Flashcards in Drugs With Important Actions On Blood, Inflammation, & Gout Deck (74):
What is the only indication for iron administration?
Prevention or treatment of iron deficiency anemia.
How is iron deficiency anemia treated (pharmacologically)?
By dietary ferrous iron supplement :
1. Ferrous sulfate
2. Ferrous gluconate
3. Ferrous fumarate
By parenteral iron preparations :
1. Iron dextran
2. Sodium ferric gluconate complex
3. Iron sucrose
What is the anemia that iron is contraindicated ?
In hemolytic anemia.
What are the signs and symptoms of acute iron toxicity?
1. Necrotizing gastroenteritis
3. Metabolic acidosis
What is the treatment of acute iron intoxication?
1. Removal of unabsorbed tablets from the gut.
2. Correction of acid-base and electrolyte abnormalities.
3. Deferoxamine : chelation.
What is the treatment of chronic iron toxicity?
1. Usually phlebotomy (for hereditary hemochromatosis).
2. Deferasirox - chelation for frequent transfusions.
What are the two available forms of vitamin B12?
Hydroxocobalamin and cyanocobalamin.
Mention some important erythropoiesis-stimulating agents (ESAs).
2. Epoetin alfa (recombinant human erythropoietin)
3. Darbepoetin alfa (much longer half-life)
4. Methoxy polyethylene glycol-epoetin beta (long lasting form of erythropoietin)
What are the most common complications of ESA therapy?
Mention 2 major myeloid growth factors.
1. Filgrastim (G-CSF)
2. Sargramostim (GM-CSF)
What is the clinical use of filgrastim and sargramostim?
1. Accelerate recovery of neutrophils after chemo.
2. Treatment of other primary/secondary neutropenias.
Mention some important megakaryocyte growth factors.
1. Oprelvekin (IL-11)
What are the most common adverse effects of Oprelvekin ?
4. Fluid retention
What are the two major categories of drugs used in clotting disorders?
1. Anticlotting drugs
2. Drugs that facilitate clotting
What are the three major categories of anticoagulants ?
1. Heparin and related products (parenterally)
2. Direct thrombin and factor X inhibitors (parenterally or orally)
3. Coumarin derivatives (warfarin - orally active)
How is heparin administrated ?
To avoid risk of hematoma.
Mention a LMW heparin.
What are the benefits of LMW heparins?
1. Greater bioavailability
2. Longer durations
3. Thus, doses can be given less frequently (subcutaneously).
What is fondaparinux ?
Small synthetic drug that contains the active pentasaccharide present in unfractionated and LMW heparins.
Subcutaneously, once a day.
What is the mechanism of action of unfractionated heparin?
1. Binds to endogenous antithrombin III (ATIII).
2. Inactivation of thrombin and factor Xa.
3. The action is monitored with the activated partial thromboplastin time (aPTT).
What is the main difference between unfractionated heparin and LMW heparins ?
The latter fail to affect thrombin, thus aPTT test is not reliable for monitoring the anticoagulant activity.
What is the clinical use of heparin?
1. Rapid effect - used when anticoagulation is needed immediately.
2. Treatment of DVT
3. Pulmonary embolism
4. Acute MI
5. In angioplasty and placement of coronary stents.
What are the adverse effects of heparin?
1. Increased bleeding (Protamine lessens the risk of serious bleeding).
2. Heparin induced thrombocytopenia (HIT).
Mention some important direct thrombin inhibitors.
5. Dabigatran (the only one orally - the rest parenterally).
What is the clinical use of direct thrombin inhibitors?
1. As an alternative to heparin - in patients with HIT.
2. Bivalirudin used with aspirin during percutaneous coronary angiplasty.
Mention 2 major direct oral factor Xa inhibitors.
What is the clinical use of direct oral factor Xa inhibitors?
Rivaroxaban is approved for prevention of venous thromboembolism following hip or knee surgery + prevention of stroke in patients with atrial fibrillation.
What is the mechanism of action of warfarin ?
1. Highly bound to plasma proteins (>99%).
2. Interfere with post translational modification of clotting factors in the liver - process that needs reduced vitamin K.
3. Inhibition of vitamin K epoxide reductase.
Where is warfarin contraindicated ?
Mention some important thrombolytic drugs.
What is the general mechanism of action of thrombolytic drugs?
Catalyze the conversion of plasminogen to plasmin.
What is the major clinical use of thrombolytic drugs?
1. As an alternative to percutaneous coronary angioplasty in the emergency treatment of coronary artery thrombosis - cerebral hemorrhage must be positively ruled out before use.
2. Can also be used in case of severe pulmonary embolism.
What is the most serious potential manifestation of thrombolytic agents?
Mention some important antiplatelet drugs.
1. Aspirin + other NSAIDs.
2. GPIIbIIIa receptor inhibitors :
3. Antagonists of ADP receptors :
4. Inhibitors of phosphodiesterase 3 :
What drugs involves the treatment of bleeding disorders?
1. Administration of vitamin K.
2. Preformed clotting factors.
3. Antiplasmin drugs
Mention some important antiplasmin drugs.
1. Aminocaproic acid
2. Tranexamic acid
What adverse effects can antiplasmin agents elicit?
What are the main lipid-lowering drugs in use?
1. HMG-CoA reductase inhibitors
What is the rate-limiting step in hepatic cholesterol synthesis?
Conversion of hydroxymethylglutaryl CoA (HMG-CoA) to mevanolate by HMG-CoA reductase.
Mention some important statins (HMG-CoA analogs) that competitively inhibit the HMG-CoA reductase.
1. Lovastation (prodrugs)
2. Simvastatin (prodrugs)
What are the principal toxic effects of statins?
1. Mild elevation of serum aminotransferases - not often associated with hepatic damage.
2. Increase in creatine kinase in about 10% of patients.
3. In a few, severe muscle pain, even rhabdomyolysis may occur.
4. Inhibitors of P450 increase the risk for myopathies.
5. Avoid in pregnancy.
Mention some important bile acid-binding resins.
What is the action of resins?
Cause a modest reduction in LDL, but little effect on HDL or triglycerides.
What is the clinical use of resins?
1. Patients with hypercholesterolemia.
2. To reduce pruritus in patients with cholestasis and bile salt accumulation.
What are the adverse effects of resins?
3. Unpleasant gritty taste
4. Impaired absorption of vitamins (K, folates) and drugs (thiazide diuretics, warfarin, pravastatin, fluvastatin).
Mention briefly some important features of ezetimibe.
1. Prodrug, converted in the liver to the active glucuronide form.
2. Inhibits a transporter that mediates GI uptake of cholesterol and phytosterols.
3. As monotherapy, it reduces LDL cholesterol by about 18%.
4. Used for treatment of hypercholesterolemia and phytosterolemia (rare genetic disorder).
What is the mechanism of action of niacin (nicotinic acid)?
1. In the liver : reduces VLDL synthesis (in turn reduces LDL).
2. In adipose tissue : activate signaling pathway that reduces hormone sensitive lipase activity - decreases plasma fatty acids.
3. Reduces catabolism of HDL.
4. Decreases circulating fibrinogen and increases t-PA.
What are the adverse effects of niacin?
1. Cutaneous flushing (most common)
2. Dose dependent nausea + abdominal discomfort.
4. Moderate elevation of liver enzymes + even severe hepatotoxicity occur.
5. Hyperuricemia (20%) + carbohydrate tolerance may be moderately impaired.
What is the mechanism of action of fibric acid derivatives ?
1. Ligands for peroxisome proliferator-activated receptor-alpha (PPAR-α) protein.
2. Increased synthesis by adipose tissue of lipoprotein lipase - enhance clearance of triglycerides.
3. In the liver : increase fatty acid oxidation and decrease VLDL synthesis.
4. Increase indirectly HDL levels.
5. In patients with familial combined hyperlipoproteinemia, they can increase LDL.
What is the clinical use of gemfibrozil and other fibrates?
To treat hypertriglyceridemia.
What are the main fibric acid derivatives used ?
What are the adverse effects of all members of fibric acid derivatives?
1. Nausea (most common)
2. Skin rashes (common with gemfibrozil)
3. Increased risk of gallstones.
4. Few patients show decrease in Ht or WBC count.
Mention some important NSAIDs.
What is the major functional difference between aspirin and other NSAIDs?
Aspirin inhibits irreversibly COX.
What are the three therapeutic dose ranges of aspirin?
1. Low range (<300mg/d) : effective in reducing platelet aggregation.
2. Intermediate range (300-2400mg/d) : have antipyretic and analgesic effects.
3. High doses (2400-4000mg/d) : anti-inflammatory effects.
What is the half-life of aspirin at low and at high doses?
Low doses : 3-5 hours
High doses : 15 hours or more
What is the most common adverse effect from therapeutic anti-inflammatory doses of aspirin?
Mention some important adverse effects of aspirin?
1. Gastric ulceration
2. Upper GI bleeding
3. Renal effects (acute failure and interstitial nephritis)
4. Increased bleeding time
5. Aspirin induced asthma : from increased production of leukotrienes.
What are the adverse effects of aspirin at higher doses?
1. Tinnitus (ringing of the ears)
4. Respiratory alkalosis
5. Metabolic acidosis
What is the main disadvantage of COX-2-selective inhibitors?
Increased risk of myocardial infarction and stroke.
What is the main clinical use of acetaminophen?
For the same indications as intermediate dose aspirin - half life : 2-3 hours.
What are the disease-modifying antirheumatic drugs (DMARDs)?
1. Heterogenous group of agents.
2. Anti-Inflammatory actions in several connective tissue diseases.
3. Disease-modifying because some evidence shows slowing or even reversal of joint damage.
4. Slow acting (6 weeks to 6 months).
Mention some important DMARDs.
8. Anti-IL6 drugs (tocilizumab)
9. Anti TNF-α drugs
10. Gold compounds
Mention some important anti-TNF-α drugs.
Mention 6 DMARDs that are administered orally.
With what is gout associated?
With increased serum concentration of uric acid.
What are the treatment strategies for gout?
1. Reducing inflammation during acute attacks (colchicine, NSAIDs or glucocorticoids).
2. Accelerating renal excretion of uric acid.
3. Reducing the conversion of purines to uric acid by xanthine oxidase.
What is the mechanism of action of the NSAIDs and colchicine in treatment of gout?
NSAIDs : reduction of prostaglandin formation and inhibition of crystal phagocytosis by macrophages.
Colchicine : selective inhibitor of microtubule assembly, reduces leukocyte migration and phagocytosis.
What is the clinical use of colchicine?
1. Can be used for acute attacks - causes GI disturbance (diarrhea).
2. Lower doses used to prevent attacks of gout.
3. Also used in Mediterranean fever.
What is the toxicity of anti-inflammatory drugs used for gout?
NSAIDs : renal damage - bone marrow depression (indomethacin).
Glucocorticoids : behavioral changes and impaired glucose control.
Colchicine : severely damage the liver and kidney - OD is fatal.
What are the major uricosuric agents used in gout?
What are the two major xanthine oxidase inhibitors ?
What are the adverse effects of allopurinol?
1. GI upset
3. Peripheral neuritis (rarely)
4. Vasculitis (rarely)
5. Bone marrow dysfunction - aplastic anemia (rarely).
6. Inhibits the metabolism of mercaptopurine and azathioprine.