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Flashcards in Histamine and Inflammation drugs Deck (54):
1

H1 receptor antagonist

Class: ___
Mech: H1 receptor antagonist; rapidly absorbed orally, widely distributed, rapidly metabolized via liver microsomes
Thera: Allergic reactions (rhinitis, urticaria, conjunctivitis), motion sickness, nausea and vomiting in pregnancy, sleep aids
Important SE's: Sedation, anti-muscarinic action, poisoning (especially children) with convulsions, allergy, local anesthesia (has actions not ascribable to H1 blockade because of muscarinic cholinoceptor, a-adrenoceptor, serotonin, local anesthetic receptor sites)
Misc: Older agents cross CNS to cause central effects

2

Diphenhydramine (Benadryl)

Class: Ether/ethanolamine derivitive
Mech: H1 receptor antagonist
Important SE's: Anti-muscarinic, sedating

3

Tripelennamine (Pyribenzamine)

Class: Ethylenediamine derivitive
Mech: H1 receptor antagonist
Thera: OTC sleep aid; moderate sedation

4

Meclizine (Marezine)

Class: Piperazine derivative
Mech: H1 receptor antagonist
Thera: Motion sickness

5

Promethazine (Phenergan)

Class: Phenothiazine derivative
Mech: H1 receptor antagonist
Thera: Antiemetic
Important SE's: Anti-muscarinic, sedating (because of cholinergic receptors, dry mouth, urinary retention, sinus tachy; because of alpha-adre, hypotension, dizziness, reflex tachy)

6

Chlorpheniramine (Chlor-Trimeton)

Class: Alkylamine derivitive
Mech: H1 receptor antagonist
Thera: Component of "cold" medications
Important SE's: Less sedating

7

Loratadine (Claritin)

Class: Piperidine derivitive
Mech: 2nd generation H1 receptor antagonist
Thera: Allergic rhinitis
Important SE's: No sedation
Other SE's: Cardiovascular effects (rare, with high doses)
Misc: Poorly crosses BBB, so fewer central and side effects; once daily dosing

8

Fexofenadine (Allegra)

Class: Piperidine derivitive
Mech: 2nd generation H1 receptor antagonist
Thera: Allergic rhinitis
Important SE's: No sedation
Other SE's: Cardiovascular effects (rare, with high doses)
Misc: Poorly crosses BBB, so fewer central and side effects; once daily dosing

9

Azelastine (Astelin)

Mech: 2nd generation H1 receptor antagonist
Thera: Allergic rhinitis (intranasal spray), allergic conjunctivitis (ophthalmic solution)
Important SE's: No sedation
Misc: Poorly crosses BBB, so fewer central and side effects

10

Cetirizine (Zyrtec)

Mech: 2nd generation H1 receptor antagonist
Thera: Allergic rhinitis
Important SE's: No sedation
Misc: Poorly crosses BBB, so fewer central and side effects

11

Cimetidine (Tagamet)

Mech: H2 receptor antagonist; blocks gastric acid secretion (more so with nocturnal acid secretion than meal secretion)
Thera: Dyspepsia, duodenal and gastric ulcers, hypersecretory conditions
Important SE's: Antiandrogen (causing impotence and gynecomastia), inhibition of P450 enzymes
Other SE's: CNS dysfunction possible
Misc: Most side effects of H2-blocker class

12

Ranitidine (Zantac): how different from cimetidine?

Important SE's: Liver toxicity

13

Famotidine (Pepcid): how different from cimetidine?

No Important SE's or misc

14

Nizatidine (Axid): how different from cimetidine?

Misc: Least side effects of H2-blocker class

15

Cyproheptadine (Periactin)

Mech: Antihistaminic and antiserotinergic
Thera: Skin allergies (urticaria, anti-5HT1), diarrhea of carcinoid syndrome (anti-5HT2)
Other SE's: Sedation, antimuscarinic

16

Ketanserin

Mech: Selective 5HT2A,2C receptor antagonist, as well as α1 and H1 receptor antagonist
Thera: Antihypertensive (relaxes vascular and tracheal smooth muscle), antiplatelet aggregation

17

Odansetron (Zofran)

Mech: 5HT3 receptor antagonist
Thera: Nausea and vomiting in chemotherapy

18

Ergot alkaloids

Mech: Agonist and antagonist actions at 5HT and α-adrenergic receptors
Important SE's: Powerful hallucinations, smooth muscle contraction (vascular and uterine, latter leading to abortion)

19

Ergotamine (Ergomar)

Class: Ergot alkaloid
Mech: Nonspecific partial agonist at all 5HT1,2 receptors; partial agonist at α-adrenergic receptors
Thera: Prodrome of migraines
Other SE's: N/V, cumulative and prolonged vasoconstriction

20

Methysergide (Cycloset)

Class: Ergot alkaloid
Mech: Partial agonist at all 5HT1 receptors, antagonist at 5HT2
Thera: Prophylaxis of migraines
Other SE's: GI disturbances, inflammatory fibrosis (chronic use), hallucinations
Misc: Withdrawn from U.S. market

21

Ergonovine

Class: Ergot alkaloid
Thera: Postpartum hemorrhage (Oxytocic)

22

Bromocriptine (Sansert)

Class: Ergot alkaloid
Mech: Dopamine agonist (D2)
Thera: Hyperprolactinemia (suppress prolactin secretion from pituitary cells)

23

Triptans (Suma, nara, riza, zolmi)

Class: Non-ergot serotonin analogs
Mech: 5HT1B,D receptor agonist
Thera: Effective (70%) migraine treatment

24

Acetylsalicylic acid (ASA, Aspirin)

Class: Salicylate
Mech: Acetyl-salicylic acid irreversibly acetylates COX-1 and -2; metabolite (salicylic acid) reversibly inhibits COX-1 and -2
Thera: Antiplatelet (inhibit TXA2 synthesis; 80-160 mg), analgesic (inhibition of eicosanoid-induced sens of pain receptors and transmission to relay neurons in dorsal horn; 650-975 mg) and antipyretic (blocks pyrogen-induced eicosanoid synthesis, PGE2, in vicinity of hypo; 650-975 mg), and anti-inflammatory (inhibit eicosanoid formation; 3-6 g) (in ascending order of amount taken); often taken as a "baby aspirin" to prevent MI, CVA
Important SE's: GI irritation (lose PGE2 and PGI2, dyspepsia), bleeding and anemia, hepatotoxicity (Reye's syndrome), and salicylate toxicity
Other SE's: Nephrotoxicity in elderly or hypovolemic patients (renal failure with less vasodilation and lack of renal vasodilator eicosanoids); rare hypersensitivity reaction (aspirin-induced airway hyperactivity and bronchoconstriction and urticaria)
Misc: peak plasma salicylate level 1-2 hrs; rapidly absorbed by passive diffusion from stomach (non-ionized) and upper small intestine (ionized)

25

Diflunisal (Dolobid)

Class: Salicylate
Mech: Difluorophenyl derivitive of salicylic acid, which reversibly inhibits COX-1 and -2
Thera: Osteoarthritis, musculoskeletal strains/sprains, pain after dental extraction, and postepisiotomy pain
Important SE's: Fewer GI side effects and less effect on platelets than aspirin
Misc: analgesic, weak antipyretic activity, and longer half life;

26

Acetaminophen (Tylenol)

Class: Para-amino phenol
Mech: Reversibly inhibits COX-1 and -2 (favors COX-1)
Thera: Analgesic and antipyretic effect similar to aspirin, but weak anti-inflammatory effects
Important SE's: Renal tubular necrosis if chronically abused with other NSAIDs; hepatic necrosis with overdose
Other SE's: GI irritation (less than aspirin)
Misc: Poor function in presence of peroxides (as found in sites of inflammation); mostly metabolized via conjugation, but minor pathway via P450 enzymes may lead to toxic intermediate (N-acetyl-benzoquinoneimine); used in more combo products than any other drug

27

Indomethacin (Indocin)

Class: Indole
Mech: Reversibly inhibits COX-1 and -2 (favors COX-1)
Thera: Rhematoid arthritis (10X as potent as aspirin), ankylosing spondylitis, osteoarthritis, acute gout
Important SE's: At times, thrombocytopenia, aplastic anemia, and severe frontal headaches
Other SE's: Nephrotoxicity in elderly or hypovolemic patients
Misc: Toxicity causes >25% of patients to discontinue use

28

Sulindac (Clinoril)

Class: Indole
Mech: Reversibly inhibits COX-1 and -2 (favors COX-1)
Thera: Rhematoid arthritis, ankylosing spondylitis, osteoarthritis, acute gout
Important SE's: At times, thrombocytopenia, aplastic anemia, and severe frontal headaches
Other SE's: Nephrotoxicity in elderly or hypovolemic patients
Misc: Half as potent as indomethacin; side effects less frequent

29

Ibuprofen (Advil, Motrin)

Class: Proprionic acid dervitive
Mech: Reversibly inhibits COX-1 and -2 (favors COX-1)
Thera: Rheumatic disorders, osteoarthritis, ankylosing spondylitis, postpartum pain, dysmenorrheal pain, and many types of surgeries
Important SE's: GI irritation; hepatotoxicity (less frequent than aspirin)

30

Flurbiprofen (Ocufen)

Class: Proprionic acid dervitive
Mech: Reversibly inhibits COX-1 and -2 (favors COX-1)
Thera: Rheumatic disorders, osteoarthritis, ankylosing spondylitis, postpartum pain, dysmenorrheal pain, and many types of surgeries
Important SE's: GI irritation; hepatotoxicity (less frequent than aspirin)

31

Naproxen (Aleve)

Class: Proprionic acid dervitive
Mech: Reversibly inhibits COX-1 and -2 (favors COX-1)
Thera: Rheumatic disorders, osteoarthritis, ankylosing spondylitis, postpartum pain, dysmenorrheal pain, and many types of surgeries
Important SE's: GI irritation; hepatotoxicity (less frequent than aspirin)
Misc: Longer half-life than most proprionic acid derivitives (13 hours vs. 1-2 hours)

32

Oxaprozin (Daypro)

Class: Proprionic acid dervitive
Mech: Reversibly inhibits COX-1 and -2 (favors COX-1)
Thera: Rheumatic disorders, osteoarthritis, ankylosing spondylitis, postpartum pain, dysmenorrheal pain, and many types of surgeries
Important SE's: GI irritation; hepatotoxicity (less frequent than aspirin)
Misc: Much longer half-life than most proprionic acid derivitives (50 hours vs. 1-2 hours)

33

Piroxicam (Feldene)

Class: Enolic acid
Mech: Reversibly inhibits COX-1 and -2 (favors COX-1)
Thera: Long-term treatment of rheumatoid arthritis or osteoarthritis; also, ankylosing spondylitis, acute musculoskeletal disorders, acute gout
Other SE's: Same as aspirin
Misc: Very long half-life (45 hours) permits single daily dose

34

Ketorolac (Toradol)

Class: Heteroaryl acetic acids
Mech: Reversibly inhibits COX-1 and -2 (favors COX-1)
Thera: Post-operative pain; inflammatory eye conditions
Other SE's: Same as aspirin; relatively nonirritating
Misc: Injectable (one of few NSAIDs available for this)

35

Celocoxib (Celebrex)

Class: COX-2 inhibitor
Mech: Selectively inhibits COX-2 (too bulky to reliably interact in COX-1 site); 10-20 fold greater selectivity for COX-2 to COX-1
Thera: Same anti-inflammatory, antipyretic, and analgesic effects as NSAIDs
Important SE's: Less GI toxicity than traditional NSAIDs
Misc: Contraindicated in patients with heart problems/pregnancy

36

Etoricoxib (Arcoxia)

Class: COX-2 inhibitor
Mech: Selectively inhibits COX-2 (too bulky to reliably interact in COX-1 site)
Thera: Same anti-inflammatory, antipyretic, and analgesic effects as NSAIDs
Important SE's: Less GI toxicity than traditional NSAIDs
Misc: Contraindicated in patients with heart problems/pregnancy

37

Inflammatory processes occur in three distinct phases:

1. acute transient phase (local vasodilation and increased capillary permeability)
2. Delayed, subacute phase (infiltration of leukocytes and phagocytotic cells)
3. Chronic proliferative phase (tissue degen and necrosis)

38

Histamine is a biologically ____, an ____, synthesized from ____ and stored primarily in _____ in many tissues; it is a mediator of what reactions? How does it act?

active amine; autacoid; histidine; mast cells and basophils;
immediate type I hypersens reactions;
1. increases blood flow by capillary dilation
2. causes edema by increasing pcv permeability
3. Causes itching by sensitizing primary sensory neurons

39

Kinins are ____ that are formed from _____. Enzymes responsible for their formation, the ____, are released from ____ or activated by _____ in plasma. Kinins have what effects?

two related peptides; plasma globulins (kininogens);
kallikreins; tissues; clotting factors;
1. acute: excitation of primary sensory neurons
2. chronic: capillary dilation, increase in pcv perm, and activation of AA release (slower to act than histamine!!

40

Cytokines are released from ___ and ____, and the major players are what? What do these players do?

lymphoid; non-lymphoid cells;
IL-1: made particularly by macrophages and induces inflamm responses (increases eicosanoid synthesizing enzymes, collagenase), regulates B and T cells, induces fever
IL-8 and chemokines: powerful chemotactic agents;
TNF: regulates production of other cytokines and induces fibrosis and tissue catabolism

41

AA is released from ____ and is metabolized by either ____ to make what, and _____, to make what?

phopholipids of cell membrane;
lipooxygenase, to make leukotrienes;
cyclooxygenase, to make prostaglandines, prostacyclines, thromboxanes

42

COX-1 is produced _____, and is involved in? PRIG

constitutively;
1. gastric cytoprotection
2. initiation of parturition
3. renal blood flow autoregulation
4. Platelet aggregation

43

COX-2 is induced _____; it makes ____ at the sites of inflammation and/or tissue damage; what are both COX-1 and -2 inhibited by?

during inflammation; prostaglandins;
NSAIDs

44

COX-2 constitutive and inducible functions are what?

Constitutive: 1. renal electrolyte homeostasis 2. Renal blood flow maintenance
Inducible: 1. Pain 2. Fever 3. Inflammation

45

Largest concentration of histamine is found where?

Skin, lungs, GI and nasal mucosa, and blood

46

Histamine is stored where and can be synthesized rapidly in what circumstances?

1. Mast cells and basophils
2. With appropriate stimuli, the paracrine cells of the gastric fundus and histaminergic neurons

47

Stimuli that can help with release of histamine from mast cells?

1. Antigens and anaphylatoxins (IgE crosslinking on surface of sensitized mast cells and membrane Ca channels opened to activate enzymes leading to histamine release)
2. Certain basic drugs that increase GTP (morphine, codeine, tubo)
3. Chemical or mech injury: degranulation usually due to increased Na

48

All histamine receptors have ___ membrane-spanning regions and G protein use; what G proteins are used by each receptor type?

7; H1 with Gq, H2 with Gs, H3 and H4 with Gi

49

Most important physiological effect on humans regarding histamine? Other effects?

Peripheral vasodilation with H1 and H2, which can lead to pronounced drop in BP and anaphylactic shock!!
1. Bronchiolar smooth muscle with minor effect on bronchoconstriction unless asthmatic
2. GI tract with gastric acid and pepsin secretion via H2
3. Nervous system: sensory nerve endings stimulated and itching (H1); also H3 receptors are presynaptic autoreceptors on histaminergic neurons

50

What can you give to counter histamine effects?

Epi, cromolyn sodium (prophylactic treatment of exercise or seasonal asthma); ALSO HISTAMINE RECEPTOR ANTAGONISTS

51

Pharmacologic actions of 5-HT?

1. GI tract contraction; look for carcinoid syndrome with 5-HT and autacoid release; high 5-HIAA in urine is diagnostic
2. Cardiovascular system: vasoconstrictor in smooth muscle, vasodilator in skeletal muscle and heart; have platelet aggregation with 5-HT2
3. Nervous system: peripheral (sensory nerve endings stimulated with pain and itching), central (involved in mood, food intake, sleep, reg of pituitary secretions)

52

How is there regulation with serotonin?

1. Auto-reg with 5-HT1A receptor (somatodendritic autoreg)
2. Auto-reg with 5-HT 1D/1B receptor (presynaptic autoreg)

53

Aspirin is effective in treating what types of pain, but NOT one particular type?

Joint inflammation, myalgias, headaches, arthralgias, dysmenorrhea, but NOT visceral pain!!!

54

Key adverse effects of giving antihistamines (particularly H1 receptor antagonists?)

Sedation; atropine like effects: blurred vision, dry mouth, urinary retention, constipation;
poisoning; CNS stimulation at high doses (convulsions), allergy, local anesthetic!!