nplex combination review immunology / toxicology paul s. anderson, nd medical board review services...
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NPLEX Combination ReviewImmunology / Toxicology
Paul S. Anderson, ND
Medical Board Review Services
Copyright MBRS
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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.
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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
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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.
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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).
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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.
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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)
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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
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THYROID HORMONE SYNTHESIS
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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
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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).
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• 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
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• 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
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• 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.
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• 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
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• 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
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Antimicrobial and
Dermatologic
Pharmacology
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Antifungal, helminthic and protozoal Pharmacology
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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 unguiumAlso 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
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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
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Nystatin
• Multiple forma available.
• Topical kill – even in the GI tract.
• GI Infections:– 500,000 – 1 Million Units po tid
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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.
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Terbinafine
• Fingernail onychomycosis:– 250mg qd for 6 weeks
• Toenail onychomycosis:– 250mg qd for 12 weeks
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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
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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
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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
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• Amebicide – Iodoquinol– Metronidazole (Flagyl)– Paromomycin sulfate (Humatin)
• Anti Pneumocystis– Atovaquone (Mepron)– Pentamidine isethionate (Pneumopent)
ANTIPARASITIC DRUGS
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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
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Antibiotic Pharmacology
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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.
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ANTIMICROBIAL OVERVIEW
(Gent. / Tobra. & Streptomycin)
(-floxacin’s)
• macrolides
• quinolones
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So,Lets talk about side effects and
antibiotic prescriptions:
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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.
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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.
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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
“
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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
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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
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Cephalosporins MOA Uses Adverse Effects Other
Cephalexin[Keflex] 1st 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]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
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Rx:
• Cefalexin 500 mg– # 30– Sig 1 po q-6-h
• Cefaclor 500mg– # 30– Sig 1 po q-8-h
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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]
“ BronchitisNon-gonococcal urethritis, cervicitis, chanroid
“ SAME
Azithromycin[Zithromax]
“ LESS GI effect, Less medication needed to achieve effect.
SAME
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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.)
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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 enamelInterferes with oral contraceptive effectiveness
Doxycycline Minocycline
“ “ “ Less nephrotoxic
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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.
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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.
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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, traveler’s 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
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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.
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Fluoroquino-lones
MOA Uses Adverse Effects Other
Ciprofloxacin[Cipro]And all other “-flox’s”
Gatifloxacin [Tequin ]Levofloxacin [Levaquin ]Lomefloxacin Moxifloxacin [Avelox ]Norfloxacin [Noroxin] Ofloxacin [Ocuflox] Trovafloxacin [Trovan] Enoxacin
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
Achilles' Tendon Rupture
Can arrest growth plate in children
Do not use under age 18
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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.
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Aminoglycosides MOA Uses Adverse Effects
Gentamicin [Garamycin] Kanamycin [Kantrex]
Neomycin [Mycifradin]
Netilmicin [Netromycin] Streptomycin
Tobramycin [Nebcin]
Paromomycin [Humatin]
Bactericidal by interfering with bacterial DNA synthesis
Use for serious infections of Enterobacter, E. coli, K. pneumonia, Pseudomonas
Pneumocystis pneumonia
Ototoxic, nephrotoxic, seizures, anaphylaxis, neurotoxic
Severe Ototoxicity
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Antituberculosis MOA Uses Adverse Effects Other
Isoniazid
RifampinRifabutinRifapentene
Pyrazinamide
Inhibits cells wall synthesis in Mycobacterium tuberculosis
Impares RNA synthesis
UNKNOWN
TB
TBTBTB
TB Additive Tx.
Neuropathies, hepatotoxic, GI disturbance, fever, rash
MANY““
“
All are Hepatotoxic
Give with B-6
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Topical Antibiotics
MOA Uses Adverse Effects Other
Bacitracin[Bactin]
Inhibits cell wall synthesis of bacteria
Topical infections
Skin rash, allergic dermatitis
Neomycin [Neosporin]
Disrupts bacterial protein synthesis
Topical bacterial infections
Contact dermatitis, rash, may be nephrotoxic or ototoxic
Mupirocin[Bactroban]
Bacterial RNA inhibition
Impetigo, MRSA prophylaxis…
Low Expensive
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Mupirocin
Mupirocin Rx:
• #1 - 15gram tube
• Sig: Apply to affected areas bid
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Antiviral Pharmacology
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Antivirals MOA Uses Adverse Effects Other
Acyclovir[Zovirax]
Valacyclovir[Valtrex]
Famcyclovir[Famvir]
Inhibits viral multiplication by interfering with DNA synthesis
HSV types I & II, Varicella, Herpes encephalitis (Mollerets’ Syndrome)
Val. and Fam. both metabolize to Acyclovir in the body, but require lower dosing.
Nausea, vomiting, headache, seizures, coma, rash
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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
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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
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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
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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
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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
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Biologics and Immune Modulating Drugs
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EICOSANOIDS
MEMBRANE PHOSPHOLIPID
ARACHADONATE
LEUKOTRIENESPROSTAGLANDINS /
THROMBOXANES
Lipoxygenase Cyclooxygenase
Phospholipase A2
Stimulated by: Angiotensin - 2 / Bradykinin / Epinephrine / Thrombin
Inhibited by: CORTICOSTEROIDS
Inhibited by:
NSAID’S
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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.
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Leukotriene receptor antagonistAdverse Reactions• Cardiovascular
– Cardiac complications, palpitations (postmarketing).• CNS
– 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– Atopic dermatitis, dermatitis, eczema, skin infection, urticaria (at least 2%); rash (2%); vasculitic rash
(postmarketing).• EENT
– Conjunctivitis, ear pain, myopia, otitis, pharyngitis, rhinorrhea, sinusitis, tonsillitis (at least 2%); nasal congestion (2%); epistaxis (at least 1%).
• GI– Diarrhea, dyspepsia, gastroenteritis, laryngitis, nausea, tooth infection (at least 2%); dental pain, infectious
gastroenteritis (2%); pancreatitis, vomiting (postmarketing).• Hematologic-Lymphatic
– Bruising, eosinophilia, increased bleeding tendency (postmarketing).• Hepatic
– Cholestatic hepatitis, hepatocellular liver-injury, mixed-pattern liver injury (postmarketing).• Lab Tests
– ALT/AST increased (2%); pyuria (1%).• Musculoskeletal
– Arthralgia, myalgia (including muscle cramps) (postmarketing).• Respiratory
– 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).
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Leukotriene receptor antagonist• Montelukast SodiumSingulair
- Tablets 10 mg- Tablets, chewable 4 mg- Tablets, chewable 5 mg- Granules 4 mg/packet
Dose in adults: 10 mg QDALSO:
• Zafirlukast (za-FIR-loo-kast) Accolate
• Zileuton Extended-Release Tablets Zyflo CR Extended-Release Tablets
Zyflo CR
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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.
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GENERIC: InterferonBRAND 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,
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Immune Cell Lines
Bone Marrow:
Hemocytoblast
Lymphoid Stem Cells
B-Cells NK Cells
Peripheral Tissues:
Cell Mediated Immunity Ab (Humoral) Immunity Immunological Surveillance
Thymus:
Lymphoid Stem Cells
T-Cell Lines
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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.
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TacrolimusDosage 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 DermatitisAdults 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.
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TacrolimusPronouncation: (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%
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Pimecrolimus
Dosage Form: Cream 1%• TRADE NAME: Elidel®FOR DERMATOLOGIC USE ONLYNOT FOR OPHTHALMIC USEElidel ® (pimecrolimus) Cream 1%
contains the compound pimecrolimus, the immunosuppressant 33-epi-chloro-derivative of the macrolactam ascomycin.
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PimecrolimusIndications and Usage for Elidel• Elidel ® (pimecrolimus) Cream 1% is indicated as
second-line therapy for the short-term and non-continuous 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).
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LOCAL AND SURFACE ACTING DRUGSProtectants MOA Uses Adverse Effects Other
Petroleum
Other occlusive products
Moisturizing skin protectant
Apply to skin surrounding wart before removing
Topical analgesics
MOA Uses Adverse Effects Other
Capsaicin[Zostrix]
Likely depletes substance P
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!
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Anti-inflammatory
MOA Uses Adverse Effects Other
Hydrocortisone Unknown; chemical identical to that of cortisol
Inflammation, antipruritic, vasoconstictive, antiproliferative
Atrophy, pruritus, irriation, similar effects of oral steroids
Weakly active!
TriamcinoloneBetamethasoneEtc…
Longer acting, MUCH more potent than hydrocortisone
“ “ Inhaled & intranasal version for asthmatics
Calcipotriene(Dovonex)
Niacinamide ointment
Tretinoin(Retin-A)
Isotretinoin(Accutane)
Vit. D3 analog
Vit B-3
Retinoic Acid
ORAL DRUG
Psoriasis
Acne
Acne
Severe Acne
Inflammation
Few
Rebound inflammation
TeratogenicPseudotumor cerebri
3-5% Concentration
Must have negative PG testConsent needed
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Miscellaneous
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Chelators: MOA Uses Adverse Effects Other
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
Na-EDTA
Ca-EDTA
Chelates metals, lead, calcium, aluminum…
(Long IV format)
(Shorter IV format)
Lead poisoning,
hypercalcemia
excessive doses: renal failure, tubular necrosisHypocalcemia ,
Hypercalcemia
Headache and joint pain from detoxification process
DMPS Generally IV form.
Used for provocative heavy metal testing.
Can be used for Tx.
Chelates mercury, and some other heavy metals.
Mercury poisoning Hypomagnesmeia
Headaches, depression and suicidal thoughts usually due to the mercury poisoning
Detoxing affects the endocrine system: watch for fatigue, anger, mood-swings; Supplement with water and detox supplements.
DMSA[Chemet]
Oral pharmaceutical for Mercury, heavy metal and lead detoxification.
Lead, mercury, or other heavy metal poisoning
Same as DMPS Schedule and can take year(s) depending on the individual