Autacoids Flashcards
H1 Receptors
Type
Location
Action
- Gq-coupled. Nerves, smooth muscle, bronchi, intestines.
- Causes vasodilation, capillary permeability (edema, hives), bronchoconstriction, pain, itch, and intestinal smooth muscle contraction.
H2 Receptors
Type
Location
Action
- Gs-coupled. Gastric mucosa, heart, and mast cells.
- Vasodilation, increased HR via reflex tachycardia (due to decreased baroreceptor firing following vasodilation) and direct stimulation, gastric acid secretion.
H3 Receptors
Type
Location
Action
Gi-coupled (inhibitory). Autoreceptors on histaminergic neurons.
H4 receptors
Type
Location
Gi-coupled. Eosinophils, neutrophils, CD4 T cells.
Diphenhydramine Brand Name Generation Receptor Tx Adverse Effects Precautions
Benadryl, Sominex
• 1st generation. H1 inverse agonist
• Tx allergic rhinitis, sneezing, itching, urticaria, insomnia (produces sedation).
• Antimuscarinic (Ach) activity – treats motion sickness (NV, vertigo). Also has antiparkinsonian effects.
Adverse Effects
• CNS: confusion, dizziness, sedation
• Antimuscarinic effects: mydriasis (pupil dilation), xerostomia (dry mouth), reduced bronchial secretions, tachycardia, constipation, urinary retention
• Avoid in people w/ glaucoma due to mydriasis.
• Greatly metabolized by 2D6. Avoid in people w/ hepatic disease.
Cetirizine Brand Name Generation Receptor Tx Adverse Rxns Precautions
Zyrtec 2nd generation. H1 inverse agonist. • Tx allergic conditions • Less sedating than 1st gen. • Minimal antimuscarinic activity • Few adverse rxns. Xerostomia. • Do not exceed 5 mg / day if CrCL less than 31 mL / min.
Fexofenadine Brand Name Generation Receptor Tx Adverse Effects Precautions
Allegra 2nd generation. H1 inverse agonist. • Tx allergic conditions • No antimuscarinic effects • Few adverse rxns. • Avoid taking w/ fruit juices due to decreased absorption
Loratadine Brand Name Generation Receptor Tx Adverse Effects
Claritin 2nd generation. H1 inverse agonist. • Tx allergic conditions • Little / no antimuscarinic activity • Few adverse rxns.
Cimetidine
Receptor
Tx
Adverse Effects
H2 inverse agonist
• Tx for peptic ulcer disease, GERD, and dyspepsia (indigestion)
• May cause moderate / severe headaches and rare blood dyscrasia (neutropenia, leukopenia, etc)
Ergotamine Receptor Mechanism Tx Adverse Rxns Precautions
Serotonin partial agonist / antagonist. Causes vasoconstriction.
• Tx migraines
• Oxytocic agent → uterine contractions. Decreases postpartum bleeding via constriction.
• Metabolized by 3A4
Adverse rxns: NVD, xerostomia
• Ergotism: angina, asthenia, coronary vasospasm, cramps, myalgia, paresthesias, changes in HR; vasoconstriction may result in hypothermia or tissue necrosis
Precautions – avoid when vasoconstriction would cause problems
• CV: angina, arteriosclerosis, coronary artery disease, hypertension, peripheral vascular disease, Raynaud’s disease, thrombophlebitis, MI, stroke
• Hepatic disease, biliary tract disease, cholestasis
• Renal failure or impairment
• FDA Pregnancy Risk Category X (due to labor induction)
Sumatriptan Receptor Tx Adverse Rxns Precautions
Agonist at 5HT-1D autoreceptors (system inhibition) and 5HT-1B → vasoconstriction
• Tx migraines. Not for prophylaxis.
Adverse rxns
• Fatal CV events (coronary artery vasospasm, arrhythmias, MI)
• GI: NVD, vasospasm → bowel ischemia, abdominal pain, bloody diarrhea
Precautions – again, sxs that vasoconstriction would exacerbate.
• CV: angina, arteriosclerosis, arrhythmias, coronary artery disease, hypertension, peripheral vascular disease, Raynaud’s disease, thrombophlebitis, MI, stroke; evaluate CV function before prescribing
• Ischemic bowel disease
Thromboxane (TXA2)
Vasoconstriction and platelet aggregation. TP receptors.
Prostacyclin (PGI2)
Vasodilation and inhibited platelet aggregation. Physical antagonist of thromboxane. IP receptors.
PGD2
Smooth muscle contraction and inhibited platelet aggregation. DP receptors.
PGE2
Vasodilation, pain, fever, diuresis, immunomodulation. EP receptors.
PGF-a
Smooth muscle contraction: vasoconstriction, bronchoconstriction, uterine contraction. FP receptors.
LTB4 Released by Target Action Receptors
Released by and acts on neutrophils (autoregulation). → plasma exudation. BLT1 and BLT2 receptors.
Cysteinyl Leukotrienes Types Released by Action Receptors
Include LTC4, LTD4, and LTE4 – released by mast cells, basophils, and eosinophils. → bronchoconstriction, vasoconstriction, decreased blood flow, decreased contractility, and plasma exudation. CysLT1 and CysLT2 receptors.
Lipoxins
Types
Receptor
Action
LXA4 and LXB4 bind ALX receptors. Antagonize effects of leukotrienes (cause relaxation). Competitively inhibit CysLT1 receptors.
Systemic effects of cortisol
Stimulates GNG, immunosuppressive / anti-inflammatory effects. Also increased blood glucose and insulin, lipolysis and lipogenesis, stimulates protein / bone catabolism
Anti-inflammatory effects of corticosteroids
Increases?
Decreases?
- Increases: annexin 1 (inhibits PLA2), SLPI (secretory leukoprotease inhibitor), IL-10 (inhibits cytokines), and NFkB-inhibitor (nuclear factor kB, activates immune system).
- Decreases: COX-2, cytokines (IL-1, 2), chemokines (IL-8), CAMs, inflammatory enzymes
Hydrocortisone Action Tx Adverse Effects Precautions
Natural steroid hormone. Inhibits COX-2 expression, decreases cytokines, induces apoptosis of eosinophils.
• Tx anti-inflammatory: anaphylaxis, asthma, COPD, IBD, rheumatism, dermatoses
• DOC for glucocorticoid replacement therapy
• No adverse rxns w/ acute use. Prolonged use may result in dependence due to HPA suppression → hyperglycemia, immunosuppression, cataracts, glaucoma
• Precautions – abrupt DC of prolonged systemic therapy and Cushing’s Syndrome
Prednisone Action Tx Metabolism Adverse Rxns Precautions
Represses COX-2 expression, decreases cytokines, apoptosis of eosinophils
• Tx for autoimmune disorders (asthma, IBD, rheumatoid) and allograft rejection
• Prodrug of prenisolone (active)
Adverse Rxns
• CNS: headache, insomnia, vertigo, depression, anxiety, euphoria, personality changes, psychosis
• GI: NVD, anorexia, gastritis
• Cataracts
• Opportunistic infections (thrush, fungal infection in oral cavity due to immunosuppresion)
Precautions – Cushing’s, abrupt DC of prolonged therapy, cataracts
Fluticasone Mechanism Tx Adverse effects Precautions
Medium potency – same mechanism as others.
• Tx for dermatoses (psoriasis), allergic / nonallergic rhinitis, and asthma prevention only.
• Adverse effects: pruritis, burning, hypertrichosis (hair overgrowth), hoarseness, irritation, 2ndary infections (thrush)
• Precautions – Cushing’s, avoid DC for prolonged use, cataracts
Dexamethasone
Corticosteroid
Very strong anti-inflammatory effects.
Long duration
Aspirin Brand Name Action Tx Adverse Rnxs Precautions
Bayer
Irreversible COX inhibitor. 5x selective for COX-1
• Tx for thrombosis prevention – reduces risk of MI, stroke, TIA, etc. Other general NSAID actions as well.
• Antiplatelet effect lasts 8-10 days b/c new platelets have to be made.
• Metabolized in liver to salicylic acid
Adverse Rxns
• GI disturbances (2-30%): NVD, mucosal damage, bleeding, pain
• Tinnitus or hearing loss with high doses
• Hypersensitivity and anaphylactic reactions in pxs w/ chronic urticaria (20%), asthma (4%), or chronic rhinitis (1.5%)
• Sensitivity manifests as bronchospasm in asthmatics and is commonly associated with nasal polyps
• Aspirin Triad – aspirin hypersensitivity, asthma, and nasal polyps
• Precautions – Children Reye’s syndrome), renal disease, bleeding disorders
Ketorolac Action Tx Adverse Rxns Precautions
Competitive inhibitor of COX. 100x selective for COX-1.
• Short-term use as strong analgesic (opioid level) following surgery
• 90% excretion in urine
Adverse rxns:
• CNS: headaches, dizziness, drowsiness
• GI: NVD, mucosal damage, gastric bleeding, abdominal pain
• Precautions – salicylate sensitivity, aspirin triad, CrCL less than 30 mL / min
Indomethacin Action Tx Adverse Rxns Precautions
Competitive inhibitor of COX. 3-5x selective for COX-1.
• Accelerates closure of ductus arteriosus in premature infants. Duct normally maintained by prostaglandins, which decrease after normal birth.
• Other normal anti-inflammatory effects.
• Indole group may effect serotonin → CNS problems
Adverse rxns:
• CNS: headache (>10%), dizziness, fatigue, depression, tremor, ataxia
• GI: VND, mucoal damage, etc.
• Precautions – salicylate sensitivity, aspirin triad, CNS disorders, Pregnancy Risk Category D in 3rd trimester
Naproxen Brand Name Action Tx Adverse Rxns Precautions
Aleve
Competitive inhibitor of COX. 3-5x selective for COX-1.
• Better for lower back pain that other NSAIDs.
• Long duration of action due to long half-life
Adverse Effects
• GI: risk of upper GI bleeding is double that of OTC ibuprofen
• DERM: rashes, urticaria, alopecia (hair loss)
Precautions: salicylate sensitivity, aspirin triad
Meloxicam Action Tx Adverse Rxns Precautions
Competitive inhibitor of COX. 10x selective for COX-2.
• Used for Rheumatoid and osteoarthritis
• Good choice if px needs chronic NSAID use (due to COX-2 selectivity)
• Adverse Rxns: GI (pain, dyspepsia, nausea)
• Precautions: salicylate sensitivity, aspirin triad, normal others
Celecoxib Brand Name Action Adverse Rxns Precautions
Celebrex
Competitive inhibitor of COX. 10-20x selective for COX-2.
• First FDA-approved selective COX-2 inhibitor.
• Adverse Rxns: GI, dizziness, rash
• Precautions: same as others
Diclofenac Action Metabolism Adverse Rxns Precautions
Competitive inhibitor of COX. 10-20x selective for COX-2.
• Metabolized by CYP2C9 followed by glucuronidation / sulfation
Adverse rxns
• GI: upset stomach, heartburn, bleeding, ulceration, perforation, elevated LFTs
• Renal: decreased blood flow and GFR. If balance is shifted toward thromboxane, vasoconstriction may occur → renal damage.
• Precautions – same as others. Mainly focus on hepatic disease.
Acetaminophen Brand Name Action Tx Limit Metabolism Antidote Adverse Rxns Precautions
Tylenol
Competitive COX inhibitor (only in CNS). Binds to cannabinoid receptors in spinal cord.
• Analgesic and antipyretic, but NO anti-inflammatory / platelet effects
• Good for pxs who can’t use aspirin (pxs w/ clotting disorders or triad)
• Do not exceed 4g / day
• Metabolized by liver. Most undergoes glucuronidation or sulfation, but 10-15% converted to reactive hepatotoxic metabolites by CYP enzymes. Intermediates react w/ sylfydryls → protein interaction → cell death.
• Antidote is N-acetyl cysteine, which has sulfhydryls and acts as “decoy” to prevent toxic intermediates from forming.
Adverse rxns
• Skin: rash, pruritis, urticaria
• GI disturbances (high dose): NV, anorexia, and abdominal pain usually occur within 2-3 hr after ingestion of toxic doses
• Hepatotoxicity; in acute overdose, 2-3 days pass before maximum liver damage becomes apparent.
• Renal tubule necrosis with high or chronic doses
• Precautions: alcoholism, hepatic disease, renal disease, tobacco smoking (CYP inducer → more reactive metabolites), salicylate sensitivity
Alprostadil Action Tx Adverse Rxns Precautions
Synthetic PGE1. Agonist at EP receptors → cAMP → vasodilation
• Tx for erectile dysfunction (EP receptors for ED) and maintains patency of ductus arteriosus
• Injected into penis
Adverse rxns
• ED: penile pain, prolonged erection, penile fibrosis
• PEDS: fever, apnea, flushing
Precautions – follow up w/ penis exam, use lowest possible dose w/ infants
Latanoprost Action Tx Metabolism Adverse Effects Precautions
Synthetic PGF2a. Agonist at FP receptor
• Tx reduces elevated IOP in pxs w/ open-angle glaucoma. Increases outflow.
• Prodrug – esterases in cornea hydrolyze to active form.
• Adverse effects: blurred vision, burning, itching, increased iris pigmentation (melanin), thicker eyelashes.
• Precautions – intraocular inflammation, remove contacts for 15 min
Zileuton Action / Types Tx Metabolism Adverse Effects Precautions
5-LOX inhibitor (decreases LTB4, LTC4, LTD4, and LTE4). Inhibits leukocyte migration, aggregation, adhesion, capillary permeability, and smooth muscle contractions
• Used for prophylaxis asthma treatment (NOT bronchodilator)
• Substrate for 1A2, 2C9, and 3A4.
• Adverse Rxns: dyspepsia, elevated LFTs
• Precautions – liver disease (do LFTs before and after tx), alcoholism, smoking, age
Zafirlukast Action Tx Adverse Effects Precautions
Antagonist at G protein cysteinyl leukotriene receptors (CysLT1) in airway smooth muscle, mast cells, and neutrophils.
• Prophylaxis of asthma (NOT bronchodilator). Inhibits bronchoconstriction, edema, and mucous.
• Metabolized by 3A4 and 2C9
• Few adverse rxns. Rare elevated LFTs.
• Precautions – hepatic disease
Montelukast Action Tx Excretion Adverse Rxns Precautions
CysLT1 antagonist in airway smooth muscle, mast cells, neutrophils
• Tx allergic rhinitis and asthma prophylaxis (NOT bronchodilator). Inhibits bronchoconstriction, edema, and mucous secretion
• 3A4 and 2C9 metabolism. Excreted through bile.
• Few adverse rxns
• Precautions – liver disease, alcoholism, smoking, age
• Person w/ impaired renal function might be better off w/ montelukast than zafirlukast
Ibuprofin
Action
Adverse Rxns
Precautions
Competitive inhibitor of COX. 2x selective for COX-1.
Adverse Rxns:
CNS - dizziness, heachache, nervousness
GI - NVD, damage to mucosa, gastric bleeding, abdominal pain
Rash
Tinnitus
Blurred vision
Precautions: salicylate sensitivity, aspirin triad, normal others (heart, hepatic, GI bleeding, bleeding disorders.
Misoprostol Action Tx Adverse Effects Precautions
Agonist at EP receptors on parietal cells –> low cAMP –> decreases stomach acid secretion AND increases mucous / bicarb production. 2 fold.
Tx for gastric ulcers. Not as effective as H2 antagonists. May be used to counteract stomach bleeding w/ NSAIDS.
Also induces PG termination ( contractions and dilates cervix. Labor induction.
Adverse Effects: headache, diarrhea, pain, NV
Precautions: pregnancy risk category X
