Term
| Which system is the first responder to an offending agent? |
|
Definition
|
|
Term
| How does the innate immune system recognize antigens? |
|
Definition
By pattern recognition receptors:
- Toll-like receptors (TLRs) recognise bacterial LPs
- Dectin-1 recognizes fungal Beta-glucans |
|
|
Term
| T/F: innate immune system had memory and the response will be the same upon repeated exposure? |
|
Definition
| False, innate immune system lack memory |
|
|
Term
| How is the adaptive immune system stimulated? |
|
Definition
| It neutralize the infectious agent or engulf----phagocytosis of an offending agent digest macromelecule into fragments (antigens)---antigens are displayed on the surface of antigen presenting cells---antigen presenting cells stimulate the adaptive immune system |
|
|
Term
| What is the major arm of innate immune system? |
|
Definition
| Granulocytes, contain chemical mediators that are released upon stimulation (neutrophils, eosinophils, basophils, and mast cells) |
|
|
Term
| What complex is involved in the adaptive immunity? |
|
Definition
| Major histocompatibility complex (MHC) proteins at the cell surface |
|
|
Term
| T/F: B cells and T cells are part of the adaptive immunity? |
|
Definition
True, B cells fction as antigen presenting cells, they synthesize and secrete antibodies
T cells: Cytotoxic T cells (Tc)=cellular adaptive immunity
Helper T cells (Th)= regulate adaptive responses (Th1,Th2) |
|
|
Term
| What are the differences between innate immunity and acquired immunity? |
|
Definition
Innate immunity: immediate onset of action, recognizes antigen through receptors, cell types: macrophages, neutrophils, mast cells, natural killer cells, complement interferon
Acuired immunity: it takes days to wks for onset of action, recognize antigen through unique antigen specific receptors (T-cell, B-cell receptor), cell types: antigen presenting cells, T & B lymphocytes |
|
|
Term
| What is the mechanism of action of antigen presenting cells? |
|
Definition
| They process the macromolecules of invading agent into fragments, display them to T cells and provide costimulatory signals for T cell activation |
|
|
Term
| What two cells function as antigen presenting cells (APC)? |
|
Definition
- Macrophages: as APC (adapive immunity), and as phagocytosis of cellular debris & foreign particles (innate immunity), involved in chronic inflammation
- Dentritic cells: engulf antigens fron one location, then travel & present the antigen to T cells at different location |
|
|
Term
| Where does the MHC class I protein bind with degraded protein fragment (antigen)? |
|
Definition
|
|
Term
| T/F: MHC I is tranported to the cell surface, where it serves as a fingerprint for all proteins expressed by that cell (self)? |
|
Definition
|
|
Term
| T/F: MHC I has a CD4 binding site that ensures that the interaction occurs only with cytotoxic T cells? |
|
Definition
| False: has CD8 binding site that do that |
|
|
Term
| T/F: all nucleated human cells express MHC I proteins? |
|
Definition
|
|
Term
| T/F: MHC II is transported to the cell surface, where it serves as fingerprint for all self antigen? |
|
Definition
False, serves as fingerprint for nonself antigen
MHC I serves as fingerprint for self antigen |
|
|
Term
| T/F: MHC II has CD4 binding site that ensure that the interaction occurs only with helper T cells? |
|
Definition
|
|
Term
| T/F:cytotoxic T cells (Tc) express T-cell receptors (TCR) and CD4. The TCR indentifies nonself antigens bound the MHC proteins, and CD4 ensures that Tc cells interact only with cells on MHC I proteins? |
|
Definition
| False, Tc express TCR and CD8, and CD8 ensures Tc interaction with MHC I |
|
|
Term
| T/F: Th express TCR and CD4, and CD4 binds to MHC II? |
|
Definition
|
|
Term
| T/F: Th cells interact only with cells expressing MHC II? |
|
Definition
|
|
Term
| Interaction of CD28 on Th cells with which proteins is required for Th activation? |
|
Definition
with B7 (costimulatory molecule) family on APC
This is a costimulatory signal, required for response of Tcells |
|
|
Term
| What is secreted by an activated Th cells? |
|
Definition
| IL-2, which expressed IL-2 receptor and stimulates further Th-cell proliferation and activation |
|
|
Term
| T/F: IL-2 and other cytokines secreted by Th cell activate not only Th cells, but also Tc and B cells? |
|
Definition
|
|
Term
| What is an acute inflammation? |
|
Definition
Initial response to tissue injury/infection, involves the innate immunity (mostly neutrophyls accumulate)
Its a self-limited process |
|
|
Term
What is released in an acute inflammation?
|
|
Definition
Autacoids (histamine, bradykinin, prostaglandins, leukotrienes), cytokines and chemokines
|
|
|
Term
| What is a chronic inflammation? |
|
Definition
Sustained and inappropriate response to inflammatory stimulus (pathogen, self-antigens), predominant accumulation of macrophages, involves the adaptive immunity (lymphocytes)
implicated in atoimmune disease and organ plant rejections |
|
|
Term
| What are membrane derived lipid mediators? |
|
Definition
| Prostaglandins, leukotrienes, and platelet activation factor (PAF) |
|
|
Term
| What is produced through degranulation? |
|
Definition
| Histamine, heparin, serotonin, proteases |
|
|
Term
| Where is histamine synthesized and stored? |
|
Definition
| in granules of mast cells and basophils |
|
|
Term
| What is the function of histamine? |
|
Definition
Act as an initiator of inflammatory process
It's a vasocative amine-dilates arterioles and postcapillary venules, constriction of veins |
|
|
Term
| T/F: complement are activated in response to injury, adaptive immunity? |
|
Definition
|
|
Term
|
Definition
A system of serine proteases
C3a, C3b |
|
|
Term
| How does complement trigger inflammatory reaction? |
|
Definition
| upon activation they attract phagocytes to the area. phagocyte engulf and digest dead cells and bacteria |
|
|
Term
| Which cells are target for pharmacological interventions? |
|
Definition
|
|
Term
| Which chemical mediators act as vasodilators? |
|
Definition
| Prostaglandins (PGI2, PGE1, PGE2, PGD2), nitric oxide (NO) |
|
|
Term
| Which chemical mediators increase vascular permeability? |
|
Definition
- Histmine
- C3a, C5a
- Bradykinin
- Leukotrienes (LTC4, LTD4, LTE4)
- Platelet-activating factor
- Substance-P |
|
|
Term
| Which chemical mediators act as chemotaxis and leukocyte activators? |
|
Definition
-C3a, C5a
-LTB4
-Lipoxins
-Bacterial products |
|
|
Term
| Which chemical mediators produce tissue damage? |
|
Definition
- Neutrophil
- macrophages lysosomal products
- Oxygen radicals
- NO |
|
|
Term
| Which chemical mediators cause pain? |
|
Definition
- PGE2
- PGI2
- Bradykinin
- CGRP |
|
|
Term
| Which chemical mediators produce fever? |
|
Definition
|
|
Term
| In what disease states does Eiconanoids act? |
|
Definition
- Inflammatory conditions
- Autoimmune dz
- Asthama
- Glomerulonephritis
- Cancer
- Sleep disorders
- Alzheimer's dz |
|
|
Term
|
Definition
Arachidonic acid derived:
Prostaglandin
Thromboxanes
Leukotrienes
act as proinflammatory and anti-inlfammatory |
|
|
Term
| T/F: arachidonic acid is part of membrane phospholipids? |
|
Definition
|
|
Term
| How is arachidonic acid released? |
|
Definition
| Upon hydrolysis of membrane phosoholipids by PLA2 |
|
|
Term
| T/F: production of a specific PG is independent of cell-specific enzymes, and PGs have long t1/2? |
|
Definition
| False, PG are dependent on cell-specific enzymes, and have short t1/2 |
|
|
Term
| In what organs is Cox-1 expressed? |
|
Definition
| Gastric mucosa, kidneys, platelets and endothelial cells |
|
|
Term
| T/F: Cox-1 undergo induction anf is responsible of housekeeping functions: vascular homeostasis, regulation of renal and GI blood flow, renal function? |
|
Definition
False, no inductions
2nd part is true |
|
|
Term
| Cox-2 is inducible by which inflammatory cells? |
|
Definition
| Proinflammatory cytokines: TNF-a, IL-1, IL2, EGF, IFN-g |
|
|
Term
Which of the followings are pathophysiological implications of Cox-1?
I) Housekeeping fct, renal fct
II) Fever
III) Intestinal mucosal proliferation
IV) platelet fct
V) Anti-thrombogenesis
A) I, II, & V are correct
B) only I is correct
C) I, III, IV & V are correct
d) All are correct |
|
Definition
| C) I,III, IV & V are correct |
|
|
Term
| What chemical structure is shared by protaglandins? |
|
Definition
|
|
Term
Which protaglandin act as vasodilator, inhibition of platelet activation, sleep, and alzeimer's dz?
a) PGE2
b)PGD2
c) PGF2a
d) PGI2 |
|
Definition
| b)PGD2, found in mast cells and neurons |
|
|
Term
Which prostaglandin act as a protector of gastric mucosa, vasodialtion, hyperalgesia, cytoprotective (GI), acid secretion (GI), mucus formation?
a) PGE2
b)PGF2a
c)PGD2
d) PGI2 |
|
Definition
a) PGE2, found in many tissues,
macrophages and mast cells |
|
|
Term
T/F: TXA2 act ad vasoconstrictor, bronchoconstrictor and platelet aggregation?
|
|
Definition
|
|
Term
| Which prostaglandin act as vasodilator and inhibition of platelet activation? |
|
Definition
| PGI2 (prostacyclin), found in endothelial cells |
|
|
Term
What are the major actions of PGF2a?
a) vascular tone
b) Reproductive physiology
c) Bronchoconstriction
d) all of the above |
|
Definition
| d) all of the above, found in vascular smooth muscles and uterine smooth muscles |
|
|
Term
| How are prostaglandins released from cells? |
|
Definition
| Released from cells in response to chemical stiuli or physical trauma to perform local action |
|
|
Term
| T/F: Prostaglandins ptomote tissue inflammtion by stimulating inflammatory cell chemotaxis, causing vasoconstriction and increasing capillary permeability and edema? |
|
Definition
| False, causing vasodilation |
|
|
Term
Which ones below are relatively selective Cox-2 inhibitors?
a)Nabumetone
b) Etodolac
c) Meloxicam
d) all of the above |
|
Definition
|
|
Term
| Which cox inhibitors are selective cox-2 inhibitors? |
|
Definition
| Celecoxib (celebrex), rofecoxib (vioxx), and valdecoxib (bextra) |
|
|
Term
Which NSAID is the most potent?
a)Aspirin
b) Ketorolac
c) Naproxen
d) Indomethacin |
|
Definition
| b) Ketorolac is most potent |
|
|
Term
Which NSAID is least potent?
a) Keterolac
b) Celecoxib
c) Aspirin
d) Ibuprofen |
|
Definition
|
|
Term
| What is the therapeutic effect of NSAIDs? |
|
Definition
Inhibition of PG synthesis |
|
|
Term
| T/F: Inhibition of PG synthase in gastric mucosa results in GI damage (dyspepsia, gastritis)? |
|
Definition
|
|
Term
| What are common ADE of NSAIDs? |
|
Definition
- Gastritis and peptic ulcer w/bleeding
- Acute renal failure
- Sodium and water retention and edema
-Analgesic nephropathy
-Prolomgation of gestation and inhibition of labor
- GIT bleeding and perforation
- PG inhibition-mediated hypersensitivity
- Platelet dysfunction |
|
|
Term
| T/F: NSAIDs decrease PG-mediated capillary permeability resulting reduction in edema, swelling and local warmth? |
|
Definition
|
|
Term
| T/F:Acetaminophen does decrease swelling? |
|
Definition
|
|
Term
| T/F: reversal of only the peripheral not central sensitization of pain receptos contribute to the analgesic activity of NSAIDs? |
|
Definition
| False, reversal of both peripheral and central sensitization |
|
|
Term
| What is the pain (nociception) pathway? |
|
Definition
1) Thermal, mechanical and chemical---nearby cell damage
2) Nociceptor activation
3) CGRP and substance-P released by activated nociceptors
4) Blood vessel dilation and mast cell degranulation |
|
|
Term
| What is the cause of fever? |
|
Definition
| Fever results due to altered hypothalamic thermoregulatory mechanisms |
|
|
Term
| T/F: All NSAIDs relieve fever by inhibiting PG synthesis in the hypothalamus, but they are not capable of reducing body temperature below normal? |
|
Definition
|
|
Term
| T/F: Basal temperature is affected by NSAIDs? |
|
Definition
| Fasle, its unaffected by NSAIDs |
|
|
Term
| T/F: Aspirin inhibits platelet aggregation and is used to prevent and treat arterial thromboembolic disorders? |
|
Definition
|
|
Term
| T/F: Traditional NSAIDs are thought to afford cardioprotection (short t1/2, reversibility of binding w/ COX enzyme)? |
|
Definition
| False, are not thought to do so, however Naproxen is an exception (~10% reduction of MI compared to 25% with low dose aspirin)(epidimiologic studies) |
|
|
Term
| What are the most important prostaglandins affecting platelet aggregation? |
|
Definition
| Prostacyclin PGI2 and TXA2 |
|
|
Term
| T/F: PGI2 synthesized by vascular endothelial cells and promotes platelet aggregation? |
|
Definition
False, inhibits platelet aggregation
TXA2 promotes platelet aggregation |
|
|
Term
| T/F: Cox-1 is the predominant COX isoform in platelets? |
|
Definition
|
|
Term
| T/F: endothelial cells express only Cox-2? |
|
Definition
| False, express both Cox-1 and Cox-2 |
|
|
Term
| What is the mechanism of aspirin-induced cardioprotection? |
|
Definition
| Low dose aspirin inhibits Cox-1 and Cox-2 (more Cox-1), therefore inhibit conversion of PGG2 to PGH2. (no more PGI2 and TXA2 formation) |
|
|
Term
| Why do we use low dose of aspirin? |
|
Definition
| Because low dose aspirin selectively inhibit synthesis of TXA2 without affecting protacyclin |
|
|
Term
| T/F: Like other NSAIDs aspirin reversibly inhibits cyclooxygenase enzyme (Cox-1) that catalyzes an early step on TXA2 synthesis? |
|
Definition
| False, unlike other NSAIDs aspirin irreversibly inhibits Cox-1 |
|
|
Term
| How do NSAIDs cause gastric damage (ulceration)? |
|
Definition
| By inhibiting PG synthesis and blocking Cox-1 enzyme in GI (can occur w/ PO, IV and transdermal administration of NSAIDs) |
|
|
Term
|
Definition
| It is a PGE1 analog has protective effects on GI, may give w/ NSAIDs |
|
|
Term
| T/F: PGE2 and PGF2-a induce uterine contraction? |
|
Definition
| Tru, therefore NSAIDs prolong labor by inhibiting PGE2 and PGF2-a production |
|
|
Term
| Use of NSAIDs in latre pregnancy may increase risk of postpartum hemorrhage. the patency of the doctus arteriosus (required for fetal circulation(aorta--lung)) is maintained by PGE2. NSAIDs during late pregnancy/labor induce prematue closure, thus impaired fetal circulation and cardiopulmonary issues |
|
Definition
|
|
Term
| How does patent ductus arteriosus PDA develop? |
|
Definition
| At birth, failure of ductus arteriosus to close results in PDA which can lead to pulmonary HTN, CHF, anbd cardiac arrythmias to neonate |
|
|
Term
| What can be used to treat PDA? |
|
Definition
| NSAIDs: indomethacin or ibuprofen injection can be used to treat PDA |
|
|
Term
| T/F: chronic uses of high doses of NSAIDs may cause analgesic nephropathy (slowly progressive renal failure)? |
|
Definition
|
|
Term
| T/F: regular use of NSAID has been shown to increase risk of developing colorectal cancer (especially Cox-2 selective NSAIDs)? |
|
Definition
False, decrease risk
aspirin showed--50% reduction in risk of colon cancer |
|
|
Term
| T/F: Recent studies have shown that NSAIDs can delay or slow the progress of alzheimer's dz? |
|
Definition
|
|
Term
| What are drug interactions with NSAIDs? |
|
Definition
- ACE inhibitors (decrease effectiveness, increase risk of bradycardia and syncope in elderly and HTN, diabetes and heart pts)
- Cortocosteroids (increase frequency and severity of GI ulceration)
- Warfarin (increase plasma level, increase risk of bleeding)
- increase toxicity with methotrexate, warfarin, sulfonylurea (display from protein binding) |
|
|
Term
| What amount of aspirin will cause tinnutis and hearing loss? |
|
Definition
|
|
Term
| what amount of aspirin is lethal? |
|
Definition
4 g in children
20-25 g in adults |
|
|
Term
| How is salicylism manifested? |
|
Definition
Vomiting, sweating, tinnitus, dizziness, hallucination and convulsions
respiratory alkalosis and decreased plasma buffering capacity |
|
|
Term
| T/F: at doses>4g/d, salicylates compete with uric acid secretion, causing increased UA retention in blood? |
|
Definition
False, <2g/d will do that
>4g/d will block UA reabsorption--increased UA excretion |
|
|
Term
| At what doses salicylates will not affect UA excretion? |
|
Definition
|
|
Term
| What are drug interactions with salicylates? |
|
Definition
- Warfarin: risk of bleeding
- Aspirin toxicity when used w/ acididying drugs (ascorbic acid)
- Glucocorticoids: risk GI ulcers
- Ethanol: gastric erosion |
|
|
Term
| T/F: Diflunisal (Dolobid) used for osteoarthritis musculoskeletal strains or sprains is 3-4 * more potent than aspirin because, of peripheral effect? |
|
Definition
|
|
Term
| T/F: diflunisal has antipyretic effect? |
|
Definition
| False, does not because has low access to CNS hypothalamus |
|
|
Term
| What are the advantage of diflunisal? |
|
Definition
- No auditory SE,
- Less intense GI effects
- Not metabolized to salicylate (less SE)
Note: has cross sensitivity with other NSAIDs |
|
|
Term
| T/F: Inhibition of cox-2 causes platelet activation and aggregation and vasodilation leading to increased tisk of MI, heart attack, stroke and thrombosis? |
|
Definition
| False everything is correct but vasodilation it causes vasoconstriction |
|
|
Term
| T/F: Cox-2 inhibitors alter the vascular homeostasis by removing the cardioprotective effects of PGI2, leaving the atherogenic properties of TXA2 intact? |
|
Definition
|
|
Term
| T/F: Acetaminophen selectively inhibit Cox-3 in the CNS? |
|
Definition
|
|
Term
| Which leukotrienes are consiodered as bronchoconstrictors? |
|
Definition
| LTC4, LTD4 and LTE4 known as cysteinyl leukotrienes |
|
|
Term
| T/F: zafirlukast and montelukast are slective competitive antagonists for cy-LT1 receptors? |
|
Definition
|
|
Term
| What are ADE of zafirlukast? |
|
Definition
Eosinophilia and vasculitis
DI: increase prothrombin time w/ warfarin
metabolized by CYP2C9 |
|
|
Term
|
Definition
| Inhibit influx of basophils and lymphocytes into the airways (LTC4, LTD4, LTE4) |
|
|
Term
| T/F: montelukast has DI with warfarin? |
|
Definition
|
|
Term
| What is the MOA of colchicine? |
|
Definition
Inhibit microtuble assembly
- Decrease release of chemotactic factors by activated neutrophils
- Decrease histamine release from mast cells
- Decrease neutrophil motility and adhesion |
|
|
Term
| What are ADE of colchicine? |
|
Definition
- Diarrhea, N/V, abdm pain
- Myelosuppression
- Neuromyopathy |
|
|
Term
|
Definition
Cyclosporine, tacrolimus, or verapamin increase plasma levels of colchicine (inhibit excretion of colchicine from bile, C & T from urine)
CYP3A4 substrate (cimetidine) increase colchicine plasma levels and toxicity |
|
|
Term
| What are ADE of allopurinol? |
|
Definition
Rash
Nephritis
Hepatitis
Kidney stones |
|
|
Term
| Important DI w/ allopurinol? |
|
Definition
| Azathioprine and 6-mercaptopurine |
|
|
Term
| T/F: When administered with allopurinol, the dose of 6-mercaptopurin or azathioprine should be reduced? |
|
Definition
|
|
Term
|
Definition
Hemolysis (G6PD-deficient pts)
Methemoglobinemia
Acute renal failure
Anaphylaxis
GI problems
Fever
HD, etc.. |
|
|
Term
| T/F: Probenecid inhibits uric acid reabsorption by enhancing URATE-1 transporter? |
|
Definition
| False, by inhibiting URATE-1 transporter |
|
|
Term
| Hematologic toxicity is important with which Uricosuric agent? |
|
Definition
|
|
Term
| T/F: Low dose aspirin antagonize probenecid action? |
|
Definition
|
|
Term
| Which uricosuric agent has antiplatelet activity, thus caution w/ othe anticoagulan or antiplatelets)? |
|
Definition
|
|
Term
|
Definition
| Delays excretion of penicilin, nitrofurantoi and other anionic compounds |
|
|
