Anti-histamine and NSAIDs Flashcards
H2 receptor mechanism
Gs coupled: increase cAMP
H1 receptor signaling mechanism
Gq couples: PLC > IP-3, DAG (mobilizes Ca2+ > histamine degranulation, smooth muscle constriction)
H3 receptor mechanism
Gs coupled: increase cAMP
H4 receptor mechanism
Gs coupled: increase cAMP
Vascular smooth muscle (H1, (H2))
histamine induced NO release > SM relaxatoin + vasodilation
Symptom: hypotension, flushing, headache, anaphylaxis
Endothelium (H1)
Induce actin/myosin contraction, separate endothelial cells
Symp:edema
Cardiac muscle (H1)
Decreased HR and atrial contractility
Cardiac muscle (H2)
Increased HR and contractility
Bronchiolar smooth muscle (H1)
Constriction
Symp: decreased airway size + difficulty breathing
Uterine smooth muscle (H1)
Constriction
Gastric smooth muscle (H1)
constriction
Symp: diarrhea
Sensory nerves (H1)
stimulation
Symp: pain + itching
CNS in hypothalamus (H1)
Arousal
Symp: increased wakefulness
CNS in emetic center (H1)
emesis
Symp: vomiting, nausea
CNS (H1 + H2)
Effects on thirst, BP, perception of pain
Gastric secretion (H2)
Increased acid production, pepsin and IF
Symp: mucosal erosion + ulceration
Cromolyn (Intal)
Prophylactic in longer term maintenance therapy fo rasthma
Inhibits degranulation of mast cells (inhibit Ca2+ channels, inhibit Cl- channels > decreased nerve activity + cough)
Lacks utility due to topical absorption of poorly soluble salts (inhaled powder aerosol)
Nedocromil (Tilade)
Prophylactic in longer term maintenance therapy fo rasthma
Inhibits degranulation of mast cells (inhibit Ca2+ channels, inhibit Cl- channels > decreased nerve activity + cough)
Lacks utility due to topical absorption of poorly soluble salts (inhaled powder aerosol)
H1 Receptor antagonists
Act as inverse agonist (block histamine at H1 receptors)
Uses: allergic rhinitis and uticaria (H1 antagonist), motion sickness/emesis (H1 antagonist + antimuscarinic effect)
SE: sedation (1st Gen Drugs: CNS Hypothalamic response, cross BBB)
Non-H1 effects: first gen H1 anta similar to muscarinic cholinoreceptor (dry mouth, urinary retention, tachycardia), a-adrenoceptor (orthostatic hypotension), anit-serotonin (increased appetite), local anesthetic (block Na channels)
Diphenhydramine (Benadryl)
1st Gen: H1 antagonist = antihistamine
Other Uses: motion sickness
Also a muscarinic antagonists (prevent parasympathetics)
Dimenhydrinate (Dramamine)
1st Gen: H1 antagonist = antihistamine
Other Uses: motion sickness
Salt of diphenhydramine
Cyclizine (Marezine)
1st Gen: H1 antagonist = antihistamine
Other Uses: motion sickness
Promethazine (Phenergan)
1st Gen: H1 antagonist = antihistamine
Other Uses: antiemetic
Most effective drugs for motion sickness and emesis
promethazine, cyclizine and diphenhydramine
Loratadine
(Claratin): 2nd Gen antihistamine
Highly selective for H1 sites, few anti-cholinergic SE, poorly cross BBB > less sedative effects
Cetrizine
(Zyrtec): 2nd Gen antihistamine
Highly selective for H1 sites, few anti-cholinergic SE, poorly cross BBB > less sedative effects
Fexofenadine
(Allegra): 2nd Gen antihistamine
Highly selective for H1 sites, few anti-cholinergic SE, poorly cross BBB > less sedative effects
Prostaglandin E2
Site of synthesis: Most tissues
Half-life: 30 sec
Oppose thromboxanes > suppress TXA
Prostaglandin I2 (prostacyclin)
Site of synthesis: Endothelium, vascular smooth muscle
Half-life: 3 min
Oppose thromboxanes > suppress TXA
Thromboxane A2
Site of synthesis: Platelets, macrophages
Half-life: 30 sec
Proinflammatory
Aspirin
Acetyl salicylic acid (Irreversible inhibitor of COX-1 + COX-2) > 15 min > salicylic acid (reversible inhibitor of both)
More potent inhibitor or COX-1
COX-2 is responsible for prostanoid production during inflammation
Use: OTC analgesic/antipyretic, CARDIOVASCULAR PROPHYLAXIS
Ketorolac (Toradol)
Selectivity of COX-1 vs COX-2 = 395
Use: post surgical analgesic
Indomethacin (Indocin)
Parenteral (high potency for COX-1)
Selectivity of COX-1 vs COX-2 = 10
Use: Rx arthritis/anti-inflammatory
high frequency of intolerance
Naproxen (Aleve, Bayer)
Selectivity of COX-1 vs COX-2 = 3.8
Use: aspirin: analgesic/antipyretic, Rx anti-inflammatory
Ibuprofen (Motrin, Advil)
Selectivity of COX-1 vs COX-2 = 2.6
Analgesic/antipyretic
Diclofenac (Voltaren, Cataflam)
Selectivity of COX-1 vs COX-2 = 0.3 (More potent towards COX-2)
combined with misoprostol (Arthrotec)
Uses: Rx arthritis/anti-inflammatory
Etodolac (Lodine)
Selectivity of COX-1 vs COX-2 = 0.1
Use: Rx arthritis
Meloxicam (Mobic)
Selectivity of COX-1 vs COX-2 = 0.04
Use: Rx arthritis
Misoprostol
PGE1 analog: used to protect against COX-1 inhibition by NSAIDs to allow prostglandins for the decreases in acid production, increased mucus formation in the stomach = prevent ulcers
Acetaminophen (tylenol)
Non-selective Cox inhibitor
Activity reduced in presence of peroxide (often located at inflamed site)
Uses: analgesic and antipyretic (no anti-inflammatory activity)
SE: hepatotoxicity with overdose
Celecoxib (Celebrex)
Only legal US Cox-2 selective NSAID: 10X selectivity
Uses:analgesic, rheumatoid arthritis
Reduces incidene of GI effects
SE: for all COX-2 selective inhibitors = increased cardiovascular events: hypertension, heart attack, stroke
Rofecoxib (Vioxx)
Cox-2 Selective NSAID: 200X selectivity (most selective)
Uses: analgesis, Rx arthritis
Valdecoxib (Bextra)
similiar to rofecoxib: COX-2 selective inhibitor: 200X selectivity
Zileuton
Leukotriene pathway synthesis inhibitor: inhibits 5-lipoxygenase > no LTB4/LTD4 synthesis
Uses: long-term maintenance therapy for asthma (oral)
SE: liver toxicity, inhibited activity of Cyt P450 1A2, 2C9, 3A4
Zafirlukast (Accolate) + Montelukast (Singular)
Longer term asthma maintenance
LTD4 receptor antagonist > reduced bronchoconstriction + edema from inflammatory response
