, moisture and dry air by packaging in well sealed containers and storing in a cold place. Vaccines Liquid vaccines are to be stored between 2⁰ - 8⁰C and should not be frozen. All lyophilized vaccines should be stored between 2⁰- 8⁰C and for long term storage can be kept at or below -20⁰C or otherwise as specifed in the individual mono- graphs. Communicatng the Prescripton to the Patent It is important that the drugs reach the patent in good and potent conditons and the patent should know and under- stand fully how to keep them tll they are consumed. It is equally important that the patent should know the way each medicine is used. Communicatng how and where to store the drugs to the Patent: The following table may be used to guide and provide infor- maton on the way to store the drugs when they are dispensed to the patents. This is based on the recommended storage conditons as given on the labels of the drug products and Indian Pharmacopoeial notes in the General Chapters. On the label Meaning Tell the Patent/ Representatve of the Patent Do not store To be stored in Keep in the General over 8⁰C refrigerator Compartment of the (from +2⁰C to +8⁰C refrigerator and do not keep in the place where you make Ice. Do not store To be stored at room Keep in any part of the over 30 ⁰C temperature house, except in Bath room/ (from +2⁰C to +30⁰C) Kitchen. Do not To be kept in Keep in the General freeze refrigerator (from Compartment of the +2⁰C to +8⁰C but refrigerator and do not keep not in the freezer in the place where you make chamber) Ice. Keep to be provided by in any part of the house, the manufacturer in except in Bath room/Kitchen.

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Auriacombe M order accutane 30 mg on-line skin care summer, Fatséas M order 20 mg accutane overnight delivery acne wikipedia, 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. Reed K, Bond A, Witton J et al (2011) The changing use of prescribed benzodiazepines and z-drugs and of over-the-counter codeine-containing products in England: a structured review of published English and international evidence and available data to inform consideration of the extent of dependence and harm. Schweitzer E & Rickels K (1998) Benzodiazepine dependence and withdrawal: a review of the syndrome and its clinical management. Royal College of Psychiatrists (1997) Benzodiazepines: risks, benefits or dependence: a re-evaluation. American Psychiatric Association (1994) Diagnostic and statistical manual of mental disorders (4e). Vandrey R & Haney M (2009) Pharmacotherapy for cannabis dependence: how close are we? Darke S & Hall W (2003) Heroin overdose: research and evidence-based intervention. Strang J, McCambridge J, Best D et al (2003) Loss of tolerance and overdose mortality after inpatient opiate detoxification: follow-up study. 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. Australasian Professional Society on Alcohol and Other Drugs Conference 2010 Paper 122. Minozzi S, Amato L, Vecchi S et al (2011) Oral naltrexone maintenance treatment for opioid dependence. Castells X, Casas M, Pérez-Mañá C et al (2010) Efficacy of psychostimulant drugs for cocaine dependence. Lussier J, Heil S, Mongeon J et al (2006) A meta-analysis of voucher-based reinforcement therapy for substance use disorders. Prendergast M, Podus D, Finney J et al (2006) Contingency management for treatment of substance use disorders: a meta-analysis. Stulza N, Gallop R, Lutzc W et al (2010) Examining differential effects of psychosocial treatments for cocaine dependence: an application of latent trajectory analyses. Gossop M, Stewart D & Marsden J (2008) Attendance at narcotics anonymous and alcoholics anonymous meetings, frequency of attendance and substance use outcomes after residential treatment for drug dependence: a 5-year follow-up study. National Institute for Health and Clinical Excellence (2010) Pregnancy and complex social factors. Archie C (1998) Methadone in the management of narcotic addiction in pregnancy (editorial). National Institute for Health and Clinical Excellence (2007) Methadone and buprenorphine for the management of opioid dependence. Royal College of General Practitioners, Royal Pharmaceutical Society & The Secure Environment Pharmacist Group (2011) Safer prescribing in prisons. Stewart D (2010) Drug use and perceived treatment need among newly sentenced prisoners in and. Singleton N, Meltzer H, Gatward R et al (1998) Psychiatric morbidity among prisoners in England and Wales. Boys A, Farrell M, Bebbington P et al (2002) Drug use and initiation in prison: results from a national prison survey in England and Wales. Strang J, Gossop M, Heuston J et al (2006) Persistence of drug use during imprisonment: relationship of drug type, recency of use and severity of dependence to use of heroin, cocaine and amphetamine in prison.

The pre-sentence report from the Probation Service explained that he was a self-confessed addict who had taken a deliberate decision to supply drugs in order to raise the funds to satisfy his addiction 5mg accutane with visa acne jawline. He had explained that his only real choice was either to go back to committing burglaries and robberies to raise funds discount accutane online visa acne near mouth, or to cooperate with his supplier. He was desperate not to return to the cycle of violence that had characterised his life during his youth, so he had agreed to work with this supplier, which he viewed as the lesser of the two evils. No person further up the supply chain, including the defendant’s own supplier, was prosecuted. Among respondents to the Northern Ireland Crime Survey who had reported taking cannabis in the last year, 34. Specifically in relation to drug use, these surveys are likely to be under-representative as they commonly miss students and homeless people, who have a higher consumption rate than the general population. Further information on the limitations of general population surveys can be found at www. Young adults aged under 35 years are much more likely than older adults to use drugs, with recent and current use highest in the under-25 age group. In England and Wales in 2009-2010, the proportion of recent drug users reporting concurrent harmful alcohol use was at least 90 per cent for all drugs, and as high as 98 per cent for cocaine powder and amyl nitrite. This has important policy implications, which are discussed in more detail in Chapter 11. According to Smoking, drinking and drug use amongst young people in England 2011, 12 per cent of 11- to 15-year-old pupils reported taking drugs in the last year, and 6 per cent did so in the last month. Repeated drug use, on more than ten occasions was reported by 3 per cent of pupils • those pupils reporting Class A drug use were more likely to take drugs at least once a month. As these were only recently brought under control of the Misuse of Drugs Act 1971, there is only limited information on their use in the general population. A significant rise in the use of mephedrone was reported in 2009, which led to its control under the Misuse of Drugs Act 1971 in 2010. Younger adults (aged 16 to 24 years) were more likely to have used recently classified drugs in the last year than adults aged 25 years and over. While there has been limited systematic research in this area, a number of surveys and polls provide an indication of public opinion on drug use. Smoking, drinking and drug use amongst young people in England 2011 found that relatively small proportions of pupils thought it was acceptable for someone of their age to try cannabis (9%), sniffing glue (7%) or taking cocaine (2%). Even smaller proportions thought it would be acceptable for someone their age to take any of these drugs once a week (cannabis 4%, sniffing glue 2%, cocaine 1%). Information on the global drug markets provides an indication of recent global trends. The most notable global trend is the growth of indoor cultivation, in particular in Europe, Australia and North America. Less than 10 per cent of pupils interviewed in England in 2010 thought use of any illicit drugs was acceptable. This can include deaths from overdose, long-term adverse effects on health, dependence, and harms to families and communities. The harms associated with the regulatory framework of drug prohibition are considered in Chapter 6. Harm is also influenced by the setting in which the substances are used and the combination of substances used. The level of harm is affected by: • the dosage of the drug – the more of a drug that is taken on a specific occasion, the higher the risk of the user experiencing acute effects, including intoxication and overdose. The greater the amount taken over time, the higher the risk of chronic toxic effects. An additional risk with illicit drugs is that a user may be unaware of the exact dose they are taking; a dose that is higher than expected will increase the risk of harm or fatality • the pattern of drug use – which is determined by the frequency and variability of drug use • the mode of administration – which depends on the way the drug is ingested (eg swallowed, snorted, injected, etc). Many illicit drugs are commonly found to contain adulterants that can increase the risk of morbidity and mortality (see Section 3. It is worth noting that, while these evaluations do not directly consider the epidemiology of the respective drugs, some of the criteria (eg the harm that a drug causes to those other than the user) indirectly take account of the number of users. In 2010, a Dutch addiction medicine expert group conducted a risk assessment of 19 recreational drugs (17 illicit drugs plus alcohol and tobacco), and ranked them on the basis of acute and chronic toxicity, addictive potency and social harm. Each drug was scored out of 100 points based on 16 criteria, nine of which related to the individual harms, and seven to the harms caused to others. It is important to note that the methodology for these studies evaluating and ranking drug harms has been questioned by Rolles and Measham9 and Caulkins et al. Acute toxicity can lead to short-term harms, ranging from unpleasant side-effects such as vomiting and fainting, to more serious impacts such as seizures, tissue and neural damage or death. In the longer term, repeated drug use can lead to chronic physical and psychological health effects, as well as dependence. Deaths in all age groups decreased from the previous year, with the exception of the oldest age group (60 plus years) (see Figure 5). The difference in trends for the 20 to 29 and 40 to 49 years age groups in Figure 5 (with an ageing trend observed among overdose deaths) suggests there may be an ageing cohort effect. Interpretation of these data should be treated with caution, as death certificates do not always state specific drug types, which could lead to under-reporting, or deaths may be counted in more than one category. Various studies have estimated that the annual death rate for ‘high-risk’ drug users, such as those who illegally inject opioid drugs, is between 1. Amphetamine and methamphetamine Acute and chronic amphetamine and methamphetamine use is associated with a wide range of complications, although their incidence is unclear. The use of methamphetamine (injected or smoked) in its crystal form (crystal meth) is also associated with a high potential for psychological as well as physical dependence. Acute cannabis intoxication (at high doses) can result in anxiety and panic attacks, paranoia, dysphoria, cognitive impairment, perceptual distortions and confusion/delirium. Chronic use is associated with impaired pulmonary function, recurrent bronchitis, worsening of asthma and lung cancer (from carcinogens in cannabis and tobacco smoke). There is broad agreement in the medical community that: • regular heavy users may suffer repeated, short episodes of psychosis and effectively maintain a chronic psychotic state c The evidence for the association between cannabis and lung cancer is unclear, owing to the difficulty in ruling out tobacco use as a confounder. At an individual level, cannabis users have a two-fold increase in the relative risk for later developing schizophrenia, while at a population level, the effect size is relatively small, as eliminating its use in those at risk would reduce the incidence of schizophrenia by 8 per cent. A 2012 study found that persistent regular cannabis use over 20 years was associated with neuropsychological decline broadly across the domains of functioning (ie executive function, memory, processing speed, perceptual reasoning and verbal comprehension). It is also associated with a range of psychological effects, including anxiety, visual hallucinations and paranoia. In the short term, acute intoxication causes a range of common side-effects (eg nausea, vomiting, constipation, drowsiness and mental confusion), and in some cases hallucinations, dysphoria, sweating and itching. When untreated, approximately 30 per cent of heroin-dependent individuals will have died by 10 years from overdoses,24 or as a result of secondary complications, as described in Section 3. Withdrawal from opioid dependence is rarely life threatening, but can lead to a range of unpleasant symptoms (eg nasal discharge, sweating, sleep disturbance, anorexia, restlessness, irritability, tremor, weakness, depression, nausea, vomiting, abdominal cramps, muscle spasms and diarrhoea). In the short term, their use leads to an increased risk of accidental death, violence and injuries, owing to perceptual distortions and impaired decision making. Chronic heavy use of ketamine can lead to ulcerative cystitis (marked thickening of the bladder wall and severe inflammation)82-84 and abdominal pain.