Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
253 Cards in this Set
- Front
- Back
|
what are the cellular components of the immune system derived from?
|
pluripotent hematopoietic stem cells
|
|
|
at six weeks, hematopoiesis shifts from _____ to ______.
|
fetal liver to bone marrow
|
|
|
Where do T cells develop?
Where do B cells develop? |
T cells - thymus
B cells - Bone marrow |
|
|
Cell mediated immunity involves which type of lymphocyte?
|
T cells
|
|
|
humoral immunity involves which type of lymphocyte?
|
B cells
|
|
|
regarding costimulation of T cells - what happens if...
1. there is no 2nd signal? 2. there is a 2nd signal? |
1. T cells will not be stimulated
2. T cells will produce IL-2: this causes differentiation of T cells into effector cells and memory cells. |
|
|
what is the first cosignal involved in T cell stimulation?
|
CD4 binding to MHC class II
OR CD8 binding to MHC class I |
|
|
what are the 2 subsets of CD4 T cells?
|
Th1 (T helper 1)
Th2 (T helper 2) |
|
|
1. What does Th1 secrete?
2. What is the Th1 response important in? |
1. IL-2 and IFN-gamma
2. important in: delayed hypersensitivity rxns. macrophage activation opsonization compliment |
|
|
1. What does Th2 secrete?
2. What is the Th2 response important in? |
1. IL-3, 4, 5,
2. aids in synthesis of IgE and eosinophils |
|
|
What type of antibodies do B cells have on their cell surface?
|
(membrane bound) IgM
|
|
|
which cell type of the immune system is able to kill virally infected cells w/o previous sensitization?
|
NK cells
|
|
|
what are the two major types of APCs in the immune system?
|
macrophages
dendritic cells |
|
|
1. macrophages present their antigens to?
2. dendritic cells present their antigens to? |
1. T cells
2. activated CD4+ cells (interdigitating) B cells (follicular) |
|
|
macrophages look for what coating (opsonization) molecules?
|
IgG
C3b |
|
|
1. where are interdigitating dendritic cells found?
2. where are follicular dendritic cells found? |
1. under epithelia and in interstitium
2. in germinal centers of lymphoid follicles |
|
|
Histocompatibility class I is effective against what type of microbe?
|
Viruses
(It binds to peptides synthesized within cells) |
|
|
Histocampatibility class II is effective against which class of microbes?
|
exogenous microbes, bacteria
(binds peptides that are internalized and processed in lysozomes) |
|
|
which histocompatibility class is expressed on all nucleated cells and platelets?
|
MHC Class I
|
|
|
which histocompatibility complex is expressed on APCs? (B cells, macrophages)
|
MHC Class II
|
|
|
which types of hypersensitivity are antibody mediated?
|
I, II, III
|
|
|
describe a type I hypersensitivity
|
First and Fast
antigen binds to IgE on mast cells and basophils: this triggers release of vasoactive amines. |
|
|
What are some primary mediators in a Type I hypersensitivity?
|
1. Biogenic amines(Histamines)
2. enzymes (chymase, tryptase, acid hydrolase) 3. Proteoglycans (heparin and chondroitin sulfate) |
|
|
what are the actions of histamine in a type I hypersensitivity?
|
smooth muscle contraction resulting in increased vascular permeability. This results in increased secretions
|
|
|
what are the actions of enzymes such as chymase, tryptase and acid hydrolase in a type I hypersensitivity?
|
cause tissue damage by generating kinins and complement fragments
|
|
|
Leukotrienes C4 and D4 are secondary mediators in a type I hypersensitivity. what is their role?
|
chemotactic for neutrophils, eosinophils, monocytes
|
|
|
which secondary mediator of a type I hypersensitivity causes increased bronchospasm and mucus secretion?
|
Prostaglandin D2
|
|
|
which secondary mediator of a type I hypersensitivity causes platelet aggregation, histamine release, bronchospasm, vasodilation and vascular permeability?
|
PAF (Platelet Activating Factor)
|
|
|
what is the role of eosinophils in the type I hypersensitivity response?
|
amplify and sustain inflammatory response
(they produce major basic protien and eosinophilic cationic protien) |
|
|
What is atopy?
|
a genetically determined susceptibility to a type I hypersensitivity reaction
|
|
|
what changes are seen in the serum levels of an atopic individual?
|
higher IgE levels
more IL-4 producing Th2 cells |
|
|
give some examples of type I hypersensitivity reactions
|
anaphylaxis
asthma hives, allergies local wheal and flare |
|
|
describe the general mechanism of a type II hypersensitivity reaction
|
IgM and IgG bind to antigen of "enemy cell" leading to cytotoxicity
|
|
|
what are the three mechanisms of antibody mediated injury in a type II hypersensitivity?
|
1. Compliment mediated and Opsonization
2. Antibody Dependent Cell Mediated Cytotoxicity (ADCC) 3. Antibody Mediated Cellular Dysfunction |
|
|
Give some examples of Complement mediated and opsonization pathologic conditions seen in type II hypersensitivity rxns.
|
transfusion reactions
drug reactions autoimmune hemolytic anemias erythroblastosis fetalis |
|
|
Which hallmark thing is seen in complement mediated and opsonization cytotoxicity?
|
MAC (membrane attack complex)
|
|
|
describe the mechanism of antibody dependent cell mediated cytotoxicity
|
DOES NOT INVOLVE COMPLIMENT
IgG coats target cells. then nonsensitized cells (monocytes, neutrophils, NK cells) kill the target cells. |
|
|
describe the mechanism of antibody mediated cellular dysfunction
|
antibody impairs cell function without cell injury or death
|
|
|
Give two examples of a type II hypersensitivity caused by antibody mediated cellular dysfuntion.
|
1. Myasthenia Gravis (antibodies impair Ach receptor)
2. Graves Disease (hyperthyroidism) |
|
|
cyroglobulinemias, Henoch-Schonlein purpura, SLE and Rheumatoid arthritis are examples of?
|
Type III hypersensitivity
|
|
|
describe the mechanism of a type III hypersensitivity rxn
|
TYPE III = III things stuck together (antigen-antibody-compliment)
antigen-antibody complexes activate compliment, which attracts neutrophils. Neutrophils release lysosomal enzymes. |
|
|
what happens to the immune complex formed in the type III hypersensitivity rxn?
|
it is deposited on tissues
|
|
|
two types of inflammatory reactions can occur in a type III hypersensitivity.
1. Which one is systemic? 2. Which one is local? |
1. Serum Sickness
2. Arthrus rxn |
|
|
compare the timeframes of the arthrus reaction to serum sickness.
|
arthrus rxn: appears in 2-6 hrs.
serum sickness: appears in 6 days, lasts at least 10. |
|
|
describe the three phases of serum sickness.
|
1. Phase I: Immune complex formation
2. Phase II: Immune complex deposition 3. Phase III: Immune complex mediated inflammation |
|
|
describe the arthus rxn
|
antibody-antigen complexes cause local tissue necrosis. result is edema, hemorrhage, fibrinoid necrosis.
|
|
|
antibodies are not involved in a type IV hypersensitivity rxn. What, then, initiates this rxn?
|
initiated by soluble circulating antigens
these antigens activate T cells |
|
|
what are the two types of Type IV hypersensitivity rxns and which cell types mediate them?
|
1. Delayed-type hypersensitivity (CD4+)
2. Direct T cell toxicity (CD8+) |
|
|
what is the classic example of a delayed type hypersensitivity?
Describe the time frame of this example |
tuberculin reaction
redness, induration -> 8-12 hrs peaks 24-48 hrs |
|
|
transplant rejection is an example of which type of hypersensitivity?
|
Type IV
|
|
|
myasthenia gravis is an example of which type of hypersensitivity?
|
Type II (cytotoxic)
|
|
|
SLE is an example of which type of hypersensitivity?
|
Type III (Immune complex)
|
|
|
Sjogren syndrome is an example of which type of hypersensitivity?
|
Type IV
|
|
|
rheumatic fever is an example of which type of hypersensitivity?
|
Type II (cytotoxic)
|
|
|
which type of hypersensitivity is a classic reponse to mycobacterium tuberculosis?
|
Type IV
|
|
|
when you see a granuloma you should think this kind of hypersensitivity
|
Type IV (delayed type)
|
|
|
what are some examples of delayed type (IV) hypersensitivity? (3)
|
contact dermatitis
type I diabetes MS |
|
|
In the type IV hypersensitivity, CD8+ T cells kill cells by what two major mechanisms?
|
1. perforin/granzymes
2. Fas-Fas ligand |
|
|
what are the glycoprotiens that stud the HIV viral envelope?
function? |
gp120 and gp41
gp 120 binds to the host CD4+ T cell gp 41 penetrates membrane so HIV can enter host cytoplasm |
|
|
what are the three subgroups of HIV-1?
|
1. M - most
2. O - outliers 3. N - neither |
|
|
what type of host cells does HIV target? (3)
|
1. T cells
2. macrophages 3. dendritic cells |
|
|
what must happen in order for a person to have "full blown AIDS"
|
CD4+ count must be below 500/mL
|
|
|
what is the significance of macrophages and HIV?
|
microphages are a virus factory (they don't lyse like the T cells do). So they carry the virus throughout the body (especially to the nervous system)
|
|
|
where in the body are the major sites of HIV infection and persistance?
|
lymphoid tissues
|
|
|
which organisms cause opportunistic pulmonary infection in AIDS? (3)
HHV8 causes what in AIDS patients? |
1. P. carinii (jerovicii)(2/3)
2. CMV 3. Myobacterium avium Kaposi's sarcoma |
|
|
what type of antibodies are diagnostic of SLE?
|
antibodies to dsDNA and Smith(Sm) antigen
|
|
|
why would lupus pts have a false test for syphilis?
|
SLE antibodies against phospholipid B2-glycoprotien complex also bind cartiolipin antigen (used in syphilis test)
|
|
|
what is the antiphospholipid antibody syndrome seen in SLE?
|
procoagulant and anticoagulant features.
anticoagulant - antibodies interfere with PTT procoagulant - associated with miscarriages, cerebral or occular ischemia |
|
|
Besides SLE, what other type of lupus exists?
|
Drug-Induced Lupus
|
|
|
Which three drugs are associated with inducing Lupus?
|
Procainamide
Hydralazine Isoniozid |
|
|
What is the ANA targeted towards in drug-induced Lupus?
|
ANA is target towards histones
|
|
|
what is the most common autoimmune disease after SLE?
|
Sjogren's syndrome
|
|
|
what is the triad of symptoms commonly seen in Sjogrens syndrome?
|
Xeropthalmia (dry eyes)
Xerostomia (dry mouth) Arthritis |
|
|
in Sjogrens syndrome: what is observed in lacrimal and salivary glands?
|
lymphocytic infiltrate
fibrosis |
|
|
serologic markers of Sjogren's disease?
|
SS-A (Ro)
SS-B (La) |
|
|
significance of lymphocyte abnormality in Sjogren's syndrome?
|
*increased risk of B cell lymphoma
* increased occurance of another autoimmune disorder |
|
|
what is the underlying pathology behind scleroderma?
|
- excessive collagen deposition in skin and internal organs
- caused by abnormal immune response resulting in growth factors that act on fibroblasts to stimulate collagen production. |
|
|
what are the two types of scleroderma?
|
1. Diffuse
2. limited (CREST) form |
|
|
1. what is the antibody type specific to diffuse scleroderma?
2. what is the antibody type specific to the CREST variant of scleroderma? |
1. antibody to Scl-70
2. Anti-centromere antibodies |
|
|
describe some skin/skeletal changes seen in Scleroderma (3)
|
1. Claw-like flexion deformity (Sclerodactyly)
2. Cutaneous ulceration 3. thick, tough skin (due to dense collagen in dermis) |
|
|
describe two vascular changes that occur in scleroderma
|
1. thickening and fibrosis of vessel walls
2. occlusion by a thrombus |
|
|
what are three renal changes seen in scleroderma?
|
1. cortical infarcts
2. fibrinoid necrosis of renal vessels 3. hypertension (30%) |
|
|
how often are renal changes observed in scleroderma?
|
2/3 of scleroderma patients have renal symptoms
|
|
|
how often are GI tract symptoms seen in scleroderma
what are three GI symptoms seen in scleroderma? |
90% of the time
esophageal dysfunction GERD Malabsorption syndrome |
|
|
what are the two organ systems effected in Goodpasture's syndrome?
|
1. Renal (Glomerulus)
2. Pulmonary "2 Good Pastures for this disease: Glomerulus and Pulmonary" |
|
|
what type of hypersensitivity is Goodpasture's disease?
|
Type II
(2 good pastures = type 2) |
|
|
1. In Goodpastures: describe the pattern of anti-glomerular basement membrane antibodies on immunoflourescence
2. In SLE: describe the pattern of antiglomerular basement membrane antibodies via immunoflourescence |
1. linear staining
2. "wire loop" lesions |
|
|
What are the three characteristics of a biofilm?
|
1. Attached to a surface
2. Secretion of EPS ("slime layer") 3. Altered phenotype |
|
|
define:
1. sessile 2. planktonic |
1. attached to a surface
2. free |
|
|
what is the connection between biofilms and bacterial resistance?
|
biofilms increase the resistance of the bacteria
|
|
|
why is biofilm more resistant than planktonic bacteria?
|
biofilm is a molecular filter
(therefore will not allow antimicrobial "through") |
|
|
what is the tradeoff for bacteria in a biofilm that has antimicrobial resistance?
|
bacteria in a biofilm grow more slowly than planktonic bacteria
|
|
|
the property of a biofilm to sense when the minimal population has been achieved is called_________?
|
Quorum sensing
|
|
|
In quorum testing, what occurs once the minimal population has been achieved?
|
gene expression is regulated
|
|
|
which operon is associated with quorum sensing?
|
The Lux operon
|
|
|
where is the LuxR/LuxI regulatory (quorum) system seen?
|
it is seen in over 25 species of Gram negative bacteria
|
|
|
what are five examples of Biofilms causing human infections?
|
1. Native Valve Endocarditis
2. Otitis Media 3. Chronic Bacterial Prostatitis 4. Cystic Fibrosis 5. Peridontitis |
|
|
which organism has an 80% colonization rate as a biofilm in Cystic Fibrosis?
|
P. auruginosa
|
|
|
P. auruginosa produces what molecule that forms the biofilm?
|
alginate
|
|
|
which two organisms most often form biofilms that cause native valve endocarditis?
|
streptococcus
staphylococcus |
|
|
what are some medical devices that commonly get biofilms?
|
Prosthetic Heart Valves
Central venous catheters urinary catheters IUDs (contact lenses, dental unit water lines) |
|
|
why can't the host immune system get rid of these biofilm infections?
|
biofilm prevents access to the bacteria to be killed.
|
|
|
what toxic thing can bacteria in the biofilm release?
|
endotoxins
|
|
|
what is the "definition" of asthma?
|
chronic INFLAMMATORY disorder of the airways, usually associated with widespread but variable airflow OBSTRUCTION
|
|
|
at what time(s) of day would a coughing pattern make us suspicious of asthma?
|
* Night and early morning
(non-asthmatics usually don't experience that) * always returns to baseline |
|
|
What is the effect of inflammation on the bronchioles?
|
hyperresponsiveness
(bronchospasms & asthma easily triggered) |
|
|
what occurs (cellular level)in the early asthmatic reaction?
|
allergen causes IgE to bind to mast cell. mast cell is activated and degranulates, releasing many inflammatory factors. this results in acute bronchoconstriction
|
|
|
what contents are released when a mast cell degranulates?
|
histamine
PGD2 LTs PAF chemotactic factors (for neutrophils and eosinophils) |
|
|
what physical symptoms are associated with acute airway obstruction? (3)
|
1. bronchoconstriction
2. microvascular leakage with edema 3. reduced mucous clearance |
|
|
compare the timeframes of the acute and late asthmatic reaction
|
acute - onset: minutes
lasts 1.5-2 hrs. chronic - onset: 2-8 hrs lasts: days to weeks |
|
|
what are the cellular "happenings" responsible for the late allergic reaction?
|
In the acute phase, cytokines are released from mast or T cells. they attract eosinophils and neutrophils -> they get there and induce inflammation: this results in late allergic rxn.
|
|
|
what physical symptoms are associated with the late asthmatic reaction?
|
submucosal edema
mucous hypersecretion increased hyperresponsiveness |
|
|
what class of drug do we use to target:
1. the early phase of an asthma reaction 2. the late phase of an asthma reaction |
1. bronchodilators (most often B2 agonists)
2. antiinflammatories |
|
|
regarding corticosteroid use in asthma: which route would you administer for:
1. an acute reaction 2. long term control |
1. systemic (want to prevent a late phase reaction)
2. inhaled (local) |
|
|
what are the three classes of bronchodilators used to treat acute asthma?
|
1. B2 agonists
2. Anticholinergics 3. Methylxanthines |
|
|
what is the MOA of Theophylline?
|
*phosphodiesterase (PDE) inhibitor*
prevents the breakdown of cAMP resulting in cAMP accumulation. Excess cAMP stimulates bronchorelaxation. |
|
|
MOA of anticholinergics?
|
anticholinergics inhibit the parasympathetic effects (vagal tone = bronchoconstriction)
Parasympathetic effects are mediated by Acetylcholine |
|
|
do Beta agonists have antiinflammatory activity?
|
NO, they do not have any clinically significant antiinflammatory activities
|
|
|
what are the effects of B2 agonists combined with steroids?
|
SYNERGISTIC EFFECTS
1. B2 augments inhibitory activity of steroids on cell activation 2. steroids increase B2 receptors 3. inhibit inflammatory mediator release from airway smooth muscle cells. |
|
|
B2 agonists have what effect on:
1. late allergic response 2. inflammation 3. airway hyperresponsiveness |
NO EFFECT ON ANY OF THOSE!
(this is why they can't be prescribed as monotherapy) |
|
|
which bronchodilator has equal B1-B2 activity?
|
Isoproteronol
|
|
|
which bronchodilators are B2 selective (3)
|
1. Albuterol (least selective of the 3)
2. Salmeterol 3. Formoterol |
|
|
which bronchodilator is the anticholinergic?
|
Ipratropium
|
|
|
1. which B2 agonist is used for acute asthma?
2. which B2 agonists are long acting and therefore are used for long term asthma treatment? |
1. Albuterol
2. Salmeterol, Formoterol |
|
|
what is the medication of choice for EIB (excercise induced bronchospasm)?
|
Short Acting B2 Agonists
|
|
|
To treat COPD exacerbation: what medication can we combine with a short acting B2 agonist?
|
ipratropium
|
|
|
in what form do Salmeterol and Formoterol come?
use? |
powder for inhalation
*used for chronic maintenance of asthma* |
|
|
adverse effects of B2 agonists?
|
tremor
arrythmia tachycardia |
|
|
when prescribing salmeterol: what must you educate patient about?
|
* recognizing signs of deteriorating asthma control, then seek medical help*
*also emphasize that it is not an acute bronchodilator* (a sign of deteriorating asthma control is more frequent need for the short acting bronchodilator) |
|
|
what are the two sites/mechanisms of action of Theophylline?
|
1. nonselective PDE inhibition
2. competitive antagonist of adenosine receptors (results in bronchodilation) |
|
|
why is theophylline not used so much in asthma anymore?
- what is it still used for? |
it is TOXIC (small therapeutic index)
- still used for COPD |
|
|
why is theophylline useful in COPD?
|
1. respiratory stimulant
2. bronchodilation 3. increase diaphragmatic contractility |
|
|
what is one reason why theophylline is so toxic?
|
it is involved with the P450 system
|
|
|
what is the therapeutic range of theophylline?
|
5-15 mcg/mL
MUST MONITOR SERUM LEVELS |
|
|
would we use theophylline in chronic or acute asthma?
|
chronic
|
|
|
regarding anticholinergics:
1. do they have antiinflammatory activity? 2. which is a stronger bronchodilator: this or B2 agonists? |
1. no
2. B2 agonists |
|
|
what is the difference between ipratropium and tiotropium?
|
dosing:
ipratropium - 4x per day tiotropium (Spiriva) - once daily |
|
|
what type of asthma attack would anticholinergics be useful for?
|
acute asthma attacks
|
|
|
what can be combined with ipratropium to make it more useful in the treatment of acute asthma and COPD?
|
albuterol
(Combivent, DuoNeb) |
|
|
what are the 3 classes of antiinflammatory agents used in asthma treatment?
|
1. Corticosteroids
2. Mast cell stabilizers 3. Leukotriene modifiers |
|
|
what are the two types of allergic rhinitis?
|
1. SAR - seasonal allergic rhinitis (outdoor allergens)
2. PAR - perennial allergic rhinitis (indoor allergens) |
|
|
what is the chronic allergic respiratory syndrome hypothesis?
|
the thought that rhinitis and asthma may be manifestations of one syndrome
|
|
|
do antihistamines treat nasal congestion?
|
NO
that is why we have decongestant/antihistamine combinations |
|
|
which histamine receptor is relevent to s/s of allergic rhinitis?
|
H1
(H2 = gastric acid) |
|
|
what is the difference between first and second generation antihistamines?
|
first generation - drowsy
second generation - non-drowsy EQUAL IN EFFICACY |
|
|
what is the only OTC second generation antihistamine?
|
Loratadine (Claritin)
|
|
|
MOA of antihistamines?
|
competitive Histamine antagonist at the H1 receptor
(not currently true - inverse agonist of H1 receptor) |
|
|
other effects of antihistamines besides inhibition at H1 receptor?
|
anticholinergic
antiserotonergic local anesthetic effect |
|
|
which antihistamine is known for the serotonergic blockade?
|
cyproheptadine
|
|
|
which antihistamine is known for the local anesthetic effects?
|
diphenhydramine (benadryl)
(seen in Calamine) |
|
|
which second generation antihistamine is the only one to have absolutely NO sedation effects?
|
fexofenadine (Allegra)
|
|
|
which effect of antihistamines is responsible for the most adverse effects?
|
anticholinergic activity causes the most adverse effects
(2nd generation has less anticholinergic activity) |
|
|
what is the molecular explanation for the first generation antihistamines causing sedation (and the 2nd generation not)?
|
1st generation easily penetrate the BBB - they are not recognized by the efflux pump so they build up there.
(2nd gen. has little BBB crossing) |
|
|
what is Azelastine?
|
H1 antagonist nasal spray
(not often used due to many adverse effects) |
|
|
what is the MOA of decongestants?
|
VASOCONSTRICTION in mucosa of respiratory tract
a-adrinergic receptor agonist |
|
|
what is the most common oral decongestant?
what about intranasal decongestants? |
pseudoephedrine
xylometazoline(Afrin) |
|
|
what is often seen in intranasal decongestant use?
|
rebound rhinitis
(headaches and worse congestion appear 3-5 days after use) |
|
|
MOA of cromolyn?
|
MAST CELL STABILIZER
prevents release of mediators from mast cells. effective for prophylaxis of asthma/acute allergic response |
|
|
what are two other uses (besides allergies) of first generation antihistamines?
|
motion sickness
sleep aid |
|
|
what is considered the "gold standard" of treatment for Allergic Rhinitis?
|
Intranasal Steroids (Corticosteroids)
(prophylaxis of AR) |
|
|
what is an adverse effect of intranasal steroids that is rare but serious when it happens?
|
septal perforation
(advise administration away from septum) |
|
|
MOA of corticosteroids?
|
PHOSPHOLIPASE A2 INHIBITOR
(inhibit formation of arachadonic acid from membrane phospholipids) inhibits the synthesis of virtually all cytokines (thereby inhibiting inflammation) |
|
|
what is the main leukotriene modifier used to treat seasonal AR?
|
Montelukast (Singulair)
|
|
|
what is an advantage of leukotriene inhibitors (vs. intranasal steroids)?
|
LIs can be used at a young age
|
|
|
MOA of leukotriene inhibitors? (2)
|
- block leukotriene receptors (Zafirlukast, Montelukast)
- inhibit conversion of arachadonic acid to leukotrienes (lipoxygenase inhibitor)(Zileuton) |
|
|
what is the only rhinitis medication that does not improve rhinorrhea?
|
decongestants
|
|
|
what is the only rhinitis medication that does not improve congestion?
|
anticholinergics
(antihistamines also have little effect) |
|
|
classes of rhinitis medications that improve eye symptoms? (3)
|
antihistamines
LT inhibitors Nasal steroids |
|
|
In relation to treatment of asthma: which corticosteroid has more adverse effects?
|
ORAL - more effects
(low adv. effects with inhaled steroids) |
|
|
how can the local adverse effects of inhaled corticosteroids be reduced?
|
- use spacers, chambers
- rinse mouth out after each dose (reduces candidiasis) |
|
|
what drug can you add for increased efficacy of inhaled corticosteroids?
examples? |
bronchodilators
- Salmeterol/inhaled steroid (fluticasone) - Formeterol/inhaled steroid |
|
|
when would we use oral systemic corticosteroids in the treatment of asthma?
|
use for acute attacks
(intranasal steroids are a chronic maintenance dose) |
|
|
what are the 2 mast cell inhibitors and when would they be used?
|
1. cromolyn sodium, nedocromil
2. used to prevent EIB, also used in allergic rhinitis and conjunctivitis |
|
|
does cromolyn sodium function as a bronchodilator?
|
NO
it functions as an NSAID |
|
|
what is the name of the pathway that yields leukotrienes?
|
Lipogenase pathway yields Leukotrienes
|
|
|
functions of leukotrienes? (3)
|
1. contraction of smooth muscle:
bronchoconstriction, vasoconstriction -> increased vascular permeability 2. recruit and activate eosinophils and basophils in airway 3. increase mucous secretions |
|
|
which is a more potent bronchoconstrictor: histamine or leukotrienes?
|
leukotrienes
(1000 x more potent) |
|
|
name the two LT receptor antagonists
|
Zafirlukast
Montelukast |
|
|
name the leukotriene that is a 5-lipoxygenase inhibitor
|
Zileuton
|
|
|
which anti-asthmatic drugs are associated with Churg-Strauss Syndrome?
|
Zafirlukast
Montelukast (unknown if causal) |
|
|
what is omalizumab (Xolair)
|
new drug for moderate-severe allergy induced asthma (that is poorly controlled with inhaled steroids)
|
|
|
MOA of Omalizumab?
|
monoclonal Ab that binds to IgE - this prevents binding of IgE to mast cells and basophils
|
|
|
1. how is omalizumab administered?
2. adverse effects (2) |
1. SubQ every 2-4 wks (long 1/2 life)
2. anaphylaxis, malignant neoplasms (0.4%) |
|
|
what are the four classes of asthma?
|
1. Class I (Intermittent)
2. Class II (Mild Persistent) 3. Class III (Moderate Persistent) 4. Class IV (Severe Persistent) |
|
|
what is the treatment of choice for intermittent (Class I) asthma?
|
inhaled, short acting B2 agonist
|
|
|
what is the treatment of choice for mild persistent (Class II) asthma?
|
low dose inhaled steroid
(for long-term control combine with long-acting inhaled B2 agonist) |
|
|
what is the preferred long-term treatment of severe persistent asthma?
|
high dose inhaled steroid AND long acting B2 agonist
|
|
|
when does the peak serum concentration of cortisol occur?
|
between 6 and 8 AM
|
|
|
if you wanted to minimize the effects of cortisol the most, when would you administer it?
|
in the evening
(negative feedback will inhibit ATCH and cortisol from peaking in the morning) |
|
|
if you wanted to maximize the effects of cortisol when would you dose it?
|
in the morning
(Mimic natural cortisol peak - produce less adrenal suppression) |
|
|
how do corticosteroids get to the nucleus and alter protein synthesis
|
- diffuse across lipid bilayer
- binds to intracellular cytoplasmic receptors/activate the receptor - glucocorticoid/receptor complex translocates to nucleus - binds to DNA: either stimulates or represses genes involved in synthesis of protiens |
|
|
what is the effect of glucocorticoids on neutrophils?
|
- Neutrophilia (lots of bands)
can alter CBC when looking for infection - little effect on function |
|
|
what cells do glucocorticoids reduce?
|
REDUCES INFLAMMATORY CELLS
Monocytes Lymphocytes Eosinophils Basophils (also a decrease in function) |
|
|
Why do glucocorticoids have such widespread activity?
|
inhibit phospholipase A2, a precursor for many inflammatory mediators
|
|
|
what effect do glucocorticoids have on blood glucose?
|
INCREASE blood glucose
- watch for hyperglycemia or diabetic induced state |
|
|
Lipid effects of glucocorticoids
|
redistribution of body fat
- buffalo hump - moon facies - supraclavicular area |
|
|
Skin effects of glucocorticoids
|
thinning of skin
easy bruising |
|
|
corticosteroids with mineralcorticoid activity have what effects?
|
ALDOSTERONE LIKE EFFECTS
Na+ reabsorption w/ K+ elimination - Ca++ effects (reduced GI absorption, increased urinary excretion) |
|
|
Cardiovascular effects of glucocorticoids?
|
- HTN
- increased vascular reactivity to vasoactive substances (increases a-adrinergic receptors = vasoconstriction) |
|
|
skeletal muscle effects of glucocorticoids?
|
- skeletal muscle wasting and weakness (myopathy)
(mostly proximal limb muscles) |
|
|
what are the advantages of using synthetic corticosteroids?
|
- greater antiinflammatory potency
- little or no mineralcorticoid activity - increase or decrease absorption - longer 1/2 lives |
|
|
1. what is the most common oral corticosteroid used?
2. what is the most common IV, IM corticosteroid? |
1. prednisone
2. Methylprednisolone |
|
|
which corticosteroids have the highest mineralcorticoid activity?
|
hydrocortisone
cortisone (highest Na+ retaining potency) |
|
|
which corticosteroids have the lowest antiinflammatory potency and the highest equivalent dose?
|
hydrocortisone
cortisone |
|
|
short acting corticosteroids?
|
hydrocortisone
cortisone |
|
|
intermediate acting corticosteroids
|
prednisone
prednisolone methylprednisolone triamcinolone |
|
|
what is the difference between prednisone and prednisolone?
|
prednisone must be metabolized to an active metabolite for activity, prednisolone doesn't
|
|
|
uses of triamcinolone?
|
joint injections
IM injections (ie. allergy) |
|
|
long acting corticosteroids?
|
dexamethasone (oral or IV)
betamethasone (inhaled/intranasal) |
|
|
a cushingoid like adverse effect is...?
|
redistribution of body fat in the characteristic manner
|
|
|
what are some ocular adverse effects of glucocorticoids? (3)
|
cataracts
glaucoma infections (with local eye drops) |
|
|
which musculoskeletal adverse effect, if we see it, we can be almost sure it was caused by corticosteroids?
|
aseptic necrosis of femoral or humeral head
|
|
|
what is the mechanism of steroid-induced osteoporosis?
|
- decreased absorption of Ca++ and PO4(secondary hyperparathyroidism)
- inhibition of osteoblasts |
|
|
what is the time frame of steroid induced osteoporosis?
|
6-12 mo. - rapid bone loss
|
|
|
what is the prednisone dose that (above it) significant bone loss will occur?
|
5 mg
|
|
|
how can we prevent steroid induced osteoporosis
|
- supplemental Ca++ intake
- supplemental vitamin D - raloxifene (SERM) - Biphosphonates - Calcitonin nasal spray |
|
|
what happens if steroid withdrawal is not tapered?
|
adrenal suppression will occur
|
|
|
what is considered long term steroid use?
|
>4 wks
takes HPA axis over a year to return to normal function |
|
|
signs/symptoms of a steroid withdrawal that is too rapid?
|
- addison's like s/s
(feel horrible, ORTHOSTATIC HYPERTENSION, neurological symptoms) |
|
|
what are three things you can do to lower the adverse effects and HPA suppression?
|
1. Shortest term and lowest dose
2. alternate day administration 3. early morning dosing |
|
|
how many cells in the following parasites?
1. protozoa 2. helminths (nematodes) 3. arthropods |
1. single celled
2. multicellular 3. multicellular |
|
|
ascaris is an example of?
|
a helminth (ascaris)
|
|
|
how can parasites be identified in the human host (in the lab)? (2)
|
blood smears
"stylized" eggs in feces |
|
|
what is the name of the host type where sexual reproduction occurs?
|
definitive host
|
|
|
where do protozoa undergo sexual and asexual reproduction?
|
both in definitive host
|
|
|
where do helminths undergo sexual and asexual reproduction?
|
sexual - definitive host
asexual - non-definitive host |
|
|
protozoa that move by..
1. ameboid 2. cilia 3. flagella 4. none ...are called |
1. amoebae
2. ciliates 3. flagellates 4. sporozoans |
|
|
what are the top two locations in a human for parasite colonization?
|
1. intestinal
2. blood |
|
|
what is the name of the protozoa that causes malaria?
|
Plasmodium
|
|
|
what is the definitive host of the plasmodium spp?
|
mosquito
|
|
|
once plasmodium is injected into the human - where does it go?
|
the liver
(Schizonts) |
|
|
after the liver - where does the plasmodium go?
|
to the RBCs
(Merozoites) |
|
|
how is plasmodium transferred?
|
mosquito bites infected human, blood with protozoa enters GI tract of mosquito. plasmodium transforms and enters salivary gland - then mosquito bites an uninfected person
|
|
|
what are the two categories of helminths?
|
1. platyhelminthes (flatworms)
2. Nematodes (roundworms) |
|
|
two groups of flatworms (Platyhelminthes)?
|
trematodes (flukes)
cestodes (tapeworms) |
|
|
type of roundworm?
subtype of medical interest? |
Annelids (segmented worms)
leech is only one of clinical interest. |
|
|
what characteristic do all or most trematodes have in common? (3)
|
1. two anterior suckers, one ventral sucker
2. most are hermaphroditic 3. all must infect a mollusc (snail) host. |
|
|
what is a clinically important trematode (flatworm)?
|
Schistosoma
(blood fluke) |
|
|
what is different about schistosoma compared to other trematodes?
|
they are not hermaphroditic
they mate for life |
|
|
how does schistosoma infect humans?
|
lives in (snail in) water, then leaves snail to penetrate the skin of a human that is in that water
|
|
|
regarding cestodes (tapeworms):
the adults are divided into what 3 segments? |
1. scolex (head)
2. strobilia (segmented body) 3. proglottids (at neck - each a self contained hermaphroditic reproductive unit) |
|
|
how does schistosoma evade the immune system?
|
the eggs absorb human antigens onto their surfaces.
|
|
|
name a type of cestode (tapeworm)
|
Taenia saginata
(tapeworm occupies beef) |
|
|
what is the role of the proglottid in a cestode?
|
old mature proglottids rupture and disintegrate -> releases eggs that exit with feces.
|
|
|
Taenia - how is it transmitted to humans?
|
from grass - to cattle - burrows in muscle of cattle - humans eat cattle
SOLUTION: cook meat well |
|
|
which type of helminth has both an "in" and "out" hole?
|
Nematodes (roundworms)
|
|
|
where do nematodes like to colonize?
|
the intestine
|
|
|
what is an example of a nemotode that lives in human muscle but shouldn't be there?
|
Trichinella
(from uncooked pork) |
|
|
what is unique about the sex of nematodes?
|
no hermaphrodites
all separate sexes, even have a reproductive system! |
|
|
what is the most common intestinal nematode?
|
"giant roundworm of man"
Ascaris lumbricoides |
|
|
what is a place ascaris likes to colonize?
|
the lungs, respiratory system and throat!
|
|
|
how does hookworm get into humans?
|
bare feet
(larva lay in soil) |
|
|
what is the memory key for symptoms of SLE?
|
I'M DAMN SHARP
Immunoglobulins (anti-dsDNA, antiSm, antiphospholipid) Malar rash Discoid rash Antinuclear antibody Mucositis (oropharyngeal ulcers) Neurologic disorders Serositis (pleuritis, pericarditis) Hematologic disorders Arthritis Renal disorders Photosensitivity |
