Histamine And Antihistamines

Front 1

what processes does histamine play a role in?

Back 1

allergy, inflammation, anaphylaxis, gastric secretion, sleep-wake cycle, feeding, cognition, memory; more recently shown to be involved in proliferation and differentiation of cells, hematopoiesis, embryonic development, regeneration, wound healing

Front 2

distribution of histamine?

Back 2

skin, mucous membranes of respiratory and gi tract

Front 3

histamine synthesized from?

Back 3

histidine via histidine decarboxylase

Front 4

what stimulates histamine release?

Back 4

antigen-antibody reaction (immediate hypersensitivity)

Front 5

how is histamine stored?

Back 5

mast cells, basophils: granules bound to heparin, similar to neurotransmitter;
non-mast cell pool: brain and gastric mucosa, neural elements

Front 6

chemicals causing histamine release?

Back 6

any that cause frank tissue damage, some organic bases (morphine and other opiates, d-tubocurarine, antihistamines)

Front 7

why do antihistamines not completely resolve all allergic effects?

Back 7

histamine is not the only mediator of allergic response

Front 8

most common histamine recetpor and its location?

Back 8

H1 found in smooth muscle, endothelium, brain (post synaptic)

Front 9

mechanism of H1 receptor?

Back 9

Gq/11 leading to phospholipase C activation --> increased Ca2+ --> phosphorylation of myosin light chain to cross bridge cycling and contraction

Front 10

where are H2 receptors found and what is the mechanism of action?

Back 10

gastric mucosa, cardiac muscle, mast cells, brain (post synaptic): Gs --> increased cAMP

Front 11

what type of receptors are H3 receptors?

Back 11

autoreceptors (regulate itself) and heteroreceptors (regulate release of other neurotransmitters)

Front 12

blood pressure response to histamine?

Back 12

drop like a rock

Front 13

heart reponse to histamine?

Back 13

rate increases reflexively to baroreceptors; H2 directly causes (+) iontropic and (+) chronotropic effects

Front 14

why do arterioles dilate in response to histamine?

Back 14

H1 effect is mediated by endothelial cells which respond by releasing NO [EDRF] which causes relaxation

Front 15

vasculature response to histamine?

Back 15

arterioles dilate decreasing bp; large veins constrict, small veins dilate; capillaries dilate passively; venule permeability increased --> protein leakage into ecf

Front 16

triple response?

Back 16

localized red spot, red flush or flare, wheal

Front 17

pathogenesis of localized red spot?

Back 17

H1 causing dilation

Front 18

pathogenesis of red flush or flare?

Back 18

local axon reflex resulting in dilation

Front 19

pathogenesis of wheal?

Back 19

H1 causing increased venular permeability

Front 20

histamine stimulation to parietal cells?

Back 20

increases HCl, pepsin, intrinsic factor output

Front 21

histamine effect on exocrine glands?

Back 21

gastric secretagogue; bronchial, nasal, lachrymal secretions increased

Front 22

histamine involvement in nervous system?

Back 22

stimulate peripheral sensory nerve endings: axon reflex, itch, pain on deep injection; neuromodulator in CNS and PNS (wakefulness and arousal)

Front 23

clinical uses of histamine?

Back 23

none; gastric function tests

Front 24

when is histamine released in response to drugs and chemicals?

Back 24

when administered iv in fairly large doses

Front 25

how is histamine metabolized?

Back 25

N-methylation (brain and other tissues) and oxidation

Front 26

steps of immediate hypersensitivity reaction?

Back 26

dendritic cell recognition of immune complexes --> activates T cell to secrete cytokines --> appropriate B cell activate to transform to plasma cell --> secrete antibodies --> immune complexes bind to mast cell --> release of mediators

Front 27

what inflammatory mediators are secreted from mast cells?

Back 27

histamine, serotonin, leukotrienes, prostaglandins, bradykinins, proteases, eosinophil chemotactic factor, neutrophil chemotactic factor

Front 28

what are the effects of inflammatory mediators released from mast cells?

Back 28

smooth muscle contraction, vasodilation, increased vascular permeability, platelet aggregation, complement activation, eosinophil and neutrophil chemotactic factor, mucus secretion

Front 29

what clinical symptoms seen with immediate hypersensitivity?

Back 29

asthma, hay fever, skin rashes, local anaphylaxis, systemic anaphylaxis

Front 30

transduction system of H1 receptors?

Back 30

Gq/11 --> phospholipase C --> increased IP3/DAG --> increased Ca2+ intracellular

Front 31

signal transduction pathway of H2 receptors?

Back 31

Gs --> adenylate cyclase --> increased cAMP

Front 32

why is histamine no longer used for gastric function tests?

Back 32

pentagastrin does the same and has fewer side effects

Front 33

mechanism of action of antihistamines?

Back 33

inverse agonists (higher affinity for inactive form of a receptor)

Front 34

which 1st generation antihistamines have good anti-cholinergic activity with marked sedation and anti-motion sickness activity?

Back 34

dimenhydrinate (dramamine), diphenhydramine (benadryl)

Front 35

dramamine (dimenhydrinate)?

Back 35

very good anti-cholinergic activity, marked sedation, anti-motion sickness activity

Front 36

diphenhydramine (benadryl)?

Back 36

very good anti-cholinergic activity, marked sedation, anti-motion sickness activity

Front 37

phenothiazine derivatives: promethazine (phenergan)?

Back 37

very good anti-cholinergic activity, marked sedation, antiemetic

Front 38

chlorpheniramine?

Back 38

some anti-cholinergic activity with slight sedation

Front 39

which of 1st generation antihistamines only produced slight sedation?

Back 39

chlorpheniramine

Front 40

why are 2nd generation antihistamines less likely to produce sedation?

Back 40

do not cross the blood brain barrier

Front 41

pharmacokinetics of antihistamines?

Back 41

readily absorbed from gi, take effect within 1-3 hrs with average duration of 4-24 hrs; 2nd generation have longer half lives and usually require only once-daily dosing

Front 42

2nd generation antihistamines?

Back 42

cetirizine, desloratadine, fexofenadine, levocetirizine, loratadine

Front 43

cetirizine aka?

Back 43

zyrtec

Front 44

desloratadine aka?

Back 44

clarinex (metabolite of loratadine)

Front 45

fexofenadine aka?

Back 45

allegra

Front 46

levocetrizine aka?

Back 46

xyzal

Front 47

loratadine aka?

Back 47

claritin

Front 48

clinical uses of antihistamines?

Back 48

allergy, anaphylaxis, asthma, motion sickness, sedation, OTC cold remedies, ophthalmic, cardiovascular

Front 49

antihistamine success in treating allergy?

Back 49

useful in allergic rhinitis (nasal congestions refractory), conjunctivitis, urticaria

Front 50

antihistamines effective at treating allergy?

Back 50

olopatadine, azelastine (both oral and topical preparations)

Front 51

most effective agents for allergic rhinitis?

Back 51

nasal steroids

Front 52

examples of corticosteroid nasal sprays for allergic rhinitis?

Back 52

budesonide, fluticasone propionate, mometasone furoate

Front 53

side effects of nasal steroids?

Back 53

epistaxis, nasal ulceration, dryness, irritation or burning of nasal mucosa, possible nasal septum performation, localized candida infections, rise in intraocular pressure, cataracts

Front 54

H1 and H2 blockers use for anaphylaxis?

Back 54

not generally (epi much better) but some beneficial effect on shock

Front 55

use of antihistamines for asthma?

Back 55

2nd generation play limited adjunctive role

Front 56

use of antihistamines for motion sickness?

Back 56

best prophylactically 30 min prior to exposure

Front 57

which antihistamines used for motion sickness?

Back 57

dimenhydrinate, promethazine

Front 58

mechanism of antihistamines in colds?

Back 58

anticholinergic drying effect (1st generations)

Front 59

which antihistamines are used for sedation/insomnia and peri-operative sedation?

Back 59

diphenhydramine, promethazine (1st generation)

Front 60

antihistamines used for local anesthetics?

Back 60

promethazine, diphenhydramine (1st generation)

Front 61

when use antihistamines as local anesthetics and why generally not recommended?

Back 61

if allergic to both types of local anesthetics; but not generally recommended topically due to contact dermatitis

Front 62

cns effects of 1st generation antihistamines?

Back 62

sedation, drowsiness, impairment of psychomotor performance (may be considered under the influence)

Front 63

antihistamine side effects on gi, respiratory, gu, ophthalmic?

Back 63

gi: epidgastric distress, anorexia, nausea, vomiting, diarrhea, constipation;
respiratory: dry nose, mouth and throat, nasal stuffiness, thickened bronchial secretions, tightness in chest, wheezing;
gu: exacerbate BPH;
ophthalmic: blurred vision, possible exacerbation of narrow angle glaucoma

Front 64

which antihistamines are teratogenic?

Back 64

cyclizine, meclizine, azelastine

Front 65

signs and symptoms of antihistamine overdose?

Back 65

from cns depression (drowsiness, sedation, diminished mental alertness, apnea, cardiovascular collapse) to cns stimulation (insomnia, hallucinations, tremors, convulsions), may include dizziness, tinnitus, ataxia, blurred vision, hypotension

Front 66

which symptoms are likely in children overdosed with antihistamines?

Back 66

cns stimulation and atropine-like signs (dry mouth; fixed, dilated pupils, hyperthermia, flushing, gi distrubances

Front 67

antihistamine drug interactions?

Back 67

alcohol, sedatives, other cns depressants