Histamine/PG

Question 1

Autocoids

Answer 1

endogenous substances in the body (histamine, serotonin, peptides, prostaglandins, leukotrienes)

• short duration of action, act near site of synthesis/release
• high levels cause inflammation, pain, bronchospasm, anaphylactic shock

Question 2

Histamine

Answer 2

• Synthesized from L-histidine
• Delivered by degranulation of basophils and mast cells at sites of injury (via IgE cross linking0
• Acts in brain as NT
• Enterochromaffin like cells in stomach which activate acid production (H2 receptor)

Question 3

Immunologic histamine release

Answer 3

• Crosslinked IgE causes degranulation releasing histamine
• Causing Type 1 allergic reactions- hay fever, urticaria and inflammation and immune modulation (blood vessel dilation, complement activation, cytokine, T and B cell modulation

Question 4

Chemical induced histamine release

Answer 4

-morphine, tubocurarine, cpd 48/80, mast cell injury

first two lead to release of histamine

Question 5

Cromolyn

Answer 5

Inhibits histamine release

Also nedocromil

Question 6

H1 receptor mediated response

Answer 6

-urticarial response, respiratory neuron singaling, vasodilation via NO release (reflex tachycardia), edema, bronchoconstriction, contraction of intestinal smooth muscle

Question 7

First gen antihistamines

Answer 7

Carbinoxamine, dimenhydrinate, diphenhydramine (more sedative effect), hydroxyzine, cyclizine, meclizine, brompheniramine, chlorpheniramine, promethazine, cyproheptadine

anti cholinergic activity causes sedation, anti-motion sickness activity, and some anti emesis (promethazine)

4-6 hrs duration of action

Question 8

Second gen antihistamine

Answer 8

Fexofenadine, loratidine (long acting), cetirizine, azelastine, desloratidine

12-24 hr duration of action

Question 9

Use of H1 receptor antagonist

Answer 9

• allergic reactions- hay fever, urticaria, not utilized for bronchial asthma
• motion sickness- prevention
• local anesthetic (diphenhydramine and promethazine more potent than procaine)

-antiparkinsonian, anticholinergic, adrenergic blocking, serotonin blocking

Question 10

Toxicity and drug interactions of H1 receptor antagonist

Answer 10

sedation, anti muscarinic (urinary retention), blurred vision

-interacts with cyp450 (inhibition),

Question 11

H2 receptor mediated responses

Answer 11

• secretory in parietal cells (gastric acid secretion)
• CV system: high doses of histamine- cAMP dep vasodilation and direct stimulation (inc contractility and pacemaker), antagonists have little effect on cardiac function

Question 12

H2 receptor antagonists

Answer 12

reduce gastric acid secretion- peptic ulcer, gerd, hypersecretory diseases
(do not impact intestinal secretion or oher peripheral H2 receptor mediated effects like HR)

cimetidine, famotidine, nizatidine, ranitidine

Question 13

H3 receptor mediated response

Answer 13

Nervous system- presynaptic receptor modulates NT release

Metabolic effects

thioperamide (also H4 blocker), chlobenpropit, iodophenpropit

Question 14

Eicosanoids

Answer 14

• Family of oxygenation products of polyunsaturated LCFA

- wide spectrum of biologic activity

Question 15

Arachidonic acid

Answer 15

most abundant eicosanoid

• liberated by phospholipase a2 from glycophospholipids
• oxidated by COX, LOX (to form leukotrienes), CYP450, and nonezmatic (free radicals)

Question 16

COX

Answer 16

Convert AA to prostaglandins

Question 17

COX1

Answer 17

constitutively expressed, widely distributed, houskeeping

Question 18

COX2

Answer 18

inducible, production of inflammatory molecules
expressed in vascular endothelium (prostacyclin- PGI2)
-renal cox2 essential for normal fxn

Question 19

PGH2

Answer 19

Thromboxanes, prostaglandins, prostacyclins are derived from PGH2 (which is derived from AA)

Question 20

Eicosanoid receptors

Answer 20

G protein coupled, with cAMP or Ca++ being second messengers

Question 21

PG effect on vasculature

Answer 21

TXA2 and PGF2a- vasoconstriction

PGE2 and PGI2-vasodilation (inc cAMP, dec Ca)

Question 22

PG effect on GI tract

Answer 22

longitudinal muscle contraction and relaxation of circular muscles. cause colicky cramps
PGE2

Question 23

PG effect on Airway

Answer 23

PGE2 and PGI2- relaxation

PDG2, TXA2, PGF2a- contraction

Question 24

Platelets and PGs

Answer 24

TXA2 enhances platelet aggregation

Question 25

PGs on Kidney

Answer 25

Medulla and cortex synthesize PGs- PGE2 and PGI2 Maintain bp and renal fxn via vasodilation Regulation of water and electrolyte secretion via COX1 and COX2 products: - COX1- promote salt excretion in collecting ducts - COX2- increase medullary blood flow and inhibit tubular sodium reabsorption Loop diuretics have effects in part due to inc cox activity (inhibitors can reduce effect)

Question 26

PGs male reproductive

Answer 26

found in semen PG levels correlate with fertility and enhanced by testosterone PGE1- enhances penile erection by relaxing smooth muscles in corpus cavernosum

Question 27

PGs- female reproductive

Answer 27

PGF2a and low PGE2 promotes uterine contraction | High PGE2 concentration--> relaxation

Question 28

Misoprostol

Answer 28

1st and 2nd trimester abortion oral PGE1 tx of NSAID induced ulcer

Question 29

Dinoprostone

Answer 29

PGE2 vaginally for abortion by stimulating contraction of uterus inducing labor

Question 30

Carboprost

Answer 30

PGF2a | contract uterus to control post partum hemorrhage

Question 31

AE of PG on female repro

Answer 31

vomiting, fever, diarrhea, bronchoconstriction, altered bp, flushing

Question 32

PG inflammation and immunity

Answer 32

PGE2 and PGI2- inc edema and vascular permeability | PGD2 released from mast cells to recruit eosinophils

Question 33

Alprostadil

Answer 33

relaxes smooth muscle PDA, erectile dysfunction, impotence PGE1

Question 34

Latanoprost

Answer 34

PGF1a- topical | tx of open angle glaucoma

Question 35

Dysmenorrhea

Answer 35

inc endometrial synthesis of PGE2 and PGF2a

Question 36

Prostacyclin

Answer 36

PGI2- inhibits platelets and is a vasodilator | used for pulmonary hypertension because dec pulmonary, peripheral and coronary resistance

Question 37

Tx of pulmonary htn

Answer 37

Prostacyclin Epoprostenol (flushing, headache, hypotension, nausea, diarrhea)-requires continuous IV infusion Iloprost- inhaled 6-9 times per day Treprostinil- sc injxn of iv because half life 4 hrs

Question 38

NSAIDs

Answer 38

Salicylates- aspirin, salicylic acid Other- ibuprofen, indomethacin, ketorolac, naproxen, oxaprozin, piroxicam, sulindac COX2 inh- celecoxib analgesic antipyretic and antiinflammatory

Question 39

Leukotriene biosynthesis

Answer 39

LTC4 and LTD4- potent bronchoconstrictors cause asthma and anaphylaxis Formed via LOX from AA

Question 40

Leukotrienes in inflammation

Answer 40

chemoattractants of eosinophils and monocytes | Proinflammatory mediators of asthma and IBD

Question 41

LTs in heart and smooth muscle

Answer 41

cause cardiac depression by reducing myocardial contractility and reducing coronary blood flow GI- IBD by recruitment of PMNs Airways- bronchoconstrictors which inc microvascular permeabilit, mucus secretion, chemotaxis of eosinophils

Question 42

Zileuton

Answer 42

5-LOX enzyme inhibitor | inhibits leukotriene biosynthesis

Question 43

Leukotriene receptor antagonist

Answer 43

Montelukast | given for asthma