-
LTB4
neutrophil chemoattractant
-
LTC4, LTD4, LTE4
- bronchoconstrict
- vasoconstrict
- contract smooth muscle
- increase vascular permeability
-Leukotrienes come from Hydroperoxides (HPETEs)--LOX path-->
-
PGI2 (Prostacyclin)
- inhibit platelet aggregation
- vasodilate
-
PGE2
- decrease vascular tone
- increase pain
- increase uterine tone
- increase temp!
-
TXA2
- increase platelet aggregation
- vasoconstrict
-
-
In motion sickness, M1, H1 pathways are stimulated--> nausea, vomiting.
1st gen Antihistamines are effective in preventing these sympotms but are sedating! -so use Scopolamine.
What are the SE?
dry mouth, blurry vision, palpitations, urinary retention, constipation
-
1st generation H1 blockers
- Diphenhydramine
- Dimenhydrinate
- Chlorpheniramine
-
Diphenhydramine
Dimenhydrinate
Chlorpheniramine
- 1st gen H1 blockers
- reversible
USE- allergy, motion sickness, sleep aid
SE- sedation, anti-muscarinic (blurry vision, dry mmouth, urinary retention), anti- adrenergic (postural dizziness), anti-serotonergic (appetite suppressant)
-
2nd generation antihistamines
- Loratadine
- Fexofenadine
- Desloratadine
- Cetirizine
-
Loratadine
Fexofenadine
Desloratadine
Cetirizine
2nd gen antihistamines
USE- allergy
Much less sedation than 1st gen. because less crossing of BBB--> less CNS effects!
-
Isoproterenol
- Astha drug
- nonspecific beta agonist
- -relax bronchial smooth muscle (beta2)
USE- asthma
SE- tachycardia (beta-1)
-
Of the numerous inflammatory mediators postulated to play role in pathogenesis of allergic asthma, only Leukotrienes (LTC3, LTD4, LTE4), Ach produce bronchospasm that is relieved by pharmacologic antagonists!
Histamine bronchoconstricts too, but antihistamines do NOT cause bronchodilation!
-
Albuterol
- beta-2 agonist
- relax bronchial smooth muscle
- bronchodilate
USE- acute exacerbation of asthma
SE- tremor, arrythmia
-
Salmeterol
- beta-2 agonist
- long acting
USE- prophylaxis of asthma
SE- tremor, arrhythmia
-
Theophylline
- methylxanthine
- inhibit PDE--> decr cAMP breakdown--> incrs cAMP
- narrow TI
- -metabolized by CYP
- -block action of Adenosine!
USE- asthma (limited use)
SE- cardiotoxicity, neurotoxicity, block action of Adenosine!
-
Ipratropium
- Muscarinic blocker
- competative block M--> prevent bronchoconstrict
USE- Asthma, COPD
-
Cromolyn
- Astha drug
- -block release of mediators from Mast cells
- USE- only Prophylaxis of asthma
- -useless for actue asthmatic attack
-
Beclomethasone
- Corticosteroid
- -inhibit synthesis of all cytokines!
- -inactivate NF-kB (block TX of TNF-aphla)
USE- Ist line for Chronic asthma
-
Prednisone
- Corticosteroid
- -inhibit synthesis of all cytokines!
- -inactivate NF-kB (block TX of TNF-alpha)
- -rapid symptom relief, most potent antimflammatory, but SE..
USE- 1st line for Chronic asthma
SE- increase neutrophil count (demargination- fever, chills, severe fatigue), decrease bone density (pathologic fractures)- inhibit Collagen synthesis, Inhibit GnRH--> hypogonadism
-
Zileuton
- anti-Leukotriene
- -block 5-LOX pathway inhibitor
- -block AA--> leukotriens
USE- asthma
-
Zafirlukast
- anti-leukotriene
- -block leukotriene receptors
USE- good for Aspirin-induced asthma
-
Montelukast
- anti-leukotriene
- -block leukotriene receptors
USE- good for Aspirin-induced asthma
-
Inhaeld glucocorticoids re the most effectivew aniti-nflammatory agents from chronic preventative treatment of bronchial ashtma.
-No role in acute episodes
-inhibit cytokine synthesis, induce apoptosis of inflammaotry cells, decrease mucus
No direct bronchodilatory but reduce airway hyperresponsiveness.
-
Asthma path
Exposure to antigen--> antigen+ IgE on Mast cells--> mediator release (leukotriene, histamine)--> early response : bronchoconstrict, late response: inflammation (bronchial hyperreactivity)!
Beta-agonist, theophylline, M-antagonists inhibit early response!
Steroids inhibit late response!
-
AC--> cAMP in asthma
cAMP--> bronchodilate
Ach, Adenosine--> bronchoconstrict
-
Guaifenesin
- Expecorant
- -remove excess sputum
- -does NOT suppress cough reflex
USE- Asthma
-
N-acetylcystein
Mucolytic
- USE- loosen mucous plugs for CF patients
- -antidote for Acetominophen overdose
-
Bosentan
- block Endothelin-1 receptors
- -decrease pulm vascular resistance
USE- Pulm HTN!
-
Aspirin
-low dose
-medium dose
-high dose
irreversibly inhibit COX by covalent binding--> decrease both TXA, PGs
- low dose- decrease platelet agg
- medium dose- antipyretic, analgesic
- high dose- anti-inflammatory
- SE- GI bleed
- Samter's triad: asthama, aspirin hypersensitivity (nasal, bronchospasm, pnasal polyposis-from Leukotrien increase)
- Salicysm- vertigo, tinnitus, hearing loss
- very high dose- metabolic acidosis + resp alkalosis
-
NSAIDS
Ketorolac, Ibuprofen, Naproxen, Indomethacin
- reversibly inhibit COX-1, COX-2
- block PG synthesis
- USE- antipyretic, analgesic, anti-inflammatory
- Indomethacin- close PDA!
SE- renal damage, fluid retention, aplastic anemia, GI distress, ulcers
-
Celecoxib
- COX-2 inhibitor
- reversibly inhibit COX-2 (inflammatory cells, vascular endothelium--> inflammation, pain)
- -spare COX-1 (better for gastric mucosa)
- -no GI ulcers
USE- Rheumatoid, Osteoarthritise (pts w/ gastric ulcers)
SE- Thrombosis, Sulfa-allergy
-
Acetominophen
- reversibly inhibit COX in CNS
- inactivated peripherally
- USE- antipyretic, analgesic, no anti-inflammatory properties!!
- -used instead of Aspirin to prevent Reye's in kids
SE- hepatic necrosis, deplete glutathione, FR-injury
-
Etidronate
Pamidronate
Alendronate
Risedronate
Zoledronate (IV)
- Bisphosphonate
- -inhibit osteoclastic activity (Pyrophosphate analogs)
- -reduce both bone formation, resorption of hydroxyapatite
- -careful in renal failure cuz secreted unchanged!
USE- malignancy assoc. hypercalcemia, Paget's disease, Postmenopausal osteoporosis
SE- corrosive esophagitis (except Zoledronate), nausea, diarrhea, osteonecrosis of jaw, careful in renal patients!!
-
Colchicine
- -acute gout w/ NSAID (1st line)!
- -bind stabilize tubulin--> block pol--> block leukocyte chemotaxis, degranulation
- -if elderly w/ bad kidney, give Glucocorticoids for acute gout
-
Probenecid
- Chronic gout
- -inhibit reabsorption of Uric acid in PCT
- -also inhibit penicillin secretion
-
Allopurinol
- Chronic gout
- -inhibit xanthine oxidase
- -decrease xanthine--> uric acid
- -increase conc of azathioprine, 6-MP
USE- chronic gout, prevent tumor lysis syndrome (urate nephropathy)
-Febuxostat- new xanthine oxidase inhibitor (fewer SE)
-
Diuretics and low dose Salicylates block secretion of Uric acid in PCT!
-
How to treat Osteoporosis?
Estrogen, SERMS, Bisphosphonates, Calcitonin, PTH
-
TNF-alpha inhibitors?
-name 3
- Etanercept (decoy receptor)
- Infliximab (anti-TNFa)
- Adalimumab (anti-TNFa)
-
Etanercept
recombinant TNFa receptor
USE- Rheumatoid arthritis, Psoriasis, Ankylosing spondylitis
SE- reactivation TB! do PPD skin test
-
Infliximab
anti-TNF alpha-antibody
USE- Crohn's disease, Rheumatoid arthritis, ankylosing spondylitis
SE- reactivation TB! do PPD skin test
-
Adalimumab
anti-TNF alpha-antibody
USE- Rheumatoid arthritis, Psoriasis, Ankylosing spondylitis
SE-reactivation TB! do PPD skin test
-
SE of Methotrexate?
- Hepatotoxic
- Apthous ulcers
-takes weeks to work
-
Hydroxychloroquine SE?
Retinal damage
-
Isotretinoin SE?
hypertriglycerimia, Teratogenic!!
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