Download NPLEX Combination Review Chapter 10 – Immunology / Toxicology

NPLEX Combination Review
Immunology / Toxicology
Paul S. Anderson, ND
Medical Board Review Services
Copyright MBRS
Laboratory Testing Methodologies
• PCR: Polymerase Chain Reaction
• ELISA(Enzyme Linked Immunosorbant Assay) –
Measures IgG / M / A…Used in disease detection and
Allergen identification.
• RAST
– Quantifies IgE antibodies.
• Intradermal testing
– Positive reaction demonstrates erythema at point of
injection.
• Blood immunoglobins
– IgG – Delayed hypersensitivity reaction to antigen.
– IgE – Immediate hypersensitivity reaction to antigen.
• Electrodermal allergy test
– EAV is appropriate example.
ID Immunology: General
• Cultures
– Take time
– Some things grow, some don’t
• Antibody Testing
– Good for effect
– Some better than others
• DNA (PCR) Testing
– Detects DNA of the subject of the probe
– No need for growing a culture
– No need for Ig interpretation
– Can get Quantitative (viral load) tests
Antibody Testing
• Serum tests. Serum must be separated from clot / SST Gel
within 1 hour!
– Pipette serum into a plastic transport tube
– Excessive exposure to the gel in the SST will bind antibodies, causing
false negative tests.
• Used for allergy testing, Autoimmune testing, Exposure
• Ig (Immunoglobulin) Types:
– IgG: Long term exposure, Delayed reactions (ie. Food allergy).
• IgG lasts a long time, and is a marker of EXPOSURE, not successful treatment.
– IgM: Acute phase reactions. Indicates recent infection or re-exposure.
– IgA: Secretory Ig.
• Shows mucosal response, and is a good marker of successful treatment.
• Can be measured in the serum, stool and saliva
– IgE: Anaphylaxis. (Type-1 Reaction).
• Total IgE in serum is a test for general allergic level in the patient
• Traditionally the marker used for food and Inhalant allergy, although IgG is
more helpful with most food reactions.
Antibody Testing - 2
• High IgG, Low IgM or IgA
– Probable past infection / exposure. Inactive or
cured.
– In food allergy testing IgG is always considered
active, but delayed response allergy.
• Low IgG, High IgM
– New infection / Exposure
• High IgG, High IgM
– Reactivated infection / Exposure
• High IgG, Low IgM, High IgA
– Current immune response (mucosal) that is past the
initial IgM response window. (On going problem).
Autoimmune Disorders
• Anti-nuclear antibody (ANA)
– Titer level is important: > 1:160 “positive”
– Screening test for connective-tissue diseases: RA, SLE, Lupus,
MCTD, CREST Syndrome, Scleroderma, and Polymyositis.
– Use confirmatory ANA sub-testing to confirm specific disease Dx.
• Often ordered as ANA + Reflex (7 or 9 values) run if ANAA is
positive
• Erythrocyte Sedimentation Rate (ESR)
– Nonspecific measure of inflammation
– Diagnostic in very few conditions (Giant cell arteritis)
– Can also indicate cancerous effect
• C-reactive protein (CRP)
– Screening for nondescriptive inflammatory and infection disease
processes. Also used for discriminating among DDX and monitoring
disease process
– CRP elevation: RA, Reiter’s, vasculitis, rheumatic fever, neonatal
and post-operative infections, pyelonephritis, MI and embolism.
Autoimmune Disorders
• Rheumatoid factor (RF)
– Used in the diagnosis and evaluation of RA and other CTD; Highest
in RA, but also elevated in CVD, MI, renal disease, malignancy,
thyroid and liver disease, SLE, scleroderma and polyarteritis nodosa.
• Parvo B-19 viral assay
– Consider in RF Negative woman nursing or caring for a young child
who presents with RA like symptoms.
• Human leukocyte antigen (HLA) HLA B-27 most common.
– Glycoproteins that may be serologically determined; usually
performed for transplantation matches but also elevated in AS,
Reiter’s Syndrome, MS, chronic active hepatitis, gluten-sensitive
enteropathy, SLE, DM and hemochromatosis.
• Consider Chlamydia testing (Reiter’s)
Autoimmune Disorders
• Anti-thyroid antibody (Anti Microsomal or TPO Ab)
– Used in diagnosis and classification of inflammatory and
autoimmune thyroid disease.
– Marker for Hashimoto’s thyroiditis, atrophic thyroiditis, and
Grave’s Disease.
• Antithyroglobulin Antibody (Anti TG)
– Detect and confirm autoimmune thyroiditis, Hashimoto thyroiditis
• Thyroid-Stimulating Immunoglobulin (Thytrophin Receptor Ab)
– Detect Grave’s Dz.
– Order when Grave’s Sn/Sx and TPO elevation
THYROID HORMONE SYNTHESIS
Infectious Disease Testing
• Anti-Streptolysin-O test (ASO) (>200iu/ml)
– Elevation in titers reflect immunologic response to streptococcus;
– ASO titers clinically useful if serum is obtained in 2-3 week intervals.
• Chlamydia antibody (IgG, IgM)
– Presence of IgG Ab indicates chlamydial infection in the past; highly
sensitive but has low specificity.
– Presence of IgM or 4-fold increase from acute – convalescence =
recent infection.
• Cytomegalovirus PCR
• Cytomegalovirus (CMV- IgG, IgM)
– Presence of IgM or 4-fold increase in IgG = recent infection
Infectious Disease Testing
• Epstein-Barr Virus (EBV)
– Monospot: Screening test performed with symptomatic Pt.
• (false negative in adults 10%).
• Measures IgM heterophil antibodies.
• Positive window: 4-21 days
– PCR for EBV:
• Most sensitive test is Quantitative (viral load) PCR
• Used in Chronic reactivating cases
– EBV Panel:
• Early phase – IgM: anti-VCA
• Acute illness – IgG: anti-VCA
• Acute illness – IgG anti-EA
• Convalescence – Anti-EBNA (Indicates past infection OR
Chronic reactivation in recurrent EBV patients).
• E. coli
– O157-H7 specific assay
– Stool
• Giardia
– Stool assay in symptomatic patient
• Helicobacter pylori
– Multiple methodologies:
• Nitrogen breath test (Sensitive for presence of dz and tx)
• Serum IgG: (Sensitive for PAST infection – but will not
decrease with successful tx.)
• Serum IgM: (Sensitive for current infection but will
decrease in 2-4 weeks regardless of infection.)
• Serum, Salivary or Stool IgA: (Rises with presence of
infxn / falls with effective tx.)
– Stool IgA is preferred test now by IDSA
• Hepatitis (A,B,C,D,E) virus
– HAV:
• IgM titers reflect acute infection.
• IgG titers identified years after acute illness.
– HBV: HbsAg: detected 1–4 months post-infection.
• Patients with this antigen present > 6 months exhibit chronic hepatitis.
– ANTI-HBs Ab:
• Patients with this Ab are considered protected against the HBV infection
– HbcAg – IgM most useful marker to determine the “window”: (HbsAg
disappears and ANTI –HbsAg appears; usually demonstrates present
infection.)
• The presence of ANTI – HbcAg IgG indicates previous HBV infection
and persists indefinitely.
– HCV – Ab – Patients with this Ab have four-fold increase for HCC
– HCV PCR is available as well.
– HDV - co-exists with hepatitis b infection. Maked Hep-B more deadly.
Worst in pregnancy.
– HEV – Not generally tested for: cases out of U.S.
• Test if foreign travel in the past 60 days
• Herpes simplex virus (HSV-1; HSV-2)
– Antibodies:
• IgM – Current infection.
• IgG Infection in the past.
– IgG/M Type (1or2) specific serology is best DDX
– PCR is available
– Virus isolation (Tzank smear) is OLD method to confirm
an HHV infection:
• Can have false positives if other HHV infection is present
• NOT specific to HHV 1 or 2
– Generally** HSV –1 above waist while HSV – 2 affects below
waist. But this is not always the case.
• Human Immunodeficiency Virus (HIV)
– Standard method for diagnosis:
• ELISA measured anti-HIV titers. Confirmed by Western Blot
Analysis. (MAY TAKE 6 MONTHS TO SERO-CONVERT)
– Decreased CD4/CD8 ratio
– Newly diagnosed condition:
• T-Cell subset (CD3, CD4, CD8).
– Earliest diagnosis: PCR for HIV
• Human Papilloma Virus (6,11,16,18,31,33)
– HPV 16, 18, 31, 33 are common causes for cervical
cancer.
• Available as PCR on Pap sample
– HPV 6, 11 common causes for plantar and genital warts.
• NOT generally cancerous or pre-cancerous
• Rubella titer
– Presence of IgM and / or four-fold increase in IgG = present
infection.
• Syphyllis (VDRL / RPR)
– Nontreponemal tests used primarily for detection of primary
syphilitic infection.
• Tuberculosis
– Intradermal skin test: Read 48-72 hours for induration.
– BCG: Post –ID; check serology results.
• Lyme disease (> 250 antibody reaction units)
– Skin, blood, synovial or CSF.
– ELISA or Western blot checking for antibody detection.
– PCR Now available
Antimicrobial
and
Dermatologic
Pharmacology
Antifungal, helminthic and
protozoal Pharmacology
Antifungals
MOA
Uses
Adverse Effects
Other
Nystatin
Disrupts fungal cell
wall
Intestinal, cutaneous,
vaginal and
mucocutaneous
infections caused by
Candida
Contact dermatitis
Poorly or not
absorbed. Good
topical agent / GI
Agent.
Miconazole
Disrupts fungal cell
wall
Tinea pedis, cruris,
versicolor, corporis,
cutaneous candida
infection and
vulvovaginal
candidiasis
Pruritus, skin irritation,
burning, contact
dermatitis
Clotrimazole
Disrupts fungal cell
wall
Griseofulvin
Fungicidal
Tinea pedis, tinea
unguium
Also Tinea corporis,
capitis and cruris
Headache, dizziness,
GI upset, nausea,
vomiting, rash,
urticaria, hepatic toxic
Boric Acid
Fungastatic agent
Vaginal candidiasis
Local irritation
Gentian Violet
Fungicidal
Oral Candida
Mouth rinse, may stain
skin or clothing
Acetic Acid
[VoSol Otic]
Inhibits or destroys
bacteria in the ear
Otic solution for
external ear infections
Ear irritation, urticaria
“
Nausea, vomiting,
vaginal burning or
irritation with
application, erythema,
pruritus, increased
liver function tests
Teratogenic
Do not use on
ulcerative wounds
on the face
ANTIFUNGAL DRUGS - 2
• Amphotericin
– I.V. Only (unless compounded)
– Two types
– Strong / High potential side effect profile (I.V.)
• Triazole class
– Fluconazole (Diflucan)
• Inhibits Fungal p-450, degrading fungal cell wall
– Ketoconazole (Nizoral)
– Itraconazole (Sporonox)
– Voriconazole (V-Fend)
• Terbinafine (Lamisil)
– Topical and Oral forms
Nystatin
• Multiple forma available.
• Topical kill – even in the GI tract.
• GI Infections:
– 500,000 – 1 Million Units po tid
Fluconazole
• Absorbs – so more systemic kill and more
systemic side effect.
– Primary site of activity – Liver
• Dosing strategies vary widely based on
immunocompetence and type of infection.
• May be as low as 150-200mg in a single dose
for uncomplicated fungal vulvovaginosis to as
much as 200 mg bid for long term (2-4 weeks),
or 100mg daily for months.
• If using it long term I normally treat on a 5 days
on / 2 days off rotation.
Terbinafine
• Fingernail onychomycosis:
– 250mg qd for 6 weeks
• Toenail onychomycosis:
– 250mg qd for 12 weeks
ANTIPARASITIC DRUGS
Topical
MOA
Uses
Adverse Effects
Lindane
[Kwell]
Penetrates exoskeleton
inducing seizures and death of
arthropods
Scabies, pediculosis
Seizures, irritation, CNS
disturbance
Permethrin
[Elimite] / [Nix]
Causes paralysis by disrupting
sodium current in the parasite
Scabies, pediculosis
Pruritus, edema, rash,
burning, or stinging
Antihelminthics
MOA
Uses
Adverse Effects
Mebendazole
[Vermox]
Irreversibly inhibits nutrient
uptake by helminthes
Pinworms,
roundworms,
hookworms
Abdominal pain,
diarrhea, fever
Other
Other
Mebendazole
• Pinworm:
– 100mg po as a single dose.
– Repeat in 2-3 weeks
• Roundworm, Whipworm, Hookworm:
– 100mg po bid X 3 days
– Repeat in 3 weeks
ANTIPARASITIC DRUGS
Antiprotozoal
MOA
Uses
Adverse Effects
Other
Metronidazole
Inhibits DNA synthesis in
microorganism causing
cell death
Amoebas,
trichomoniasis,
giardia
GI distress, seizures,
ataxia, cramping, rash,
joint pain.
** Do not take with
Potentates drugs
metabolized by
P450 system;
ETOH (acts like
Antabuse)
Antimalarial
MOA
Uses
Adverse Effects
Chloroquine
Unknown
Malaria,
extraintestinal
amebiasis
Headache, dizziness,
pruritus, neuropathy,
seizures, retinal
changes and ototoxic
Quinine
Unknown
Malaria
Extremely toxic,
cinchonism, shock
Other
ANTIPARASITIC DRUGS
• Amebicide
– Iodoquinol
– Metronidazole (Flagyl)
– Paromomycin sulfate (Humatin)
• Anti Pneumocystis
– Atovaquone (Mepron)
– Pentamidine isethionate (Pneumopent)
Metronidazole
• Intestinal amebiasis
– 750mg po bid 5-7 days, then iodoquinol Rx.
• Trichomoniasis
– 750mg po tid X 7 days OR 1 gram po bid X 1
day: Repeat this dose Rx in 4-6 weeks.
• Bacterial vaginosis
– 500mg po bid X 7days
Antibiotic
Pharmacology
Antibiotic classes and Targets
• Bactericidal antibiotics that target bacterial cell wall;
– penicillins, cephalosporins
• or cell membrane;
– polymixins
• or interfere with essential bacterial enzymes;
– quinolones, sulfonamides usually
• Bacteriostatic ABX are those which target protein
synthesis;
– aminoglycosides, macrolides and tetracyclines
Adapted from: Finberg RW, Moellering RC, Tally FP, et al (November 2004). "The importance of
bactericidal drugs: future directions in infectious disease". Clin. Infect. Dis. 39 (9): 1314–20.
doi:10.1086/425009. PMID 15494908.
ANTIMICROBIAL OVERVIEW
•
macrolides
(Gent. / Tobra. &
Streptomycin)
(-floxacin’s)
•
quinolones
So,
Lets talk about side effects and
antibiotic prescriptions:
Antibiotics:
• GI Tract
– Symbiotic – beneficial flora kill
– Overgrowth of flora - dysbiosis
– Pseudomembranous Colitis (C. diff)
• Kidneys
– Most ABX are polar. Lots of Ki excretion
– Often in IV use they can cause Ki failure if
administered improperly
• Liver
– Liver effect possible, but less common than Ki
• “Superinfection”
– Systemic infection with bacteria or fungi that are not
effected by the ABX you have given – like a systemic
dysbiosis.
ABX and “Good Flora” Supplements
• ABX given with beneficial flora supplements
(acidophilus, bifidus…) will kill many of those bugs
as well.
• Some wait to repopulate the gut until after the Rx.
• If you are concerned that the patient will get too
behind (ie too much good flora kill) you may
supplement beneficial flora during the ABX course,
AND after.
– If doing this DO NOT have the patient take the good flora
supplement while the ABX pills are in the stomach.
– Alternate time of dose between flora and ABX.
Penicillin
MOA
Uses
Adverse Effects
Other
Penicillin
(Pen Vee-K)
Break down / Inhibit
bacterial cell wall
synthesis
Gram + cocci,
anaerobic
bacteria, syphilis
Nausea, vomiting,
rash, seizures,
anaphylaxis,
neurotoxic,
nephrotoxic
Not effective
against lactamase
producing
organism or
Gram –
anaerobes
Ampicillin
Inhibits cell wall
synthesis
Some Gram + and
Gram –
organisms,
prophylaxis for
dental procedures
Nausea, vomiting,
diarrhea, seizures,
rash, urticaria,
anaphylaxis
Not effective
against lactamase
producing
organism
Amoxicillin
Inhibits cell wall
synthesis
Some Gram + and
Gram –
organisms,
prophylaxis for
dental procedures
“
Amoxicillin and
Clavulanate
[Augmentin]
Inhibits cell wall
synthesis and
Clavulanate makes it
effective against lactamase producing
organisms
Gram +, Gram -,
and -lactamase
producing
organism
“
NOTE:
• All Rx’s are for the longer term
– (i.e. 10 day instead of 7 day).
– Some INDICATIONS REQUIRE FEWER Tx
days – see Sanford Guide etc.
• All are in Adult Doses unless otherwise
noted.
– An “Adult” is a 150 Pound Human
Rx:
• Adult:
– PEN-VK 500mg tablets
– #30
– Sig: 1 po tid
• Child:
– Amoxicillin (Or Amox / Clav)
– 80-90 mg/kg of the amoxicillin component in
daily divided doses. Rx X 7-10 days
Cephalosporins
Cephalexin
[Keflex]
1st generation
MOA
Bactericidal by
inhibiting cell wall
synthesis
Uses
Adverse Effects
Other
URI, GI
infections,
cutaneous
infections, soft
tissue infections
Nausea, diarrhea,
maculopapular
rash, anaphylaxis,
serum sickness, GI
distress
10-15% of
patients have
cross allergy
between
penicillin and
cephlosporins
Cefaclor
[Ceclor]
2nd generation
“
UTI, URI, OM
“
“
Cefixime
[Suprax]
3rd generation
“
More resistant
to Gram - lactamase
producing
organism
“
“
Cefepime
[Maxipime]
4th generation
“
E.coli, Proteus,
K.pneumoniae,
Enterobacter,
B.fragilis,
Staph/Strep
“
IV Dose form
Rx:
• Cefalexin 500 mg
– # 30
– Sig 1 po q-6-h
• Cefaclor 500mg
– # 30
– Sig 1 po q-8-h
Macrolides
MOA
Uses
Adverse Effects
Other
Erythromycin
Interferes with
bacterial DNA
synthesis
Drugs of
choice for
M.pneumonia,
pertussis,
neonatal
C.pneumonia
Strep throat,
URI,
Abdominal pain,
nausea,
diarrhea,
vomiting,
anaphylaxis
Contraindica
ted in
Pregnancy;
caution with
impaired
renal function
“
SAME
LESS GI effect,
Less medication
needed to
achieve effect.
SAME
Clarithromycin
[Biaxin]
“
Azithromycin
[Zithromax]
“
Bronchitis
Nongonococcal
urethritis,
cervicitis,
chanroid
Rx:
• Erythromycin 333mg
– #30
– Sig 1 tid
• (I use this as it is less GI upsetting than the 500 mg strength – I
give WITH food)
• Erythromycin 500mg
– #20
– Sig 1 bid
• Azithromycin 250mg
– #6 (“Z-Pak”)
– Sig 2 po Day-1, 1 po qd days 2-5
– (Some suggest #3 (“3-Pak) in uncomplicated dz.)
Tetracycline
MOA
Uses
Adverse Effects
Other
Tetracycline
Interferes with
bacteria protein
synthesis
Susceptible
Gram + and
Gram –
organisms
including
chlamydia and
lyme disease
Intracranial
hypertension, GI
distress, nausea,
vomiting,
diarrhea, rash,
photosensitivity,
increased
pigmentation
Not for use
in children
under 9
years old
because of
permanent
discoloratio
n of teeth
enamel
Interferes
with oral
contraceptive
effectiveness
Sebulytic
(Acne)
Doxycycline
Minocycline
“
“
“
Less
nephrotoxic
Doxycycline
• General oral Rx:
• Doxycycline 100 mg tablets
– Sig: 1 po q-12-h
– Treat for 7 days for most infections
– (Acne prophylaxis 50-100mg, qd-bid)
Doxy is INEXPENSIVE.
Minocycline
• General oral Rx:
• Minocycline 100 mg tablets
– Sig: 1 po q-12-h
– Treat for 7 days for most infections
– (Acne prophylaxis 50-100mg, qd-bid)
• Minocycline is 95% absorbed in the stomach,
and has a very low GI flora kill rate.
Sulfonamides
MOA
Uses
Adverse Effects
Other
Co-trimoxazole /
Trimethoprim/Sulf
amethoxazole
[Septra] /
[Bactrim]
Interfere with
bacterial folic
acid synthesis
UTI, OM, URI,
pneumocystis
carinii,
traveler’s
diarrhea
Nausea,
vomiting,
diarrhea, rash,
seizures, toxic
nephrosis,
hepatic necrosis,
dermatitis,
SJS/TEN,
anaphylaxis
MANY
Potential
side effects.
UTI, URI
Sulfisoxazole
[Gantrisin]
Sulfamethoxazole
[Gantanol]
Sulfadiazin
[Coptin]
Interfere with
oral
contraceptive
effectiveness
Nitrofurantoin monohydrate/ macrocrystals
TRADE NAME: Macrobid
Specific UTI Indication
CONTRAINDICATIONS:
– Anuria, oliguria, or significant impairment of renal function (creatinine
clearance under 60 mL per minute or clinically significant elevated serum
creatinine) are contraindications. Treatment of this type of patient carries an
increased risk of toxicity because of impaired excretion of the drug.
– Because of the possibility of hemolytic anemia due to immature erythrocyte
enzyme systems (glutathione instability), the drug is contraindicated in
pregnant patients at term (38-42 weeks gestation), during labor and
delivery, or when the onset of labor is imminent. For the same reason, the
drug is contraindicated in neonates under one month of age.
DOSAGE AND ADMINISTRATION:
• Macrobid capsules should be taken with food.
• Adults and Pediatric Patients Over 12 Years: One 100 mg capsule
every 12 hours for seven days.
Fluoroquinolones
MOA
Uses
Adverse Effects
Other
Ciprofloxacin
[Cipro]
And all other “flox’s”
Bactericidal by
interfering with
bacterial DNA
synthesis
Wide spectrum:
URI, UTI,
cutaneous
infections, bone
or joint
infections,
abdominal
infections
Rash,
arthralgias,
nausea, diarrhea,
seizures,
GI and CNS effects
Can arrest
growth plate
in children
Gatifloxacin
[Tequin ]
Levofloxacin
[Levaquin ]
Lomefloxacin
Moxifloxacin
[Avelox ]
Norfloxacin
[Noroxin]
Ofloxacin
[Ocuflox]
Trovafloxacin
[Trovan]
Enoxacin
Achilles'
Tendon
Rupture
Do not use
under age
18
Ciprofloxacin
• 100 - 750 mg PO q-12-h
• Dose based on severity of infection and
current indication.
• There is some variability of effectiveness
among the various FQ agents.
Aminoglycosides
MOA
Uses
Adverse Effects
Gentamicin
[Garamycin]
Bactericidal by
interfering with
bacterial DNA
synthesis
Use for serious
infections of
Enterobacter,
E. coli,
K. pneumonia,
Pseudomonas
Ototoxic,
nephrotoxic,
seizures,
anaphylaxis,
neurotoxic
Kanamycin
[Kantrex]
Neomycin
[Mycifradin]
Severe
Ototoxicity
Netilmicin
[Netromycin]
Streptomycin
Tobramycin
[Nebcin]
Paromomycin
[Humatin]
Pneumocystis
pneumonia
Antituberculosis
MOA
Uses
Adverse Effects
Other
All are
Hepatotoxic
Isoniazid
Inhibits cells wall synthesis
in Mycobacterium
tuberculosis
TB
Neuropathies,
hepatotoxic, GI
disturbance, fever,
rash
Rifampin
Rifabutin
Rifapentene
Impares RNA synthesis
TB
TB
TB
MANY
“
“
Pyrazinamide
UNKNOWN
TB Additive Tx.
“
Give with B-6
Topical
Antibiotics
MOA
Bacitracin
[Bactin]
Inhibits cell wall
Topical
synthesis of bacteria infections
Skin rash,
allergic dermatitis
Neomycin
[Neosporin]
Disrupts bacterial
protein synthesis
Contact
dermatitis,
rash, may be
Uses
Topical
bacterial
infections
Adverse Effects
Other
nephrotoxic or
ototoxic
Mupirocin
[Bactroban]
Bacterial RNA
inhibition
Impetigo,
MRSA
prophylaxis…
Low
Expensive
Mupirocin
Mupirocin Rx:
• #1 - 15gram tube
• Sig: Apply to affected areas bid
Antiviral Pharmacology
Antivirals
MOA
Uses
Adverse Effects
Acyclovir
[Zovirax]
Inhibits viral
multiplication by
interfering with DNA
synthesis
HSV types I & II,
Varicella, Herpes
encephalitis
(Mollerets’
Syndrome)
Nausea, vomiting,
Valacyclovir
[Valtrex]
Famcyclovir
[Famvir]
Val. and Fam.
both metabolize
to Acyclovir in
the body, but
require lower
dosing.
headache,
seizures, coma,
rash
Other
Acyclovir
• Genital herpes
– Initial: 200mg q-4-h or 400mg q-8-h
– Recurrent: 200 mg q-4-h (5X daily)
– (I often add an rx for Acyclovir cream – bid)
• Suppressive tx for recurrent genital herpes
– 400 mg po bid
• Varicella-Zoster
– 800mg po q-4-h (5X daily) for 7-10 days
Valacyclovir
• Genital herpes
– Initial: 1gram po bid X10 days
– Recurrent: 500mg po bid X5 days
• Suppressive tx for recurrent genital herpes
– 9 or fewer outbreaks / year: 500 mg qd
– >9: 1gram qd
• Varicella-Zoster
– 1gram po tid X 5-7 days
Famcyclovir
• Oral herpes
– 1500mg as a single dose
• Genital herpes
– Initial: No data
– Recurrent: 1000mg bid X 1 day
• Suppressive tx for recurrent genital herpes
– 250mg bid
• Varicella-Zoster
– 500mg q-8-h X 7 days
ANTIVIRAL THERAPY - 2
• Human Herpes Virus 1 – 7 (except CMV)
– Acyclovir, Valcyclovir, Famcyclovir
• CMV
– Cidofovir, Foscarnet, Gancyclovir
• Hepatitis B&C
– Interferon alpha, Pegylated Interferon
– Ribavirin
– Lamivudine (3tc) [Hepatitis B]
• Influenza
– Zanamivir
– Oseitamivir
ANTIVIRAL THERAPY – HIV
• Nucleoside Reverse-transcriptase Inhibitors (NRTI)
– Type A: Zidoiudine (ZDV), Stavudine (d4T)
– Type B: Dianosine (ddl), Zalcitabidine (ddc), Lamivudine (3tc)
– Other: Abacavir
• Non Nucleoside Reverse-transcriptase Inhibitors (NNRTI)
– Neuirapine
– Delaviridine
– Efavirenz
• Protease Inhibitors
–
–
–
–
–
Saquinavir
Idinavir
Ritonavir
Nelafavir
Amprenavir
• Triple Therapy: 2 NRTI’s and P.I. or NNRTI
Biologics and
Immune Modulating Drugs
EICOSANOIDS
MEMBRANE PHOSPHOLIPID
Stimulated by: Angiotensin - 2 /
Bradykinin / Epinephrine /
Thrombin
Phospholipase A2
Inhibited by: CORTICOSTEROIDS
ARACHADONATE
Inhibited by:
Lipoxygenase
LEUKOTRIENES
Cyclooxygenase
NSAID’S
PROSTAGLANDINS /
THROMBOXANES
Leukotriene receptor antagonist
• Pharmacology
– Binds to cysteinyl leukotriene receptor 1 in the upper and
lower airways to prevent leukotriene-mediated effects
associated with asthma and allergic rhinitis.
• Indications and Usage
– Prophylaxis and chronic treatment of asthma in patients
12 mo of age and older; relief of symptoms of seasonal
allergic rhinitis in patients 2 yr of age and older; relief of
symptoms of perennial allergic rhinitis in patients 6 mo of
age and older.
– Prevention of exercise-induced bronchoconstriction (EIB)
in patients 15 yr of age and older.
• Unlabeled Uses
– Chronic urticaria, atopic dermatitis.
Leukotriene receptor antagonist
Adverse Reactions
•
Cardiovascular
–
•
CNS
–
•
Arthralgia, myalgia (including muscle cramps) (postmarketing).
Respiratory
–
•
ALT/AST increased (2%); pyuria (1%).
Musculoskeletal
–
•
Cholestatic hepatitis, hepatocellular liver-injury, mixed-pattern liver injury (postmarketing).
Lab Tests
–
•
Bruising, eosinophilia, increased bleeding tendency (postmarketing).
Hepatic
–
•
Diarrhea, dyspepsia, gastroenteritis, laryngitis, nausea, tooth infection (at least 2%); dental pain, infectious
gastroenteritis (2%); pancreatitis, vomiting (postmarketing).
Hematologic-Lymphatic
–
•
Conjunctivitis, ear pain, myopia, otitis, pharyngitis, rhinorrhea, sinusitis, tonsillitis (at least 2%); nasal
congestion (2%); epistaxis (at least 1%).
GI
–
•
Atopic dermatitis, dermatitis, eczema, skin infection, urticaria (at least 2%); rash (2%); vasculitic rash
(postmarketing).
EENT
–
•
Headache (18%); asthenia/fatigue, dizziness (2%); abnormal dreams, depression, drowsiness, hallucinations,
insomnia, paraesthesia/hypoesthesia, psychomotor hyperactivity (including agitation, aggressive behavior,
irritability, restlessness, and tremor), seizures (postmarketing).
Dermatologic
–
•
Cardiac complications, palpitations (postmarketing).
Influenza (4%); cough (3%); acute bronchitis, pneumonia, upper respiratory tract infection, wheezing (at least
2%); worsening of pulmonary symptoms (postmarketing).
Miscellaneous
–
Abdominal pain (3%); fever, varicella, viral infection (at least 2%); trauma (1%); edema, hypersensitivity
(including anaphylaxis, hepatic eosinophilic infiltration, pruritus, and urticaria) (postmarketing).
Leukotriene receptor antagonist
• Montelukast Sodium
Singulair
- Tablets 10 mg
- Tablets, chewable 4 mg
- Tablets, chewable 5 mg
- Granules 4 mg/packet
Dose in adults: 10 mg QD
ALSO:
• Zafirlukast (za-FIR-loo-kast)
Accolate
• Zileuton Extended-Release Tablets Zyflo CR Extended-Release
Tablets
Zyflo CR
Interferon
• Any of a group of proteins produced by cells in the body in
response to an attack by a virus.
– A cell infected by a virus releases minute amounts of interferons,
which attach themselves to neighboring cells, prompting them to start
producing their own protective antiviral enzymes.
– The result is impairment of the growth and replication of the attacking
virus. Interferon has also been shown to have some antitumor
properties.
• There are three known classes of interferons: alpha-, beta-,
and gamma-interferons.
– Although they were discovered in the 1950s, the medical use of
interferons was impractical until the recombinant DNA techniques of
genetic engineering made it possible to mass produce them.
– Interferons used as drugs include alpha-interferon, for hepatitis B and
C, human papillomavirus, hairy-cell leukemia, and Kaposi's sarcoma,
and beta-interferon, for multiple sclerosis.
The Columbia Encyclopedia. Copyright © 2001-08 Columbia University Press. All rights reserved.
GENERIC:
Interferon
BRAND NAMES: Roferon-A, Intron-A, Rebetron, Alferon-N, Peg-Intron, Avonex, Betaseron, Infergen,
Actimmune, Pegasys
• Classes:
– Alpha, beta and gamma.
• Actions:
– direct the immune system's attack on viruses, bacteria, tumors and other foreign
substances that may invade the body.
• Used in:
– Leukemia, Hepatitis B, C, Genital Warts
– The beta interferons have been found useful in managing MS
• Adverse Effects:
–
–
–
–
Flu-like symptoms following each injection occur with all interferons.
Depression and suicide are possible, but not common
HYPOTHYROIDISM
Other side effects with all interferons (may be caused by higher doses)
•
•
•
•
•
•
Fatigue
diarrhea, nausea, vomiting, abdominal pain, anorexia
joint aches, back pain and dizziness.
congestion, increased heart rate, confusion,
low white blood cell count, low platelet count, low red blood cell count,
increase in liver enzymes, increase in triglycerides,
Immune Cell Lines
Thymus:
Bone Marrow:
Hemocytoblast
Lymphoid Stem Cells
Lymphoid Stem Cells
T-Cell Lines
B-Cells
NK Cells
Peripheral Tissues:
Cell Mediated Immunity
Ab (Humoral) Immunity
Immunological Surveillance
Tacrolimus
• Pharmacology
– Suppresses cell-mediated immune reactions and some humoral
immunity, but exact mechanism is not known. The mechanism of
action in atopic dermatitis is not known.
• Indications and Usage
– PO and IV Prophylaxis of organ rejection in patients receiving
allogenic liver, kidney, or heart transplants. Used in conjunction with
adrenal corticosteroids.
– Topical As second-line therapy for the short-term and noncontinuous
chronic treatment of moderate to severe atopic dermatitis.
• Unlabeled Uses
– PO and IV Prophylaxis of rejection for patients receiving bone marrow,
pancreas, pancreatic island cell, and small bowel transplantation.
– Topical Treatment of vitiligo in children; facial, flexural, and
intertriginous psoriasis.
Tacrolimus
Dosage and Administration
• Prophylaxis of Organ Rejection, Liver Transplants
Adults PO 0.1 to 0.15 mg/kg/day in 2divided daily doses every 12 h no
sooner than 6h after transplantation. IV 0.03 to 0.05mg/kg/day as
continuous infusion.
• Children PO 0.15 to 0.2 mg/kg/day in 2divided daily doses every 12 h. IV
0.03 to 0.05mg/kg/day as continuous infusion.
• Topical Dermatitis
Adults Topical Apply thin layer of 0.03% or 0.1% to affected skin areas
twice daily; rub in gently and completely; continue for 1 wk after clearing
of atopic dermatitis.
• Children (2 yr of age and older) Topical Apply thin layer of 0.03% to
affected skin areas twice daily; rub in gently and completely; continue for
1 wk after clearing of atopic dermatitis.
General Advice
• Do not use occlusive dressings with topical use.
Tacrolimus
Pronouncation: (tak-ROE-li-mus)
Trade Names:
Prograf
- Capsules 0.5 mg
- Capsules 1 mg
- Capsules 5 mg
- Injection 5 mg/mL
Trade Names:
Protopic
- Ointment 0.03%
- Ointment 0.1%
Pimecrolimus
Dosage Form: Cream 1%
• TRADE NAME: Elidel®
FOR DERMATOLOGIC USE ONLY
NOT FOR OPHTHALMIC USE
Elidel ® (pimecrolimus) Cream 1%
contains the compound pimecrolimus,
the immunosuppressant 33-epi-chloroderivative of the macrolactam
ascomycin.
Pimecrolimus
Indications and Usage for Elidel
• Elidel ® (pimecrolimus) Cream 1% is indicated as
second-line therapy for the short-term and noncontinuous chronic treatment of mild to moderate
atopic dermatitis in non-immunocompromised
adults and children 2 years of age and older, who
have failed to respond adequately to other topical
prescription treatments, or when those treatments
are not advisable.
• Elidel Cream is not indicated for use in children less
than 2 years of age (see WARNINGS, boxed
WARNING, and PRECAUTIONS, Pediatric Use).
LOCAL AND SURFACE ACTING DRUGS
Protectants
MOA
Uses
Petroleum
Moisturizing skin
protectant
Apply to skin
surrounding wart
before removing
Topical
analgesics
MOA
Capsaicin
[Zostrix]
Likely depletes
substance P
Other occlusive
products
Adverse Effects
Other
Uses
Adverse Effects
Other
Topical for pain
associated with
HSV, neuralgia,
diabetic
neuropathies OA,
RA
Stinging or burning
pain upon application,
may irritate respiratory
passages
External use only
– NEVER on
mucus
membranes /
eyes!
Antiinflammatory
MOA
Uses
Adverse Effects
Other
Inflammation,
antipruritic,
vasoconstictive,
antiproliferative
Atrophy, pruritus,
irriation, similar effects
of oral steroids
Weakly active!
Hydrocortisone
Unknown; chemical
identical to that of cortisol
Triamcinolone
Betamethasone
Etc…
Longer acting, MUCH
more potent than
hydrocortisone
Calcipotriene
(Dovonex)
Vit. D3 analog
Psoriasis
Inflammation
Niacinamide
ointment
Vit B-3
Acne
Few
Tretinoin
(Retin-A)
Retinoic Acid
Acne
Rebound inflammation
Isotretinoin
(Accutane)
ORAL DRUG
Severe Acne
Teratogenic
Pseudotumor cerebri
“
“
Inhaled &
intranasal version
for asthmatics
3-5%
Concentration
Must have
negative PG test
Consent needed
Miscellaneous
Chelators:
MOA
Uses
Adverse Effects
Penicillamine
Chelates heavy metals,
esp. copper
Wilson’s Disease,
RA, mercury or
lead poisoning
Optic neuritis, GI
distress, stomatitis,
nephrotic syndrome,
GN, leukopenia, skin
rash, arthralgia
EDTA
Chelates metals, lead,
calcium, aluminum…
Lead poisoning,
Na-EDTA
(Long IV format)
hypercalcemia
excessive doses:
renal failure, tubular
necrosis
Hypocalcemia ,
Ca-EDTA
(Shorter IV format)
DMPS
Generally IV form.
Mercury poisoning
Hypomagnesmeia
Headaches,
depression and
suicidal thoughts
usually due to the
mercury poisoning
Can be used for Tx.
Chelates mercury, and
some other heavy metals.
Oral pharmaceutical for
Mercury, heavy metal and
lead detoxification.
Headache and
joint pain from
detoxification
process
Hypercalcemia
Used for provocative
heavy metal testing.
DMSA
[Chemet]
Other
Lead, mercury, or
other heavy metal
poisoning
Same as DMPS
Detoxing affects
the endocrine
system: watch
for fatigue, anger,
mood-swings;
Supplement with
water and detox
supplements.
Schedule and
can take year(s)
depending on the
individual