AREA DRUGS & THERAPEUTICS COMMITTEE : 7TH JUNE 2004 ADTC M ; 04 3 Minutes: 24 36 GREATER GLASGOW HEALTH BOARD Minutes of a Meeting of the Area Drugs and Therapeutics Committee held in the Conference Room Management Building Southern General Hospital on Monday, 7th June 2004 at 2.00 p.m. PRESENT Professor M J Brodie in the Chair ; Dr K Beard Dr D Brown Dr J Burns Dr H Elliott Mrs A Lee Mrs M A Mackie Dr C McKean Dr E McLellan Dr G J Macphee Dr K R Paterson Dr A Power Dr P J Redding Dr I Struthers Ms A Thompson.

By comparison, the side effects associated with cannabis are typically mild and are classified as "low risk." Euphoric mood changes are among the most frequent side effects. Cannabinoids can exacerbate schizophrenic psychosis in predisposed persons. Cannabinoids impede cognitive and psychomotor performance, resulting in temporary impairment. Chronic use can lead to the development of tolerance. Tachycardia and hypotension are frequently documented as adverse events in the cardiovascular system. A few cases of myocardial ischemia have been reported in young and previously healthy patients. Inhaling the smoke of cannabis cigarettes induces side effects on the respiratory system. Cannabinoids are contraindicated for patients with a history of cardiac ischemias. In summary, a low risk profile is evident from the literature available. Serious complications are very rare and are not usually reported during the use of cannabinoids for medical indications and vancomycin and truvada. If you suspect that you took more than the prescribed dose of TRUVADA, contact your local poison control center or emergency room right away. As with all medicines, TRUVADA should be kept out of reach of children. Emtricitabine did not affect fertility in male rats or in female and male mice at respective approximate exposures AUC ; of 130 and 50-80 times the exposure in humans. The fertility of offspring was unaffected by treatment of mice from early gestation to the end of lactation 50 times the human exposure ; . Use in Pregnancy Pregnancy Category B3 No clinical data are available for pregnant women being treated with tenofovir disoproxil fumarate or emtricitabine. No embryofoetal development studies have been conducted with tenofovir disoproxil fumarate and emtricitabine in combination. Reproductive toxicity studies performed in rats and rabbits did not reveal any evidence of harm to the foetus due to tenofovir at respective exposures AUC ; of 4-13 and 66-fold the human exposure. Subcutaneous treatment of pregnant rhesus monkeys with a dose of 30 mg kg day of the tenofovir base during the last half of pregnancy resulted in reduced foetal serum phosphorus concentrations. No evidence of embryofoetal toxicity or teratogenicity was observed in mice or rabbits at respective emtricitabine exposures AUC ; of 50 and 130 fold the clinical exposure. Impaired weight gain observed in pregnant rabbits at doses resulting in emtricitabine exposures AUC ; at least 33 times the clinical exposure was not associated with any adverse foetal effects. Because animal reproduction studies are not always predictive of human response, TRUVADA should be used during pregnancy only if clearly needed. Use in Lactation It is not known whether tenofovir or emtricitabine are excreted in human milk. Because of the potential for HIV transmission and for serious adverse reactions in nursing infants, mothers should be instructed not to breast feed if they are receiving TRUVADA. Use in Children Safety and effectiveness in paediatric patients have not been established. Use in the Elderly Clinical studies of tenofovir and emtricitabine did not contain sufficient numbers of patients aged 65 years and over to determine whether they respond differently from younger patients. In general, dose selection for the elderly patient should be cautious, keeping in mind the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy see DOSAGE AND ADMINISTRATION ; . Effects on ability to drive and use machines No studies on the effects of TRUVADA on the ability to drive and use machines have been performed. However, patients should be informed that dizziness has been reported during treatment with both tenofovir disoproxil fumarate and emtricitabine and vaniqa!

Time to peak concentration : oral : emtricitabine, 1 to 2 hours; tenofovir, approximately 1 hour prod info truvada tm ; , 2004; prod info emtriva tm ; , 2003; kahn et al, 1998; wang et al, 1995; prod info viread r ; , 2003. Khomeini, Imam Ruhollah. "Imam Khomeini's Message for the 5th of June 15th of Khordad." Tehran: Council for the Celebrations of the Third Anniversary of the Victory of the Islamic Revolution, 1982. 96p. DS 318 K4265 1982 "The Pillars of an Islamic State" and "The Necessity of Islamic Government." Excerpted in Contemporary Debates in Islam: An Anthology of Modernist and Fundamentalist Thought, Mansoor Moaddel and Kamran Talattof, eds. New York: St. Martin's Press, 2000. BP 163 C64 2000 Loeffler, Reinhold. Islam in Practice: Religious Beliefs in a Persian Village. Albany: SUNY Press, 1988. 312p. BP 192.7 I7 L63 1988 [Section 4: The Effect of the Revolution] Malone, Joseph. "The Islamic Republic of Iran and Gulf Security." In International Security in Southwest Asia, Hafeez Malik, ed. New York: Praeger, 1984. UA 830 I58 1984 Menashri, David, ed. The Iranian Revolution and the Muslim World. Boulder: Westview Press, 282p. DS 63.2 I68 I73 1990 Middle East Institute. The Iranian Islamic Clergy: Governmental Politics and Theocracy. Washington, DC: 1984. 130p. DS 318.8 I718 1984 Mirsepassi, Ali. Intellectual Discourse and the Politics of Modernization: Negotiating Modernity in Iran. Cambridge: Cambridge University Press, 2000. 227p. DS 316.6 M57 2000 [Chapter 6: The Tragedy of the Iranian Left] Moaddel, Mansoor. Class, Politics and Ideology in the Iranian Revolution. New York: Columbia University Press, 1992. 346p. DS 318.81 M64 1992 Mortimer, Edward. Faith and Power: The Politics of Islam. New York: Random House, 1982. 432p. BP 63 A4 N425 1982 [Chapter 9: Iran Shi'ism and Revolution] Moshiri, Farrokh. The State and Social Revolution in Iran: A Theoretical Perspective. New York: Peter Lang, 1985. 232p. BP 63 I68 M67 1985 Mottahedeh, Roy. The Mantle of the Prophet: Religion and Politics in Iran. Oxford: Oneworld Publications, 2000. 416p. BP 192.7 I68 M67 2000 Mutahhari, Ayatollah Murtaza. A Discourse on the Islamic Republic. Tehran: Islamic Propagation Organization, 1985. 78p. BP 63 I68 M868 1985 "The Nature of the Islamic Revolution." Excerpts of speeches in Iran: A Revolution in Turmoil, Haleh Afshar, ed. Albany: SUNY Press, 1985. 262p. DS 318 I686 1985 Nasr, Seyyed Hossein, et al., eds. Expectation of the Millennium: Shi'ism in History. Albany: SUNY Press, 1989. 460p. BP 194.185 E96 1989 [Section VI: Shi'ism in the Modern World: Later Political Views] Organization of Iranian Moslem Students. The Rise English Defense Publication ; and Leaflets in English. Wilmette, IL: 1979. 158p. DS 319 I7 R7 Rahnema, Ali. An Islamic Utopian: A Political Biography of Ali Shari'ati. London: I.B. Tauris, 1998. 418p. BP 80 S53 R34 1998 14. Floating q ; were similar to the 4-parameter model Ml. Striatum Results are presented in Table 4 and Figures 5, 6 and 7.

Anemia low red blood cells ; leading to discontinuation in Study 934 was determined by each investigator. * The most common side effects in the TRUVADA group were nausea, diarrhea, dizziness, tiredness, depression, headache, runny nose, persistent cough, common cold, and rash and tums. In summary, i pleased with our performance during the third quarter, especially the early uptake of atripla in the and the continued growth of truvada in europe. Were terminated by the addition of "SDS-stop solution." The phosphorylated samples were then heated at 95C for 2 min and subjected to SDS PAGE. followed bv autoradioaraphv of the dried aels. Phosphorylated bands corresponding to the k, 2 1, 000 phosphoprotein were cut out of the gel and the amount of 3zP-radioactivity incorporated was determined by liquid scintillation spectrometry in 3 ml Liquistint. The "substrate activity" of ARPP-21 is defined as the picomoles of 32P-phosphate incorporated into the M, 21, 000 band using this assay. Two-dimensional thin-Iayerphosphopeptide mapping. Gel pieces containing phosphorylated ARPP-2 1 were subjected to proteolysis within the gel by a-method described previously Hemmings et al., 1984c ; exceot that the nrotease used for digestion was 75 &ml TPCK-trypsin. Elec&ophoresis and chromatography of the try& digests were-performedas described previously Hemmings et al., 1984c ; . Analvtical HPLC Deotide maot?ina. ARPP-2 1A and ARPP-2 1B were reduced, S-14C-carboxymethylatkd and digested with TPCK-trypsin by a method described previously Williams et al., 1986 ; . The resulting tryptic peptides were analyzed by reverse-phase HPLC as described Williams et al., 1986 ; , except that a Vydak C-4 column was used. Peptides were eluted with linear gradients containing increasing concentrations of solvent B 10.05% vol vol ; trifluoroacetic acid and 80% vol vol ; acetonitrile] into solvent A [d.OS% vol vol ; trifluoroacetic acid] as follows: O-90 min O-37.5% B ; , 90-135 min 37.5-75% B ; . Dephosphoryation OfphosphorylatedARPP-21 by variouspurifiedprotein phosphatases. Purified protein phosphatase- 1, -2A, -2B, and -2C and phosphorylated phosphorylase kinase were prepared, and dephosphorylation assays performed as described by Hemmings et al. 1984a ; . Purified ARPP-2 1 A and B ; was phosphorylated to a stoichiometry of 0.8-l .O mol3 * P mol protein and purified from unreacted Y- ; ~P-ATP by dialysis and ion-exchange chromatography using DE-Sephacel. Radioiodination ofARPP-21. Purified ARPP-21 5 wg ; was radioio.-. dinated by the method of Bolton and Hunter 1973 ; using 2 mCi of diiodinated 1251-Bolton-Hunter reagent. Iodination by the chloramine T method was ineffective due to the absence of tyrosine residues in ARPP-21 see below ; . ` * + labeled ARPP-21 was separated from the reaction mixture by gel filtration through Sephadex G-25 fine ; as described Hemmings and Greengard, 1986 ; and stored at - 70C in small aliquots. This procedure resulted in a preparation of lZSI-labeled ARPP21 in which 85-100% of the total lz51 radioactivity was contained in intact ARPP-2 1 as determined by SDS PAGE. Antibody detection assay. Rabbit and mouse sera, hybridoma culture supematants and ascites fluid were analyzed for anti-ARPP-21 antibodies by their ability to precipitate 1251-labeled ARPP-2 1 using fixed Protein A-bearing Staphylococcus aureus cells Pansorbin, CalbiochemBehring ; as an immunoadsorbent as described previously for DARPP32 Hemmings and Greengard, 1986 ; , with the following modification: rabbit anti-mouse antiserum Cappell Laboratories ; was added to the immunoprecipitation assay as a second antibody at a final dilution of 1: 500. Preparation of rabbit anti-ARPP-21 antibodies. Antiserum to ARPP21 was raised in 3 female New Zealand white rabbits 1.5-2 kg ; as described previously for DARPP-32 Hemmings and Greengard, 1986 ; , exceot that 100 ua oer rabbit of Durified ARPP-2 1 A and B ; emulsified in Freund's complete adjuvant-was injected on day 0, and 50 rg per rabbit of purified ARPP-21 in Freund's incomplete adjuvant was injected on days 14 and 28. The rabbits were bled on day 38, and the antiserum was collected and stored at - 70C in small aliquots. Preparation of mouse anti-ARPP-21 monoclonal antibodies. Monoclonal antibodies were produced in BALB c mice essentially by the method of Kiihler and Milstein 1975 ; as described previously for DARPP-32 Hemmings and Greengard, 1986 ; . This procedure yielded 10 stable anti-ARPP-2 1 antibody-producing hybrid cell lines, from 2 separate cell fusions, designated 21-lA, 21-3D, 21-4B, Ascites was inducedin pristane-primed BALB c mice using each cell line, and the y-globulin fractions were obtained by precipitation of the ascitic fluid with 45% saturated ammonium sulfate at 4C. The precipitated proteins were dialyzed into PBS and stored at 70C in small aliquots. Miscellaneous methods. Determination of Stokes radius by gel filtration and of sedimentation coefficient by linear sucrose density gradient ultracentrifugation Hemmings et al., 1984b ; , identification of phosphorylated amino acids Hemmings et al., 1984c ; , amino acid analysis Hemmings et al., 1984d ; , and protein determinations using a modification Peterson, 1977 ; of the method of Lowry et al. 195 1 ; were carried. NVP ; is an alternative in women with a CD4 count of less than 250 cells mL and men with a CD4 count below 400 cells mL, in whom the risks of hepatotoxicity are minimized. Lopinavir LPV ; boosted with ritonavir RTV ; is the PI for which the data on long-term vilorogical outcome is strongest in a PI-naive population. Alternatives are saquinavir SQV ; boosted with RTV and fosamprenavir boosted with RTV, but substantive direct comparisons between RTV-boosted PIs in such populations are not available. The Committee believes that there is insufficient data to recommend RTV-boosted atazanavir. However, if in trials that are currently in progress, the efficacy and durability of this regimen can be confirmed, the once-daily dosing and freedom from serum lipid abnormalities would be an advantage of this regimen. Nucleoside analogues that should be considered when constructing a 2-nucleoside reverse transcriptase inhibitor NRTI ; backbone for initial regimens include: zidovudine ZDV ; , lamivudine 3TC ; , abacavir ABC ; , tenofovir TDF ; , didanosine ddI ; and emtricitabine FTC ; . Three 2NRTI combinations are available as co-formulated pills: Kivexa ABC and 3TC ; , Truvada FTC and TDF ; and Combivir ZDV and 3TC ; . While this adds to the convenience of the regimen, the Committee did not feel that this was sufficient to pay a large premium for a combination pill rather than using the components individually. Data suggests that ZDV 3TC is less well tolerated than TDF FTC and produces a lower CD4 count rise than ABC 3TC, although the clinical significance of this is unknown. ZDV 3TC is likely to become considerably cheaper in the next 2 years as generic ZDV becomes available. The extent of the continuing use of ZDV 3TC combinations in the future is likely to depend upon the propensity of ZDV to produce lipodystrophy, which is in itself costly to treat and will be associated with poor adherence [2]. The choice between ABC 3TC and TDF FTC requires a discussion with the patient about the short-term toxicity of ABC and its management vs. the lack of long-term toxicity data for TDF in clinic populations as opposed to selected patients in randomized controlled trials: in this uncertain situation with no clear data, the relative costs of the two combinations will legitimately be an important consideration. As an alternative approach to the dielectron measurement we have studied the possibility of detecting vector mesons , J ; via their decay into - + pairs. The idea is to suppress the hadrons with several absorber layers located behind the Silicon Tracking System. In order to match the muons which pass the absorber to the tracks measured by the Silicon tracker which defines the momentum ; one has to track all charged particles through the absorber. This is done by highly granulated and fast detectors which are located in each gap between the absorber layers. The simulations are based on track reconstruction algorithms taking into account a realistic response of the STS and a position resolution of the muon chambers of 100 m see A. Kiseleva et al., this report ; . The studies demonstrate that for example the meson can be measured in central Au + Au collisions at 15 25, 35 ; AGeV with a signal-to-background ratio of S B 0.16 0.14, ; and with an efficiency of 0.022 0.033, 0.044 ; . J mesons can be identified with a signal-to-background ratio of about 100 and an efficiency of 0.13 for central Au + Au collisions at 25 AGeV. Such a number would be sufficient for the identification of ' mesons in Au + collisions. For the charmonium experiments the total thickness of the hadron absorber has to be increased as compared to measurements of low-mass vector mesons. The challenge for the muon chambers and for the track reconstruction algorithms is the huge particle density of up to hit cm2 per event in the first detector layers. Therefore, detector R&D concentrates on the design of fast and highly granulated gaseous detectors based on GEM technology. In the preliminary development of the FE model, the geometry of the specimens as shown in Table 3.1 and the testing setup configurations of the small scale test were obtained from Abdullah 2004 ; . The concrete cracking parameters. Taken together, the three hiv treatments generated $ 1 san jose mercury news, gilead reports 2m profit for q4 - jan 23, 2008 sales of those drugs - truvada, atripla, viread and emtriva - rose to 2 million in the quarter, up from 4 million in the fourth quarter of 200 bizjournals , gilead sciences tops estimates - jan 23, 2008 of note, atripla sales totaled 7 million while truvada sales were 8 million.