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Flashcards in 14 Antihistamines Deck (49):
1

which inflammatory cytokines do tissue cells release in times of stress or injury, or in response to T-cell cytokines?

IL-1, IL-6

2

What do phagocytes release in response to inflammatory stimuli?

inflammatory cytokines TNFalpha, IL-1, and IL-6; cytotoxic agents; proteases for degrading tissue; and lipid mediators to enhance local inflammation

3

What is the effect of inflammatory cytokines in the hypothalamus? in the liver?

in the hypothalamus, cytokines produce fever, and in the liver they induce the acute phase response

4

which class of drugs commonly target the cytokines that promote inflammatory activity (TNFalpha, IL-1)?

Disease-modifying antirheumatic drugs (DMARDS)

5

Infliximab, adalimumab, and etantercept are all examples of what type of drug?

Anti-TNFalpha agents

6

What are anti-TNFalpha agents and what is their mechanism of action?

anti-TNFalpha agents are either antiTNFalpha antibodies (infliximab and adalimumab) or other proteins (etanercept) that bind to TNFalpha to prevent its interaction with its receptor

7

what are the therapeutic applications of anti-TNFalpha agents, and what is the typical route of administration?

often used to treat rheumatoid arthritis and Crohn's; parenteral administration is required

8

what is the main complication associated with anti-TNFalpha agents?

increased susceptibility to infection, especially upper respiratory and urinary infections

9

what type of drug is anakinra and what is its mechanism of action?

anakinra is an anti-IL1 agent that is a competitive IL-1 receptor antagonist

10

what type of drug is tofacitinib and what is its mechanism of action?

tofacitinib is a Jak kinase inhibitor that inhibits all activity of cytokines required for adaptive immunity

11

what are the therapeutic applications of anti-TNFalpha agents, and what is the typical route of administration?

often used to treat rheumatoid arthritis and Crohn's; parenteral administration is required

12

What causes mediator release from activated leukocytes?

Lipid mediators are released in response to signals that activate phospholipase A2

13

How does phospholipase A2 cause the release of lipid mediators from leukocytes?

PLA2 hydrolyzes membrane phosphatidylcholine to release arachidonic acidAA is the substrate for production of lipid mediators of inflammation – cyclooxegenases produce prostaglandins, and lipoxygenases produce leukotrienes.

14

T or F: Stored mediators such as histamine are released from leukocytes in response to signals that activate phospholipase C

T

15

T or F: annexins/lipocortins inhibit PLC activity

F; they inhibit PLA2

16

What class of drugs inhibit cyclooxygenase, and what effect does this produce?

NSAIDS; decreased production of prostaglandin

17

What drug inhibits lipoxygenase, and what effect does it produce?

Zileuton; decreased production of prostaglandins

18

Cromolyn and nedocromil both inhibit which process?

They inhibit PLC mediated degranulation of stored mediators from leukocytes

19

What do glucocorticosteroids inhibit, and what effects do they produce?

Glucocorticosteroids inhibit PLA2 to reduce production of prostaglandins and leukotrienes, and they also inhibit production of chemotactic factors, which results in decreased recruitment of leukocytes

20

Glucocorticosteroids induce transcription of which gene, and why?

Induce transcription of annexins/lipocortins, which inhibit PLA2

21

T or F: Glucocorticosteroids reduce leukocyte recruitment and mediator release by inducing transcription of various genes, such as those for cyclooxygenase, interleukins, and chemotaxins

F; it represses transcription to produce those effects

22

What is the precursor for histamine synthesis, and what enzyme is used to convert it into histamine?

Histidine decarboxylase converts histidine to histamine

23

Explain the two step degradation of histamine to methylimidazole acetic acid, including the enzymes involved.

1) Imidazole-N-Methyltransferase converts histamine to methylhistamine2) Diamine oxidase converts methylhistamine to methylimidazole acetic acid

24

Which enzyme converts histamine to imidazoleacetic acid?

Diamine oxidase

25

What are the two possible breakdown products of histamine degradation?

Methylimidazole acetic acid and imidizoleacetic acid

26

Histamine intolerance results from deficiency of which enzyme?

Diamine oxidase

27

What Histamine receptor subtypes are present on vascular smooth muscle, and what effects and resulting symptoms do they produce?

Receptor: H1, H2Effects: induces NO release to promote smooth muscle relaxation and vasodilationSymptoms: hypotension, flushing, headache, anaphylaxis

28

What Histamine receptor subtypes are present on the vascular endothelium, and what effects and resulting symptoms do they produce?

Receptor: H1Effects: induces actin/myosin contraction which results in separation of endothelial cellsSymptoms: edema

29

What Histamine receptor subtypes are present on cardiac muscle, and what effects and resulting symptoms do they produce?

Receptor: H1, H2Effects: H1 decrease heart rate and atrial contractility, and H2 increase rate and contractilitySymptoms: unknown

30

What Histamine receptor subtypes are present on bronchiolar smooth muscle, and what effects and resulting symptoms do they produce?

Receptor: H1Effects: constriction of smooth muscleSymptoms: difficulty breathing due to airway constriction

31

What Histamine receptor subtypes are present on uterine smooth muscle, and what effects and resulting symptoms do they produce?

Receptor: H1Effects: constriction of smooth muscleSymptoms: premature labor, anaphylaxis

32

What Histamine receptor subtypes are present on gastric smooth muscle, and what effects and resulting symptoms do they produce?

Receptor: H1Effects: constriction of smooth muscleSymptoms: diarrhea

33

What Histamine receptor subtypes are present on sensory nerves, and what effects and resulting symptoms do they produce?

Receptor: H1Effects: stimulation of neuronsSymptoms: pain, itching

34

What Histamine receptor subtypes are present on the hypothalamus, and what effects and resulting symptoms do they produce?

Receptor: H1Effects: arousalSymptoms: increased wakefulness

35

What Histamine receptor subtypes are present on the emetic center in the CNS, and what effects and resulting symptoms do they produce?

Receptor: H1Effects: emesisSymptoms: nausea, vomiting

36

What Histamine receptor subtypes are present on the CNS in general, and what effects do they produce?

Receptor: H1, H2Effects: effects on thirst, BP control, and pain perception

37

What Histamine receptor subtypes are present on gastric secretory cells, and what effects and resulting symptoms do they produce?

Receptor: H2Effects: increased pepsin, intrinsic factor, and acid productionSymptoms: mucosal erosion and ulceration

38

What are the typical cutaneous signs of the histamine triple response?

Wheal and flare response, redness, itching

39

What are physiological antagonists, and what is an example of a physiological antagonist for histamine?

Agents that have opposing effects on smooth muscle but are mediated through different receptors; An example for histamine is epinephrine

40

What are release inhibitors, and what are some examples of release inhibitors of histamine?

Inhibitors that prevent degranulation of a substance; examples include cromolyn and nedocromil

41

What are the main clinical uses of H1 receptor antagonists?

Allergic rhinitis and uticaria and motion sickness/emesis

42

What is the main adverse affect that results directly from inhibition of H1 receptors?

Sedation due to CNS depression

43

T or F: many first generation H1 receptor antagonist have non-H1 adverse effects due to their similarity to other drug classes, such as anticholinergics and antiadrenergics.

T

44

What is the difference between first and second generation antihistamines?

Second gen antihistamines have higher selectivity for H1 receptors and penetrate poorly into the CNS, and so have less sedative effects and non H1 effects

45

What type of drug is diphenhydramine, and what are its major effects and uses?

It is a first generation antihistamine; it has a strong sedative effect and is used for motion sickness

46

What type of drug is dimenhydrinate, and what are its major effects and uses?

It is a first generation antihistamine; it has a strong sedative effect and is used for motion sickness

47

What type of drug is cyclizine, and what are its major effects and uses?

It is a first generation antihistamine; it has a slight sedative effect and is used for motion sickness

48

What type of drug is promethazine, and what are its major effects and uses?

It is a first generation antihistamine; it has a strong sedative effect and is used as an antiemetic

49

Loratidine, cetirizine, and fexofenadine all belong to which class of drugs?

Second generation antihistamines