Dutta last quiz Flashcards
What is renin
Renin pathway drug
- Often described as active renin to differentiate from its inactive precursor Prorenin
- Aliskiren- first and only Renin Inhibitor in use
Aliskerin
First?
Synthetic compound having _______
Indicated for the treatment of? Either ____ or ___
___ absorbed, but ____ is low, high ___ decreases absorption
Half-life?
90% eliminated? Other part?
Adverse effects?
- First and only renin inhibitor, directly inhibits renin and prevents formation of Ang I
- Chiral centers
- HTN, as monotherapy or in combination
- Orally absorbed, but absolute bioavailability is low, high fat meals decrease absorption
- Half life is 44 hours
- 90% unchanged in feces, rest metabolized by CYP3A4
- AEs
- Diarrhea and other GI, Hyperkalemia, headache, Dizziness, rash
- ARBs are contraindicated during pregnancy. Co-administration with Ibesartan reduces the plasma levels and efficacy of Aliskiren, might require dose-adjustment
Inflammation
Acute
Chronic
Rheumatic disease RA, OA, Gout Symptoms
Mediators of inflammation
- Acute- involvesvascular response neutrophiles and/or mast cells
- Chronic- Mononuclear cells, macrophages, lymphocytes, plasma cells, proliferation of connective tissuefibroblasts
- Redness, heat, swelling, stiffness, and pain
- RA- Unknown initiation factor causes production of antigenic IgG (rheumatoid factor); IgG activates compliment system leukocytes
- Mediators- Oxygen radicals, prostaglandins, Leukotrienes, Kinins, Interleukins I
Classes of Drugs NSAIDs
Classicals?
Newer?
MOA?
Therapy effect?
Toxicity?
- Salicylaes and other nonsteroidal acidic agents
- COX-2 inhibitors
- Inhibition of prostaglandin biosynthesis
- Analgesic and Antiinflammatory
- Relatively safe
- NSAIDs dont stop the underlying disease
Disease modifying Antirheumatic Drugs (DMARDs)
Structurally diverse compounds
MOA?
Therapy?
Toxicity?
- Anticancer agents, Immunosupressants, antimalarials, gold compounds
- Many with unknown MOA
- No immediate analgesic or anti-inflammatory effect, slow acting, can take months to produce therapeutic effect
- Can cause severe SEs
- Can retard or stop the progression of the disease
Inflammation mediators
Eicosanoids?
Pharm properties?
- Prostaglandins, Thromboxane, Prostacyclin, Leukotrienes
- Potent regulators of normal function: BP, Renal(blood flow), Platelet aggregation, Gastric secretion, Labor
- Pathological: Pain, Fever, Inflammation
Prostanoid Biosynth flow chart
COX presents of Fe2+ and O2
Prostaglandin, Thromboxane, Prostacyclin contd?
Thromboxanes and Aspirin?
COX-1 and COX-2 Structurally similar enzymes
Properties of selected Prostanoids
Prostaglandin analogues in therapeutics?
- Dinoprostone PGE2- Induction of labor
- Onset 10 minutes
- Increase Uterine contraction
- Frequency, amplitude, Cervical ripening
- SEs- fever, nausea, allergic rxn, Cramping
- Alprostadil (PGE1)
- Vasodilator, Increases blood flow
- Maintaining an open ductus arteriosus in newborns with congenital defects that restrict pulmonary or systemic blood flow until surgery can be performed
- Male erectile dysfunction: Penile suppository, or, injected directly into penis
- Onset 2-25 minutes lasts for an hour
Other prostaglandin analogues in therapeutics?
- Misoprostol:
- Prevention/treatment of NSAID-induced gastric ulcers
- Orally active
- Methyl ester increases antisecretory effect, increases duration of action, conversion to acid (active)
- Increase GI mucosal and bicarb formation: Decreasing acid secretion, blocks NSAID induced GI bleeding
- SE:Diarrhea
- Contraindication in pregnant women
- Labor induction, also used vaginal in combination with methotrexate for termination of early stage pregnancy
- Latanaprost
- Structurally modified PDF analog
- Reduces intraocular pressure by increasing the outflow of aqueous humor
- Available as ophthalmic solution for glaucoma treatment
- Causes growth and darkening of existing eyelashes!
