Biochemistry Medications (Chapters 27-37)
§ Orlistat/ Xenical – Drug that inhibits pancreatic lipase and gastric lipase, therefore decreases absorption of about 30% of dietary fats. Leads to weight loss.
§ Olestra – Artificial fat substitute similar to TAG, but using a sucrose polymer instead of glycerol for the backbone. Not digested or absorbed and passes through system. Excess use can lead to fat-soluble vitamin deficiency.
§ Anti-Inflammatory Glucocorticoids – Inhibit prostaglandin synthesis by blocking PhospholipaseA2, thus cannot produce arachidonic acid from membrane phospholipids.
§ NSAIDs – Nonsteroidal anti-inflammatory drugs (Generally block primarily COX1 vs. COX2, therefore some anti-inflammatory action, but also causes stomach irritation).
o Aspirin / ASA / Acetyl Salicylic Acid – Covalently binds to Cyclooxygenase reaction, irreversibly inhibits.
o Indomethacin / Ibuprofen – Competitive inhibitor of COX reaction
§ Zyflo – Blocks Lipooxygenase reaction, thus inhibiting leukotriene synthesis.
§ Accolate – Blocks leukotriene receptors.
§ Celebrex – COX2 specific inhibitor, thus decreases pain, inflammation.
§ Statins – Block HMG-CoA Reductase, thus decreasing cholesterol synthesis.
§ Oral Bile Salts – Primarily decrease risk of gallstone formation.
§ Cholestyramine – Binds bile salts and lowers cholesterol (increases risk of gallstone formation).
§ Caffeine / Theophylline (Methylxanthines) – Inhibit phosphodiesterase, thus sustains elevated cAMP levels.
§ Dinitrophenol – Respiratory chain uncoupler. DNP binds protons and enters the mitochondrial matrix (due to its hydrophobicity) thus diminishing the pH gradient. The respiratory chain works hard to correct this loss of the gradient, but is unsuccessful and heat is generated from the energy. ( Respiratory rate, TCA/PDH, ¯ Lactate, ¯ ATP synthesis)
§ Oligomycin – Antibiotic that binds the Fo proton channel of the ATP synthase complex and blocks its activity. This prevents the use of the pH gradient and consequently backs up the resp. chain. (¯ Respiratory rate, ¯ TCA/PDH, Lactate, ¯ ATP synthesis)
§ NADH-Q Complex I Inhibitor – diminishes the flow of electrons through complex I. (¯ Respiratory rate, ¯ TCA/PDH, Lactate, ¯ ATP synthesis (still some via complex II))
§ Cyanide – While not a medication, it blocks the respiratory chain at complex 4, and leads to death. (blocks cytochrome oxidase)
Biochemistry Medications (Chapters 38-52)
§ Sulfonylureas (glyburide/glipizide) – drugs that aid diabetic patients who have sluggish insulin release by stimulating calcium influx (by closing potassium channels) that stimulates insulin release. Bypasses the glucose pathway.
§ Thiazolidinediones (ACTOS) – increases insulin sensitivity. Increases adiponectin and decreases resisten.
§ Biguanides (Glucophage/Metformin) – Increases insulin sensitivity, decreases hepatic gluconeogenesis and intestinal glucose absorption.
§ α-glucosidase Inhibitors – block digestion of oligosaccharides and disaccharides.
§ Captopril (Lisinopril) – Inhibits angiotensin I to angiotensin II converstion in the lungs by blocking Angiotensin converting enzyme (ACE) in pulmonary circulation. (ACE Inhibitor).
§ Sartans – block Angiotensin II receptors, therefore decrease aldosterone release, sodium retention, blood pressure.
§ Spironolactone – aldosterone receptor antagonist, therefore decreased sodium retention, elevated aldosterone. (mimics aldosterone resisitence). Potassium sparing diuretic.
§ Atrial Natriuretic Peptide – counters angiotensin II effects on aldosterone release. Lowers renin release and blood pressure.
§ Flutamide – 5α-Reductase-2 inhibitor, used to treat benign prostatic hyperplasia.
§ Phytoestrogens – chemicals derived from plant sources that may be beneficial because of estrogen like effects. Possible value in post-menopausal women in conjunction with other therapies. May also lead to decreased endogenous estrogen synthesis (down-side).
§ Bromocryptine – long acting dopamine receptor agonist that boots tonic inhibition of prolactin release. Use to treat prolactinomas.