Block 2: NSAIDs and Histamine

Question 0

irreversible inhibitor of COX-1 and COX-2

Answer 0

aspirin

Question 1

which NSAID does not have anti-inflammatory properties?

Answer 1

acetaminophen

Question 2

aspirin: mechanism, distribution, metabolism

Answer 2

acetylation of a serine moiety of COX-1 and COX-2

distribution: crosses blood-brain barrier and placental barrier
metabolism: renal elimination, plasma half-life is dose-dependent

Question 3

effects of aspirin not related to inhibition of cyclooxygenase

Answer 3

uricosuric (increases uric acid excretion), CNS effects (crosses the blood-brain barrier)

Question 4

what is the mechanism behind NSAID hypersensitivity? what are the symptoms?

Answer 4

shunting of arachidonic acid pathway from cyxlooxygenase pathway to lipoxygenase pathway –> leukotrienes
symptoms: bronchoconstriction, edema

Question 5

effects of aspirin on kidneys, mechanism, what kind of patients should this concern

Answer 5

decreased renal blood flow and GFR, salt and water retention
mechanism: inhibition of COX-1 and COX-2 derived vasodilatory prostaglandins
patients dependent on vasodilatory prostaglandins (CHF, renal or liver disease, elderly)

Question 6

aspirin effects on pregnancy

Answer 6

amy cause decreased uterine contractions because prostaglandins stimulate uterine contractions
increased risk of postpartum hemorrhage
maintain patent ductus arteriosus

Question 7

what compound is responsible for the symptoms of aspirin overdose?

Answer 7

salicylic acid

Question 8

what is the common side renal effect across all NSAIDs?

Answer 8

decreased renal blood flow in patients dependental on vasodilatory prostaglandins

Question 9

NSAID proprionic derivative

Answer 9

ibuprofen

Question 10

sulfasalazine: mechanism, therapeutic uses

Answer 10

effect is independent of COX inhibition: inhibition of cytokine production, inhibition of lipoxygenase
uses: local effect in GI to inhibit inflammation; ulceritive colitis and rheumatoid arthritis

Question 11

celecoxib: mechanism, side effects, therapeutic uses

Answer 11

selective COX-2 inhibitor that binds to a lipophilic side pocket
side effects: increased GI and CV effects
uses: acute pain, colorectal polyps, primary dysmenorrhea

Question 12

acetaminophen: mechanism, metabolism, adverse effects, therapeutic uses

Answer 12

not well understoond (no affinity for COX-1 or COX-2 active site)
metabolism: renal excretion
adverse effects: well tolerated, no GI effects, hepatotoxicity due to a highly reactive intermediate (treated with N-acetylcysteine)
uses: pain, fever (no anti-inflammatory effects)

Question 13

where are the places in the body with highest amount of histamine?

Answer 13

lung, skin, GI tract

Question 14

effects of histamine release (5)

Answer 14

burning/itching, intense warmth, skin reddens, BP decreases, heart rate increases

Question 15

mechanism for mast cell histamine release

Answer 15

antigen-antibody reaction

Question 16

what is required for histamine release from mast cells?

Answer 16

increase in intracellular calcium

Question 17

drugs that inhibit release of histamine from mast cell (2)

Answer 17

cromolyn sodium and omalizumab

Question 18

cromolyn sodium: mechanism, therapeutic uses

Answer 18

stabilizes mast cell membrane and prevents antigen-antibody release of histamine
uses: prevents asthma and bronchospasm

Question 19

omalizumab: what is it, mechanism, adverse effects, therapeutic use

Answer 19

monoclonal antibody that binds to freely circulating IgE and prevents IgE-mediated sensitization of mast cells
adverse effects: life-threatening anaphylaxis
use: allergic asthma

Question 20

effects of histamine on CV system (3)

Answer 20

dilates resistance vessels, increases vascular permeability, and causes an overall fall in BP

Question 21

which histamine receptor is coupled to increase in calcium?

Answer 21

H1

Question 22

which histamine receptor is coupled to increase in cAMP?

Answer 22

H2

Question 23

which histamine receptor controls blood pressure?

Answer 23

both H1 and H2

Question 24

which histamine receptor is responsible for increased vascular permeability and how?

Answer 24

H1, increase in calcium causes endothelial cells to contrat and expose the basement membrane

Question 25

which histamine receptor is predominant in the heart and what are its actions?

Answer 25

H2, increases contractility and electrical conduction

Question 26

which histamine receptor is involved in bronchoconstriction?

Answer 26

H1

Question 27

which histamine receptor is responsible for gastric acid secretion and where are they located?

Answer 27

H2, parietal cells

Question 28

which histamine receptor is involved in pain and itching? where are these located?

Answer 28

H1, peripheral nerve endings

Question 29

name a first generation H1 blocker (antihistamine)

Answer 29

diphenhydramine

Question 30

name 4 second generation (nonsedating) antihistamines

Answer 30

fexofenadine, loratadine, desloratadine, cetirizine

Question 31

what is special about second generation antihistamines?

Answer 31

they do not cross the blood-brain barrier so they are nonsedating

Question 32

what do H1 receptor blockers NOT affect? (2)

Answer 32

BP, bronchoconstriction

Question 33

histamine receptor blocker have anti-inflammatory effects and what other types of effects? (3)

Answer 33

CNS effects, peripheral and central anticholinergic effects (dry mucus membranes, urinary retention), local anesthetic effects

Question 34

mechanism of sedation caused by first generation antihistamines (2)

Answer 34

- enters CNS and blocks H1 receptors that mediate wakefulness - block cholinergic receptors in CNS that also cause sedation

Question 35

second generation antihistamine with the most sedative effect

Answer 35

cetirizine

Question 36

anticholinergic (anti-muscarininc) effects of first generation antihistamines (3)

Answer 36

dry mouth, urinary retention, dryness of respiratory passages

Question 37

antihistamine used for motion sickness

Answer 37

diphenhydramine

Question 38

antihistamine used for non-prescription sleeping tablets

Answer 38

diphenhydramine

Question 39

H2 receptor blockers: therapeutic uses

Answer 39

relief of symptome of peptic ulcer disease, GERD, gastric injury caused by NSAIDs

Question 40

name 2 H2 receptor blockers

Answer 40

cimetidine, ranitidine

Question 41

which H2 receptor blocker interferes with P450 metabolism of other drugs?

Answer 41

cimetidine

Question 42

acetaminophen-induced liver toxicity

Answer 42

acetaminophen is usually metabolized by a P450 enzyme to a minor metabolite that is reduced by glutathione to a nontoxic metabolite that is excreted. when acetminophen is high, levels of glutathione are not sufficient to inactive the toxic product