Final Exam Review Flashcards
0
Q
What is the MOA of Thiazide Diuretics?
A
MOA of Thiazide Diuretics: Inhibit sodium and chloride reabsorption in the thick ascending loop and early distal tubule. This loss of ions increases urine volume.
Can cause hypokalemia.
1
Q
What is the MOA of ACE Inhibitors? What is the well-known side effect?
A
ACE Inhibitors –> Drugs causing reduction of cardiac workload
Angiotensin-converting enzyme (ACE) inhibitors: improve symptoms, slow progression of heart failure, and prolong survival. Also used in tx of hypertension.
MOA of ACE Inhibitors:
- block the synthesis of angiotensin II, a potent vasoconstrictor
- reduce aldosterone secretion from adrenal cortex resulting in net water loss
Side Effects of ACE Inhibitors:
- headaches, dizziness, abdominal pain, confusion, renal failure and impotence
- ACE Inhibitors can also cause dry, irritating cough
2
Q
What is MOA of Loop Diuretics? What are the undesirable side effect of Loop Diuretics?
A
MOA of Loop Diuretics: inhibit chloride reabsorption in the ascending loop of Henle. They are used in th tx of pulmonary edema because of their potent and rapid action.
Undesirable effects of Loop Diuretics:
hyponatremia (level of sodium in blood too low)
hypokalemia (level of potassium in blood too low)
hypocalcemia (level of calcium in blood too low)
hypomagnesia (level of magnesium in blood too low)
hyperglycemia (high blood glucose)
hyperuricemia (high level of uric acid in blood)
ototoxicity (ear poisoning – drugs that damage the inner ear)
3
Q
What is the MOA of cardiac glycosides? Example.
What are precautions when taking these drugs?
List their toxicities.
A
MOA of cardiac glycosides: They inhibit NA+-K+-ATPase. This causes an increase in the level of sodium ions in the myocytes, which leads to a rise in the level of intracellular calcium ions. This occurs because the sodium/calcium exchanger on the plasma membrane depends on a constant inward sodium gradient to pump out calcium. Digoxin decreases sodium concentration in myocardiocytes. Thus the force of myocardial contraction is increased.
Important to note: Cardiac Glycosides have a low therapeutic index which means that the plasma concentration that causes serious toxicity is only slightly higher than the therapeutic dose. Toxicity resulting from cardiac glycosides can be manifested by:
arrhythmias
anorexia
nausea and diarrhea
drowsiness and fatigue
visual disturbances
4
Q
What is MOA of Class I Antirrhythmics? Give Examples.
A
MOA Class I Antiarrhythmic: (sodium channel blockers) They block sodium entry into the cell during depolarization. This decreases the rate of rise of Phase 0 of the action potential.
Class IA: useful in tx of atrial and ventricular arrhythmias (all-purpose) –> Procainamide (Pronestyl)
Class IB: used in tx of ventricular arrhythmias (ventricular tachycardia, ventricular fibrillation, and ventricular ectopy) –> Lidocaine (Xylocaine)
5
Q
What is MOA of Class II antiarrhythmics? Give Example
A
MOA Class II Antiarrhythmic: (B-adrenoreceptor blockers) are potentially useful in the suppressing the tachyarrhythmias that result from increased sympathetic activity. They stabilize cardiac membrane, slow down conduction through SA and AV nodes, and increase the refractory period.
Propranolol (Inderal) –> most commonly used to tx arrhythmia patients
6
Q
What is MOA of Class III Antiarrhythmics? Give examples.
A
MOA of Class III Antiarrhythmics: (K+ channel blockers) they prolong repolarization. Useful in treating intractable ventricular arrhythmias –> Amiodarone: effective in tx and prevention of ventricular fibrillation and ventricular tachycardia.
7
Q
What is MOA of Class IV antiarrhythmics? Give examples.
A
MOA of Class IV antiarrhythmics: (Ca++ channel blockers) by slowing the inward calcium current, these drugs slow conduction and prolong the effective refractory period, especially in the AV node. They are the most effective against atrial than ventricular arrhythmias.
- Verapamil
- Diltiazem
8
Q
What is MOA of organic nitrates in relieving angina? What is the drug of choice for acute coronary spasm? What are the routes of administration?
A
MOA of organic nitrates for angina:
- they dilate the large myocardial arteries to increase the blood supply of the heart.
- also reduce cardiac preload by reducing venous tone.
- Nitrates –> increase Nitrites –> increase Nitric Oxide –> cGMP
- -> Dephosphorylationof myosin light chain –> vascular smooth muscle relaxation
***drug of choice for acute coronary spasm –> nitroglycerine: useful in tx of all types of angina. Often administered sublingually for rapid onset of action (2 min), but it can be applied transdermally for a longer duration of action…
9
Q
What is the MOA of Beta Blockers in relieving angina? What are contraindications? These drugs should be tapered off how and why?
A
MOA of Beta Blockers for angina:
- they decrease oxygen demand of the myocardium by lowering both thte rate and the force of contraction of the heart.
- the cardioselective beta blockers are preferred. they suppress the activation of the heart by blocking B1 receptors.
- they are particularly useful in the tx of patients with MI and have been shown to prolong survival.
Contraindications of Beta Blockers for angina: asthma, diabetes, severe bradycardia, peripheral vascular disease, or COPD.
Cautions of Beta Blockers for angina: do not discontinue Beta Blocker therapy abruptly. The dose should be gradually tapered off over 5-10 days to avoid rebound angina or hypotension.
10
Q
List group of hypertensive drugs useful in tx of diabetes patients?
A
ACE Inhibitors do not affect glucose levels, so are useful for tx of diabetes patients with hypertension.
ACE Inhibitors are particularly useful in hypertension that is a result of increased renin levels.
***ACE Inhibitors may not be effective in lowering blood pressure in African American patients.
11
Q
List group of hypertensive drugs useful in tx of African American patients?
A
African American patients respond well to treatment of hypertension with calcium blockers.
12
Q
List group of hypertensive drugs useful in tx of patients with angina?
A
Beta Blockers are particularly useful for treatment of hypertension with patients with angina or those with migraines.
***Beta Blockers may not be affective in treatment of hypertension in African American patients.
13
Q
List group of hypertensive drugs useful in tx of pregnant women.
A
Central acting adrenergic drugs specifically Methyldopa (Aldomet) is used to treat hypertension in pregnant women.
14
Q
What antihypertensive drug can be used on patients with renal disease?
A
Central acting adrenergic drugs, specifically Clonidine (Catapress) is an A2 agonist that reduces central sympathetic outflow. It has no direct effect on the kidneys and can be used in patients with renal disease.
15
Q
List important antiplatelet drugs. What is the MOA of aspirin and clopidegrol.
A
Antiplatelet drugs inhibit platelet aggregation.
***Aspirin –> MOA: Inhibits platelet aggregation by inhibiting thromboxane A2 synthesis in the platelets, and thus prolongs bleeding time. Reduces the risk of MI, and stroke.
***Clopidegrol (Plavix) –> MOA: Blocks platelet aggregation by irreversibly inhibiting the binding of ADP to its receptor on platelets and, thus inhibit the activation of GP IIb/IIIa receptors required for platelets to bind to fibrinogen; thus it blocks platelet aggregation
***Abciximab (Reopro)–> MOA: Prevent platelet aggregation by blocking and binding of fibrinogen to the glycoprotein IIb/IIIa receptor on the surface of the platelet.
16
Q
What is the action of heparin? What is the important side effect? What drug is used to treat that side effect?
A
Heparin is an anticoagulant – they inhibit the development and enlargement of clots.
Heparin and LMWH class –>
MOA of Heparin:
-Interfere with the clotting factor activation in both the intrinsic and extrinsic pathways.
-The prinipal anticoagulant actions of heparin are a result of its binding to antithrombin III with the subsequent rapid inactivation of coagulation factors, especially thrombin and Xa.
- **Side effect of heparin: hemorrhage
- **Protamine is a specific heparin antagonist that can be used to treat heparin-induced hemorrhage.
17
Q
What is the MOA of oral anticoagulants? Give an example.
A
MOA of oral anticoagulants: they antagonize Vitamin K, interfere with the synthesis of Vitamin K dependent clotting factors (II, VII, IX, X)
Warferin (Coumadin)
***Administration of Vitamin K can overcome anticoagulant effects of the oral anticoagulants, but the effect takes about 24 hours.
18
Q
Define thrombolytic drugs. What is the MOA? Give an example.
A
Thrombolytic drugs are used to lyse already formed clots.
MOA of thrombolytic drugs: activate plasminogen to plasmin. Plasmin digests fibrin forming degradation products.
-Clot dissolution is more likely if therapy is initiated early after clot formation. Clots becomes more difficult to lyse as they age.
- **Streptokinase
- **Tissue plasminogen activator (t-PA)
19
Q
List the drugs used to treat anemia in end-stage renal failure and megaloblastic anemia?
A
***Erythropoietin is synthesized in the kidney in response to hypoxia or anemia. It stimulates erythropoiesis. Used to treat end-stage renal failure.
***Epoetin alpha, darbepoetin alpha –> human recombinant erythropoietin effective in the treatment of anemia caused by end-stage renal disease.
***Cyanocobalamin (Vitamin B12) –> used to treat megaloblastic anemia
20
Q
What is the mechanism of action of HMG-CoA reductase inhibitors? What are their side effects? List important drugs of this group.
A
MOA of HMG-CoA reductase inhibitors –>
- **first choice of for treatment of patients with hypercholesterolemia.
- They are structural similar to HMG-CoA reductase which is a precursor of cholesterol.
- They inhibit HMG-CoA reductase, the enzyme that controls the rate-limiting step in cholesterol synthesis.
- They decrease cholesterol, LDL, VDL and Triglycerides (TG) and increases HDL.
***Side Effects: Liver fx abnormalities, myopathy, rhabdomyolysis (disintegration of muscle) etc.
Grapefruit juice is prohibited.
Drugs:
Simvastatin (Zocor)
Atrovastatin (Lipitor) **most potent
Rosuvastatin (Crestor) **most potent
21
Q
What are the mechanisms of actions of Niacin? What are the adverse effects of Niacin?
A
MOA of Niacin: strongly inhibits lipolysis in adipose tissue; decreases cholesterol, TG, LDL, VLDL, and increases HDL.
***Adverse effects of Niacin: flush and pruritus
22
Q
What is the MOA of Ezetimibe (Zetia)?
A
MOA of Ezetimibe --> cholesterol absorption of dietary and biliary cholesterol --> they inhibit intestinal absorption of dietary and biliary cholesterol; they cause: -decrease in LDL, -increase in HDL, -decrease in Triglycerides
23
Q
Captopril (Capoten)
A
**Drugs causing reduction of cardiac workload
Captopril (Capoten): ACE Inhibitors
(block the synthesis of angiotensin II, a potent vasoconstrictor;
reduce aldosterone secretion from adrenal cortex resulting in net water loss)
**infrequently causes agranulocytosis or neutropenia
24
What are the major side effects of ACE Inhibitors?
headache, dizziness, abdominal pain, confusion, renal failure, and impotence... can also cause a dry, irritating cough
25
Enalapril (Vasotec)
***Drugs causing reduction of cardiac workload
Enalapril (Vasotec): ACE Inhibitors
(block the synthesis of angiotensin II, a potent vasoconstrictor;
reduce aldosterone secretion from adrenal cortex resulting in net water loss)
26
Losartan (Cozaar)
***Drugs causing reduction of cardiac workload
Losartan (Cozaar): Angiotensin II Receptor Antagonists
(These drugs interfere with the binding of angiotensin II with its receptors. They do not produce cough. Also used in tx of hypertension).
27
Minoxidil (Loniten)
***Drugs causing reduction of cardiac workload
Minoxidil (Loniten): Direct vasodilator
(directly relaxes arterioles)
***side effect: unwanted hair growth; also marketed for topical tx of male pattern baldness.
28
Chlorthiazide (Diuril)
***Drugs causing control of excessive fluid: diuretics
Chlorthiazide (Diuril): Thiazide diuretic
(inhibit sodium and chloride reabsorption in the thick ascending loop and early distal tubule. This loss of ions increases urine volume. They can cause hypokalemia - low potassium)
***side effects: hyponatremia, hypokalemia, hyperglycemia, hyperuricemia, hypercalcemia
29
Furosemide (Lasix)
***Drugs causing control of excessive fluid: Diuretics
Furosemide (Lasix): Loop Diuretic
(inhibit chloride reabsorption in the ascending loop of Henle. They are used in the tx of pulmonary edema because of their potent and rapid action)
***side effects: hyponatremia, hypokalemia, hypocalcemia, hypomagnesia, hyperglycemia, hyperuricemia, ototoxicity
30
Ethacrynic Acid (Ethacrynate)
***Drugs causing Control of excessive fluid: diuretics
Ethacrynic Acid (Ethacrynate): Loop Diuretics
***most ototoxic
(inhibit chloride reabsorption in the ascending loop of Henle. They are used in the tx of pulmonary edema because of their potent and rapid action)
***side effects: hyponatremia, hypokalemia, hypocalcemia, hypomagnesia, hyperglycemia, hyperuricemia, ototoxicity
31
Spironolactone (Aldactone)
***Drugs causing control of excessive fluids: Diuretics
Spironolactone (Aldactone): Potassium Sparing Diuretics
***underdesirable effect: hyperkalemia
(they enhance sodium excretion and retain potassium by an action in the distal tubule. They are often used in combination with the other diuretics to help maintain the potassium balance).
32
Digoxin (Lanoxin)
***Drugs causing enhancement of contractility
Digoxin (Lanoxin): Cardiac glycoside
***cardiac glycosides have a low therapeutic index which means that the plasma concentration that causes serious toxicity is only slightly higher than the therapeutic dose. Toxicity resulting from cardiac glycosides can be manifested by arrythmias; anorexia; nausea; and diarrhea; drowsiness and fatigue; visual disturbances...
33
Dobutamine (Dobutrex)
***Drugs causing enhancement of contractility
Dobutamine (Dobutrex): Sympathomimetics
is a Beta1 agonist
***In patients with impaired renal function, the use of dopamine (instead of dobutamine) may preserve renal blood flow and, as a result, renal function.
34
Nitroglycerine
***Drugs to treat angina pectoris
Nitroglycerine: Organic Nitrate
useful in treating all forms of angina. It is the drug of choice for relieving acute coronary spasm. It is often administered sublingually for rapid onset (2 min), but i can be applied transdermally for a longer duration of action.
* **headache and postural hypotension are common side effects
* **drug interaction with Sildenafil (Viagra)
35
Isosorbide dinitrate (Isordil)
***Drugs to treat angina pectoris
Isosorbide dinitrate (Isordil): organic nitrates
used for prophylaxis of angina not for acute attack
36
Diltiazem (Cardizem)
***Drugs to treat angina pectoris
Diltiazem (Cardizem): Calcium Blocker
(block calcium influx into the smooth muscle cells of the arteries causing them to dilate)
***side effects: headache, dizziness, hypotension, etc.
37
Amlodipine (Norvasc)
***Drugs to treat angina pectoris
Amlopdipine (Norvasc): calcium blocker
(they block calcium influx into the smooth muscle cells of the arteries causing them to dilate)
***common side effects: headache, dizziness, hypotension, etc.
38
Atenolol (Tenormin)
***Drugs used to treat hypertension
Atenolol (Tenormin): beta blocker: B1 antagonist
(prevent sympathetic stimulation of the heart thereby causing decreased heart rate and cardiac output).
39
Metoprolol (Lopressor)
***Drugs used to treat hypertension
Metoprolol (Lopressor): beta blockers: B1 antagonist
(prevent sympathetic stimulation of the heart thereby causing decreased heart rate and cardiac output)
40
Methyldopa (Aldomet)
***Drugs to treat hypertension
Methyldopa (Aldomet): Central acting adrenergic drugs: A2 agonist that reduces central sympathetic outflow
* **it has no direct effect on the kidneys and can be used in patients with renal disease
* **used to treat hypertension in pregnant women
41
Minoxidil (Loniten)
***Drugs used to treat hypertension
Minoxidil (Loniten): direct vasodilators
***side effect: unwanted hair growth; also marketed for topical treatment of mail pattern baldness
42
Sodium nitroprusside
***Drugs used in hypertensive crisis
Sodium nitroprusside
(given IV; causes prompt vasodilation; capable of reducing BP in all patients regardless of the cause of hypertension)
***poisonous if given orally because of its hydrolysis to cyanide, antidote is sodium thiosulfate
43
Procainamide (Pronestyl)
***antiarrhythmic drugs
Procainamide (Pronestyl): Class 1a
useful in the treatment of atrial and ventricular arrhythmias -- all purpose
44
Lidocaine (Xylocaine)
***anti-arrhythmic drugs
Lidocaine (Xylocaine): Class 1b
(ventricular fibrillation and ventricular ectopy)
45
Propranolol (Inderal)
***anti-arrhythmic drugs
Propranolol (Inderal): Class II (B-adrenoceptor blockers)
(useful in suppressing tachyarrhythmias that result from increased sympathetic activity. They stabilize cardiac membrane, slow down conduction through SA and AV node, and increase the refractory period).
46
Amiodarone
***anti-arrhythmic drugs
Amiodarone: Class III: Potassium channel blockers
(effective in the tx and prevention of ventricular fibrillation and ventricular tachycardia)
47
Aspirin
***antiplatelet drugs
Aspirin
(inhibits platelet aggregation by inhibiting thromboxane A2 synthesis in the platelets, and thus prolongs bleeding time)
***reduces the risk of MI & stroke
48
Clopidegrol (Plavix)
***anti-platelet drugs
Clopidegrol (Plavix)
(blocks platelet aggregation by irreversibly inhibiting the binding of ADP to its receptors on platelets and thus inhibit the activation of GP IIb/IIIa receptors required for platelets to bind to fibrinogen; thus it blocks platelet aggregation)
49
Abciximab (Reopro)
***antiplatelet drugs
Abciximab (Reopro): Glycoprotein IIb/IIIa receptor antagonists
(prevent platelet aggregation by blocking the binding of fibrinogen to the glycoprotein IIb/IIIa receptor on the surface of the receptor
50
Heparin
***anticoagulants
Heparin
(interfere with clotting factor activation both intrinsic and extrinsic)
***adverse effects: hemorrhage
Protamine is a specific heparin antagonist that can be used to treat heparin-induced hemorrhage
51
Enoxaparin (Lovenox)
***anticoagulants
| Enoxaparin (Lovenox)
52
Warferin (Coumadin)
***anticoagulants
Warferin (Coumadin): oral anticoagulants
(antagonize vitamin K, interfere with the synthesis of Vitamin K dependent clotting factors (II, VII, IX, X)
Antidote: administration of vitamin K can overcome the anticoagulant effects of the oral anticoagulants, but the effect takes 24 hours
53
Argatroban
***anticoagulants
| Argatroban: Thrombin inhibitor
54
Streptokinase
***Thrombolytic drugs
Streptokinase
(they activate plasminogen to plasmin. Plasmin digests fibrin forming degradation products).
55
Aminocaproic Acid
***drugs used to treat bleeding
Aminocaproic Acid
(inhibits plasminogen activation)
56
Vitamin K
***drugs used to treat bleeding
Vitamin K
(can overcome the anticoagulant effects of oral agents)
57
Simvastin (Zocor)
Atravastatin (Lipitor): most potent
Rosuvastatin (Crestor): most potent
***antihyperlipidemic drugs
Simvastin (Zocor): HMG - CoA reductase inhibitor
***HMG - CoA reductase inhibiror is first choice of tx for patients with hypercholesterolemia
***adverse effects: liver fx abnormalities, myopathy, rhabdomyolysis (disintegration of muscle)
Concomitant use of grapefruit juice is prohibited
58
Ezetimibe (Zetia)
***antihyperlipidemic drugs
Ezetimibe (Zetia): cholesterol absorption inhibitors
(they inhibit intestinal absorption of dietary and biliary cholesterol; they cause decrease in LDL, increase HDL and decrease in Triglycerides)
59
List the important drugs used to treat hyperthyroidism, What are the mechanisms of actions of Methimazole and Propylthiouracil?
Hyperthyroidism:
* **Methimazole (Tapazole): inhibits iodination of tyrosine groups and coupling of these groups to form thyroid hormone.
* **Propylthiouracil (PTU): inhibits iodination of tyrosine groups and coupling of these groups to form thyroid hormone. also inhibits peripheral conversion of T4 to T3.
* **Iodine/Iodide: Inhibits release of thyroxine from thyroid gland; useful for 2 weeks; then the gland adopts and resumes thyroxine secretion.
* **Propranolol (Inderal): Beta-blocker. Suppress tachycardia and other catecholamine effects; used for emergent preparation of hyperthyroid patients for surgery, thyrotoxicosis in pregnancy and thyroid storm.
* **
60
What are the complications of using Glucocorticoids?
Glucocorticoids are used in replacement therapy in adrenocortical insufficiency states, such as Addison's; also in inflammatory disorders such as rheumatoid arthritis; also of allergic conditions such as asthma, allergic rhinitis, etc.
***Abrupt withdrawal of glucocorticoids causes acute adrenal insufficiency syndrome that can be lethal. So the drugs must be tapered off slowly.
***preferred drug for replacement therapy: Hydrocortisone
Prednisone
61
What are the uses of Spiranolactone?
Inhibitors of adrenal hormone synthesis and action
***Spiranolactone (Aldactone): antihypertensive drug; competes for the aldosterone receptor and thus inhibits sodium reabsorptionin the kidneys; also antagonizes aldosterone and testosterone synthesis; effective against hyperaldosteronism and hirsutism in women (interfere androgen receptor of the hair follicle).
62
What are the uses of Ketaconazole?
***inhibitors of adrenal hormone synthesis and action
Ketaconazole (Nizoral): an antifungal agent that strongly inhibits all gonadal and adrenal steroid hormone synthesis; also used in the treatment of Cushing's syndrome.
63
What are the uses of Raloxifene, Clomiphene, Medroxyprogesterone, and Mifepristone?
***Sex Steroids (estrogens, progesterone and androgens)
***Raloxifene (Evista): Selective Estrogen Receptor Modulators (SERMs) --> has agonist activity in the bone, and antagonist activity in the breast and endometrial tissue. Binds to estrogen receptors and induces expression of genes to maintain bone density; used to treat and prevent osteoporosis.
***Clomiphene (Clomid): SERMs --> by acting as a partial estrogen receptor agonist in the hypothalamus, it interferes with the negative feedback of estrogens. It binds to the estrogen receptors and causes hypothalamus to sense a lack of estrogen. This results in an increase in the release of GnRH and gonadotropins leading to the stimulation of ovulation. Used to tx infertility in women.
***Medroxyprogesterone (Depo-provera): progestins
(contraceptive; hormone replacement therapy; tx of dysfunctional uterine bleeding (DUB), dysmenorrhea, and management of endometriosis)
***Mifepristone: antiprogestins --> it works to terminate pregnancy by breaking down the uterine lining.
64
What are the major side effects of oral contraceptives? What is the special risk for smokers and more than 35 years of age group?
Major side effects of oral contraceptives: breast fullness, nausea, vomiting (estrogen), depression, and edema (progestin).
***There is an increased incidence of abnormal clotting in women who smoke and who are over the age of 35.
65
What are the two groups of anti-androgens? What are the uses of Finasteride and Flutamide?
Antiandrogens counter male hormonal action by interfering with the synthesis of androgens or by blocking their receptors.
2 groups of antiandrogens:
1. 5-alpha-reductase inhibitors: inhibit the enzyme that converts testosterone to dihydrotestosterone (DHT) which is the major intracellular androgen in most target tissues. The resulting decrease in formation of DHT in the prostate leads to a reduction in prostate size.
- Finateride (Propecia): used to tx benign prostatic hyperplasia (BPH) and at lower doses, to stimulate hair growth in male pattern baldness.
2. Androgen receptor antagonists: competitive inhibitors of androgens in target cells; used to tx excessive hair growth in women and prostate cancer in men.
- Flutamide: tx of prostate carcinoma in males
66
What are the MOA of lowering blood glucose by alpha-glucoside inhibitors? List important drugs?
alpha-glucoside inhibitor MOA: they slow carbohydrate digestion by inhibiting alpha-glucosidase of intestinal brush border and pancreatic amylase resulting in lower serum glucose levels after meals
***Acarbose (Precose): alpha-glucosidase inhibitor
side effects: flatulence, diarrhea and abdominal pain are most common side effects
67
Which hypoglycemic drug has been proven to decrease cardiovascular mortality?
Metformin (Glucophage): Biguanide
MOA: reduces hepatic glucose output largely inhibiting hepatic gluconeogenesis; slows intestinal absorption of sugars; increases sensitivity to insulin; reduces hyperlipidemia; decreases LDL and VLDL; increases HDL
***only hypoglycemic drug proven to decrease cardiovascular
mortality
***also effective in tx of polycystic ovary disease --> its ability to lower insulin resistance in these women can result in ovulation an, possibly pregnancy.
68
What is the MOA of lowering blood glucose by Glitazones? List drugs.
Thiazolidinediones (Glitazones) MOA: enhances response of target cells to endogenous insulin -- insulin sensitizer
also can cause ovulation in women with polycystic ovary disease; can cause liver toxicity, and weight gain by fluid retention and subcutaneous fat deposition. Fluid retention can worsen heart failure. Needs monitoring of LV fx.
***Rosiglitazone (Avandia): Glitazones
69
Which group of drugs are the most effective drugs available for the treatment of acute bronchospasm and for prevention of exercise-induced asthma? Examples
Beta2 Adrenergic Agonists are the most effective drugs available for the tx of acute bronchospasm and for prevention of exercise-induced asthma.
MOA of Beta2 Adrenergic Agonists: they cause bronchodilation by activation of B2 adrenergic receptors on the bronchial smooth muscle.
***Albuterol (Ventolin): drug of choice for the tx of acute bronchospasm and for prevention of exercise-induced asthma.
***Terbutaline (Brethaire)
***Salmeterol (Serevent): Long acting B2 agonist (at least 12 hours); used for long-term prevention of asthma symptoms, nocturnal symptoms, and for prevention of exercise-induced bronchospasm; not for acute exacerbations.
70
In which condition inhaled corticosteroids are the drugs of choice for asthma patients? What may be their side effects? Give an example.
Inhaled glucocorticoids are the drugs of choice in patients who require B2 agonists more than 2x per week. Severe asthma may also require systemic glucocorticoids.
MOA of corticosteroids: they reduce inflammation by reversing mucosal edema, decreasing the permeability of capillaries, and inhibiting the release of leukotrienes. Also enhance activity of sympathomimetics of hypoxic and acidotic states.
***the inhaled ones usually do not induce systemic toxicity, but increase the risk of oral candidiasis (Thrush) infection.
***Beclomethasone (Beclovent)
71
What is the MOA of Cromolyn?
***Drugs to tx asthma
Cromolyn (Intal): inflammatory cell stabilizer
MOA: prevent release of inflammatory mediators (e.g. histamine) from mast cells, macrophages, neutrophils and eosinophils
***used for prophylaxis of asthma attacks
72
What is MOA and use of Montelukast?
***drugs used to tx asthma
Montelukast (Singulair): Leukotriene modifiers
(Leukotrienes - products of arachidonic acid metabolism - increase eosinophil migration, mucus production and airway wall edema, and cause bronchoconstriction)
Montelukast (Singulair) MOA: blocks binding of leukotriene D4 (LTD4) to its receptor; used prophylaxis and chronic asthma tx
73
What are the uses of surfactant and Dornase alfa?
***miscellaneous respiratory drugs
***Surfactant (Exosurf): administered endotracheally in infant respiratory distress syndrome
***Dornase Alfa (DNase) (Pulmozyme): Administered by inhalation to patients with cystic fibrosis to decrease the viscosity of bronchial secretions.
74
What is the MOA of Sildenafil in treating erectile dysfunction? What is the danger of using it with nitrates?
***Drugs to tx erectile dysfunction
Phosphodiasterase-5 (PDE-5) inhibitors: Nitric Oxide (NO) released from the nerve endings and endothelial cells binds to receptors on the smooth muscle of the corpus cavernosum and causes relaxation of smooth muscle, allowing engorgement. This process is reversed by a phosphodiasterase-5. These drugs inhibit phosphodiasterase.
***all these drugs potentiate the hypotensive action of nitrates. Their use together with nitrates could result in fatal drop of BP
***Sildenafil (Viagra)
should be taken approx 1 hour before sexual activity
75
What are the MOA and uses of biphosphonates? Give an example. What are the other groups of drugs used in the treating of osteoporosis?
***drugs to tx osteoporosis
Biphosphonates inhibit osteoclastic activity and decrease bone turnover and resorption; these agents have been shown to improve bone mass in established osteoporosis. also used in Paget's disease.
Must be taken with a full glass of water first thing in the morning; should stay upright for at least 1 hour before eating breakfast.
***Alendronate (Fosamax): biphosphonate
Other groups of drugs to tx osteoporosis:
- Selective Estrogen Receptor Modulators (SERMS)
- Estrogens
- Calcitonin
- Vitamin D and calcium supplements
76
Classify anti-obesity drugs. What is the MOA of Orlisat.
* **anti-obesity drugs
1. Anorexiants (Fen Phen)
2. Lipase inhibitor
* **Orlisat (Xenical): is a reversible pancreatic lipase inhibitor approved for the management of patients with body mass index greater than 30 kg...
77
What is the difference between Bacteriostatic and Bactericidal antibiotics?
Bacteriostatic --> a drug that arrests the growth and replication of a bacterium is bacteriostatic
Bacteriocidal --> kills the bacteria
78
List antibiotics that act by inhibiting bacterial cell wall synthesis.
***antibiotics
Inhibitors of Cell Wall Synthesis MOA: inhibit the formation of cross-linking of adjacent peptidoglycan strands in the bacterial cell wall. The penicillins and cephalosporins are structurally similar to the terminal portion of the peptidoglycan strands and can compete for and bind to the enzymes that catalyze the cross-linking
1. B-Lactam antibiotics (contain a B-Lactam ring in their structure)
- penicilins
- cephalosporins
- carbapenems
- monobactams
2. Other antibiotics
- bacitracin
- vancomycin
3. B-Lactamase inhibitors: some bacteria contain an enzyme called B-lactamase that can open the B-lactam ring. This leads to inactivation of the antibiotic. These drugs prevent enzymatic hydrolysis of B-lactam antibiotics, and prolong their actions.
- Clavulanic Acid
- Salbactam
- Tazabactam
79
What is the best drug for treating syphilis patients? Which penicillins are effective against pseudomonas aeriginosa?
***penicillins
Benzathine Penicillin G is the best choice for tx of syphilis patients
Antipseudomonal Penicillins are most effective against pseudomonas aeruginosa.
- Piperacillin is the most potent of this group
- Carvenicillin
- Ticarcillin
80
What is the action of Clavulanic Acid in Augmentin?
Amoxicillin + clavulanic acid (Augmentin): Clavulanic acid inhibits penicillinases
81
What are the uses of third generation cephalosporin -- Ceftriaxone?
Third generation cephalosporin are broad spectrum; resistant to most cephalosporinases
- Ceftriaxone (Rocephin): first-line drug in the tx of gonorrhea; also drug of choice in the tx of meningitis in children because of its effectiveness against Hemophyllus infulenzae
82
What are the side effects of Aminoglycosides? How Penicillins and Aminoglycosides are synergistic? What is the use of oral neomycin?
Aminoglycosides bind to the 30s ribosomal subunit thereby inhibiting protein synthesis.
***Side effects are nephrotoxicity and ototoxicity and neuromuscular toxicity. Ototoxicity involves both the vestibular and cochlear divisions of the eighth cranial nerve thereby causing hearing loss as well as vertigo and loss of balance.
Margin of safety for these drugs is small.
These drugs need to gain entry into cell.
***Penicillins and aminoglycosides are synergistic when given together. Penicillins cause cell wall abnormalities that allow aminoglycosides to gain entry into the bacteria.
***Neomycin: used orally in hepatic coma to decrease the coliform flora, thus decreasing the production of ammonia; also used topically for skin infections.
83
What are the uses and side effects of Tetracyclines?
Tetracyclines bind to the 30s ribosomal subunit thereby inhibiting protein synthesis
***most effective agent in the tx of rickettsiae, chlamydia and mycoplasma, and borrelia infections
***food impairs the absorption of tetracyclines...
- forms chelates with calcium, magnesium and other metals so use with antacids is not advised.
Tetracyclines are associated with staining of teeth, retardation of bone growth, and photosensitivity. Not recommended for use in children or pregnant women and renal impairment.
84
What are the uses of Macroglides? Give examples.
***inhibitors of protein synthesis
Macrolides MOA: bind to 50S ribosomal subunit thus inhibiting the translocation steps of protein synthesis; they may also interfere at other sites such as transpeptidation.
Macrolides are of particular use in the treatment of patients with mycoplasma pneumonia, legionnaire's disease, chlamydial infections, diptheria, and pertussis.
* **they are safe to use in pregnancy.
* **Drugs of choice for tx of pneumonia cause by legionella and mycoplasma:
- erythromycin
- azithromycin
85
What are the adverse effects of chloramphenicol?
Chloramphenicol is associated with bone marrow depression and aplastic anemia that is usually fatal.
- also can cause gray baby syndrome in infants. This is characterized by abdominal distention, vomiting, cyanosis, hypothermia, decreased respiration and vasomotor collapse.
86
What is the use of Clindamycin? What adverse effect can be caused by its use?
Clindamycin has the same mechanism of action as macrolides.
***Clindamycin is the drug of choice of anaerobic GI infections. Use of this drug is associated with pseudomembranous colitis, because of C.deficile is resistant to it.
87
What is the mechanism of action of Trimethoprim-Sulfamethoxazole (Cotrimoxazole)? What are its uses?
antimicrobials - folate antagonists
* **The combination of sulfonamides and trimethoprim is synergistic.
* **Trimethoprim/sulfamethoxazole (Cotrimoxazole): is the most commonly used drug in this group; used for UTI and pneumocystitis carinii pneumonia among other things.
88
What are the MOA and adverse effects of Quinolones? List the important drugs in this group.
Fluroquinolones inhibit DNA gyrase and topoisomerase IV, and thereby inhibit bacterial DNA replication.
* **these drugs are considered to be broad spectrum antimicrobial agents.
* **these drugs have caused damage to the growing cartilage in animals -- not recommended for children.
* **ingestion with antacids containing aluminum and magnesium can interfere with their absorption.
- Norfloxacin: used to treat common urogenital, respiratory, bone and joint infections, prostatitis and GI infections caused by gram negative organisms.
- Ciprofloxacin
- Levofloxacin
89
What are the uses of Metronidazole?
Metronidazole inhibits DNA synthesis.
***Drug of choice for trichomoniasis (STD), Amebiasis (Dysentery), and Giardiasis (Dysentery)
***Also drug of choice for antibiotic associated enterocolitis - pseudomembranous colitis caused by Clostridium Dificil
90
Why are anti-tubercular drugs are given as combination therapy? What are the adverse effects of Isoniazid? How peripheral neuropathy can be prevented?
Anti-tubercular drugs are given as combination therapy to prevent the emergence of resistant strains. It is vital to employ combination therapy with as many as four or five agents to which the organism is sensitive.
One regimen consists of 2 months of isoniazid, rifampin, and prazinamide, followed by 4 months of isoniazid and rifampin. Sometimes ethambutol is added to the initial 2-month regimen.
The drugs are most commonly divided into 2 groups: 1st line and 2nd line drugs.
* **Isoniazid: inhibits synthesis of mycolic acids.
- Isoniazid is associated with hepatotoxicity and peripheral neuropathy.
- Vitamin B6 is usually prescribed with INH to prevent complications like peripheral neuritis.
- Drug of choice for chemoprophylaxis in recent convertors.
91
What are the effects of Rifampin on the liver?
Rifampin inhibits RNA synthesis by formation of a stable complex with the DNA-dependent RNA polymerase. It is metabolized in the liver and is potent inducer of the cytochrome P-450 enzymes.
* **Can cause hepatitis and may color secretions red-orange.
* **Rifabutin is an analogue of rifampin that has some activity against rifampin-resistant Mycobacterium tuberculosis.
92
What is the adverse effect of Ethambutol?
Ethambutol can cause optic neuritis.
93
What is the mainstay treatment of leprosy? Which drug is both an antileprosy and anti-TB drug?
Current recommendations are that all forms of leprosy be treated with a combo of drugs.
***Dapsone is mainstay treatment of leprosy. Dapsone is a structural analogue of para-aminobenzote acid (PABA) and is a competitive inhibitor of folic acid synthesis
***Rifampin is an active antileprosy drug as well as anti-TB drug
94
What is the most commonly used antifungal drug to treat serious disseminated infections? What is its most common toxicity?
Amphotericin B is the most commonly used anti-fungal drug used to treat serious disseminated yeast and fungal infections, particularly in immunocompromised patients.
***The most serious and most common toxicity of amphotericin B is Nephrotoxicity.
95
What is the MOA of Reverse Transcriptase Inhibitors used in the treatment of HIV infection? Name its 3 subgroups. Give examples of nucleosides. What combo of drugs is given to healthcare providers after accidental needle sticks?
Reverse Transcriptase Inhibitors (RTIs) inhibit the formation of viral DNA from RNA by RT. Mutation of the reverse transcriptase enzyme is very rapid. The use of at least 2 RT inhibitors simultaneously slows the emergence of resistant virus. There are two groups of RTIs.
- Nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs)
- Nonnucleoside reverse transcriptase inhibitors (NNRTIs)
Nucleosides (NRTIs):
- Zidovudin
- Lamivudine
***Zidovudine + Lamivudine (Combivir) is given to healthcare providers after accidental needle stick.
96
What is the mechanism of action of Protease Inhibitors? Give examples. What are their side effects?
Protease Inhibitors: The HIV protease enzyme is involved in the maturation of newly forming viral particle. By inhibiting the HIV protease, these drugs interfere with the processing of viral protein, thus preventing formation of new viral particles.
* **Atazanavir
* **Fosamprenavir: is a prodrug of amprenavir
Side effects: hyperbilirubinia and jaundice; diarrhea, nausea, vomiting, rash, and hyperlipidemia.
97
What are the drugs used to treat influenza? What are their MOA?
The mainstay of protection against influenza has always been vaccination.
***Amantidine: inhibits virus uncoating. It is used for the tx and prevention of influenza type A infections.
Neuroaminidase inhibitors: They block the release of influenza virus from infected cells by inhibiting neuraminidase which is inserted into the host cell membrane for the purpose of releasing newly formed virions. They are used for the prevention and treatment of both influenza A and B infections.
***Zanamivir: neuroaminidase inhibitor
98
What is the MOA of Amantidine? List important drugs used to treat herpes and cytomegalovirus infections.
Amantidine MOA: inhibits virus uncoating. It is used for the tx and prevention of influenza type A infections.
Drugs for herpes virus: inhibit viral DNA synthesis.
* **Acyclovir: effective against Herpes Simplex Virus types 1 and 2 (HSV-1 and HSV-2), varicella zoster virus (VZV), Epstein Barr Virus (EBV) and Cytomegalovirus (CMV) - used topically, IV and orally for tx of herpes.
* **Foscarnet: approved CMV retinitis, and acyclovir resistant HSV and VZV
* **Gancyclocir: drug of choice for cytomegalovirus infections
99
What is the use of Ribavirin?
Ribavirin: interferes with viral messenger RNA; used in tx of Respiratory syncytial viral infections (RSV) in infants and young children, not in adults
100
List important drugs used to treat Hepatitis B and Hepatitis C. What is the MOA of interferons?
Hepatitis B Virus (HBV) infection
- Aedefovir
- Tenofovir
Hepatitis C Virus (HCV) infection
- Pegylated interferon alpha-2a or Pegylated interferon alpha-2b
- Ribavirin
Interferon MOA: induces host cell enzymes that inhibit viral RNA translation, ultimately leading to the degradation of viral mRNA and tRNA.
101
What are the MOA and adverse effects of Cyclophosphamide?
***anticancer drugs
Cyclophosphamide: Alkylating agent --> most commonly used alkylating agent; can cause hemorrhagic cystitis
Alkylating Agents: They all work by adding an alkyl group to components of DNA called alkylation of DNA. They are prone to cause local tissue necrosis and damage.
102
What are the MOA and uses of Methotrexate?
***anticancer drugs
Methotrexate: Antimetabolites
binds and competitively inhibits the enzyme dihydrofolate reductase. It is used to treat psoriasis and severe active rheumatoid arthritis in addition to a whole variety of cancers. It can be administered intrathecally. Leucovorin prevents methotrexate from inhibiting dihydrofolate reductase and reverses all of its adverse effects except neurotoxicity.
Antimetabolities: interfere with the availability of normal purine or pyrimidine bases either by inhibiting their synthesis, or by competing with them in DNA or RNA synthesis. Their maximum cytotoxic effects are S-phase specific.
103
What are the MOA and adverse effects of Doxorubicin? What is the adverse effect of Bleomycin?
***anticancer drugs
Doxorubicin MOA: disrupt DNA fx (S and G2 phase); can cause cardiotoxicity as well as alopecia and bone marrow depression
Bleomycin: can cause fatal pulmonary fibrosis. Extreme caution must be used in patients with a pre-existing history of lung disease.
104
What are the mechanism of action and adverse effects of Vinca Alkaloids -- Vincristine and Vinblastine?
***anticancer drugs - microtubule inhibitors: they bind to the tubules and disrupt the spindle apparatus during cell division.
Vinca alkaloids:
Vincristine: has neurologic toxicity
Vinblastine: has bone marrow toxicity
105
Classify hormonal agents used to treat cancers. List a drug of each group.
Hormonal Agents: These drugs are used to treat hormonally sensitive tumors, such as tumors of the breast, prostate, and uterus. The goal is to 1. reduce the level of hormone that is stimulating growth of the tumor or 2. block the receptor of the hormone. 3. But glucocorticoids produce cytotoxic effect.
Classify Hormonal Agents:
1. Glucorticoids
- Prednisone --> used to induce remission in patients wiht acute lymphocytic leukemia and in the tx of both Hodgkin's and non-Hodkin's lymphoma
2. Aromatase Inhibitors
- Anastrozole --> used in the tx of estrogen-dependent breast cancer resistant to tamoxifen.
3. Antiestrogens
- Tamoxifen is a competitive antagonist of estrogen receptor; first-line agent in the tx of estrogen receptor-positive breast cancer
4. Androgen receptor antagonists
- Flutamide --> used in tx of prostate cancer
5. GnRH Analogs
- Leuprolide --> used in metastatic prostatic cancer
106
What are the uses of imatinib, cisplatin, and Bacille Calmette-Guerin (BCG) vaccine in cancer?
***anticancer drugs - other anticancer drugs
***Imatinib: used in the tx of chronic myeloid leukemia
***cisplatin and carbaplatin: used for the tx of testicular carcinoma, ovarian carcinoma, and bladder carcinoma
***Bacille Calmette-Guerin (BCG) vaccine: is a tuberculosis vaccine that appears to be most effective in treating small localized superficial urinary bladder carcinoma, and is approved for intravesicular use. It is non-specific stimulant of the reticuloendothelial system
107
What is the mechanism of action of NSAIDS? What serious adverse effect can happen when using aspirin in viral infections? What is a special use for indomethacin?
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): they act primarily by inhibiting the cyclooxygenase enymes that catalyze the first step in prostaglandin biosynthesis. This leads to decrease prostaglandin synthesis with both beneficial and unwanted effects. Long-term treatment with COX-2 specific inhibitors has been shown to increase the risk of myocardial infarctions and strokes, and several of these drugs have been withdrawn.
***Aspirin can cause Reye syndrome if given in viral infections, especially in children. Aspirin is an irreversible inhibitor of COX.
***Indomethacin: used in patent ductus arteriosus (PDA) in newborn babies.
108
What is the use of and advantage of using COX-2 inhibitors? Give an example.
Selective COX-2 Inhibitors: does not inhibit platelet aggregation and has a lower risk for GI bleeding; good for chronic use; may cause hypertension. Long-term tx with COX-2 specific inhibitors has been shown to increase the risk of myocardial infarctions and strokes...
* **Celocoxib (Celebrex)
* **Rofecoxib (Vioxx): has been withdrawn
109
What are the actions, mechanism of action, and limitations of using Acetaminophen?
***other analgesics
Acetaminophen: inhibits prostaglandin synthesis in the CNS. This explains its antipyretic and analgesic properties. Acetominophen has less effect on cyclooxygenase in peripheral tissues, which accounts for its weak anti-inflammatory activity.
***pain reliever
110
What are the uses of methotrexate, D-penicillamine, and infliximab? What is the mechanism of action of Infliximab?
***anti-inflammatory drugs
Infliximab: Drugs for arthritis --> binds to TNF-alpha and neutralizes that cytokine; used in Crohn's disease
Disease-modifying anti-rheumatic drugs (DMARDs)
* **Methotrexate: rheumatoid arthritis
* **D-Penicillamine: rheumatoid arthritis; also used as a chelating agent in the tx of heavy metal poisoning and in Wilson's disease.
111
What is the MOA of Allopurinol, Colchicine and Probanacid in Gout?
* **drugs for gout
* **Allopurinol: inhibits xanthine oxidase thereby reducing uric acid formation
* **Colchicine: decreases the migration of neutrophils to the site of inflammation; also inhibits synthesis d release of leukotrienes; used in acute attack of gout.
* **Probenecid: increases uric acid excretion by the kidneys (uricosuric drugs)
112
What is the MOA, uses and toxic effects of Cyclosporine?
***immunosuppresive drugs - used to inhibit rejection of transplanted tissue
selective inhibitors of cytokine production and function
***Cyclosporine (CsA): Agent of choice in preventing and treating transplanted organ rejection because it is a specific T cell inhibitor. It binds with calcineurin ultimately inhibiting the synthesis of IL-2 which is responsible T cell growth and function.
Toxic effects of cyclosporine (CsA): nephrotoxicity, thromboembolism, neurotoxicity, seizure, etc. Because of its severe adverse reaction, it is used in conjunction with azathioprine which reduces the required dose.
