1. NPLEX Combination Review Immunology / Toxicology
Paul S. Anderson, ND
Medical Board Review Services
Copyright MBRS

2. 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.

3. 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

4. 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.

5. Antibody Testing - 2 High IgG, Low IgM or IgA Low IgG, High IgM
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).

6. 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.

7. 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)

8. 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

9. THYROID HORMONE SYNTHESIS

10. 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

11. 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: 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).

12. E. coli Giardia Helicobacter pylori O157-H7 specific assay Stool
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

13. 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

14. 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.

15. 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

16. Lyme disease (> 250 antibody reaction units)
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 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

17. Antimicrobial and Dermatologic Pharmacology

18. Antifungal, helminthic and protozoal Pharmacology

19. Nystatin Miconazole Clotrimazole Griseofulvin Boric Acid
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
Tinea pedis, cruris, versicolor, corporis, cutaneous candida infection and vulvovaginal candidiasis
Pruritus, skin irritation, burning, contact dermatitis
Clotrimazole “
Nausea, vomiting, vaginal burning or irritation with application, erythema, pruritus, increased liver function tests
Griseofulvin
Fungicidal
Tinea pedis, tinea unguium
Also Tinea corporis, capitis and cruris
Headache, dizziness, GI upset, nausea, vomiting, rash, urticaria, hepatic toxic
Teratogenic
Boric Acid
Fungastatic agent
Vaginal candidiasis
Local irritation
Gentian Violet
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

20. Terbinafine (Lamisil)
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

21. Nystatin Multiple forma available.
Topical kill – even in the GI tract.
GI Infections:
500,000 – 1 Million Units po tid

22. 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 mg 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.

23. Terbinafine Fingernail onychomycosis: Toenail onychomycosis:
250mg qd for 6 weeks
Toenail onychomycosis:
250mg qd for 12 weeks

24. 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
Pruritus, edema, rash, burning, or stinging
Antihelminthics
Mebendazole
[Vermox]
Irreversibly inhibits nutrient uptake by helminthes
Pinworms, roundworms, hookworms
Abdominal pain, diarrhea, fever

25. Mebendazole Pinworm: Roundworm, Whipworm, Hookworm:
100mg po as a single dose.
Repeat in 2-3 weeks
Roundworm, Whipworm, Hookworm:
100mg po bid X 3 days
Repeat in 3 weeks

26. 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 ETOH (acts like Antabuse)
Potentates drugs metabolized by P450 system;
Antimalarial
Chloroquine
Unknown
Malaria, extraintestinal amebiasis
Headache, dizziness, pruritus, neuropathy, seizures, retinal changes and ototoxic
Quinine
Malaria
Extremely toxic, cinchonism, shock

27. ANTIPARASITIC DRUGS Amebicide Anti Pneumocystis Iodoquinol
Metronidazole (Flagyl)
Paromomycin sulfate (Humatin)
Anti Pneumocystis
Atovaquone (Mepron)
Pentamidine isethionate (Pneumopent)

28. Metronidazole Intestinal amebiasis Trichomoniasis Bacterial vaginosis
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

29. Antibiotic Pharmacology

30. 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: / PMID

31. ANTIMICROBIAL OVERVIEW
macrolides
(Gent. / Tobra. & Streptomycin)
(-floxacin’s)
quinolones

32. So, Lets talk about side effects and antibiotic prescriptions:

33. Antibiotics: GI Tract Kidneys Liver “Superinfection”
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.

34. 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.

36. Penicillin MOA Uses Adverse Effects Other (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 “
Amoxicillin and Clavulanate
[Augmentin]
Inhibits cell wall synthesis and Clavulanate makes it effective against -lactamase producing organisms
Gram +, Gram -, and -lactamase producing organism

37. 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

38. Rx: Adult: Child: PEN-VK 500mg tablets #30 Sig: 1 po tid
Amoxicillin (Or Amox / Clav)
80-90 mg/kg of the amoxicillin component in daily divided doses. Rx X 7-10 days

39. 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

40. Rx:
Cefalexin 500 mg
# 30
Sig 1 po q-6-h
Cefaclor 500mg
Sig 1 po q-8-h

41. Macrolides
MOA
Uses
Adverse Effects
Other
Erythromycin
Interferes with bacterial DNA synthesis
Drugs of choice for
M.pneumonia, pertussis, neonatal C.pneumonia Strep throat, URI,
Abdominal pain, nausea, diarrhea, vomiting, anaphylaxis
Contraindicated in Pregnancy; caution with impaired renal function
Clarithromycin
[Biaxin] “
Bronchitis
Non-gonococcal urethritis, cervicitis, chanroid
SAME
Azithromycin
[Zithromax]
LESS GI effect, Less medication needed to achieve effect.

42. Rx: Erythromycin 333mg Erythromycin 500mg Azithromycin 250mg #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.)

43. Tetracycline
MOA
Uses
Adverse Effects
Other
Interferes with bacteria protein synthesis
Susceptible Gram + and Gram – organisms including chlamydia and lyme disease
Sebulytic (Acne)
Intracranial hypertension, GI distress, nausea, vomiting, diarrhea, rash, photosensitivity, increased pigmentation
Not for use in children under 9 years old because of permanent discoloration of teeth enamel
Interferes with oral contraceptive effectiveness
Doxycycline
Minocycline “
Less nephrotoxic

44. Doxycycline General oral Rx: Doxycycline 100 mg tablets
Sig: 1 po q-12-h
Treat for 7 days for most infections
(Acne prophylaxis mg, qd-bid)
Doxy is INEXPENSIVE.

45. Minocycline General oral Rx: Minocycline 100 mg tablets
Sig: 1 po q-12-h
Treat for 7 days for most infections
(Acne prophylaxis mg, qd-bid)
Minocycline is 95% absorbed in the stomach, and has a very low GI flora kill rate.

46. 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

47. 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.

48. Achilles' Tendon Rupture
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

49. 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.

50. 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

51. Antituberculosis MOA Uses Adverse Effects Other Isoniazid Rifampin
Rifabutin
Rifapentene
Pyrazinamide
Inhibits cells wall synthesis in Mycobacterium tuberculosis
Impares RNA synthesis
UNKNOWN TB
TB Additive Tx.
Neuropathies, hepatotoxic, GI disturbance, fever, rash
MANY “
All are Hepatotoxic
Give with B-6

52. Contact dermatitis, rash, may be nephrotoxic or ototoxic
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

53. Mupirocin Mupirocin Rx: #1 - 15gram tube
Sig: Apply to affected areas bid

54. Antiviral Pharmacology

55. Inhibits viral multiplication by interfering with DNA synthesis
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

56. Acyclovir Genital herpes Suppressive tx for recurrent 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

57. 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

58. Famcyclovir Oral herpes Genital 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

59. Human Herpes Virus 1 – 7 (except CMV) CMV Hepatitis B&C
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

60. 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

61. Biologics and Immune Modulating Drugs

62. MEMBRANE PHOSPHOLIPID
EICOSANOIDS
MEMBRANE PHOSPHOLIPID
Stimulated by: Angiotensin - 2 / Bradykinin / Epinephrine / Thrombin
Inhibited by: CORTICOSTEROIDS
Phospholipase A2
ARACHADONATE
Inhibited by:
NSAID’S
Cyclooxygenase
Lipoxygenase
PROSTAGLANDINS /
THROMBOXANES
LEUKOTRIENES

63. 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.

64. Leukotriene receptor antagonist
Adverse 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).

65. 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

66. 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.
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67. Classes: Actions: Used in: Adverse Effects: Alpha, beta and gamma.
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,

68. Immune Cell Lines Bone Marrow: Thymus: Hemocytoblast
Lymphoid Stem Cells
B-Cells NK Cells
Thymus:
Lymphoid Stem Cells
T-Cell Lines
Peripheral Tissues:
Cell Mediated Immunity Ab (Humoral) Immunity Immunological Surveillance

69. Tacrolimus Pharmacology Indications and Usage Unlabeled Uses
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.

70. 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.

71. 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%

72. 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-chloro-derivative of the macrolactam ascomycin.

73. Pimecrolimus Indications 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). 

74. LOCAL AND SURFACE ACTING DRUGS
Protectants
MOA
Uses
Adverse Effects
Other
Petroleum
Other occlusive products
Moisturizing skin protectant
Apply to skin surrounding wart before removing
Topical analgesics
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!

75. 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!
Triamcinolone
Betamethasone
Etc…
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
Severe Acne
Inflammation
Few
Rebound inflammation
Teratogenic
Pseudotumor cerebri
3-5% Concentration
Must have negative PG test
Consent needed

76. Miscellaneous

78. 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 necrosis
Hypocalcemia ,
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