Drug List Block 2 Reversed Flashcards
Synthetic analog of PGE2
Therapeutic uses:
- Cervical ripening
- Terminating early pregnancy/abortion
Mechanism:
1. Activation of collagenase also relaxing cervical smooth muscle EP4 receptor subtype (for cervical ripening)
- Uterine contractions via EP1/3 receptors
SE:
GI related (nausea, vomiting, diarrhea)
Fever
Uterine rupture: contraindicated in women having history fo cesarean section or other uterine surgery
Dinoprostone
Analog of PGF2alpha
Therapeutic use:
- Termination of pregnancy in 2nd trimester
- Control postpartum hemorrhage that is not responding to conventional treatment methods
Mechanism:
- Stimulates uterine contractility by action at FP receptors
- Postpartum, the drug cause myometrial contractions via FP receptors. This provides hemostasis at the stie of placenta formation
SE: GI related (nausea, vomiting, diarrhea) Fever Uterine rupture (contraindicated in women having history of cesarean section or other uterine surgery) Rare case of bronchoconstrictino
Carboprost
PGE1 analog
Therapeutic use:
Replacement therapy for prevention of ulcers caused by long term NSAIDS
Mechanism:
Suppresses gastric acid secretion by stimulating EP3 receptors on parietal cells; causes decrease in cAMP
Increase mucin and bicarbonate secretion
Increase mucosal blood flow
SE: Diarrhea-common and contraindicated in pregnancy
*(Misoprostol used with methotrexate or mifepristone for termination of early pregnancy)
Misoprostol
PGE1
Use:
- Impotence/ED
- Maintenance of patent ductus arteriosus
Mechanism of action
- Increase in cAMP which relaxes smooth muscle fo corpus cavernosum
- cAMP mediated relaxation of ductus arteriosus smooth muscle
SE:
1. Pain at site of injection (reason for intra-urethral formulation)
Priapism: prolonged erection
2. Apnea in 10% of neonates,
Alprostadil
PGI2 agonist
Therapeutic use: Primary pulmonary hypertension.
Mechanism: cAMP mediated dilation of pulmonary artery vascular smooth muscle
SE: Nausea, vomiting, headache, flushing
Epoprostenol
Prostaglandin PGF2alpha analog
Uses: glaucoma and eyelash hypotrichosis
Mechanism: Increases outflow of aqueous humor and Increases the percent and duration of hairs in the growth phase.
Pharmacology: administered as opthalmic drops
SE: Eye redness, itching, permanent changes in eye color (increased brown pigment), eyelid skin; may increase length and number of eyelashes
Bimatoprost
Mechanism: Blocks 11 beta hydroxylation so synthesis is stopped at 11-desoxycortisol. Does not inhibit ACTH release, so plasma ACTH increases stimulating synthesis and excretion of 17-hydroxycorticoids as 11-desoxycortisol.
Used as a diagnostic test
Metyrapone
Competitive antagonist at progesterone and glucocorticoid receptors
Progesterone antagonist- Termination of pregnancy
Glucocorticoid antagonist- Treat cushing syndrome etc.
Mifepristone
Competitive antagonists at mineralcorticoid receptor
Uses: diuretics, cardiac fibrosis/hypertrophy, HTN
Spironolactone
Competitive antagonists at mineralcorticoid receptor
Uses: diuretics, cardiac fibrosis/hypertrophy, HTN
Eplerenone
Progesterone and Mineralocorticoid and Androgen receptor antagonist
Mineralcorticoid antagonist-diuretic, antagonizes the salt retaining effects of estrogen
Progesterone Agonist- Used with estrogen to suppress ovulation and as hormone replacement therapy in post menopausal women
Androgen receptor antagonist
Drospirenone
Responses: 1. Lymphocytopenia and monocytopenia, Prevent neutrophil adherence to endothelium, Inhibit action of chemotactic factors
2. Interferes with macrophage antigen processing, blocks the actions of lymphokines, inhibits binding to Fc receptors
Toxicity: 1. Suppression of adrenal-pituitary axis (acute adrenal insufficiency on abrupt withdrawal
2. Cushing’s syndrome
Contraindication: in presence of existing infection
Uses: in combination with other drugs in autoimmune diseases and to prevent graft rejection
Prednisolone
Mechanism: Metabolized to 6-mercaptopurine, a purine antimetabolite that inhibits purine biosynthesis thereby inhibitng DNA synthesis, inhibits De novo AND salvage pathways.
Pharmacology: Orally active
Used to inhibit rejection of transplanted organs and some autoimmune diseases such as rheumatoid arthritis
SE: Bone marrow depression, GI and hepatic toxicity
Azathioprine
Mechanism: alkylating agent that cross links DNA to kill replicating and nonreplicating cells.
Pharmacology: Toxic effect more pronounced on B cells so more effective in suppressing humoral immunity.
Orally active.
Use: treatment of autoimmune diseases in combination with other drugs.
NOT EFFECTIVE IN PREVENTING GRAFT REJECTION
SE: Bone marrow depression
Cyclophosphamide
Mechanism: inhibitor of dihydrofolate reductase, inhibits folate dependent steps in purine synthesis, inhibiting DNA synthesis
Use: treat autoimmune diseases
SE: Hepatic toxicity
Methotrexate
Mechanism: Lymphocyte selective immunosuppressant by inhibiting IMP dehydrogenase (necessary for de novo purine synthesis w no effect on salvage pathway). Lymphocytes cannot make GMP via salvage. More selective than AZA or methotrexate but equally effective
Pharmacology: Orally active
Used with cyclosporine and corticosteroids to prevent renal allograft rejection (allowing lower dose of cyclosporine)
Use: treat autoimmune diseases– rheumatoid arthritis and refractory psoriasis
Contraindications: Active GI disease, reduced renal function and infections. Also pregnancy (loss and congenital malformations)
SE: infection, leukopenia, anemia
Mycophenolate Mofetil
Mechanism: binds to cellular receptor Cyclophilin and inhibits calcineurin (a calcium dependent phosphatase), blocking activation of transcription factor NFAT necessary for IL 2 production. Blocks T cell helper function.
Pharmacology: Orally active
Use: Prevent rejection of transplanted organs. some autoimmune diseases. more effective than other agents used with fewer side effects
SE: nephrotoxicity. Hepatotoxicity
Cyclosporine
Mechanism: binds FK binding protein a cyclophilin related protein, same mechanism as cyclosporine. Spectrum is same but 50-100 more potent
SE: less nephro and hepatotoxicity
Tacrolimus
Mechanism: Inhibits T cell activaiton and proliferation downstream of IL-2. Binds FKBP-12, binds and inhibits mTOR (not calcineurin), this mTOR is a kinase involved in cell cycle progression blocking G1->S transition
Use: Same as cyclosporine. Coating of cardiac stents.
Sirolimus
Mechanism: Irreversible inhibitor of cyclooxygenase 1 and 2.
Uses: Cancer? CV disease (low dose) Fever, pain, (intermediate dose) Chronic inflammatory disease/rheumatoid arthritis (high dose)
SE: Typical NSAIDs side effects + Salicylism + Reye’s Syndrome
Pharmacology:
Non COX inhibition effects (1. Uric acid excretion 2. CNS 3. Respiration)
- At low dose decrease uric acid secretion. at high dose increase uric acid excretion.
- CNS (b/c crosses BBB) delirium psychoses, nausea, vomiting.
- Respiration (Direct stim of respiratory center to increase RR, leading to respiratory alkalosis, compensated by a renal excretion of bicarbonate.
- Salicylism
- Reye’s syndrome (liver failure and death related to viral epidemics
Acetylsalicylic Acid/Aspirin
Mechanism: Reversible inhibitor of COX 1 and COX 2. Naproxen has a much longer plasma half life (14 hr vs. 2) than ibuprofen
Uses:
Both: Rheumatoid disorders (including juvenile rheumatoid arthritis), osteoarthritis, mild-to-moderate pain, dysmenorrhea, fever,
Ibuprofen: Inflammatory diseases, IV preparation to induce closure of PDA in premature infants less than 32 wk gestational age when usual treatments ineffective.
Naproxen: manage ankylosing spondylitis, acute gout/bursitis/tendonitis,
SE: Less GI effects than Aspirin
Ibuprofen and Naproxen
Mechanism: Reversible inhibitor of COX 1 and COX 2
Uses:
gout
preterm labor (investigational)
IV form used for closure of patent ductus arteriosus in neonates,
not routinely used to treat pain or fever.
SE: Frequent adverse rxns, CNS severe frontal headache, better tolerated if given at night
Indomethacin
Mechanism: Reversible inhibitor of COX 1 and COX 2
Uses:
Alternative for opioid analgesics in treatment of post-operative pain (short term, and much more effective for pain than inflammation)
SE: Serious adverse effects
Ketorolac
Mechanism: Active metabolite (6methoxy2naphthylacetic acid) is reversible inhibitor of COX2 moreso than COX-1.
Uses:
Osteoarthritis
Rheumatoid arthritis
SE: Well tolerated with less GI effects
Nabumetone
Mechanism: Reversible inhibitor of COX 1 and COX 2. SUPER LONG HALF LIFE plasma T1/2 50 hours
Uses:
Symptomatic treatment of acute and chronic rheumatoid arthritis and osteoarthritis, advantage in osteoarthritis treatment because of LONG HALF LIFE.
SE: GI toxicity
Piroxicam
Mechanism: 5-aminosalicylic acid (mesalamine) active component linked to sulfapyridine (a sulfa antibiotic) by azo bond (which prevents absorption in upper GI tract). NOT CYCLOOXYGENASE INHIBITION. Possibly inhibition of IL-1, TNFalpha, lipoxygenase pathway, scavenging of free radicals oxidants, inhibition of NF-kappaB.
Uses:
Mild or moderately active ulcerative colitis (b/c of mesalamine)
Rheumatoid arthritis and ankylosing spondylitis (b/c of sulfapyridine)
SE:
High % for b/c sulfa moiety
Allergic rxns (rash, fever, hepatitis, pneumonitis, hemolytic anemia, bone marrow suppression)
Decreases number and motility of sperm
Therapeutic application: mild or moderately active ulcerative colitis, rheumatoid arthritis, and ankylosing spondylitis
Sulfasalazine
Mechanism: COX-2 selective inhibition. Metabolized by CYP450 2C9
Uses: Rheumatoid arthritis and osteoarthritis Primary dysmenorrheal Management of acute pain reduce # of intestinal polyps in familial adenomatous polyposis (COX2 contributory to certain cancers)
SE:
Hypersensitivity
Increase risk in GI irritation, ulceration, bleeding
Increased risk of adverse CV thrombotic events
Anemia (rare)
Contraindications: Sulfonamide toxicity Prior NSAID hypersensitivity CV risk factors/disease GI disease Coronary artery bypass graft surgery CYP2C9 deficiency
Celecoxib
Mechanism: No aff for COX1 or COX2 active site. inhibits reduction of COX to peroxidase form, brain selective? COX3?
Metabolized partially by liver microsomal system (CYP2E1, CYP1A2, CYP3A4), but mostly by glucoronidation and sulfation (95%)
Uses:
Treatment of mild-to-moderate pain and fever; does not have antirheumatic or anti-inflammatory effects
SE:
Well tolerated with little to no GI issues at normal doses. But with excessive use results in hepatic toxicity… evidenced by elevated liver enzymes like aminotransferase.
NAPQI (N-acetyl-p-benzoquinoneimine toxicity if glutathione reduced), covalently binds amino acids in proteins and enzymes.
N-acetylcysteine used to replenish glutathione stores to manage toxicity.
Contraindication:
Ethanol use, as alcohol induces CYP450 (producing NAPQI) and depletes glutathione.
Acetaminophen
