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Download NPLEX Combination Review Chapter 10 – Immunology / Toxicology
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NPLEX Combination Review Immunology / Toxicology Paul S. Anderson, ND Medical Board Review Services Copyright MBRS Laboratory Testing Methodologies • PCR: Polymerase Chain Reaction • ELISA(Enzyme Linked Immunosorbant Assay) – Measures IgG / M / A…Used 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. ID Immunology: General • Cultures – Take time – Some things grow, some don’t • 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 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 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). 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, Reiter’s, vasculitis, rheumatic fever, neonatal and post-operative infections, pyelonephritis, MI and embolism. 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, Reiter’s Syndrome, MS, chronic active hepatitis, gluten-sensitive enteropathy, SLE, DM and hemochromatosis. • Consider Chlamydia testing (Reiter’s) Autoimmune Disorders • Anti-thyroid antibody (Anti Microsomal or TPO Ab) – Used in diagnosis and classification of inflammatory and autoimmune thyroid disease. – Marker for Hashimoto’s thyroiditis, atrophic thyroiditis, and Grave’s Disease. • Antithyroglobulin Antibody (Anti TG) – Detect and confirm autoimmune thyroiditis, Hashimoto thyroiditis • Thyroid-Stimulating Immunoglobulin (Thytrophin Receptor Ab) – Detect Grave’s Dz. – Order when Grave’s Sn/Sx and TPO elevation THYROID HORMONE SYNTHESIS 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 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). • 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 • Hepatitis (A,B,C,D,E) virus – HAV: • IgM titers reflect acute infection. • IgG titers identified years after acute illness. – HBV: HbsAg: detected 1–4 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 • 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. • 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 • 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 Antimicrobial and Dermatologic Pharmacology Antifungal, helminthic and protozoal Pharmacology 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 Griseofulvin Fungicidal Tinea pedis, tinea unguium Also Tinea corporis, capitis and cruris Headache, dizziness, GI upset, nausea, vomiting, rash, urticaria, hepatic toxic Boric Acid Fungastatic agent Vaginal candidiasis Local irritation Gentian Violet Fungicidal Oral Candida Mouth rinse, may stain skin or clothing Acetic Acid [VoSol Otic] Inhibits or destroys bacteria in the ear Otic solution for external ear infections Ear irritation, urticaria “ Nausea, vomiting, vaginal burning or irritation with application, erythema, pruritus, increased liver function tests Teratogenic Do not use on ulcerative wounds on the face 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 Nystatin • Multiple forma available. • Topical kill – even in the GI tract. • GI Infections: – 500,000 – 1 Million Units po tid 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. Terbinafine • Fingernail onychomycosis: – 250mg qd for 6 weeks • Toenail onychomycosis: – 250mg qd for 12 weeks ANTIPARASITIC DRUGS Topical MOA Uses Adverse Effects 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 Mebendazole [Vermox] Irreversibly inhibits nutrient uptake by helminthes Pinworms, roundworms, hookworms Abdominal pain, diarrhea, fever Other Other 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 ANTIPARASITIC DRUGS 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 Potentates drugs metabolized by P450 system; ETOH (acts like Antabuse) Antimalarial MOA Uses Adverse Effects Chloroquine Unknown Malaria, extraintestinal amebiasis Headache, dizziness, pruritus, neuropathy, seizures, retinal changes and ototoxic Quinine Unknown Malaria Extremely toxic, cinchonism, shock Other ANTIPARASITIC DRUGS • Amebicide – Iodoquinol – Metronidazole (Flagyl) – Paromomycin sulfate (Humatin) • Anti Pneumocystis – Atovaquone (Mepron) – Pentamidine isethionate (Pneumopent) 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 Antibiotic Pharmacology 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): 1314–20. doi:10.1086/425009. PMID 15494908. ANTIMICROBIAL OVERVIEW • macrolides (Gent. / Tobra. & Streptomycin) (-floxacin’s) • quinolones So, Lets talk about side effects and antibiotic prescriptions: 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. 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. 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 “ NOTE: • All Rx’s 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 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 Cephalosporins Cephalexin [Keflex] 1st generation MOA Bactericidal by inhibiting cell wall synthesis Uses Adverse Effects Other 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] 2nd generation “ UTI, URI, OM “ “ Cefixime [Suprax] 3rd generation “ More resistant to Gram - lactamase producing organism “ “ Cefepime [Maxipime] 4th generation “ E.coli, Proteus, K.pneumoniae, Enterobacter, B.fragilis, Staph/Strep “ IV Dose form Rx: • Cefalexin 500 mg – # 30 – Sig 1 po q-6-h • Cefaclor 500mg – # 30 – Sig 1 po q-8-h 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 Contraindica ted in Pregnancy; caution with impaired renal function “ SAME LESS GI effect, Less medication needed to achieve effect. SAME Clarithromycin [Biaxin] “ Azithromycin [Zithromax] “ Bronchitis Nongonococcal urethritis, cervicitis, chanroid 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.) Tetracycline MOA Uses Adverse Effects Other Tetracycline Interferes with bacteria protein synthesis Susceptible Gram + and Gram – organisms including chlamydia and lyme disease Intracranial hypertension, GI distress, nausea, vomiting, diarrhea, rash, photosensitivity, increased pigmentation Not for use in children under 9 years old because of permanent discoloratio n of teeth enamel Interferes with oral contraceptive effectiveness Sebulytic (Acne) Doxycycline Minocycline “ “ “ Less nephrotoxic 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. 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. Sulfonamides MOA Uses Adverse Effects Other Co-trimoxazole / Trimethoprim/Sulf amethoxazole [Septra] / [Bactrim] Interfere with bacterial folic acid synthesis UTI, OM, URI, pneumocystis carinii, traveler’s diarrhea Nausea, vomiting, diarrhea, rash, seizures, toxic nephrosis, hepatic necrosis, dermatitis, SJS/TEN, anaphylaxis MANY Potential side effects. UTI, URI Sulfisoxazole [Gantrisin] Sulfamethoxazole [Gantanol] Sulfadiazin [Coptin] Interfere with oral contraceptive effectiveness 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 Patients Over 12 Years: One 100 mg capsule every 12 hours for seven days. Fluoroquinolones MOA Uses Adverse Effects Other Ciprofloxacin [Cipro] And all other “flox’s” Bactericidal by interfering with bacterial DNA synthesis Wide spectrum: URI, UTI, cutaneous infections, bone or joint infections, abdominal infections Rash, arthralgias, nausea, diarrhea, seizures, GI and CNS effects Can arrest growth plate in children Gatifloxacin [Tequin ] Levofloxacin [Levaquin ] Lomefloxacin Moxifloxacin [Avelox ] Norfloxacin [Noroxin] Ofloxacin [Ocuflox] Trovafloxacin [Trovan] Enoxacin Achilles' Tendon Rupture Do not use under age 18 Ciprofloxacin • 100 - 750 mg PO q-12-h • Dose based on severity of infection and current indication. • There is some variability of effectiveness among the various FQ agents. Aminoglycosides MOA Uses Adverse Effects Gentamicin [Garamycin] Bactericidal by interfering with bacterial DNA synthesis Use for serious infections of Enterobacter, E. coli, K. pneumonia, Pseudomonas Ototoxic, nephrotoxic, seizures, anaphylaxis, neurotoxic Kanamycin [Kantrex] Neomycin [Mycifradin] Severe Ototoxicity Netilmicin [Netromycin] Streptomycin Tobramycin [Nebcin] Paromomycin [Humatin] Pneumocystis pneumonia Antituberculosis MOA Uses Adverse Effects Other All are Hepatotoxic Isoniazid Inhibits cells wall synthesis in Mycobacterium tuberculosis TB Neuropathies, hepatotoxic, GI disturbance, fever, rash Rifampin Rifabutin Rifapentene Impares RNA synthesis TB TB TB MANY “ “ Pyrazinamide UNKNOWN TB Additive Tx. “ Give with B-6 Topical Antibiotics MOA Bacitracin [Bactin] Inhibits cell wall Topical synthesis of bacteria infections Skin rash, allergic dermatitis Neomycin [Neosporin] Disrupts bacterial protein synthesis Contact dermatitis, rash, may be Uses Topical bacterial infections Adverse Effects Other nephrotoxic or ototoxic Mupirocin [Bactroban] Bacterial RNA inhibition Impetigo, MRSA prophylaxis… Low Expensive Mupirocin Mupirocin Rx: • #1 - 15gram tube • Sig: Apply to affected areas bid Antiviral Pharmacology Antivirals MOA Uses Adverse Effects Acyclovir [Zovirax] Inhibits viral multiplication by interfering with DNA synthesis HSV types I & II, Varicella, Herpes encephalitis (Mollerets’ Syndrome) Nausea, vomiting, Valacyclovir [Valtrex] Famcyclovir [Famvir] Val. and Fam. both metabolize to Acyclovir in the body, but require lower dosing. headache, seizures, coma, rash Other Acyclovir • Genital herpes – Initial: 200mg q-4-h or 400mg q-8-h – Recurrent: 200 mg q-4-h (5X daily) – (I often add an rx for Acyclovir cream – bid) • Suppressive tx for recurrent genital herpes – 400 mg po bid • Varicella-Zoster – 800mg po q-4-h (5X daily) for 7-10 days Valacyclovir • Genital herpes – Initial: 1gram po bid X10 days – Recurrent: 500mg po bid X5 days • Suppressive tx for recurrent genital herpes – 9 or fewer outbreaks / year: 500 mg qd – >9: 1gram qd • Varicella-Zoster – 1gram po tid X 5-7 days Famcyclovir • Oral herpes – 1500mg as a single dose • Genital herpes – Initial: No data – Recurrent: 1000mg bid X 1 day • Suppressive tx for recurrent genital herpes – 250mg bid • Varicella-Zoster – 500mg q-8-h X 7 days ANTIVIRAL THERAPY - 2 • Human Herpes Virus 1 – 7 (except CMV) – Acyclovir, Valcyclovir, Famcyclovir • CMV – Cidofovir, Foscarnet, Gancyclovir • Hepatitis B&C – Interferon alpha, Pegylated Interferon – Ribavirin – Lamivudine (3tc) [Hepatitis B] • Influenza – Zanamivir – Oseitamivir ANTIVIRAL THERAPY – HIV • Nucleoside Reverse-transcriptase Inhibitors (NRTI) – Type A: Zidoiudine (ZDV), Stavudine (d4T) – Type B: Dianosine (ddl), Zalcitabidine (ddc), Lamivudine (3tc) – Other: Abacavir • Non Nucleoside Reverse-transcriptase Inhibitors (NNRTI) – Neuirapine – Delaviridine – Efavirenz • Protease Inhibitors – – – – – Saquinavir Idinavir Ritonavir Nelafavir Amprenavir • Triple Therapy: 2 NRTI’s and P.I. or NNRTI Biologics and Immune Modulating Drugs EICOSANOIDS MEMBRANE PHOSPHOLIPID Stimulated by: Angiotensin - 2 / Bradykinin / Epinephrine / Thrombin Phospholipase A2 Inhibited by: CORTICOSTEROIDS ARACHADONATE Inhibited by: Lipoxygenase LEUKOTRIENES Cyclooxygenase NSAID’S PROSTAGLANDINS / THROMBOXANES Leukotriene receptor antagonist • Pharmacology – Binds to cysteinyl leukotriene receptor 1 in the upper and lower airways to prevent leukotriene-mediated effects associated with asthma and allergic rhinitis. • Indications and Usage – Prophylaxis and chronic treatment of asthma in patients 12 mo of age and older; relief of symptoms of seasonal allergic rhinitis in patients 2 yr of age and older; relief of symptoms of perennial allergic rhinitis in patients 6 mo of age and older. – Prevention of exercise-induced bronchoconstriction (EIB) in patients 15 yr of age and older. • Unlabeled Uses – Chronic urticaria, atopic dermatitis. Leukotriene receptor antagonist Adverse Reactions • Cardiovascular – • CNS – • Arthralgia, myalgia (including muscle cramps) (postmarketing). Respiratory – • ALT/AST increased (2%); pyuria (1%). Musculoskeletal – • Cholestatic hepatitis, hepatocellular liver-injury, mixed-pattern liver injury (postmarketing). Lab Tests – • Bruising, eosinophilia, increased bleeding tendency (postmarketing). Hepatic – • Diarrhea, dyspepsia, gastroenteritis, laryngitis, nausea, tooth infection (at least 2%); dental pain, infectious gastroenteritis (2%); pancreatitis, vomiting (postmarketing). Hematologic-Lymphatic – • Conjunctivitis, ear pain, myopia, otitis, pharyngitis, rhinorrhea, sinusitis, tonsillitis (at least 2%); nasal congestion (2%); epistaxis (at least 1%). GI – • Atopic dermatitis, dermatitis, eczema, skin infection, urticaria (at least 2%); rash (2%); vasculitic rash (postmarketing). EENT – • Headache (18%); asthenia/fatigue, dizziness (2%); abnormal dreams, depression, drowsiness, hallucinations, insomnia, paraesthesia/hypoesthesia, psychomotor hyperactivity (including agitation, aggressive behavior, irritability, restlessness, and tremor), seizures (postmarketing). Dermatologic – • Cardiac complications, palpitations (postmarketing). Influenza (4%); cough (3%); acute bronchitis, pneumonia, upper respiratory tract infection, wheezing (at least 2%); worsening of pulmonary symptoms (postmarketing). Miscellaneous – Abdominal pain (3%); fever, varicella, viral infection (at least 2%); trauma (1%); edema, hypersensitivity (including anaphylaxis, hepatic eosinophilic infiltration, pruritus, and urticaria) (postmarketing). Leukotriene receptor antagonist • Montelukast Sodium Singulair - Tablets 10 mg - Tablets, chewable 4 mg - Tablets, chewable 5 mg - Granules 4 mg/packet Dose in adults: 10 mg QD ALSO: • Zafirlukast (za-FIR-loo-kast) Accolate • Zileuton Extended-Release Tablets Zyflo CR Extended-Release Tablets Zyflo CR Interferon • Any of a group of proteins produced by cells in the body in response to an attack by a virus. – A cell infected by a virus releases minute amounts of interferons, which attach themselves to neighboring cells, prompting them to start producing their own protective antiviral enzymes. – The result is impairment of the growth and replication of the attacking virus. Interferon has also been shown to have some antitumor properties. • There are three known classes of interferons: alpha-, beta-, and gamma-interferons. – Although they were discovered in the 1950s, the medical use of interferons was impractical until the recombinant DNA techniques of genetic engineering made it possible to mass produce them. – Interferons used as drugs include alpha-interferon, for hepatitis B and C, human papillomavirus, hairy-cell leukemia, and Kaposi's sarcoma, and beta-interferon, for multiple sclerosis. The Columbia Encyclopedia. Copyright © 2001-08 Columbia University Press. All rights reserved. GENERIC: Interferon BRAND NAMES: Roferon-A, Intron-A, Rebetron, Alferon-N, Peg-Intron, Avonex, Betaseron, Infergen, Actimmune, Pegasys • Classes: – Alpha, beta and gamma. • Actions: – direct the immune system's attack on viruses, bacteria, tumors and other foreign substances that may invade the body. • Used in: – Leukemia, Hepatitis B, C, Genital Warts – The beta interferons have been found useful in managing MS • Adverse Effects: – – – – Flu-like symptoms following each injection occur with all interferons. Depression and suicide are possible, but not common HYPOTHYROIDISM Other side effects with all interferons (may be caused by higher doses) • • • • • • Fatigue diarrhea, nausea, vomiting, abdominal pain, anorexia joint aches, back pain and dizziness. congestion, increased heart rate, confusion, low white blood cell count, low platelet count, low red blood cell count, increase in liver enzymes, increase in triglycerides, Immune Cell Lines Thymus: Bone Marrow: Hemocytoblast Lymphoid Stem Cells Lymphoid Stem Cells T-Cell Lines B-Cells NK Cells Peripheral Tissues: Cell Mediated Immunity Ab (Humoral) Immunity Immunological Surveillance Tacrolimus • Pharmacology – Suppresses cell-mediated immune reactions and some humoral immunity, but exact mechanism is not known. The mechanism of action in atopic dermatitis is not known. • Indications and Usage – PO and IV Prophylaxis of organ rejection in patients receiving allogenic liver, kidney, or heart transplants. Used in conjunction with adrenal corticosteroids. – Topical As second-line therapy for the short-term and noncontinuous chronic treatment of moderate to severe atopic dermatitis. • Unlabeled Uses – PO and IV Prophylaxis of rejection for patients receiving bone marrow, pancreas, pancreatic island cell, and small bowel transplantation. – Topical Treatment of vitiligo in children; facial, flexural, and intertriginous psoriasis. Tacrolimus Dosage and Administration • Prophylaxis of Organ Rejection, Liver Transplants Adults PO 0.1 to 0.15 mg/kg/day in 2divided daily doses every 12 h no sooner than 6h after transplantation. IV 0.03 to 0.05mg/kg/day as continuous infusion. • Children PO 0.15 to 0.2 mg/kg/day in 2divided daily doses every 12 h. IV 0.03 to 0.05mg/kg/day as continuous infusion. • Topical Dermatitis Adults Topical Apply thin layer of 0.03% or 0.1% to affected skin areas twice daily; rub in gently and completely; continue for 1 wk after clearing of atopic dermatitis. • Children (2 yr of age and older) Topical Apply thin layer of 0.03% to affected skin areas twice daily; rub in gently and completely; continue for 1 wk after clearing of atopic dermatitis. General Advice • Do not use occlusive dressings with topical use. Tacrolimus Pronouncation: (tak-ROE-li-mus) Trade Names: Prograf - Capsules 0.5 mg - Capsules 1 mg - Capsules 5 mg - Injection 5 mg/mL Trade Names: Protopic - Ointment 0.03% - Ointment 0.1% Pimecrolimus Dosage Form: Cream 1% • TRADE NAME: Elidel® FOR DERMATOLOGIC USE ONLY NOT FOR OPHTHALMIC USE Elidel ® (pimecrolimus) Cream 1% contains the compound pimecrolimus, the immunosuppressant 33-epi-chloroderivative of the macrolactam ascomycin. Pimecrolimus Indications and Usage for Elidel • Elidel ® (pimecrolimus) Cream 1% is indicated as second-line therapy for the short-term and noncontinuous chronic treatment of mild to moderate atopic dermatitis in non-immunocompromised adults and children 2 years of age and older, who have failed to respond adequately to other topical prescription treatments, or when those treatments are not advisable. • Elidel Cream is not indicated for use in children less than 2 years of age (see WARNINGS, boxed WARNING, and PRECAUTIONS, Pediatric Use). LOCAL AND SURFACE ACTING DRUGS Protectants MOA Uses Petroleum Moisturizing skin protectant Apply to skin surrounding wart before removing Topical analgesics MOA Capsaicin [Zostrix] Likely depletes substance P Other occlusive products Adverse Effects Other Uses Adverse Effects Other Topical for pain associated with HSV, neuralgia, diabetic neuropathies OA, RA Stinging or burning pain upon application, may irritate respiratory passages External use only – NEVER on mucus membranes / eyes! Antiinflammatory MOA Uses Adverse Effects Other Inflammation, antipruritic, vasoconstictive, antiproliferative Atrophy, pruritus, irriation, similar effects of oral steroids Weakly active! Hydrocortisone Unknown; chemical identical to that of cortisol Triamcinolone Betamethasone Etc… Longer acting, MUCH more potent than hydrocortisone Calcipotriene (Dovonex) Vit. D3 analog Psoriasis Inflammation Niacinamide ointment Vit B-3 Acne Few Tretinoin (Retin-A) Retinoic Acid Acne Rebound inflammation Isotretinoin (Accutane) ORAL DRUG Severe Acne Teratogenic Pseudotumor cerebri “ “ Inhaled & intranasal version for asthmatics 3-5% Concentration Must have negative PG test Consent needed Miscellaneous Chelators: MOA Uses Adverse Effects Penicillamine Chelates heavy metals, esp. copper Wilson’s Disease, RA, mercury or lead poisoning Optic neuritis, GI distress, stomatitis, nephrotic syndrome, GN, leukopenia, skin rash, arthralgia EDTA Chelates metals, lead, calcium, aluminum… Lead poisoning, Na-EDTA (Long IV format) hypercalcemia excessive doses: renal failure, tubular necrosis Hypocalcemia , Ca-EDTA (Shorter IV format) DMPS Generally IV form. Mercury poisoning Hypomagnesmeia Headaches, depression and suicidal thoughts usually due to the mercury poisoning Can be used for Tx. Chelates mercury, and some other heavy metals. Oral pharmaceutical for Mercury, heavy metal and lead detoxification. Headache and joint pain from detoxification process Hypercalcemia Used for provocative heavy metal testing. DMSA [Chemet] Other Lead, mercury, or other heavy metal poisoning Same as DMPS Detoxing affects the endocrine system: watch for fatigue, anger, mood-swings; Supplement with water and detox supplements. Schedule and can take year(s) depending on the individual