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Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,#,NPLEX Combination ReviewImmunology / Toxicology,Paul S. Anderson, ND,Medical Board Review Services,Copyright MBRS,NPLEX Combination ReviewImmun,1,Laboratory Testing Methodologies,PCR: Polymerase Chain Reaction,ELISA,(Enzyme Linked Immunosorbant Assay) Measures IgG / M / AUsed in disease detection and Allergen identification.,RAST,Quantifies IgE antibodies.,Intradermal testing,Positive reaction demonstrates erythema at point of injection.,Blood immunoglobins,IgG Delayed hypersensitivity reaction to antigen.,IgE Immediate hypersensitivity reaction to antigen.,Electrodermal allergy test,EAV is appropriate example.,Laboratory Testing Methodologi,2,ID Immunology: General,Cultures,Take time,Some things grow, some dont,Antibody Testing,Good for effect,Some better than others,DNA (PCR) Testing,Detects DNA of the subject of the probe,No need for growing a culture,No need for Ig interpretation,Can get Quantitative (viral load) tests,ID Immunology: GeneralCultures,3,Antibody Testing,Serum tests.,Serum must be separated from clot / SST Gel within 1 hour!,Pipette serum into a plastic transport tube,Excessive exposure to the gel in the SST will bind antibodies, causing false negative tests.,Used for allergy testing, Autoimmune testing, Exposure,Ig (Immunoglobulin) Types:,IgG: Long term exposure, Delayed reactions (ie. Food allergy).,IgG lasts a long time, and is a,marker of EXPOSURE, not successful treatment.,IgM: Acute phase reactions.,Indicates recent infection or re-exposure.,IgA: Secretory Ig.,Shows mucosal response, and,is a good marker of successful treatment.,Can be measured in the,serum, stool and saliva,IgE: Anaphylaxis. (Type-1 Reaction).,Total IgE in serum is a test for general allergic level in the patient,Traditionally the marker used for food and Inhalant allergy, although IgG is more helpful with most food reactions.,Antibody TestingSerum tests.,4,Antibody Testing - 2,High IgG, Low IgM or IgA,Probable past infection / exposure. Inactive or cured.,In food allergy testing IgG is always considered active, but delayed response allergy.,Low IgG, High IgM,New infection / Exposure,High IgG, High IgM,Reactivated infection / Exposure,High IgG, Low IgM, High IgA,Current immune response (mucosal) that is past the initial IgM response window. (On going problem).,Antibody Testing - 2High IgG,5,Autoimmune Disorders,Anti-nuclear antibody (ANA),Titer level is important: 1:160 “positive”,Screening test for connective-tissue diseases: RA, SLE, Lupus, MCTD, CREST Syndrome, Scleroderma, and Polymyositis.,Use confirmatory ANA sub-testing to confirm specific disease Dx.,Often ordered as ANA + Reflex (7 or 9 values) run if ANAA is positive,Erythrocyte Sedimentation Rate (ESR),Nonspecific measure of inflammation,Diagnostic in very few conditions (Giant cell arteritis),Can also indicate cancerous effect,C-reactive protein (CRP),Screening for nondescriptive inflammatory and infection disease processes. Also used for discriminating among DDX and monitoring disease process,CRP elevation: RA, Reiters, vasculitis, rheumatic fever, neonatal and post-operative infections, pyelonephritis, MI and embolism.,Autoimmune DisordersAnti-nucle,6,Autoimmune Disorders,Rheumatoid factor (RF),Used in the diagnosis and evaluation of RA and other CTD; Highest in RA, but also elevated in CVD, MI, renal disease, malignancy, thyroid and liver disease, SLE, scleroderma and polyarteritis nodosa.,Parvo B-19 viral assay,Consider in RF Negative woman nursing or caring for a young child who presents with RA like symptoms.,Human leukocyte antigen (HLA) HLA B-27 most common.,Glycoproteins that may be serologically determined; usually performed for transplantation matches but also elevated in AS, Reiters Syndrome, MS, chronic active hepatitis, gluten-sensitive enteropathy, SLE, DM and hemochromatosis.,Consider Chlamydia testing (Reiters),Autoimmune Disorders,7,Autoimmune Disorders,Anti-thyroid antibody (Anti Microsomal or TPO Ab),Used in diagnosis and classification of inflammatory and autoimmune thyroid disease.,Marker for Hashimotos thyroiditis, atrophic thyroiditis, and Graves Disease.,Antithyroglobulin Antibody (Anti TG),Detect and confirm autoimmune thyroiditis, Hashimoto thyroiditis,Thyroid-Stimulating Immunoglobulin,(Thytrophin Receptor Ab),Detect Graves Dz.,Order when Graves Sn/Sx and TPO elevation,Autoimmune DisordersAnti-thyro,8,THYROID HORMONE SYNTHESIS,THYROID HORMONE SYNTHESIS,9,Infectious Disease Testing,Anti-Streptolysin-O test (ASO) (200iu/ml),Elevation in titers reflect immunologic response to streptococcus;,ASO titers clinically useful if serum is obtained in 2-3 week intervals.,Chlamydia antibody (IgG, IgM),Presence of IgG Ab indicates chlamydial infection in the past; highly sensitive but has low specificity.,Presence of IgM or 4-fold increase from acute convalescence = recent infection.,Cytomegalovirus PCR,Cytomegalovirus (CMV- IgG, IgM),Presence of IgM or 4-fold increase in IgG = recent infection,Infectious Disease TestingAnti,10,Infectious Disease Testing,Epstein-Barr Virus (EBV),Monospot: Screening test performed with symptomatic Pt.,(false negative in adults 10%).,Measures IgM heterophil antibodies.,Positive window: 4-21 days,PCR for EBV:,Most sensitive test is Quantitative (viral load) PCR,Used in Chronic reactivating cases,EBV Panel:,Early phase, IgM: anti-VCA,Acute illness, IgG: anti-VCA,Acute illness, IgG anti-EA,Convalescence, Anti-EBNA (Indicates past infection OR Chronic reactivation in recurrent EBV patients).,Infectious Disease TestingEpst,11,E. coli,O157-H7 specific assay,Stool,Giardia,Stool assay in symptomatic patient,Helicobacter pylori,Multiple methodologies:,Nitrogen breath test (Sensitive for presence of dz and tx),Serum IgG: (Sensitive for PAST infection but will not decrease with successful tx.),Serum IgM: (Sensitive for current infection but will decrease in 2-4 weeks regardless of infection.),Serum, Salivary or Stool IgA: (Rises with presence of infxn / falls with effective tx.),Stool IgA is preferred test now by IDSA,E. coli,12,Hepatitis (A,B,C,D,E) virus,HAV,:,IgM titers reflect acute infection.,IgG titers identified years after acute illness.,HBV,: HbsAg: detected 14 months post-infection.,Patients with this antigen present 6 months exhibit chronic hepatitis.,ANTI-HBs Ab:,Patients with this Ab are considered protected against the HBV infection,HbcAg ,IgM,most useful marker to determine the “window”: (HbsAg disappears and ANTI HbsAg appears; usually demonstrates present infection.),The presence of ANTI HbcAg,IgG,indicates previous HBV infection and persists indefinitely.,HCV, Ab Patients with this Ab have four-fold increase for HCC,HCV PCR is available as well.,HDV,-,co-exists with hepatitis b infection,. Maked Hep-B more deadly. Worst in pregnancy.,HEV, Not generally tested for: cases out of U.S.,Test if foreign travel in the past 60 days,Hepatitis (A,B,C,D,E) virus,13,Herpes simplex virus (HSV-1; HSV-2),Antibodies:,IgM Current infection.,IgG Infection in the past.,IgG/M Type (1or2) specific serology is best DDX,PCR is available,Virus isolation (,Tzank smear,) is OLD method to confirm an HHV infection:,Can have false positives if other HHV infection is present,NOT specific to HHV 1 or 2,Generally*,HSV 1 above waist while HSV 2 affects below waist. But this is not always the case.,Herpes simplex virus (HSV-1; H,14,Human Immunodeficiency Virus (HIV),Standard method for diagnosis:,ELISA measured anti-HIV titers. Confirmed by Western Blot Analysis.,(MAY TAKE 6 MONTHS TO SERO-CONVERT),Decreased CD4/CD8 ratio,Newly diagnosed condition:,T-Cell subset (CD3, CD4, CD8).,Earliest diagnosis: PCR for HIV,Human Papilloma Virus (6,11,16,18,31,33),HPV 16, 18, 31, 33 are common causes for cervical cancer.,Available as PCR on Pap sample,HPV 6, 11 common causes for plantar and genital warts.,NOT generally cancerous or pre-cancerous,Human Immunodeficiency Virus (,15,Rubella titer,Presence of IgM and / or four-fold increase in IgG = present infection.,Syphyllis (VDRL / RPR),Nontreponemal tests used primarily for detection of primary syphilitic infection.,Tuberculosis,Intradermal skin test: Read 48-72 hours for induration.,BCG: Post ID; check serology results.,Lyme disease ( 250 antibody reaction units),Skin, blood, synovial or CSF.,ELISA or Western blot checking for antibody detection.,PCR Now available,Rubella titer,16,Antimicrobial and Dermatologic Pharmacology,Antimicrobial and Dermatolog,17,Antifungal, helminthic and protozoal Pharmacology,Antifungal, helminthic and pro,18,Antifungals,MOA,Uses,Adverse Effects,Other,Nystatin,Disrupts fungal cell wall,Intestinal, cutaneous, vaginal and mucocutaneous infections caused by Candida,Contact dermatitis,Poorly or not absorbed. Good topical agent / GI Agent.,Miconazole,Disrupts fungal cell wall,Tinea pedis, cruris, versicolor, corporis, cutaneous candida infection and vulvovaginal candidiasis,Pruritus, skin irritation, burning, contact dermatitis,Clotrimazole,Disrupts fungal cell wall,“,Nausea, vomiting, vaginal burning or irritation with application, erythema, pruritus, increased liver function tests,Griseofulvin,Fungicidal,Tinea pedis, tinea unguium,Also Tinea corporis, capitis and cruris,Headache, dizziness, GI upset, nausea, vomiting, rash, urticaria, hepatic toxic,Teratogenic,Boric Acid,Fungastatic agent,Vaginal candidiasis,Local irritation,Gentian Violet,Fungicidal,Oral Candida,Mouth rinse, may stain skin or clothing,Do not use on ulcerative wounds on the face,Acetic Acid,VoSol Otic,Inhibits or destroys bacteria in the ear,Otic solution for external ear infections,Ear irritation, urticaria,AntifungalsMOAUsesAdverse Effe,19,ANTIFUNGAL,DRUGS - 2,Amphotericin,I.V. Only (unless compounded),Two types,Strong / High potential side effect profile (I.V.),Triazole class,Fluconazole (,Diflucan,),Inhibits Fungal p-450, degrading fungal cell wall,Ketoconazole (,Nizoral,),Itraconazole (,Sporonox,),Voriconazole (,V-Fend,),Terbinafine (,Lamisil,),Topical and Oral forms,ANTIFUNGAL DRUGS - 2Amphoteric,20,Nystatin,Multiple forma available.,Topical kill even in the GI tract.,GI Infections:,500,000 1 Million Units po tid,NystatinMultiple forma availab,21,Fluconazole,Absorbs so more systemic kill and more systemic side effect.,Primary site of activity Liver,Dosing strategies vary widely based on immunocompetence and type of infection.,May be as low as 150-200mg in a single dose for uncomplicated fungal vulvovaginosis to as much as 200 mg bid for long term (2-4 weeks), or 100mg daily for months.,If using it long term I normally treat on a 5 days on / 2 days off rotation.,FluconazoleAbsorbs so more s,22,Terbinafine,Fingernail onychomycosis:,250mg qd for 6 weeks,Toenail onychomycosis:,250mg qd for 12 weeks,TerbinafineFingernail onychomy,23,ANTIPARASITIC DRUGS,Topical,MOA,Uses,Adverse Effects,Other,Lindane,Kwell,Penetrates exoskeleton inducing seizures and death of arthropods,Scabies, pediculosis,Seizures, irritation, CNS disturbance,Permethrin,Elimite,/,Nix,Causes paralysis by disrupting sodium current in the parasite,Scabies, pediculosis,Pruritus, edema, rash, burning, or stinging,Antihelminthics,MOA,Uses,Adverse Effects,Other,Mebendazole,Vermox,Irreversibly inhibits nutrient uptake by helminthes,Pinworms, roundworms, hookworms,Abdominal pain, diarrhea, fever,ANTIPARASITIC DRUGSTopicalMOAU,24,Mebendazole,Pinworm:,100mg po as a single dose.,Repeat in 2-3 weeks,Roundworm, Whipworm, Hookworm:,100mg po bid X 3 days,Repeat in 3 weeks,MebendazolePinworm:,25,Antiprotozoal,MOA,Uses,Adverse Effects,Other,Metronidazole,Inhibits DNA synthesis in microorganism causing cell death,Amoebas, trichomoniasis, giardia,GI distress, seizures, ataxia, cramping, rash, joint pain.,*,Do not take with ETOH (acts like Antabuse),Potentates drugs metabolized by P450 system;,Antimalarial,MOA,Uses,Adverse Effects,Other,Chloroquine,Unknown,Malaria, extraintestinal amebiasis,Headache, dizziness, pruritus, neuropathy, seizures, retinal changes and ototoxic,Quinine,Unknown,Malaria,Extremely toxic, cinchonism, shock,ANTIPARASITIC DRUGS,AntiprotozoalMOAUsesAdverse Ef,26,Amebicide,Iodoquinol,Metronidazole (,Flagyl,),Paromomycin sulfate (,Humatin,),Anti Pneumocystis,Atovaquone (,Mepron,),Pentamidine isethionate (,Pneumopent,),ANTIPARASITIC DRUGS,Amebicide ANTIPARASITIC DRUGS,27,Metronidazole,Intestinal amebiasis,750mg po bid 5-7 days, then iodoquinol Rx.,Trichomoniasis,750mg po tid X 7 days OR 1 gram po bid X 1 day: Repeat this dose Rx in 4-6 weeks.,Bacterial vaginosis,500mg po bid X 7days,MetronidazoleIntestinal amebia,28,Antibiotic Pharmacology,Antibiotic Pharmacology,29,Antibiotic classes and Targets,Bactericidal antibiotics that target bacterial cell wall;,penicillins, cephalosporins,or cell membrane;,polymixins,or interfere with essential bacterial enzymes;,quinolones, sulfonamides usually,Bacteriostatic ABX are those which target protein synthesis;,aminoglycosides, macrolides and tetracyclines,Adapted from: Finberg RW, Moellering RC, Tally FP, et al (November 2004). The importance of bactericidal drugs: future directions in infectious disease. Clin. Infect. Dis.,39,(9): 131420. doi:10.1086/425009. PMID 15494908.,Antibiotic classes and Targets,30,ANTIMICROBIAL OVERVIEW,(Gent. / Tobra. & Streptomycin),(-floxacins),macrolides,quinolones,ANTIMICROBIAL OVERVIEW (Gent.,31,So,Lets talk about side effects and antibiotic prescriptions:,So,Lets talk about side effec,32,Antibiotics:,GI Tract,Symbiotic beneficial flora kill,Overgrowth of flora - dysbiosis,Pseudomembranous Colitis (C. diff),Kidneys,Most ABX are polar. Lots of Ki excretion,Often in IV use they can cause Ki failure if administered improperly,Liver,Liver effect possible, but less common than Ki,“Superinfection”,Systemic infection with bacteria or fungi that are not effected by the ABX you have given like a systemic dysbiosis.,Antibiotics:GI Tract,33,ABX and “Good Flora” Supplements,ABX given with beneficial flora supplements (acidophilus, bifidus) will kill many of those bugs as well.,Some wait to repopulate the gut until after the Rx.,If you are concerned that the patient will get too behind (ie too much good flora kill) you may supplement beneficial flora during the ABX course, AND after.,If doing this DO NOT have the patient take the good flora supplement while the ABX pills are in the stomach.,Alternate time of dose between flora and ABX.,ABX and “Good Flora” Supplemen,34,NPLEXCombinationReviewChapter10Immunology自然疗法医师注册考试复习10章结合免疫学课件,35,Penicillin,MOA,Uses,Adverse Effects,Other,Penicillin,(Pen Vee-K),Break down / Inhibit bacterial cell wall synthesis,Gram + cocci, anaerobic bacteria, syphilis,Nausea, vomiting, rash, seizures, anaphylaxis, neurotoxic, nephrotoxic,Not effective against,-lactamase producing organism or Gram anaerobes,Ampicillin,Inhibits cell wall synthesis,Some Gram + and Gram organisms, prophylaxis for dental procedures,Nausea, vomiting, diarrhea, seizures, rash, urticaria, anaphylaxis,Not effective against,-lactamase producing organism,Amoxicillin,Inhibits cell wall synthesis,Some Gram + and Gram organisms, prophylaxis for dental procedures,“,Amoxicillin and Clavulanate,Augmentin,Inhibits cell wall synthesis and,Clavulanate makes it effective against,-lactamase producing organisms,Gram +, Gram -, and,-lactamase producing organism,“,PenicillinMOAUsesAdverse Effec,36,NOTE:,All Rxs are for the longer term,(i.e. 10 day instead of 7 day).,Some INDICATIONS REQUIRE FEWER Tx days see Sanford Guide etc.,All are in Adult Doses unless otherwise noted.,An “Adult” is a 150 Pound Human,NOTE:All Rxs are for the long,37,Rx:,Adult:,PEN-VK 500mg tablets,#30,Sig: 1 po tid,Child:,Amoxicillin (Or Amox / Clav),80-90 mg/kg of the amoxicillin component in daily divided doses. Rx X 7-10 days,Rx:Adult:,38,Cephalosporins,MOA,Uses,Adverse Effects,Other,Cephalexin,Keflex,1,st,generation,Bactericidal by inhibiting cell wall synthesis,URI, GI infections, cutaneous infections, soft tissue infections,Nausea, diarrhea, maculopapular rash, anaphylaxis, serum sickness, GI distress,10-15% of patients have cross allergy between penicillin and cephlosporins,Cefaclor,Ceclor,2,nd,generation,“,UTI, URI, OM,“,“,Cefixime,Suprax,3,rd,generation,“,More resistant to Gram -,-lactamase producing organism,“,“,Cefepime,Maxipime,4,th,generation,“,E.coli, Proteus,K.pneumoniae, Enterobacter, B.fragilis, Staph/Strep,“,IV Dose form,CephalosporinsMOAUsesAdverse E,39,Rx:,Cefalexin 500 mg,# 30,Sig 1 po q-6-h,Cefaclor 500mg,# 30,Sig 1 po q-8-h,Rx:Cefalexin 500 mg,40,Macrolides,MOA,Uses,Adverse Effects,Other,Erythromycin,Interferes with bacterial DNA synthesis,Drugs of choice for,M.pneumonia, pertussis, neonatal C.pneumonia Strep throat, URI,Abdominal pain, nausea, diarrhea, vomiting,anaphylaxis,Contraindicated in Pregnancy,; caution with impaired renal function,Clarithromycin,Biaxin,“,Bronchitis,Non-gonococcal urethritis, cervicitis, chanroid,“,SAME,Azithromycin,Zithromax,“,LESS GI effect, Less medication needed to achieve effect.,SAME,MacrolidesMOAUsesAdverse Effec,41,Rx:,Erythromycin 333mg,#30,Sig 1 tid,(I use this as it is less GI upsetting than the 500 mg strength I give WITH food),Erythromycin 500mg,#20,Sig 1 bid,Azithromycin 250mg,#6 (“Z-Pak”),Sig 2 po Day-1, 1 po qd days 2-5,(Some suggest #3 (“3-Pak) in uncomplicated dz.),Rx:Erythromycin 333mg,42,Tetracycline,MOA,Uses,Adverse Effects,Other,Tetracycline,Interferes with bacteria protein synthesis,Susceptible Gram + and Gram organisms including chlamydia and lyme disease,Sebulytic (Acne),Intracranial hypertension, GI distress, nausea, vomiting, diarrhea, rash, photosensitivity, increased pigmentation,Not for use in children under 9 years old because of permanent discoloration of teeth enamel,Interferes with oral contraceptive effectiveness,Doxycycline,Minocycline,“,“,“,Less nephrotoxic,TetracyclineMOAUsesAdverse Eff,43,Doxycycline,General oral Rx:,Doxycycline 100 mg tablets,Sig: 1 po q-12-h,Treat for 7 days for most infections,(Acne prophylaxis 50-100mg, qd-bid),Doxy is INEXPENSIVE.,DoxycyclineGeneral oral Rx:,44,Minocycline,General oral Rx:,Minocycline 100 mg tablets,Sig: 1 po q-12-h,Treat for 7 days for most infections,(Acne prophylaxis 50-100mg, qd-bid),Minocycline is 95% absorbed in the stomach, and has a very low GI flora kill rate.,MinocyclineGeneral oral Rx:,45,Sulfonamides,MOA,Uses,Adverse Effects,Other,Co-trimoxazole / Trimethoprim/Sulfamethoxazole,Septra / Bactrim,Sulfisoxazole,Gantrisin,Sulfamethoxazole,Gantanol,Sulfadiazin,Coptin,Interfere with bacterial folic acid synthesis,UTI, OM, URI, pneumocystis carinii, travelers diarrhea,UTI, URI,Nausea, vomiting, diarrhea,rash, seizures, toxic nephrosis, hepatic necrosis, dermatitis,SJS/TEN,anaphylaxis,MANY Potential side effects.,Interfere with oral contraceptive effectiveness,SulfonamidesMOAUsesAdverse Eff,46,Nitrofurantoin monohydrate/ macrocrystals TRADE NAME: Macrobid,Specific UTI Indication,CONTRAINDICATIONS:,Anuria, oliguria, or significant impairment of renal function (creatinine clearance under 60 mL per minute or clinically significant elevated serum creatinine) are contraindications. Treatment of this type of patient carries an increased risk of toxicity because of impaired excretion of the drug.,Because of the possibility of hemolytic anemia due to immature erythrocyte enzyme systems (glutathione instability), the drug is contraindicated in pregnant patients at term (38-42 weeks gestation), during labor and delivery, or when the onset of labor is imminent. For the same reason, the drug is contraindicated in neonates under one month of age.,DOSAGE AND ADMINISTRATION:,Macrobid capsules should be taken with food.,Adults and Pediatric Patient
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