Associate Professor, University of Minnesota Medical School
La bora tory va l ues mus t be a s s es s ed pri or to i ni ti a ti ng medi ca ti on; ca reful a s s es s ment of rena l functi on i s pa rti cul a rl y i mporta nt i n the el derl y popul a ti on medicine 801 norpace 150 mg otc. Pregna ncy Ri s k Fa ctorC Pregna ncy Cons i dera ti ons Dofeti l i de ha s been s hown to a dvers el y a ffect in utero growth medications 126 buy norpace cheap online, orga nogenes i s 340b medications purchase norpace with paypal, a nd s urvi va l of ra ts a nd mi ce symptoms 5 weeks pregnant purchase 150mg norpace visa. Dofeti l i de s houl d be us ed wi th extreme ca uti on i n pregna nt women a nd i n women of chi l dbea ri ng a ge onl y when the benefi t to the pa ti ent unequi voca l l y jus ti fi es the potenti a l ri s k to the fetus. La cta ti onExcreti on i n brea s t mi l k unknown/not recommended Advers e Rea cti ons Supraventricular arrhythmia patients (i nci dence > pl a cebo) >10%: Centra l nervous s ys tem: Hea da che (11%) 2% to 10%: Centra l nervous s ys tem: Di zzi nes s (8%), i ns omni a (4%) Ca rdi ova s cul a r: Ventri cul a r ta chyca rdi a (2. Tors a de de poi ntes occurs mos t frequentl y wi thi n the fi rs t 3 da ys of thera py. Risk C: Monitor therapy Anti funga l Agents (Azol e Deri va ti ves, Sys temi c): Ma y decrea s e the meta bol i s m of Dofeti l i de. Risk X: Avoid combination Ci meti di ne: Ma y decrea s e the excreti on of Dofeti l i de. Risk X: Avoid combination Tri methopri m: Ma y decrea s e the excreti on of Dofeti l i de. Risk X: Avoid combination Vera pa mi l: Ma y i ncrea s e the s erum concentra ti on of Dofeti l i de. Check s erum pota s s i um a nd ma gnes i um l evel s i f on medi ca ti ons where thes e el ectrol yte di s turba nces ca n occur, or i f pa ti ent ha s a hi s tory of hypoka l emi a or hypoma gnes emi a. As s es s res ul ts of l a bora tory tes ts, thera peuti c effecti venes s, a nd a dvers e rea cti ons a t begi nni ng of thera py a nd on a regul a r ba s i s wi th l ong-term thera py. Moni tori ng: La b Tes ts Serum crea ti ni ne; check s erum pota s s i um a nd ma gnes i um l evel s i f on medi ca ti ons where thes e el ectrol yte di s turba nces ca n occur, or i f pa ti ent ha s a hi s tory of hypoka l emi a or hypoma gnes emi a. You wi l l need regul a r ca rdi a c checkups a nd bl ood tes ts when ta ki ng thi s medi ca ti on. You ma y experi ence hea da che, di zzi nes s, or di ffi cul ty s l eepi ng (us e ca uti on when dri vi ng or enga gi ng i n ta s ks requi ri ng a l ertnes s unti l res pons e to drug i s known); or a bdomi na l pa i n, di a rrhea, or na us ea (s ma l l frequent mea l s a nd i ncrea s ed di eta ry bul k ma y hel p). Pregnancy/breastfeeding precautions: Inform your pres cri ber i f you a re or i ntend to become pregna nt. Ca ps ul e: 125 mcg, 250 mcg, 500 mcg Generi c Ava i l a bl eNo Ma nufa cturerPfi zer U. Bl ocka de of the ca rdi a c i on cha nnel ca rryi ng the ra pi d component of the del a yed recti fi er pota s s i um current. Dofeti l i de ha s no effect on s odi um cha nnel s, a drenergi c a l pha -receptors, or a drenergi c beta receptors. It i ncrea s es the monopha s i c a cti on potenti a l dura ti on due to del a yed repol a ri za ti on. Cha nges i n ca rdi a c conducti on vel oci ty a nd s i nus node functi on ha ve not been obs erved i n pa ti ents wi th or wi thout s tructura l hea rt di s ea s. The choi ce of a nti a rrhythmi c i s i mporta nt beca us e of the ri s k tha t a nti a rrhythmi c thera py ma y i ncrea s e morta l i ty i n thi s s etti ng. Dofeti l i de wa s a n effecti ve thera py for a tri a l fi bri l l a ti on i n ca reful l y s el ected a nd moni tored hea rt fa i l ure pa ti ents. Morta l i ty wa s s i mi l a r between thos e who recei ved pl a cebo a nd dofeti l i de; fewer pa ti ents on dofeti l i de were hos pi ta l i zed for hea rt fa i l ure. It s eems prudent, therefore, to ca reful l y s el ect a nd moni tor pa ti ents i n thi s s i tua ti on. Whi l e the effi ca cy da ta ha ve not been s ta ti s ti ca l l y s i gni fi ca nt, pos i ti ve trends ha ve been noted a nd further s tudy i s requi red. In hea rt fa i l ure pa ti ents, dofeti l i de ha s been reported to pres erve i notropi c a nd end-s ys tol i c i ndi ces. Dofeti l i de ca n ca us e l i fe-threa teni ng ventri cul a r a rrhythmi a s a nd s houl d therefore be us ed i n s el ect pa ti ents i n whom a tri a l fi bri l l a ti on/fl utter i s hi ghl y s ymptoma ti c. Hos pi ta l s a nd phys i ci a ns need to compl ete thei r Ti kos yn educa ti ona l progra m before dofeti l i de ca n be pres cri bed a nd di s pens ed. Intra venous Dofeti l i de Inves ti ga tors," J Am Coll Cardiol, 1997, 29(2):385-90. Da ni s h Dofeti l i de i n Atri a l Fi bri l l a ti on a nd Fl utter Study Group," Am Heart J, 1999, 137(6):1062-9.
Special populations: Pedi a tri cs: Opti ma l dos i ng i n pedi a tri c pa ti ents <6 yea rs of a ge ha s not been es ta bl i s hed; do not us e i n chi l dren <3 months of a ge due to potenti a l for kerni cterus treatment 9mm kidney stones purchase norpace line. Pregna ncy Ri s k Fa ctorB Pregna ncy Cons i dera ti ons Tera togeni c effects not obs erved i n a ni ma l s tudi es symptoms just before giving birth order norpace online now. Ata za na vi r cros s es the huma n pl a centa i n l ow/va ri a bl e a mounts; i t i s not known i f a ta za na vi r wi l l exa cerba the hyperbi l i rubi nemi a i n neona tes medications like zovirax and valtrex 100 mg norpace fast delivery. Ba s ed on l i mi ted s tudi es treatment lupus order norpace no prescription, norma l dos i ng a chi eves a dequa the s erum concentra ti ons i n pregna nt women. Advers e Rea cti ons Incl udes da ta from both trea tment-na i ve a nd trea tment-experi enced pa ti ents. Risk X: Avoid combination Anta ci ds: Ma y decrea s e the a bs orpti on of Ata za na vi r. Risk D: Consider therapy modification Anti funga l Agents (Azol e Deri va ti ves, Sys temi c): Ma y i ncrea s e the s erum concentra ti on of Protea s e Inhi bi tors. Protea s e Inhi bi tors ma y i ncrea s e the s erum concentra ti on of Anti funga l Agents (Azol e Deri va ti ves, Sys temi c). Ma na gement: Li mi t i ndi na vi r to 600mg every 8 hours wi th i tra cona zol e or ketocona zol. Risk D: Consider therapy modification Buprenorphi ne: Ata za na vi r ma y i ncrea s e the s erum concentra ti on of Buprenorphi ne. Risk D: Consider therapy modification Di da nos i ne: Ma y decrea s e the a bs orpti on of Ata za na vi r. Risk C: Monitor therapy Efa vi renz: Ma y decrea s e the s erum concentra ti on of Ata za na vi r. Risk D: Consider therapy modification Enfuvi rti de: Protea s e Inhi bi tors ma y i ncrea s e the s erum concentra ti on of Enfuvi rti de. Risk X: Avoid combination Etra vi ri ne: Ata za na vi r ma y i ncrea s e the s erum concentra ti on of Etra vi ri ne. Risk C: Monitor therapy H2-Anta goni s ts: Ma y decrea s e the a bs orpti on of Ata za na vi r. Risk D: Consider therapy modification Iri noteca n: Ata za na vi r ma y i ncrea s e the s erum concentra ti on of Iri noteca n. Risk D: Consider therapy modification Proton Pump Inhi bi tors: Ma y decrea s e the a bs orpti on of Ata za na vi r. Risk X: Avoid combination Ri fa mpi n: Ma y decrea s e the s erum concentra ti on of Ata za na vi r. Risk D: Consider therapy modification Tenofovi r: Ma y decrea s e the s erum concentra ti on of Ata za na vi r. Risk C: Monitor therapy Wa rfa ri n: Ata za na vi r ma y i ncrea s e the s erum concentra ti on of Wa rfa ri n. Risk C: Monitor therapy Etha nol /Nutri ti on/Herb Intera cti ons Food: Bi oa va i l a bi l i ty of a ta za na vi r i ncrea s ed when ta ken wi th food. As s es s a l l other pha rma col ogi c or herba l products pa ti ent ma y be ta ki ng for potenti a l i ntera cti ons or toxi ci ty; dos i ng a djus tments or a l terna ti ve a gents ma y be neces s a ry (mul ti pl e l i ver enzyme i ntera cti ons ma y i ncrea s e or decrea s e l evel s /effects of drugs a nd i ncrea s e potenti a l for s evere toxi ci ty or l os s of effecti venes s). A l i s t of medi ca ti ons tha t s houl d not be us ed i s a va i l a bl e i n ea ch bottl e a nd pa ti ents s houl d be provi ded wi th thi s i nforma ti on. Tea ch pa ti ent proper us e (eg, ti mi ng of mul ti pl e medi ca ti ons a nd drugs tha t s houl d not be us ed concurrentl y), pos s i bl e s i de effects /a ppropri a the i nterventi ons (eg, gl ucos e tes ti ng [protea s e i nhi bi tors ma y ca us e hypergl ycemi a or new-ons et di a betes], us e of ba rri er contra cepti ves [protea s e i nhi bi tors ma y decrea s e effecti venes s of ora l contra cepti ves]), a nd a dvers e s ymptoms to report. You ma y be s us cepti bl e to i nfecti on; a voi d crowds a nd expos ure to known i nfecti ons a nd do not ha ve a ny va cci na ti ons wi thout cons ul ti ng pres cri ber. Ma y ca us e body cha nges due to redi s tri buti on of body fa t, fa ci a l a trophy, or brea s t enl a rgement (norma l effects of drug); na us ea, vomi ti ng, or fl a tul ence (s ma l l frequent mea l s, frequent mouth ca re, chewi ng gum, or s ucki ng l ozenges ma y hel p); mus cl e wea knes s or fl a nk pa i n (cons ul t pres cri ber for a pproved a na l ges i c); hea da che or i ns omni a (cons ul t pres cri ber for medi ca ti on); or di a rrhea (boi l ed mi l k, buttermi l k, or yogurt ma y hel p). Inform pres cri ber i mmedi a tel y i f you experi ence hypers ens i ti vi ty (s ki n ra s h; s wel l i ng of fa ce, mouth, or tongue; di ffi cul ty s wa l l owi ng or brea thi ng) or ches t pa i n or pa l pi ta ti ons. Report mus cl e numbnes s or ti ngl i ng; unres ol ved pers i s tent vomi ti ng, di a rrhea, or a bdomi na l pa i n; cha nge i n col or of s tool or uri ne; or a ny pers i s tent a dvers e effects. Thi s drug decrea s es the effect of ora l contra cepti ves; us e of a l terna ti ve (nonhormona l) forms of contra cepti on i s recommended; cons ul t pres cri ber for a ppropri a the contra cepti ves. Ca ps ul e, a s s ul fa te: Reya ta z: 100 mg, 150 mg, 200 mg, 300 mg Generi c Ava i l a bl eNo Ma nufa cturerBri s tol -Myers Squi bb Pri ci ng: U. Na us ea, di zzi nes s, hypotens i on, a nd s yncope ha ve been reported wi th concomi ta nt us e of tra zodone a nd ri tona vi r.
Generic norpace 100mg visa. Withdrawl.
Ta ke exa ctl y a s di rected; do not a l ter dos e or di s conti nue medi ca ti on wi thout cons ul ti ng pres cri ber treatment for piles generic norpace 100mg visa. Ma y ca us e hea da che (i f unrel i eved treatment breast cancer purchase norpace in united states online, cons ul t pres cri ber); na us ea or vomi ti ng (s ma l l symptoms 0f pneumonia buy 150 mg norpace otc, frequent mea l s medicine 606 buy norpace with amex, frequent mouth ca re, chewi ng gum or s ucki ng l ozenges ma y hel p); cons ti pa ti on (i ncrea s ed di eta ry bul k a nd fl ui ds ma y hel p); or drows i nes s (us e ca uti on when dri vi ng or enga gi ng i n ta s ks tha t requi re a l ertnes s unti l res pons e to drug i s known). Report unrel i eved hea da che; vomi ti ng, cons ti pa ti on; pa l pi ta ti ons; peri phera l or fa ci a l s wel l i ng; wei ght ga i n >5 l b/week; or res pi ra tory cha nges. Denta l Hea l th: Va s ocons tri ctor/Loca l Anes theti c Preca uti ons No i nforma ti on a va i l a bl e to requi re s peci a l preca uti ons Menta l Hea l th: Effects on Menta l Sta tus Ma y ca us e drows i nes s; ra rel y ma y produce i ns omni a a nd nervous nes s Menta l Hea l th: Effects on Ps ychi a tri c Trea tmentNone reported Ca rdi ova s cul a r Cons i dera ti ons Hypertension: Aml odi pi ne thera py s houl d be conti nued for 4-6 weeks before the dos e i s i ncrea s ed. Da i l y dos es >10 mg a re a s s oci a ted wi th a n i ncrea s e i n s i de effects (eg, edema) wi thout further reducti ons i n bl ood pres s ure. Pa ti ents 40-79 yea rs of a ge were recrui ted; thei r bl ood pres s ures were ei ther >160 s ys tol i c or >100 di a s tol i c (untrea ted) or >140 s ys tol i c or >90 di a s tol i c (trea ted). Onl y a ml odi pi ne ha s been s hown not to a dvers el y a ffect s urvi va l but mos t experi ence i s not i n pa ti ents on concurrent beta -bl ockers. Anes thes i a a nd Cri ti ca l Ca re Concerns /Other Cons i dera ti ons Aml odi pi ne ma y be us ed s a fel y to trea t hypertens i on a nd/or a ngi na i n pa ti ents wi th hea rt fa i l ure. Interna ti ona l Soci ety on Hypertens i on i n Bl a cks," Arch Intern Med, 1998, 158(18):2029-34. Pros pecti ve Ra ndomi zed Aml odi pi ne Survi va l Eva l ua ti on Study Group," N Engl J Med, 1996, 335(15):1107-14. Stora geAroma ti c a mmoni a s pi ri t s houl d be protected from s unl i ght a nd s tored a t a tempera ture not exceedi ng 30°C. Contra i ndi ca ti ons Hypers ens i ti vi ty to a mmoni a or a ny component of the formul a ti on Pregna ncy Ri s k Fa ctorC Advers e Rea cti ons 1% to 10%: Ga s troi ntes ti na l: Na us ea, vomi ti ng Res pi ra tory: Irri ta ti on to na s a l mucos a, cough Drug Intera cti ons There a re no known s i gni fi ca nt i ntera cti ons. Dos i ng: Pedi a tri cMeta bol i c a l ka l os i s: Refer to a dul t dos i ng for wei ght-ba s ed equa ti ons. Admi ni s ter by s l ow i ntra venous i nfus i on to a voi d l oca l i rri ta ti on a nd a dvers e effects. Stora gePri or to us e, vi a l s s houl d be s tored a t control l ed room tempera ture of 15°C to 30°C (59°F to 86°F). If crys ta l s a re obs erved, wa rm vi a l to room tempera ture i n a wa ter ba th pri or to us. Recons ti tuti onDi l ute pri or to us e; fi na l concentra ti on s houl d not exceed 1% to 2% a mmoni um chl ori de. Variable (consult detailed reference): Di menhydri na te, pota s s i um chl ori de. Contra i ndi ca ti ons Severe hepa ti c or rena l dys functi on Wa rni ngs /Preca uti ons Concerns related to adverse effects: Ammoni a toxi ci ty: Moni tor cl os el y for s i gns a nd s ymptoms of a mmoni a toxi ci ty, i ncl udi ng di a phores i s, a l tered brea thi ng, bra dyca rdi a, a rrhythmi a s, retchi ng, twi tchi ng, a nd coma. Disease-related concerns: Res pi ra tory di s ea s e: Us e wi th ca uti on i n pa ti ents wi th pri ma ry res pi ra tory a ci dos i s or pul mona ry i ns uffi ci ency. Geri a tri c Cons i dera ti ons No s peci fi c da ta a va i l a bl e for el derl y; moni tor cl os el y wi th hepa ti c di s ea s e for s i gns of toxi ci ty. Risk C: Monitor therapy Ana l ges i cs (Opi oi d): Ammoni um Chl ori de ma y i ncrea s e the excreti on of Ana l ges i cs (Opi oi d). Risk C: Monitor therapy Pota s s i um-Spa ri ng Di ureti cs: Ma y enha nce the a dvers e/toxi c effect of Ammoni um Chl ori de. Risk D: Consider therapy modification Moni tori ng Pa ra meters Serum bi ca rbona te; s i gns a nd s ymptoms of a mmoni a toxi ci ty Moni tori ng: La b Tes ts Serum bi ca rbona the Dos a ge Forms Exci pi ent i nforma ti on pres ented when a va i l a bl e (l i mi ted, pa rti cul a rl y for generi cs); cons ul t s peci fi c product l a bel i ng. Injecti on, s ol uti on: Ammoni um 5 mEq/mL a nd chl ori de 5 mEq/mL (20 mL) [equi va l ent to a mmoni um chl ori de 267. Bra nd Na mes Amyta l Ca na di a n Bra nd Na mes Amyta l Pha rma col ogi c Ca tegoryBa rbi tura the Us e: La bel ed Indi ca ti ons Hypnoti c i n s hort-term trea tment of i ns omni a; reduce a nxi ety a nd provi de s eda ti on preopera ti vel y Us e: Unl a bel ed/Inves ti ga ti ona l Thera peuti c or di a gnos ti c "Amyta l Intervi ewi ng"; Wa da tes t Dos i ng: Adul ts Hypnotic: I. Dos i ng: Hepa ti c Impa i rmentDos i ng s houl d be reduced; s peci fi c recommenda ti ons not a va i l a bl. Do not us e more tha n 5 mL a t a ny s i ngl e s i the (ma y ca us e ti s s ue da ma ge). Fol l owi ng recons ti tuti on, s ol uti on s houl d be us ed wi thi n 30 mi nutes. Compatibility when admixed: Compatible: Ami ka ci n, a mi nophyl l i ne, s odi um bi ca rbona te. Incompatible: Cefa zol i n, ci meti di ne, cl i nda myci n, di phenhydra mi ne, droperi dol, hydroxyzi ne, i ns ul i n (regul a r), l evorpha nol, meperi di ne, morphi ne, norepi nephri ne, pa ncuroni um, penta zoci ne, peni ci l l i n G pota s s i um, proca i ne, s treptomyci n, va ncomyci n. Variable (consult detailed reference): Atra curi um, di menhydri na te, hydrocorti s one s odi um s ucci na te, i s oproterenol, meta ra mi nol, methyl dopa te, norepi nephri ne, s ucci nyl chol i ne.
Production of Light (B-Cell) or Alpha (T-Cell) Chain of a Lymphocyte Antigen Receptor While heavy chain gene segments are undergoing recombination medications not to take when pregnant order norpace 100 mg fast delivery, the enzyme terminal deoxyribonucleotidyl transferase (Tdt) randomly inserts bases (without a template on the complementary strand) at the junctions of V medicine used to stop contractions norpace 150mg online, D symptoms of a stranger norpace 150 mg line, and J segments (N-nucleotide addition) symptoms 10dpo trusted 100 mg norpace. This generates even more diversity than the random combination of V, D, and J segments alone. Bridge to Pathology Tdt is used as a marker for early stage Tand B-cell development in acute lymphoblastic leukemia. Function of Tdt Needless to say, many of these gene segment rearrangements result in the production of truncated or nonfunctional proteins. When this occurs, the cell has a second chance to produce a functional strand by rearranging the gene segments of the homologous chromosome. If it fails to make a functional protein from rearrangement of segments on either chromosome, the cell is induced to undergo apoptosis or programmed cell death. Once a functional product has been achieved by one of these rearrangements, the cell shuts off the rearrangement and expression of the other allele on the homologous chromosome-a process known as allelic exclusion. This process ensures that B and T lymphocytes synthesize only one specific antigen-receptor per cell. Because any heavy (or) chain can associate with any randomly generated light (or) chain, one can multiply the number of different possible heavy chains by the number of different possible light chains to yield the total number of possible idiotypes that can be formed. There are only 2 isotypes of light chain constant domains, named and, and one will be combined with the product of light chain variable domain rearrangement to produce the other half of the final molecule. Thus, the B lymphocyte produces IgM and IgD molecules with identical idiotypes and inserts these into the membrane for antigen recognition. The bone marrow, therefore, is considered a primary lymphoid organ in humans because it supports and encourages these early developmental changes. B lymphocytes complete their entire formative period in the bone marrow and can be identified in their progress by the immunoglobulin chains they produce. B Lymphocyte Development In essence, the rearrangement of the gene segments and the subsequent production of immunoglobulin chains drive B-cell development. Because these gene segment rearrangements occur randomly and in the absence of stimulation with foreign antigen, it stands to reason that many of the idiotypes of receptors produced could have a binding attraction or affinity for normal body 19 Part I Immunology constituents. These cells, if allowed to develop further, could develop into selfreactive lymphocytes that could cause harm to the host. Therefore, one of the key roles of the bone marrow stroma and interdigitating cells is to remove such potentially harmful products. Cells whose idiotype has too great an affinity for normal cellular molecules are either deleted in the bone marrow (clonal deletion) or inactivated in the periphery (clonal anergy). Anergic B cells express high levels of IgD on their surface rendering them inactive. The elimination of self-reactive cells in the bone marrow is intended to minimize the number of self-reactive Blymphocytes released to the periphery, only those cells that are selectively unresponsive (tolerant) to self-antigens are allowed to leave the bone marrow. B-Cell Differentiation Surface IgG+, IgA+ or IgE+ T Lymphocyte Development Immature lymphocytes destined to the T-cell lineage leave the bone marrow and proceed to the thymus, the second primary lymphoid organ dedicated to the maturation of T cells. The thymus is a bilobed structure located above the heart; it consists of an outer cortex packed with immature T cells and an inner medulla into which cells pass as they mature. Both the cortex and medulla are laced with a network of epithelial cells, dendritic cells, and macrophages, which interact physically with the developing thymocytes. They are expressed in codominant fashion, meaning that each cell expresses 2 A, 2 B, and 2 C products (one from each parent). At this point in T-cell development, the thymocytes are referred to as being single positive. A total of 9599% of all T-cell precursors entering the thymus are destined to die there. It is responsible for reacting quickly to invading microbes and for keeping the host alive while the adaptive immune system is developing a very specific response. The innate immune defenses are all present at birth; they have a very limited diversity for antigen, and they attack the microbes with the same basic vigor no matter how many times they have seen the same pathogen. Pathogen Clearance by the Innate Immune System Microbes may gain access to the tissues if the physical barriers are breached. In the tissues, they come in contact with phagocytic cells such as neutrophils, macrophages and dendritic cells, which will produce chemical messengers called cytokines that can initiate an inflammatory response. Many times the innate immune components are enough to eliminate the pathogen, but not always. The pathogens may gain access to the blood, in which the alternate pathway for complement activation may provide some additional help.
Any el ecti ve s urgery s houl d be pos tponed for 1 yea r a fter s tent i mpl a nta ti on medicine quotes purchase norpace 150mg on line, a nd i f s urgery mus t be performed symptoms lactose intolerance cheap 150 mg norpace with amex, cons i dera ti on s houl d be gi ven to conti nui ng the a nti pl a tel et thera py duri ng the peri opera ti ve peri od i n hi gh-ri s k pa ti ents wi th drug-el uti ng s tents medications jokes order norpace toronto. Hema tol ogi c s i de effects ha ve ra rel y been reported; moni tor wi th cl oza pi ne medicine 4211 v buy norpace 150 mg, ca rba ma zepi ne, a nd va l proa te. In certa i n s i tua ti ons, pa ti ents ma y even be des ens i ti zed to a s pi ri n s o tha t they ma y recei ve a s pi ri n a nd cl opi dogrel concurrentl y. In thi s tri a l, the ri s k of ma jor bl eedi ng wa s s i gni fi ca ntl y i ncrea s ed i n the cl opi dogrel group a l though l i fe-threa teni ng bl eedi ng a nd hemorrha gi c s trokes were s i mi l a r i n both groups. More recentl y, however, a 600 mg l oa di ng dos e of cl opi dogrel wa s s hown to res ul t i n ma xi ma l pl a tel et i nhi bi ti on a t 2 hours (Hochhol zer W, 2005). Cl opi dogrel wa s conti nued for 28 da ys or unti l hos pi ta l di s cha rge whi chever ca me fi rs t. Pa ti ents i n the cl opi dogrel a rm ha d a s i gni fi ca ntl y l ower dea th ra the (7. Pa ti ents were ra ndomi zed to recei ve cl opi dogrel (300 mg l oa di ng dos e, then 75 mg da i l y) or pl a cebo unti l a ngi opl a s ty, di s cha rge, or Da y 8. Pa ti ents a l s o recei ved a s pi ri n (l oa di ng dos e fol l owed by 75-162 mg/da y). For pa ti ents wi th drug-el uti ng s tents who mus t undergo a procedure tha t requi res di s conti nua ti on of thi enopyri di ne thera py, a s pi ri n s houl d be conti nued i f pos s i bl e a nd the thi enopyri di ne res ta rted a s s oon a s pos s i bl e a fter the procedure. Thi s pa ti ent group i ncl uded thos e wi th mul ti pl e a therothromboti c ri s k fa ctors, documented corona ry, cerebrova s cul a r, or peri phera l va s cul a r di s ea s. The pri ma ry outcome mea s ure wa s a compos i the of myoca rdi a l i nfa rcti on, s troke, or dea th from ca rdi ova s cul a r ca us es. The ra tes of the s econda ry endpoi nts whi ch i ncl uded hos pi ta l i za ti ons for i s chemi c events, wa s 16. A pres peci fi ed s ubgroup a na l ys i s di vi ded pa ti ents i nto a "s ymptoma ti c" group (wi th documented ca rdi ova s cul a r di s ea s e) a nd a n "a s ymptoma ti c" group (wi thout documented ca rdi ova s cul a r di s ea s e). In the pa ti ents cons i dered s ymptoma ti c, the pri ma ry event ra the wa s l ower i n the cl opi dogrel group compa red to pl a cebo (6. In pa ti ents cons i dered a s ymptoma ti c, there wa s a 20% rel a ti ve i ncrea s e i n the pri ma ry event ra the (6. The ra the of dea th from ca rdi ova s cul a r ca us es wa s a l s o hi gher i n thi s group (3. Us e of cl opi dogrel i n a ddi ti on to l ow-dos e a s pi ri n ma y be ha rmful i n pa ti ents wi th mul ti pl e a therothromboti c ri s k fa ctors wi thout ca rdi ova s cul a r di s ea s. The Ameri ca n Col l ege of Ches t Phys i ci a ns recommends a ga i ns t the routi ne us e of cl opi dogrel (i n a ddi ti on to a s pi ri n) for pri ma ry preventi on unl es s the pa ti ent ha s a n a s pi ri n a l l ergy a nd i s a t modera te-to-hi gh ri s k for a ca rdi ova s cul a r event (Becker, 2008). Anes thes i a a nd Cri ti ca l Ca re Concerns /Other Cons i dera ti ons Perioperative Management of Clopidogrel: In pa ti ents wi th corona ry s tents, the ri s k of s tent thrombos i s becomes el eva ted dependi ng on the type of s tent depl oyed (ba re meta l vs drugel uti ng s tent) a nd the ti me from i mpl a nta ti on. Ea rl y di s conti nua ti on of cl opi dogrel ma y res ul t i n s tent thrombos i s l ea di ng to nonfa ta l a nd fa ta l myoca rdi a l i nfa rcti on. The peri opera ti ve recommenda ti ons for cl opi dogrel a re bel ow (Douketi s, 2008): Patients undergoing noncardiac surgery (low risk of cardiac event without coronary stent): Cl opi dogrel a nd other a nti pl a tel et a gents s houl d be tempora ri l y di s conti nued 5-10 da ys pri or to s urgery a nd res umed ~24 hours (or the next morni ng) a fter the procedure when a dequa the hemos ta s i s i s a chi eved. If a s pi ri n i s i nterrupted, i t s houl d be rei ni ti a ted 6-48 hours a fter s urgery; ma y res ume cl opi dogrel ~24 hours (or the next morni ng) a fter the procedure when a dequa the hemos ta s i s i s a chi eved. If i ncrea s ed bl eedi ng i s a nti ci pa ted, then the procedure s houl d be del a yed unti l the a nti pl a tel et regi men i s compl eted. A Sci ence Advi s ory From the Ameri ca n Hea rt As s oci a ti on, Ameri ca n Col l ege of Ca rdi ol ogy, Soci ety of Ca rdi ova s cul a r Angi ogra phy a nd Interventi ons, Ameri ca n Col l ege of Surgeons, a nd Ameri ca n Denta l As s oci a ti on Wi th Repres enta ti on from the Amerci a n Col l ege of Phys i ci a ns," Circulation, 2007, 115(6):813-8. Ka s tra ti A, Mehi l l i J, Schuhl en H, et a l, "A Cl i ni ca l Tri a l of Abci xi ma b i n El ecti ve Percuta neous Corona ry Interventi on After Pretrea tment Wi th Cl opi dogrel," N Engl J Med, 2004, 350(3):232-8. Dos i ng: Pedi a tri c Seizures (anticonvulsant): Ora l: Children 9-12 years: Ini ti a l: 3. Geri a tri c Cons i dera ti ons Due to i ts l ong-a cti ng meta bol i te, cl ora zepa the i s not cons i dered a drug of choi ce i n the el derl y. Pregna ncy Ri s k Fa ctorD La cta ti onExcreti on i n brea s t mi l k unknown/not recommended Brea s t-Feedi ng Cons i dera ti ons No s peci fi c da ta for cl ora zepa te; however, other benzodi a zepi nes ha ve been s hown to be excreted i n brea s t mi l k. Risk C: Monitor therapy Di s ul fi ra m: Ma y decrea s e the meta bol i s m of Benzodi a zepi nes (meta bol i zed by oxi da ti on).
