2Pharm III Flashcards
Adaptive immunity, Cell mediated:
Humoral:
T-lymphocytes
B lymphocytes
Where does the body learn to recognize “self” antigens?
Thymus gland
*central tolerance
What are the 3 specialized forms of T lymphocytes?
*which do we believe is involved in autoimmunes?
Helper
Cytotoxic
*Suppressor
T/F
Suppressor T cells regulate/dampen helper and cytotoxic T cells, preventing immune rxns from damaging the self
*this is Self Tolerance
True
When the immune system properly recognizes self/non-self antigens:
When this fails:
Immunologic tolerance
Autoimmunity
T/F
Autoimmunity is in 2% of the pop and the majority are women (and elderly, genetically susceptible)
True
Hypothesis of Autoimmunity is that T and B lymphocytes escape central tolerance mechanisms in the ______ gland
Thymus
What 2 major factors are necessary to develop autoimmmune disease?
Inherited susceptibility genes
Environmental triggers
What genes predispose to autoimmune disease?
MHC - major histocompatibility complex
What is the function of MHC genes?
2
encode cytokines
are recognized by T-lymphocytes for antigen processing
What are 3 common environmental triggers for autoimmune disease?
infection
high fever
trauma
Possessing an autoimmune gene doesn’t mean an individual will always develop the disease, but what are 5 diseases that show familial autoimmunity?
thyroid disease
lupus
RA
MS
Type I diabetes
Foreign antigens release cytokines that can activate T-lymphocytes and _______ T-lymphocytes
self-reactive
*infection as a trigger
What self-antigens can deposit in various places of the body, causing vasculitis, joint damage, and kidney damage?
Autoantibodies
What autoimmune disease is initiated by the alteration/inhibition of receptor function without tissue damage?
What receptor is inhibited?
Myasthenia gravis
acetylcholine (results in paralysis)
What autoimmune disease is initiated by autoantibodies that stimulate receptors that would normally only be stimulated by a hormone?
Hyperthyroidism
Organ specific autoimmune disease is mediated by what?
What is the Tx?
T-lymphocytes
reduce inflammation with coriticosteroids, anticytokines
What is the effect of a large dose of corticosteroids when targeting organ specific autoimmune disease?
lymph tissue atrophy
*this decreases T/B cell production, increases susceptibility to infection
Immunosuppressive drugs target what cells?
T cell responses
The goals for Pharmacologic interventions in autoimmune disease are generally what?
Palliative
*address inflammation with Aspirin/NSAIDS
What is a sign of toxicity to aspirin?
Tinnitus
T/F
GI, kidney, resp system, tinnitus are all adverse effects of Aspirin use
True
What are 2 oral complications of Aspirin/NSAID use?
Bleeding
Aphthous stomatitis
What is used to Tx RA when Aspirin/NSAIDS aren’t working?
Mechanism?
sulfasalazine (Azulfidine)
prostaglandin inhibitor
sulfasalazine (used for RA) has what (4) side effects?
headache
photosensitivity
GI
Anorexia
COX-2 inhibitor:
celebrex (Celecoxib)
T/F
Do not use celebrex with low dose aspirin
False
*ok to use
If a pt is using celebrex and antihypertensives, what should we do?
*why?
Monitor BP
*celebrex decreases BP med efficacy
2 side effects of celebrex:
CV (Increased risk for stroke/heart attack)
bleeding
2 Contraindications for celebrex:
if aspirin/NSAID allergic
if allergic to sulfonamides
DMARDS:
used for:
Disease-modifying anti-rheumatic drugs
RA and if pts don’t respond to COX-2 inhibitor (celebrex)
What intervention can slow the course of RA disease progression, may induce remission, and prevents further destruction of joints/tissues?
DMARDS
T/F
DMARDS have fast onset
False
*takes 3-4 months to see effects
4 classes of DMARDS:
Immune modulators (…mab)
Antimalarials
Penicillamine
Gold compounds
What DMARD is also a heavy metal antidote?
Penicillamine
2 DMARD immune modulating drugs:
methotrexate
leflunomide
What is the drug of choice for severe RA or psoriatic arthritis that is unresponsive to NSAIDS?
methotrexate
T/F
methotrexate, being a DMARD, takes 3 to 4 months to kick in
False
3-6 weeks, faster than other DMARDS
What are the 2 uses of methotrexate?
High dose - chemo
Low dose - immune modulator for autoimmune (RA)
What is the (2) most common side effects of methotrexate?
3 others?
mucosal ulcerations, nausea
cytopenias, cirrhosis, acute pneumonia-like syndrome
What DMARD inhibits pyrimidine synthesis, reduces pain/inflammation, and slows structural damage?
leflunomide
T/F
Since leflunomide messes with the immune system by blocking pyrimidine synth, it has a whole lot of side effects (including teratogenicity)
True
What are 2 proinflammitory cytokines involved in RA?
IL-1b
TNF-alpha
What secretes IL-1b and TNF-alpha involved in RA?
What does this further stimulate?
synovial macrophage
synovial cells secrete collagenase
3 TNF-alpha blockers:
1 IL-1b receptor antagonist:
etanercept
infliximab
adalimumab
anakinra
What TNF alpha blocker binds TNF molecules, risks activation of hepatitis and TB in carriers, and has Upper Respiratory infections as side effects?
etanercept
What TNF alpha blocker is associated with developing antibodies against the Drug w/ long term use?
*side effects: pneumonia, cellulitis, dyscrasias
infliximab
What TNF alpha blocker is a recombinant monoclonal antibody that binds to receptor sites?
(used if inadequate response to other DMARDS)
adalimumab
What drug is typically used if other cytokine drugs fail?
anakinra
*IL-1b receptor antagonist
anakinra (IL-1b receptor antagonist) mechanism:
slows degradation of cartilage/bone loss
2 Antimalarials that treat RA unresponsive to NSAIDS:
chroroquine
hydroxychloroquine
How do antimalarials help with RA?
2 severe side effects:
slows erosive bone lesions, may induce remission
eye damage, blue/black intraoral pigmentation
(kind of Kaposi’s sarcoma looking)
What chelating agent slows the progression of bone destruction and RA?
Penicillamine
2 mechanisms for Penicillamine:
depresses IgM rheumatoid factor
depress T-cells
What drug for RA is used after gold, but before corticosteroids?
Penicillamine
4 oral complications to Penicillamine:
infection
delayed healing
prolonged bleeding
ulcerations
Gold compounds used to treat RA decrease inflammation and slows bone/articular destruction via multiple….
mechanisms
Why does gold require intensive monitoring?
very toxic
4 side effects of gold compounds:
Dermatitis w/ mucosal ulcerations
Proteinuria
Neutropenia
Thrombocytopenia
There are all kinds of complications with Gold, including blue-black intraoral pigmentation and _____
aphthous stomatitis
What 2 drugs cause blue-black intraoral pigmentation as a side effect to combating RA?
Antimalarials
Gold
What are 3 immunosuppressive drugs used for Refractory RA
*refractory = doesn’t respond to normal Tx
azathioprine
cyclophosphamide
cyclosporine
What immune suppressant used for Refractory RA is also used in Dentistry for severe erosive lichen planus (and 3 other mouth diseases)?
What drug is it used in combination with?
azathioprine
prednisone
4 oral diseases azathiprine + prednisone is used for:
severe erosive lichen planus
major aphthous stomatitis
erythema multiforme
benign mucous membrane pemphigoid
What immunosuppressant used for severe RA is also an antineoplastic?
*side effects: alopecia, infertility, GI, dyscrasias
cyclophosphamide
What immunosuppressant for RA is primarily used to prevent organ rejection in transplants?
cyclosporine
When is cyclosporine used to treat RA?
if methotrexate doesn’t work
What drug combats RA by inhibiting production/release of IL-II (and IL-II induced T cells)?
cyclosporine
cyclosporine is contraindicated for RA in what 3 cases?
abnormal renal function
uncontrolled hypertension
malignancies
16% of cyclosporine users will have what?
Gingival hyperplasia
3 used for Synthetic Glucocorticoid meds
steroids
Autoimmune
Immunosuppressive transplant therapy
Respiratory disease
Glucocorticoids (steroids) have anti-inflammatory effects and profound effects on number, distribution, and function of ________
What do they inhibit that decreases production of prostaglandins and leukotrienes from arachidonic acid?
peripheral leukocytes
phospholipase A
Steroids increase what peripheral leukocyte?
Decrease what peripheral leukocytes?
increase neutrophils
decrease T/B cells, monocytes, eosinophils, basophils
Steroid suppress the immune system and the adverse rxns are proportional to the _____.
Tx is considered ______
dose
palliative
With Sjogren’s Syndrome _____ % of the glandular cells remain intact, allowing for ______
50%
salivary stimulating meds
An elevated BP can always be due to what?
Chronic pain
Stress =
cortisol
What does natural cortisol regulate?
maintain?
cortisol also has _____ effects
metabolism of carb, fat, and protein
vascular reactivity
anti-inflammatory
What is the most potent activator of cortisol?
Surgery
Excessive production of cortisol:
Insufficient production of cortisol:
Cushing’s disease
Addison’s disease
A medication induced adrenal insufficiency (taking steroids will suppress own production) is what kind of disorder?
Secondary
What adrenal insufficiency is more common than Addison’s disease?
Secondary insufficiency
*associated with chronic steroid use
What is a RARE, life-threatening emergency that exacerbates symptoms like sweating, hypotension, weak pulse, dyspnea, and cyanosis?
Adrenal crisis
6 systemic disease categories for which Steroids can be used?
Replacement therapy
Arthritis
Rheumatic Carditis
Renal diseases
Collagen diseases (lupus)
Allergic diseases
T/F
Steroids function intracellularly
True
*bind receptor, come inside, regulate gene expression
How is the potency of a steroid measured?
Against Hydrocortisone
Corticosteroids are characterized by what?
Duration of action
*shore/intermediate/long
Prednisone has how much more of an anti-inflammatory effect than hydrocortisone?
4x
Equivalent doses of steroids are based on the amount normally secreted in an adult w/o stress, which is…
20 mg
3 short acting steroids:
2 intermediate:
2 long:
hydrocortisone (cortisol), prednisone, methylprednisone
triamcinolone, prenisolone
dexamethasone, betamethasone
Steroids are usually taken what time of day?
When is steroid use taken at alternate days?
morning
if taking longer than 1 month
What type of steroid therapy increases the risk for adrenal suppression?
Daily
*that’s why alternate
Any medication that exceeds _____ mg hydrocortisone equivalent may cause adrenal suppression
20-30 mg
*normal daily output
Normal cortisol output is 20 mg/day. What is max during stress?
300 mg/day
What happens if combine Chronic Steroid use w/ aspirin/NSAIDS?
Peptic ulceration
What are 3 major adverse events with Chronic Steroid use?
Moon face
Cataracts
Osteoporosis
4 oral side effects of Steroids:
Candidiasis
Poor wound healing
Mask oral infections
Xerostomia
4 contraindications to using steroids:
Systemic fungal infections
Viral infections
TB
Allergy
2 ways steroids are used in Dentistry:
reduce pain/swelling
Tx inflammatory pathologies oral mucosa
What is the most common delivery route of Steroids in Dentistry?
Topical
High potency topical steroids should only be used for how long?
2 weeks only
Using high potency topical steroids for longer than 2 weeks requires what?
What is the risk?
physician consult
adrenal suppression
What oral topical steroid is mixed with tissue adhesive?
triamcinolone
What oral topical steroid is a 0.5% gel for mild lichen planus and recurrent aphthous stomatitis?
fluocinonide
What oral topical steroid is a 0.5% gel for oral inflammation?
clobetasol proprionate
What oral topical steroid is 0.1%?
betamethasone
What are the 2 topical steroid rinses used in dentistry?
used 2-4x/day, rinse 30 secs, spit
dexamethasone elixer
prenisolone syrup
What are the 2 types of injected steroid uses?
Intralesional
Intra-articular (3 week intervals)
What are the 2 Oral preparations of steroids used before, during, after oral surgery?
methylprednisolone
prenisone
What 3 populations require special consideration when using steroids?
*but there are many more (glaucoma, hypertension, peptic ulcer, osteoporosis, diabetes, TB)
Pregnant/lactating
pediatric
geriatric (liver/kidney function = lower dose)
What type of dental procedures require steroid used before/during/after?
Only major
*routine procedures won’t stimulate cortisol production
When do cortisol levels increase in dental pts?
1-5 hrs post procedure
pain response, loss of local anesthesia
What BP levels are hypotensive?
Systolic: less than 100 mm Hg
Diastolic: less than 60 mm Hg
T/F
For a routine dental procedure, if the pt has a past history of steroid use, supplementation is necessary
False
*no supplementation necessary
3 types of lab tests to determine if pt needs steroids:
ACTH in plasma
Urine test
Stimulation test
For a pt currently taking steroids, the protocol for diagnostic/minimally invasive procedures:
(4 things)
Pt takes usual dose
Schedule in morning
Stress reduce (pain/anxiety)
monitor BP
T/F
For major invasive procedures like oral surgery a physician consult, lab testing, and steroid supplementation as needed is protocol
True
T/F
Pts either currently taking steroids (topically or orally) or with a history of taking steroids should be given no additional steroids with routine Tx
True
Schedule in morning, monitor BP - What are 2 anxiety control interventions for pts on steroids?
nitrous oxide
benzodiazepines (Valium)
Target dose of hydrocortisone for Minor oral/perio surgery:
Target dose of hydrocortisone for major oral surgery involving general anesthesia:
25 mg
50-100 mg
3 mechanisms used by Antivirals:
Alter uncoating of virus
Polymerase inhibitors
Inhibit viral protein synth
2 drugs used for Influenza A?
*Mechanism
amantadine
rimantidine
*blocks viral uncoating
Drug for either Influenza A or B:
This is a classic example of what?
This drug inhibits what enzyme
oseltamivir (Tamilflu)
Prodrug
Neuraminidase inhibitor
Neuraminidase does what?
Cuts viral progeny from cellular envelope prior to release
*inhibiting prevents viral release
What drug is used for respiratory syncytial virus?
ribavirin (Rebetol, Virazole)
