NPLEX Combination ReviewImmunology / 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

“ 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

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 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

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

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

• Amebicide – Iodoquinol– Metronidazole (Flagyl)– Paromomycin sulfate (Humatin)

• Anti Pneumocystis– Atovaquone (Mepron)– Pentamidine isethionate (Pneumopent)

ANTIPARASITIC DRUGS

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

(Gent. / Tobra. & Streptomycin)

(-floxacin’s)

• macrolides

• 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.

http://www.drugdevelopment-technology.com/projects/tygacil/

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 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

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

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

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

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

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/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

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.

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

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] 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

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

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

Mupirocin

Mupirocin Rx:

• #1 - 15gram tube

• Sig: Apply to affected areas bid

Antiviral Pharmacology

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

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

ARACHADONATE

LEUKOTRIENESPROSTAGLANDINS /

THROMBOXANES

Lipoxygenase Cyclooxygenase

Phospholipase A2

Stimulated by: Angiotensin - 2 / Bradykinin / Epinephrine / Thrombin

Inhibited by: CORTICOSTEROIDS

Inhibited by:

NSAID’S

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 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).

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

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: 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,

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

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.

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.

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%

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.

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). 

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!

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

Miscellaneous

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