-
Bile Acid Resins
- Decrease cholesterol absorption
- Cholestyramine, colestipol
- Anion exchange resins
- High non-compliance - like sand, tastes bad, steatorrhea, anal fissures, bloating
-
Cholesterol Transport inhibitor
- Zetia (Ezetimibe)
- Little effect on HDL
- Blocks chol absorption in small intestine
- Side effects - few, elevates transam's
-
Statins
- HMG CoA reductase inhibitors
- Well tol, but small chance of rhabdomyolysis (didn't see in clinical trials)
- Newer are more effective (eg crestor)
-
Niacin
- Enhances lipoprotein lipase in muscle
- #1 for increase HDL
- x: pg
- :( flushing, pruritis, (aspirin helps), n/v, hyperurecemia, hyperglycemia, hepatotox
-
Niacinamide
- Doesn't alter HDL/LDL!
- Does cause flushing like niacin
-
Fibric acid derivative
- Gemfibrozil/Clifibrate
- #1 for decreasing triglycerides
- :( dyspepsia, gallstones, myopathy
-
Cholesterol combos
- Statin + bile acid resin :) timing issues
- Statin + fibric acid - increase myopathy
- Statin + niacin - inc AST/ALT, myosistis, rhabdomyolysis - eek
- Statin + Ezetimibe = Vytorin - bigger drop in chol, but does it matter...
-
Anti-thyroid meds
- Decrease peroxidase-mediated iodination of precursor (dec T3/T4)
- Methimazole (#1)
- Propylthiouracil (PTU) (inh periph deiodination)
- only for temporary use before surgery/radioactive tx
- Risks: aganulocytosis (sore throat/fever), hepatotox
-
Anti-androgens
- GnRH antagonist: cetrorelix, degarelix (Ganirelix - prostate ca)
- Ketoconazole, spironolactone
- Flutamine, bicalutamine, nilutamide (hursuitism in women)
- Finasteride (BPH, hair loss)
-
Flutamine, bicalutamine, nilutamide
Treats hursuitism in women
-
Finasteride
- Oral
- Treats BPH
- Treats hair loss (decreases male libido/sperm potency)
-
Calcitonin
- Can treat hypercalcemia
- Suppresses bone resorption by inhibiting osteoclasts
- Normally secreted by thyroid
- Rapid/short acting
-
Glucocorticoid bone effects
- Osteoporosis, especially long bone
- Antagonize Vitamin D mediated GI absorption of calcium and phosphate, partially block in kidney, enhance bone resorption, inhibit PTH activity
-
Estrogen effect on bone
- Estrogen R in bone, unknown function
- Adsorb to bone rendering bone resistant to hydrolysis
- (inc breast ca risk, ovarian ca risk)
-
Bisphosphonates
- Prophylaxis for osteoporosis
- :( erosive esophagitis (therefore not often given as pill)
- Fosamax (q-week) (not with food, must drink water and not lie down for an hour)
- Alendronate (strongest), etidronate, pamidronate
- Inhibit osteoclasts
- Used for Paget's disease
-
-
Insulin secretagogue
- Sulfonylureas: glyburide, glipizide, glimiperide
- SU - QD or BD
- Glinides: repaglinide, nateglinide
- Take with meals - better for elderly/people that skip meals
- :( Weight gain
- Act on R on beta cell, inc intracell Ca, inc insulin release
-
Biguanides: Metformin
- Acts on liver (a bit on skel m too)
- Reduces insulin resistance
- Decreases hepatic glucose production
- BID
- :( GI, lactic acidosis, so contraindicated in kidney failure
- Does not cause hypoglycemia
- First choice in tx!
-
Thiazolidinediones
- Troglitazone (liver tox)
- Rosiglitazone (inc risk MI)
- Pioglitazone :)
- Work on skel m, nuc R, inc mRNA for glucose transporter
- Takes a month to work
- :( excess fluid retention (contraind for HF pt)
-
a-Glucosidase Inhibitors
- Acarbose/Miglitol
- Delay carbohydrate absorption at intestinal brush border by inhibiting disaccaride break down
- Still absorb as much carbs, just over more time
- Take before every meal
- :( flatulence, liver enzyme elevation(rare)
-
Combination therapy with diabetes
- Metformin first
- When A1C >7%, add
- Sulfonylurea + metformin
- Sulfonylurea + glitazone
- May require insulin after years of increased resistance
-
GLP-1
- Released from L cells in ileum/colon
- Stimulates insulin release (glc dep)
- Inhibits glucagon release (glucose dep)
- Inhibits gastric emptying - induces satiety
- Rapidly degraded by DPP-4
-
GIP
- Released from K cells in duodenum
- Stim insulin
- Rapidly degraded by DPP-4
-
DPP-4 inhibitors
- Increases GLP-1 and GIP
- Increases Insulin, dec glucagon, inc satiety
- Sitagliptin, Saxagliptin, Linagliptin B cells give limited amount of insulin, so drug doesn't cause hypoglycemia
-
Insulin
- NPH - insoluble
- Analogs - aspart, glulisine, lispro, glargine, detemir (longer lasting)
- Premix for immediate and long lasting together
-
Rapid acting Insulin Analogues
- Aspart, Glulisine, Lispro
- Limited self-aggregation (monomers act faster)
- 4-6 hours
- Better, bc mimic normal insulin release profile when taken with meals
-
Slow acting insulin analogues
-
Heparin
- Anticoagulant
- "unfractionated heparin" Lots of variability in solution
- Acts on 2a and 10a
- Short acting, infusion (for in-pt)
- Problems from misdosing
- From porcine/bovine intestine
- Monitor with aPTT
- :( HAT heparin associated thrombocytopenia (<7d, temp); HIT heparin induced thrombocytopenia (more severe, 7-14days, PLT <150, treat with direct thrombin inhibitor and warfarin)
- Safe in pg
- Reverse with protamine
-
LMWH
- Low molecular weight heparin
- Only inhibits 10a
- Enoxaparin, Dalteparin, Tinzaparin
- Less HIT, less side effects
- Indicated: DVT, PE, acute MI, TIA(stroke)
- Contraindic: kidney disease, recent surgery unless inpt, bleeding, dissecting aortic aneurym
- Safe in pg
-
Direct Thrombin Inhibitors
- Lepirudin, Argatroban, Bivalirudin
- L(from leeches, not ideal)
- A(adjust for hepatic dysf, use for HIT/coronary angioplasty)
- B(coronary angioplasty)
- :( bleeding
-
Warfarin
- Inhibits F2,7,9,10. analog for vitamin K
- Onset = 3-5 days
- Half life F2 (60 hours) ergo slower acting
- :( bleeding
- Interacts with CYP450 drugs
- Transient protein C deficiency can be induced (---> dermal vascular thrombosis/skin necrosis)
- Contraind: pg, bleeding, aneurysm, recent surgery, hypersensitivity
- Reverse with vitamin K
-
Thrombin inhibitor
- Dabigatran
- No monitoring (better than warfarin)
- Oral Prodrug
-
Anti-10a inhibitors
- Rivaroxaban, Apixaban, Fondiparinux (diff structure)
- Like LMWhep
- Inhibit CYP450
- No blood monitoring needed
- No reversing agent
-
Fibrinolytic drugs (thrombolytics)
- Streptokinase
- Recombinant tPA (alteplase, reteplase, tenecteplase)
- Urokinase
- Anistreplase
- Timing is important to prevent intracerebral bleed, esp if pt >75
-
Recombinant tissue-plasminiongen activator (tPA)
- Alteplase=tPA (widely used, DVT, PE, MI, TIA)
- -better than streptokinase bc no allergic rxn, more specific to fibrin, shorter half life
- Reteplase, tenecteplase (STEMI)
- Potentiates plasminogen to plasmin conversion (which breaks down clot)
-
Antistreplase
Streptokinase and plasminogen as complex
-
Plasminogen Inhibitor
- Aminocaproic acid, Tranexamic acid
- Bleeding emergencies
-
Antiplatelet drugs
- Aspirin
- ADP antagonists (Clopidogrel, ticlopidine, prasugrel)
- Dipyridamole
- Glycoprotein IIb/IIIa R inh (Abciximab, eptifibatide, tirofiban)
-
Aspirin (Acetylsalicylic acid)
- Irrev inhibits COX-1 (low TXA2)
- Effects last 5 days after d/c drug
- :( GI bleed, OD=salicylism (vomiting, tinnitus, dizziness)
- Uses: pts with iscemic heart disease/stroke, angina prophylaxis, MI tx, TIA tx
-
ADP Inh/P2Y12 inh
- Interferes with ADP binding to R --> inh GPIIb/IIIa act
- Can be alternatives to aspirin, used after coronary-stent procedure
- Works for a week after d/c
- :( GI bleed, neutropenia/purpura(ticlopidine-immune)
-
Dipyridamole
- Vasodilator
- Increased intracellular cAMP, inhibiting PDE (dec TXA1)
- Potentiates PGI2 to dec platelet adhesion
- Uses - w/ warfarin, after TIA
-
GPIIb/IIIa R antagonist
- Abciximab
- -(for cath lab) Long acting, acts on VWF too, given w hep or aspirin too
- Eptifibatide (for cath lab or non-invasive management)
- Tirofiban
- Acute coronary event, unstable angina
-
SERMs: Selective Estrogen R Modulators
- Raloxifene, Tamoxifen, Toremifene
- Nonsteroidal
- Agonist in bone/endometrium
- Antagonist in breast
- :( hot flashes, n/v, vaginal discharge, thrombosis, endometrial cancer
- Bones okay :)
-
Tamoxifen
- Combines SERM/R, translocates to nucleus, Inhibits DNA syn
- Increase inhibitory growth F, dec growth F
- Oral
- Uses - tx metastatic breast ca, aduvant tx, prophylactic in high risk pts
- CYP2D6 biotransformation to metabolite active = endoxifen
-
Raloxifene
- Equal to tamoxifene in trials, but not as popular
- lower incidence of thrombosis
-
Toremifene
- Like tamoxifene
- Not popular
- Lower estrogenic/anti-estrogenic ratio
-
Aromatase inhibitors
- Non-steroidal - Anastrozole, Letrozle
- Steroidal - exemestane (irrev)
- Inh androstenedione to estrone, testosterone to estradiol
- Tx of POSTmenopausal only bc only act on peripheral production of estrogen
- (in premenopausal F, would stim ovaries to make more)
- :( arthralgia/myalgia, fatigue, osteopenia, osteoporosis (use bisphosphonate), hot flashes, vag dryness
-
Premenopausal breast ca treatment
- Early:
- Chemo then SERM (tamoxifen)
- Ovarian ablation
- Tamoxifen alone
- Advanced:
- Tamoxifen
- Ovarian ablation
- chemo + tamoxifen
NEVER give chemo and hormone tx at same time
-
Postmenopausal breast ca treatment
- Tamoxifen OR aromatase inhibitor
- NEVER give chemo and hormone tx at same time
-
Gonadotropin Releasing Hormone Agonist (GnRHag or LH/FSHag)
- Goserelin, Histrelin, Leuprolide, Triptorelin
- First- sex steroid spikes, then negative feedback takes over
- Uses - prostrate/breast ca
- Results - women to post menopausal estrogen levels, men to castration testosterone levels
- All long acting
- :( hot flashes, men gynecomastia/breast tenderness, osteoporosis long term, TUMOR FLARE
-
Goserelin
- GnRH ag
- subQ q1-3mo
- :( HA, vaginitis
-
Histrelin
- GnRH ag
- Implant (q12mo)
- :( urinary retention
-
Leuprolide
- GnRH ag
- Depot injections (q1-3mo)
-
-
Anti-androgenic agents
- Nilutamide, bicalutamide, flutamide
- Nonsteroidal. bind androgen R, competitievely inh dhTestosterone and testosterone
- Treat tumor flare from GnRH agonist and hot flashes
- Combined tx with GnRH agonist for ca
-
Ketoconazole
- Antifungal which inhibits 5% testosterone production
- Last line androgen blockade
-
Abiraterone
- Anti-androgen
- Tx metastatic castration-resisant prostate ca
- Irrev inh CYP17 which processes androgens
- :( thrombocytopenia
-
Fulvestrant
- Estrogen antagonist
- Second line agents
- Competitively binds estrogen R - works like SERM but antag only
- :( hot flashes, n, weakness
-
Degarelix
- LHRH antagonist
- Dec testosterone
- No tumor flare
- :( hot flashes, injection site rxn
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