Phar 504 Midterm 3

Front 1

Innate Immune System

Back 1

Cells and mechanisms that confer immunity in non-specific manner. Cytokines, antigen presentation, complement, macrophages etc.

Front 2

Adaptive immunity

Back 2

Highly specialized cells with ability to recognize and eliminate specific antigen

Front 3

Eicosanoids

Back 3

Arachidonic acid-derived substances

Prostaglandins (PGG2, PGH2), prostacyclin (PGI2), leukotrienes etc.

pro-inflammatory

Front 4

Steroids

Back 4

Inhibit phospholipases (produce arachidonic acid from cell membrane phospholipids)

Front 5

COX-1, COX-2 inhibitors; NSAIDs (e.g. aspirin, indomethacin)

Back 5

Inhibit cyclooxygenase (arachidonic acid -< prostaglandin G2)

Decrease inflammation

Front 6

Prostaglandins

Back 6

Used for vasodilation, pain relief

Front 7

Leukotrienes

Back 7

Used to increase vascular permeability, decrease fever

Front 8

Histamine

Back 8

Used to increase vascular permeability

Front 9

Lipoxins

Back 9

Chemotaxis and leukocyte activation, fever reduction

Front 10

Aspirin

Back 10

Suicide inhibitor - acetylates platelet cyclooxygenase

Front 11

COX1

Back 11

Constitutive, has homeostatic functions, inhibition undesirable

Front 12

COX2

Back 12

Inducible, causes inflammation, inhibition desirable

Front 13

NSAIDs

Back 13

Inhibit both COX-1 and COX-2; produce side effects at kidney, platelets (prevent coagulation), and protective lining of stomach

Front 14

Celecoxib

Back 14

Selective COX-2 inhibitor, less side effects

Front 15

Anti-histamine

Back 15

Inhibits synthesis of histamine from histidine. Histamine produced mainly by mast cells as pro-inflammatory agent

Front 16

Allergy

Back 16

IgE mediated activation of mast cells resulting in release of histamine

Front 17

Cholesterol Transport

Back 17

HDL, LDL

Front 18

Triglycerides

Back 18

apoB containing chylomicrons, VLDL

Front 19

apoB lipoproteins

Back 19

Deliver fatty acids via triglycerides to muscle/tissue for ATP synthesis and adipose storage

Front 20

LDL

Back 20

All apoB chylomicrons are cleared and 50% of VLDL are; remaining VLDL is converted to LDL.

As TG removed from LDL, cholesterol content increases to form LDL

Front 21

Akt1

Back 21

Loss of Akt1 increases lesion progresion on an ApoE-/- backgroundB

Front 22

Bile

Back 22

All cells make cholesterol. Only liver can eliminate it via cholesterol esterification into bile acids.

Front 23

HDL

Back 23

Liver generates HDL (with signature apoA-1) to remove free cholesterol

Front 24

Statins

Back 24

Upregulate LDL-R for treatment of hypercholesterolemia.

Used to treat ACS and MI

Lower LDL-C and TG and increase HDL

Front 25

Cholestyramine

Back 25

Cationic polymer that binds to negatively charged bile acids in small intestine, blocking their reabsorption. Causes hepatocytes to increase 7-hydroxylase activity which consumes cholesterol

Front 26

Ezetimibe

Back 26

Inhibit NPC1L1 regulatory channel to prevent uptake of cholesterol from micelles, thus reducing cholesterol content of VLDL, LDL, and CM

Front 27

Fibrates

Back 27

Decrease apoCII synthesis, increase LPL, increase apo AI synthesis

Front 28

Niacin

Back 28

Binds to a GPCR on adipocytes and reduces hormone sensitive lipase, thus reducing FFA flux in liver. Reduces hepatic TG and limits VLDL synthesis and eventually LDL as well.

Front 29

PCSK9

Back 29

Promotes intracellular degradation of LDL-R.

Prevents recycling of LDL-R to surface

Neutralizing Ab and siRNA to PCSK9 results in additional reduction in LDL-C levels.

Front 30

Hemostasis

Back 30

Physiological process to generate a hemostatic plug that prevents blood loss at site of vascular injury

Front 31

Thrombosis

Back 31

Occurs when coagulation is inappropriately regulated, resulting in clot enlargement and occlusion of the vessel lumen.

Front 32

Virchow's Triad

Back 32

Endothelial injury, abnormal blood flow, and hyper-coagulability cause thrombosis

Front 33

Primary Hemostasis

Back 33

Assembly of a platelet rich plug

Front 34

Secondary Hemostasis

Back 34

Formation of a stable, platelet plug characterized by activation of coagulation system and fibrin deposition.

Front 35

Resolution

Back 35

Natural anticoagulant and thrombolytic factors limit hemostatic activity to the site of injury.

Front 36

Endothelin

Back 36

Vascular injury causes endothelial denudation. Endothelin, released by activated endothelium, and neurohumoral factors induce transient vasoconstriction

Front 37

von Willebrand factor

Back 37

Multi-domain protein released in response to thrombogenic stimuli. Binds exposed collagens and supports platelet adhesion under high shear stress.

Front 38

GP1b-GPIX-V

Back 38

Constitutively active; supports adhesion to immobilized vWF, not soluble vWF. vWF binding triggers platelet activation

Front 39

Bernard-Soulier syndrome

Back 39

Lack of GPIb

Front 40

von Willebrand disease

Back 40

Abnormal GP Ib-IX complex

Front 41

TxA2

Back 41

Binds receptor on smooth muscle - causes vasoconstriction

Front 42

Dipyridamole

Back 42

Inhibits phosphodiesterase, preventing breakdown of cAMP, resulting in inhibition of platelets

Front 43

Abciximab

Back 43

Mouse-human chimeric monoclonal tni-GPIIb/IIIA antibody

Front 44

Eptifibatide

Back 44

Cyclic heptapeptide alpha II b beta 3 inhibitor

Front 45

Tirofiban

Back 45

Small-molecule antagonist

Front 46

Thrombin

Back 46

Prothrombin is cleaved to thrombin by factor Xa; factor Va and Ca2+ act as cofactors in this reaction, which takes place on an activated phospholipid surface. Thrombin converts soluble plasma fibrinogen to fibrin.

Front 47

Antithrombotic factors

Back 47

PGI2, NO, t-PA

Front 48

t-PA

Back 48

Promotes fibrinolysis

Front 49

Thrombomodulin

Back 49

Blocks coagulation cascade

Front 50

Release of prostacyclin

Back 50

Inhibits platelet aggregation and vasoconstriction

Front 51

Warfarin

Back 51

Antithrombotic agent

Front 52

Heparin

Back 52

Stimulates antithrombin III, a plasma protease inhibitor

Front 53

Thrombolytic agents

Back 53

Used to lyse already-formed clots and so restore potency of an obstructed vessel

Front 54

Plasmin

Back 54

Degrades fibrin (and fibrinogen)

Front 55

Streptokinase

Back 55

Activates plasminogen to form plasmin. Systemic.

Front 56

Tenecteplace, Reteplace

Back 56

Engineered variants of recombinant t-PA with increased fibrin specificity and longer halflife

Front 57

Protamine

Back 57

Low MW polycationic protein is a chemical antagonist of heparin

Front 58

Serine-Protease Inhibitors

Back 58

Aprotinin inhibits plasmin t-PA and thrombin

Front 59

Lysine analogues

Back 59

Aminocaproic acid and tranexamic acid bind to inhibit plasminogen and plasmin

Front 60

Lysine analogues

Back 60

Aminocaproic acid and tranexamic acid bind and inhibit plasminogen and plasmin.

Front 61

Asthma

Back 61

Episodic constriction of the tracheobronchial tree

Front 62

Albuterol, terbutaline, metaproterenol

Back 62

Epinephine congener

B2-adrenergic receptor agonist

adenyl cyclase up, cAMP up, bronchodilation

Increased K+ channel conductance, leading to membrane hyperpolarization and relaxation

Secondary inhibitory action on cytokine and pro-inflammatory mediator release

Front 63

Salmeterol

Back 63

Same as albuterol, long-acting

Front 64

Phosphodiesterase Inhibitors (methylxanthine derivatives (theophylline))

Back 64

Increased cAMP, bronchodilation

Front 65

Glucocorticoids

Back 65

Block pro-inflammatory mediator production

Bind to nuclear receptors (GRs), then to GRE recognition sites on DNA.

GR also bind to the transcription factor AP-1

Front 66

Cromolyn

Back 66

Inhibits mast cell degranulation

Front 67

Leukotriene Antagonism

Back 67

Bronchodilators, anti-inflammatory

Front 68

Histamine Antagonism

Back 68

Protects against itch, edema, vasodilation

Front 69

Anaphylaxis

Back 69

Caused by a rapidly amplifying cascade of mediators leading to hypotensive shock, respiratory distress, and death.

Requires direct blood pressure and oxygenation support - a2B adrenergic receptor agonist

Front 70

Immunomodulation

Back 70

"Re-program" host immune response

Passive Immunotherapy: IgG antibody directed against IgE

Front 71

Tissue remodelling

Back 71

Replacement of normal tissue components and organ architecture by changes induced by chronic inflammation.

Progressive and irreversible

Front 72

Pharmacogenomics

Back 72

Susceptibility gene polymorphisms (e.g. b2-adrenergic receptor polymorphism associated with asthma-related phenotypes

Front 73

Macrophage migration inhibitory factor (MIF)

Back 73

Upstream cytokine

Highly correlated with asthma

Front 74

New Drug Application (NDA)

Back 74

The vehicle through which pharmaceutical agencies propose that the FDA approve a new pharmaceutical for sale and marketing.Is the drug safe and effective in its proposed use when used as directed, and do the benefits of the drug outweigh the risks?

Is the drug's proposed labeling appropriate, and what should it contain?

Are the manufacturing methods good to ensure maintenance of drug quality?

Front 75

FDA

Back 75

Regulatory agency that regulates the testing, sale, and manufacture of drugs

Front 76

Phase 3b

Back 76

Clinical trials conducted after submission of NDA but prior to approval. Meant to supplement earlier trials, complete earlier trials, or analyze quality of life/marketing etc.

Front 77

Phase 4

Back 77

Studies or trials conducted after a medicine is marketed to provide additional details about the medicine's efficacy or safety profile. Different formulations, dosages, durations of treatment, medicine interactions, and other factors may be evaluated. New age groups (particularly pediatrics) and other demographics may be studied. Quantification of adverse reactions is important.