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Flashcards in Pharm_Part1 Deck (321):
1

"Fibrates" (gemfibrozil, clofibrate, bezafibrate, fenofibrate)

Mechanism: Upregulate LPL → ↑TG clearance Toxicity: Myositis, hepatotoxicity (↑LFTs), cholesterol gallstones LDL↓; HDL↑; TG↓↓↓

2

"Monday disease" in industrial exposure of nitrate

Development of tolerance for the vasolilating action during the work week and loss of tolerance over the weekend, resulting in tachycardia, dizziness and headache on reexposure

3

5-fluorouracil (5-FU)

Mechanism: Pyrimidine analog bioactivated to 5F-dUMP, which covalently complexes folic acid. This complex inhibits thymidylate synthase → ↓ dTMP → ↓ DNA and ↓ protein synthesis Clinical use: Colon cancer and other solid tumors, basal cell carcinoma (topical). Synergy with MTX. Toxicity: 1. Myelosuppression, which is reversible with thymidine "rescue" 2. Photosensivity

4

6-mercaptopurine (6-MP)

Mechanism: Purine (thiol) analog → ↓ de novo purine synthesis. Activated by HGPRTase. Clinical use: Leukemias, lymphomas (not CLL or Hodgkin's) Toxicity: Bone marrow, GI, liver. Metabolized by xanthine oxidase; thus ↑ toxicity with allopurinol.

5

6-thioguanine (6-TG)

Mechanism: Purine (thiol) analog → ↓ de novo purine synthesis. Activated by HGPRTase. Clinical use: Acute lymphoid leukemia Toxicity: Bone marrow depression, liver. Can be given with allopurinol.

6

Abciximab

Mechanism: Monoclonal antibody that binds to the glycoprotein receptor IIb/IIIa on activated platelets, preventing aggregation Clinical use: Acute coronary syndromes, percutaneous transluminal coronary angioplasty Toxicity: Bleeding, thrombocytopenia

7

Alcohol toxicity

Page 246 of FA2011, focus on: Alcohol dehydrogenase - Fomepizole Acetaldehyde dehydrogenase - Disulfiram

8

Amiodarone

Has class I, II, III, and IV effects because it alters the lipid membrane

9

Amphetamine

Indirect sympathomimetics, indirect general agonist, releases stored catecholamines Clinical use: Narcolepsy, obesity, attention deficit disorder

10

Antacid Overuse

1. Aluminum hydroxide - constipation and hypophosphatemia; proximal muscle weakness, osteodystrophy, seizures 2. Magnesium hydroxide - diarrhea, hyporeflexia, hypotension, cardiac arrest 3. Calcium carbonate - hypercalcemia, rebound acid ↑ PS: Can also cause hypokalemia, can chelate and ↓ the effectiveness of other drugs (e.g., tetracycline)

11

Antacid use affecting the body

Can affect absorption, bioavailability, or urinary excretion of other drugs by altering gastric and urinary pH or by delaying gastric emptying.

12

Antianginal therapy

Nitrates + β-blockers; β-blockers; Nitrates **Page 281 on FA2011, comparison in different components of drug effects

13

Antianginal therapy: Calcium channel blockers

Nifedipine is similar to nitrates in effect; Verapamil is similar to β-blockers in effect

14

Antiarrhythmics - Ca2+ channel blockers (Class IV)

Verapamil, diltiazem Mechanism: ↓ conduction velocity, ↑ ERP, ↑ PR interval. Used in prevention of nodal arrhythmias (e.g., SVT) Toxicity: Constipation, flushing, edema, CV effects (CHF, AV block, sinus node depression)

15

Antiarrhythmics - K+ channel blockers (Class III): Names + Mechanism

Sotalol, ibutilide, bretylium, dofetilide, amiodarone Mechanism: ↑AP duration, ↑ERP. Used when other antiarrhythmics fail. ↑QT interval.

16

Antiarrhythmics - Na+ channel blockers (Class IA): Names + Mechanism

Quinidine, Procainamide, Disopyramide ↑AP duration, ↑effective refractory period (ERP), ↑QT interval. Affect both atrial and ventricular arrhythmias, especially reentrant and ectopic supraventricular and ventricular tachycardia

17

Antiarrhythmics - Na+ channel blockers (Class IB): Names + Mechanism

Lidocaine, Mexiletine, Tocainide ↓AP duration. Preferentially affect ischemic or depolarized Purkinjie and ventricular tissue. Useful in acute ventricular arrhythmias (especially post-MI) and in digitalis-induced arrhythmias

18

Antiarrhythmics - Na+ channel blockers (Class IC): Names + Mechanism

Flecainide, Encainide, Propafenone No effect on AP duration. Useful in V-tachs that progress to VF and in intractable SVT. Usually used only as last resort in refractory tachyarrhythmias. For patients without structural abnormalities

19

Antiarrhythmics - β-blockers (Class II)

Mechanism: ↓cAMP, ↓Ca2+ currents. Suppress abnormal pacemakers by ↓ slope of phase 4. AV node particularly sensitive - ↑ PR interval. Esmolol very short acting. Clinical use: V-tach, SVT, slowing ventricular rate during atrial fibrillation and atrial flutter. Toxicity: Impotence, exacerbation of asthma, cardiovascular effects (bradycardia, AV block, CHF), CNS effects (sedation, sleep alterations). May mask the signs of hypoglycemia. Treat overdose with glucagon.

20

Antiarrhythmics: Adenosine

↑K+ out of cells → hyperpolarizing the cell + ↓ Ica. Drug of choice in diagnosing / abolishing supraventricular tachycardia. Very short acting (~15s). Toxicity includes flushing, hypotension, chest pain. Effects blocked by theophylline

21

Antiarrhythmics: K+

Depresses ectopic pacemakers in hypokalemia (e.g., digoxin toxicity)

22

Antiarrhythmics: Mg2+

Effective in torsades de pointes and digoxin toxicity

23

Antibodies to avoid in pregnancy (8)

Sulfonamides - kernicterus Aminoglucosides - ototoxicity Fluoroquinolones - cartilage damage Metronidazole - mutagenesis Tetracyclines - discolored teeth, inhibition of bone growth Ribavirin (antiviral) - teratogenic Griseofulvin (antifungal) - teratogenic Chloramphenicol - "gray baby"

24

Antidote: Acetaminophen

N-acetylcysteine

25

Antidote: Acetylcholinesterase inhibitors, organophosphates

Atropine, pralidoxime

26

Antidote: Amphetamines (basic)

NH4Cl (acidify urine)

27

Antidote: Antimuscarinic, anticholinergic

Physostigmine salicylate

28

Antidote: Benzodiazepines

Flumazenil

29

Antidote: Carbon monoxide

100% O2, hyperbaric O2

30

Antidote: Cardiac glycosides - Digoxin

Slowly normalize K+, lidocaine, cardiac pacer, anti-dig Fab fragments, Mg2+

31

Antidote: Copper, arsenic, gold

Penicillamine

32

Antidote: Cyanide

Nitrite, hydroxocobalamin, thiosulfate

33

Antidote: Digitalis

Stop digitalis, normalize K+, lidocaine, anti-dig Fab fragments, Mg2+

34

Antidote: Heparin

Protamine

35

Antidote: Iron

Deferoxamine

36

Antidote: Lead

CaEDTA, dimercaprol, succimer, penicillamine

37

Antidote: Mercury, arsenic, gold

Dimercaprol (BAL), succimer

38

Antidote: Methanol, ethylene glycol (antifreeze)

Ethanol, dialysis, fomepizole

39

Antidote: Methemoglobin

Methylene blue, vitamin C

40

Antidote: Opioids

Naloxone, naltrexone

41

Antidote: Salicylates

NaHCO3 (alkalinize urine), dialysis

42

Antidote: TCAs

NaHCO3 (plasma alkalinization)

43

Antidote: Theophylline

β-blocker

44

Antidote: tPA, streptokinase

Aminocaproic acid

45

Antidote: Warfarin

For reversal of warfarin overdose, give vitamin K. For rapid reversal of severe warfarin overdose, give fresh frozen plasma.

46

Antidote: Warfarin (Acute, chronic)

Acute: Fresh frozen plasma Chronic: Vitamin K

47

Antidote: β-blockers

Glucagon

48

Antifungal therapy: Amphotericin B

Mechanism: Binds ergosterol (unique to fungi); forms membrane pores that allow leakage of electrolytes Clinical use: Serious, systemic mycoses. Cryptococcus, Blastomyces, Coccidioides, Aspergillus, Histoplasma, Candida, Mucor (systemic mycoses). Intrathecally for fungal meningitis; does not cross blood-brain barrier. Toxicity: Fever/chills ("shake and bake"), hypotension, nephrotoxicity, arrhythmias, anemia, IV phlebitis ("amphoterrible"). Hydration reduces nephrotoxicity. Liposomal amphotericin reduces toxicity.

49

Antifungal therapy: Azoles (Fluconazole, ketoconazole, clotrimazole, miconazole, itraconazole, voriconazole)

Mechanism: Inhibit fungal sterol (egosterol) synthesis, by inhibiting the P-450 enzyme that converts lanosterol to egosterol. Clinical use: Systemic mycoses. Fluconazole for cryptococcal meningitis in AIDS patients (because it can cross blood-brain barrier) and candidal infections of all types. Ketoconazole for Blastomyces, Coccidioides, Histoplasma, Candida albicans; hypercortisolism. Clotrimazole and micronazole for topical fungal infections. Toxicity: Hormone synthesis inhibition (gynecomastia), liver dysfunction (inhibits cytochrome P-450), fever, chills.

50

Antifungal therapy: Caspofungin

Mechanism: Inhibits cell wall synthesis by inhibiting synthesis of β-glucan Clincal use: Invasive aspergillosis Toxicity: GI upset, flushing

51

Antifungal therapy: Flucytosine

Mechanism: Inhibits DNA synthesis by conversion to 5-fluorouracil Clinical use: Used in systemic fungal infections (e.g., Candida, Cryptococcus) in combination with amphotericin B Toxicity: Nausea, vomiting, diarrhea, bone marrow suppression

52

Antifungal therapy: Griseofulvin

Mechanism: Interferes with microtubule function; disrupts mitosis. Deposits in keratin-containing tissues (e.g., nails) Clinical use: Oral treatment of superficial infections; inhibits growth of dermatophytes (tinea, ringworm) Toxicity: Teratogenic, carcinogenic, confusion, headaches, ↑P-450 and warfarin metabolism

53

Antifungal therapy: Nystatin

Mechanism: Binds ergosterol (unique to fungi); forms membrane pores that allow leakage of electrolytes. Topical form because too toxic for systemic use. Clinical use: "Swish and swallow" for oral candidiasis (thrush); topical for diaper rash or vaginal candidiasis

54

Antifungal therapy: Terbinafine

Mechanism: Inhibits the fungal enzyme squalene epoxidase Clinical use: Used to treat dermatophytoses (especially onychomycosis - fungal infection of finger or toe nails)

55

Antihypertensive therapy: CHF

Diuretics, ACE inhibitors / ARBs, β-blockers (compensated CHF), K+-sparing diuretics. PS: β-blockers are contraindicated in decompensated CHF

56

Antihypertensive therapy: Diabetes mellitus

ACE inhibitors / ARBs, calcium channel blockers, diuretics, β-blockers, α-blockers. PS: ACE inhibitors are protective against diabetic nephropathy

57

Antihypertensive therapy: Essential hypertension

Diuretics, ACE inhibitors, angiotensin II receptor blockers (ARBs), calcium channel blockers

58

Antiviral: Acyclovir

Mechanism: Monophosphorylated by HSV/VZV thymidine kinase. Guanosine analog. Triphosphate formed by cellular enzymes. Preferentially inhibits viral DNA polymerase by chain termination Clinical use: HSV, VZV, EBV. Used for HSV-induced mucocutaneous and genital lesions as well as for encephalitis. Prophylaxis in immunocompromised patients. No effect on latent forms of HSV and VZV. Toxicity: Generally well tolerated

59

Antiviral: Amantadine

Mechanism: Blocks viral penetration / uncoating (M2 protein). Also causes the release of dopamine from intact nerve terminals. Clinical use: Prophylaxis and treatment of influenza A only; Parkinson's disease. Toxicity: Ataxia, dizziness, slurred speech

60

Antiviral: Famciclovir

Mechanism: Monophosphorylated by HSV/VZV thymidine kinase. Guanosine analog. Triphosphate formed by cellular enzymes. Preferentially inhibits viral DNA polymerase by chain termination Clinical use: HSV, VZV, EBV. Used for herpes zoster. No effect on latent forms of HSV and VZV. Toxicity: Generally well tolerated

61

Antiviral: Foscarnet

Mechanism: Viral DNA polymerase inhibitor that binds to the pyrophosphate-binding site of the enzyme. Does not require activation by viral kinase. Clinical use: CMV retinitis in immunocomprimised patients when ganciclovir fails; acyclovir-resistant HSV. Toxicity: Nephrotoxicity

62

Antiviral: Ganciclovir

Mechanism: 5'-monophosphate formed by a CMV viral kinase or HSV/VZV thymidine kinase. Guanosine analog. Triphosphate formed by cellular kinases. Preferentially inhibits viral DNA polymerase. Clinical use: CMV, especially in immunocompromised patients. Toxicity: Leukopenia, neutropenia, thrombocytopenia, renal toxicity. More toxic to host enzymes than acyclovir.

63

Antiviral: Interferons

Mechanism: Glycoproteins synthesized by virus-infected cells block replication of both RNA and DNA viruses Clinical use: IFN-α - Chronic hepatitis B and C, Kaposi's sarcoma. IFN-β - MS. IFN-γ - NADPH oxidase deficiency Toxicity: Neutropenia

64

Antiviral: Ribavirin

Mechanism: Inhibits synthesis of guanine nucleotides by competitively inhibiting IMP dehydrogenase Clinical use: RSV, chronic hepatitis C Toxicity: Hemolytic anemia. Severe teratogen

65

Antiviral: Rimantidine

A derivative with fewer CNS side effects of amantadine. Does not cross the blood-brain barrier.

66

Antiviral: Zanamivir, oseltamivir

Mechanism: Inhibit influenza neuraminidase, decreasing the release of progeny virus. Clinical use: Both influenza A and B.

67

Aspirin (ASA)

Mechanism: Acetylates and irreversibly inhibits cyclooxygenase (both COX-1 and COX-2) to prevent conversion of arachidonic acid to thromboxane A2 (TxA2). ↑ bleeding time. No effect on PT, PTT. Clinical use: Antipyretic, analgesic, anti-inflammatory, antiplatelet drug. Toxicity: Gastric ulceration, bleeding, hyperventilation, Reye's syndrome, tinnitus (CN VIII)

68

Azathioprine

Mechanism: Antimetabolite precursor of 6-mercaptopurine that interferes with the metabolism and synthesis of nucleic acids. Toxic to proliferating lymphocytes. Clinical use: Kidney transplantation, autoimmune disorders (including glomerulonephritis and hemolytic anemia) Toxicity: Bone marrow suppression. Active metabolite mercaptopurine is metabolized by xanthine oxidase; thus, toxic effects may be ↑ by allopurinol

69

Basic concepts on Autonomic drugs

P235-P242 of FA2011, very important!!!

70

Bethanechol

Direct cholinomimetic agents Clinical use: Postoperative and neurogenic ileus and urinary retention Action: Activates bowel and bladder smooth muscle; resistant to AChE

71

Biguanides (first name them)

Metformin Mechanism: Exact mechanism is unknown. ↓gluconeogenesis, ↑glycolysis, ↑peripheral glucose uptake (insulin sensitivity) Clinical use: Oral, can be used in patients without islet function. Toxicity: Most grave adverse effect is lactic acidosis

72

Bile acid resins

Mechanism: Prevent intestinal reabsorption of bile acids; liver must use cholesterol to make more Toxicity: Patients hate it - tastes bad and cause GI discomfort, ↓ absorption of fat-soluble vitamins. Cholesterol gallstones. LDL↓↓; HDL↑(slightly); TG↑(slightly)

73

Bile acid resins: Names

Cholestyramine, colestipol, colesevelam

74

Bismuth, sucralfate

Mechanism: Bind to ulcer base, providing physical protection, and allow HCO3- secretion to reestablish pH gradient in the mucous layer Clinical use: ↑ ulcer healing, traveler's diarrhea

75

Bleomycin

Mechanism: Induces free radical formation, which causes breaks in DNA strands Clinical use: Testicular cancer, Hodgkin's lymphoma Toxicity: Pulmonary fibrosis, skin changes. Minimal myelosuppression.

76

Busulfan

Mechanism: Alkylates DNA Clinical use: CML. Also used to ablate patient's bone marrow before bone marrow transportation. Toxicity: Pulmonary fibrosis, hyperpigmentation

77

Calcium channel blockers: Names (a properties)

Nifedipine, verapamil, diltiazem Vascular smooth muscle - Nifedipine > diltiazem > verapamil Heart - Verapamil > diltiazem > nifedipine

78

Carbachol

Direct cholinomimetic agents Clinical use: Glaucoma, pupillary contraction, and relief of intraocular pressure Action: Carbon copy of acetylcholine

79

Cholesterol absorption blockers (ezetimibe)

Mechanism: Prevent cholesterol reabsorption at small intestine brush border Toxicity: Rare ↑ LFTs LDL↓↓; HDL-; TG-

80

Cholinesterase inhibitor poisoning

Often due to organophosphates, such as parathion, that irreversibly inhibit AchE. Causes Diarrhea, Urination, Miosis, Bronchospasm, Bradycardia, Excitation of skeletal muscle and CNS, Lacrimation, Sweating, and Salivation Antidote - atropine + pralidoxime (regenerates active AchE)

81

Cisplatin / Carboplatin

Mechanism: Cross-link DNA Clinical use: Testicular, bladder, ovary, and lung carcinomas Toxicity: Nephrotoxicity and acoustic nerve damage

82

Clinical presentation: Sulfa allergy

May develop fever, pruritic rash, Steven-Johnson syndrome, hemolytic anemia, thrombocytopenia, agranulocytosis, and urticaria (hives). Symptoms range from mild to life-threatening.

83

Clinical use: Calcium channel blockers

Hypertension, angina, arrhythmias (not nifedipine), Prinzmetal's angina, Raynaud's syndrome.

84

Clinical use: Cardiac glycosides - Digoxin

CHF (↑ contractility); atrial fibrillation (↓ conduction at AV node and depression of SA node)

85

Clinical use: Glucocorticoids

Addison's disease, inflammation, immune suppression, asthma

86

Clinical use: H2 blockers

Peptic ulcer, gastritis, mild esophageal reflux

87

Clinical use: Heparin

Immediate anticoagulation for pulmonary embolism, stroke, acute coronary syndrome, MI, DVT. Used during pregnancy (does not cross the placenta). Follow PTT.

88

Clinical use: Thrombolytics

Early MI, early ischemic stroke.

89

Clinical use: Warfarin (Coumadin)

Chronic anticoagulation. Not used in pregnant women (because warfarin, unlike heparin, can cross the placenta). Follow PT/INR values.

90

Clinical use: β-blockers

Hypertension: ↓cardiac output, ↓renin secretion (due to β-receptor blockade on JGA cells) Angina pectoris: ↓heart rate and contractility, resulting in ↓O2 consumption MI: β-blockers ↓mortality SVT (propranolol, esmolol): ↓AV conduction velocity (class II antiarrhythmic) CHF: Slows progression of chronic failure Glaucoma (timolol): ↓secretion of aqueous humor

91

Clopidogrel, ticlopidine

Mechanism: Inhibit platelet aggregation by irreversibly blocking ADP receptors, preventing glycoprotein IIb/IIIa from binding fibrinogen Clinical use: Acute coronary syndrome; coronary stenting. ↓ incidence or recurrence of thrombotic stroke. Toxicity: Neuropenia (ticlopidine)

92

Cocaine

Indirect sympathomimetics, indirect general agonist, uptake inhibitor Clinical use: Causes vasoconstriction and local anesthesia

93

Comparison between Heparin and Warfarin

P362 on FA2011, though personally do not think it to be needed if you understood the two drugs itself...

94

Contraindication: Antiarrhythmics - Na+ channel blockers (Class IC)

Post-MI

95

Contraindication: Biguanides (Metformin)

Renal failure

96

Contraindication: Hydralazine

in Angina / CAD

97

Contraindication: Metoclopramide

patients with small bowel obstruction

98

Contraindication: Misoprostol

in women of childbearing potential (abortifacient)

99

Contraindications: Pindolol, acebutolol

Angina, because they are partial β-agonists

100

Cyclophosphamide / Isosfamide

Mechanism: Covalently X-link (interstrand) DNA at guanine N-7. Require bioactivation by liver. Clinical use: Non-Hodgkin's lymphoma, breast and ovarian carcinomas. Also immunosuppressants. Toxicity: Myelosuppression; hemorrhagic cystitis, partially prevented with mesna (thiol group of mesna binds toxic metabolite)

101

Cyclosporine

Mechanism: Binds to cyclophilins. Complex blocks the differentiation and activation of T cells by inhibiting calcineurin, thus preventing the production of IL-2 and its receptor Clinical use: Suppresses organ rejection after transplantation; selected autoimmune disorders Toxicity: Predisposes patient to viral infections and lymphoma; nephrotoxic (preventable with mannitol diuresis)

102

Cytarabine (ara-C)

Mechanism: Pyrimidine analog → inhibition of DNA polymerase Clinical use: AML, ALL, high-grade non-Hodgkin's lymphoma Toxicity: Leukopenia, thrombocytopenia, megaloblastic anemia

103

Daclizumab

Mechanism: Monoclonal antibody with high affinity for the IL-2 receptor on activated T cells

104

Dactinomycin (Actinomycin D)

Mechanism: Intercalates in DNA Clinical use: Wilm's tumor, Ewing's sarcoma, rhabdomyosarcoma. Used for childhood tumors. Toxicity: Myelosuppression

105

Demeclocycline

Mechanism: ADH antagonist (member of the tetracycline family) Clinical use: SIADH Toxicity: Nephrogenic DI, photosensitivity, abnormalities of bone and teeth

106

Dobutamine

Mechanism: β1 > β2, inotropic but not chronotropic Clinical use: Heart failure, cardiac stress testing

107

DOC: Hemorrhagic cystitis

Mesna, thiol group of mesna binds toxic metabolite causing hemorrhagic cystitis

108

Dopamine

Mechanism: D1 = D2 > β > α, inotropic and chronotropic Clinical use: Shock (↑ renal perfusion)

109

Doxorubicin (Adriamycin) / Daunorubicin

Mechanism: Generate free radicals. Noncovalently intercalate in DNA → breaks in DNA → ↓ replication. Clinical use: Hodgkin's lymphomas, also for myelomas, sarcomas, and solid tumors (breast, ovary, lung) Toxicity: Cardiotoxicity, myelosuppression, and alopecia. Toxic to tissues with extravasation.

110

Drug ending category: -afil

Erectile dysfunction (Sildenafil)

111

Drug ending category: -ane

Inhalational general anesthetic (Halothane)

112

Drug ending category: -azepam

Benzodiazepine (Diazepam)

113

Drug ending category: -azine

Phenothiazine (neuroleptic, antiemetic) (Chlorpromazine)

114

Drug ending category: -azole

Antifungal (Ketoconazole)

115

Drug ending category: -barbital

Barbiturate (Phenobarbital)

116

Drug ending category: -caine

Local anesthetic (Lidocaine)

117

Drug ending category: -cillin

Penicillin (Methicillin)

118

Drug ending category: -cycline

Antibiotic, protein synthesis inhibitor (Tetracycline)

119

Drug ending category: -etine

SSRI (Fluoxetine)

120

Drug ending category: -ipramine

TCA (Imipramine)

121

Drug ending category: -navir

Protease inhibitor (Saquinavir)

122

Drug ending category: -olol

β antagonist (Propranolol)

123

Drug ending category: -operidol

Butyrophenone (neuroleptic) (Haloperidol)

124

Drug ending category: -oxin

Cardiac glycoside (inotropic agent) (Digoxin)

125

Drug ending category: -phylline

Methylxanthine (Theophylline)

126

Drug ending category: -pril

ACE inhibitor (Captopril)

127

Drug ending category: -terol

β2 agonist (Albuterol)

128

Drug ending category: -tidine

H2 antagonist (Cimetidine)

129

Drug ending category: -triptan

5-HT(1B/1D) agonist (migraine) (Sumatriptan)

130

Drug ending category: -triptyline

TCA (Amitriptyline)

131

Drug ending category: -tropin

Pituatory hormone (Somatotropin)

132

Drug ending category: -zolam

Benzodiazepine (Alprazolam)

133

Drug ending category: -zosin

α1 antagonist (Prazosin)

134

Drug group: Amiodarone

Antiarrhythmics - K+ channel blockers (Class III)

135

Drug group: Bertylium

Antiarrhythmics - K+ channel blockers (Class III)

136

Drug group: Dofetilide

Antiarrhythmics - K+ channel blockers (Class III)

137

Drug group: Ibutilide

Antiarrhythmics - K+ channel blockers (Class III)

138

Drug group: Sotalol

Antiarrhythmics - K+ channel blockers (Class III)

139

Drug reactions: Acute cholestatic hepatitis

Macrolides

140

Drug reactions: Adrenocortical insufficienty

Glucocorticoid withdrawal (HPA suppression)

141

Drug reactions: Agranulocytosis (6)

Clozapine, carbamazepine, colchicine, propylthiouracil, methimazole, dapsone

142

Drug reactions: Aplastic anemia (5)

Chloramphenicol, benzene, NSAIDs, propylthiouracil, methimazole

143

Drug reactions: Atropine-like side effects

TCAs

144

Drug reactions: Cinchonism (2)

Quinidine, Quinine

145

Drug reactions: Coronary vasospasm (2)

Cocaine, sumatriptan

146

Drug reactions: Cough

ACE inhibitors (note: ARBs like losartan - no cough)

147

Drug reactions: Cutaneous flushing (4)

VANC: Vancomycin, Adenosine, Niacin, Ca2+ channel blockers

148

Drug reactions: Diabetes insipidus (2)

Lithium, demeclocycline

149

Drug reactions: Dilated cardiomyopathy (2)

Doxorubicin (Adriamycin), daunorubicin

150

Drug reactions: Direct Coombs-positive hemolytic anemia

Methyldopa

151

Drug reactions: Disulfiram-like reaction (4)

Metronidazole, certain cephalosporins, procarbazine, 1st-generation sulfonylureas

152

Drug reactions: Fanconi's syndrome

Expired tetracycline

153

Drug reactions: Focal to massive hepatic necrosis (4)

Halothane, valproic acid, acetaminophen, Amanita phalloides

154

Drug reactions: Gingival hyperplasia

Phenytoin

155

Drug reactions: Gout (2)

Furosemide, thiazides

156

Drug reactions: Grey baby syndrome

Chloramphenicol

157

Drug reactions: Gynecomastia (6)

Spironolactone, Digitalis, Cimetidine, chronic alcohol use, estrogens, Ketoconazole

158

Drug reactions: Hemolysis in G6PD-deficient patients (6)

Hemolysis IS PAIN, Isoniazid (INH), Sulfonamides, Primaquine, Aspirin, Ibuprofen, Nitrofurantoin

159

Drug reactions: Hemorrhagic cystitis (2)

Cyclophosphamide, ifosfamide (prevent by coadministering with mesna)

160

Drug reactions: Hepatitis

INH

161

Drug reactions: Hot flashes (2)

Tamoxifen, clomiphene

162

Drug reactions: Hypothyroidism (2)

Lithium, amiodarone

163

Drug reactions: Interstitial nephritis (3)

Methicillin, NSAIDs, furosemide

164

Drug reactions: Megaloblastic anemia (3)

Phenytoin, Methotrexate, Sulfa drugs

165

Drug reactions: Nephrotoxicity / neurotoxicity

Polymyxins

166

Drug reactions: Nephrotoxicity / ototoxicity (4)

Aminoglycosides, vancomycin, loop diuretics, cisplatin

167

Drug reactions: Osteoporosis (2)

Corticosteroids, heparin

168

Drug reactions: Parkinson-like syndrome (4)

Haloperidol, chlorpromazine, reserpine, metoclopramide

169

Drug reactions: Photosensitivity (3)

Sulfonamides, Amiodarone, Tetracycline

170

Drug reactions: Pseudomembranous colitis (2)

Clindamycin, ampicillin

171

Drug reactions: Pulmonary fibrosis

Bleomycin, Amiodarone, Busulfan (BLAB)

172

Drug reactions: Rash (Steves-Johnson syndrome) (8)

Ethosuximide, lamotrigine, carbamazepine, phenobarbital, phenytoin, sulfa drugs, penicillin, allopurinol

173

Drug reactions: Seizures (3)

Bupropion, imipenem / cilastatin, isoniazid

174

Drug reactions: SLE-like syndrome (4)

Hydalazine, INH, Procainamide, Phenytoin

175

Drug reactions: Tardive dyskinesia

Antipsychotics

176

Drug reactions: Tendonitis, tendon rupture, and cartilage damage (kids)

Fluoroquinolones

177

Drug reactions: Thrombotic complication

OCPs (e.g., estrogens and progestins)

178

Drug reactions: Torsades de pointes (2)

Class III (sotalol), class IA (quinidine) antiarrhythmics

179

Echothiophate

Indirect cholinomimetic agents Clinical use: Glaucoma Action: ↑endogenous ACh

180

Edrophonium

Indirect cholinomimetic agents Clinical use: Diagnosis of myasthenia gravis (extremely short acting) Action: ↑endogenous ACh

181

Ephedrine

Indirect sympathomimetics, indirect general agonist, releases stored catecholamines Clinical use: Nasal decongestion, urinary incontinence, hypotension

182

Epinephrine

Mechanism: α & β, low doses selective for β1, high doses selective for α Clinical use: Anaphylaxis, glaucoma (open angle), asthma, hypotension

183

Etoposide (VP-16) / Teniposide

Mechanism: Inhibits topoisomerase II → ↑ DNA degradation Clinical use: Small cell carcinoma of the lung and prostate, testicular carcinoma Toxicity: Myelosuppression, GI irritation, alopecia

184

First generation Sulfonyureas (first name them)

Tolbutamide, Chlorpropamide Mechanism: Close K+ channel in β-cell membrane, so cell depolarizes → triggering of insulin release via ↑ Ca2+ influx Clinical use: Stimulate release of endogenous insulin in type 2 DM. Require some islet function, so useless in type I DM. Toxicity: Disulfiram-like effects

185

Glitazones / thiazolidinediones (first name them)

Pioglitazone, Rosiglitazone (-glitazone) Mechanism: ↑ insulin sensitivity in peripheral tissue. Binds to PPAR-γ nuclear transcription regulator. Clinical use: Used as monotherapy in type 2 DM or combined with above agents. Toxicity: Weight gain, edema. Hepatotoxicity, CV toxicity.

186

GLP-1 analogs (first name them)

Exenatide Mechanism: ↑insulin, ↓glucagon release Clinical use: Type 2 DM Toxicity: Nausea, vomiting, pancreatitis

187

Glucocorticoids: Names

Hydrocortisone, prednisone, triamcinolone, dexamethasone, beclomethasone

188

H2 blockers: Names

Cimetidine, ranitidine, famotidine, nizatidine (-tidine)

189

Heparin-induced thrombocytopenia (HIT)

heparin binds to platelet factor IV, causing antibody production that binds to and activates platelets leading to their clearance and resulting in a thrombocytopenic, hypercoagulable state.

190

Hexamethonium

Mechanism: Nicotinic antagonist Clinical use: Ganglionic blocker. Used in experimental models to prevent vagal reflex responses to changes in blood pressure - e.g., prevents reflex bradycardia caused by NE Toxicity: Severe orthostatic hypotension, blurred vision, constipation, sexual dysfunction.

191

HIV therapy: Fusion inhibitors

Enfuvirtide Mechanism: Bind viral gp41 subunit; inhibit conformational change required for fusion with CD4 cells, blocking entry and replication. Used in patients with persistent viral replication despite antiretroviral therapy Toxicity: Hypersensitivity reactions, reactions at subcutaneous injection site, ↑ risk of bacterial pneumonia

192

HIV therapy: Highly active antiretroviral therapy (HAART)

Initiated when patients present with AIDs-defining illness, low CD4-cell counts (<350 cells/mm^3), or high viral load. Regimen consists of 3 drugs to prevent resistance: [2 nucleoside reverse transcriptase inhibitors (NRTIs) + 1 protease inhibitor] OR [2 NRTIs + 1 non-nucleoside reverse transcriptase inhibitor (NNRTI-)]

193

HIV therapy: NNRTIs

Nevirapine, Efavirenz, Delavirdine Mechanism: Bind to reverse transcriptase at site different from NRTIs. Do not require phosphorylation to be active or compete with nucleotides. Toxicity: Bone marrow suppression (can be reversed with G-CSF and erythropoietin), peripheral neuropathy, lactic acidosis (nucleosides), rash (non-nucleosides), megaloblastic anemia (ZDV)

194

HIV therapy: NRTIs

Zidovudine (ZDV), Didanosine (ddI), Zalcitabine (ddC), Stavudine (d4T) Mechanism: Competitively inhibit nucleotide binding to reverse transcriptase or terminate the DNA chain (lack a 3'-OH group). Must be phosphorylated by thymidine kinase to be active. ZDV is used for general prophylaxis and during pregnancy to reduce risk of fetal transmission. Toxicity: Bone marrow suppression (can be reversed with G-CSF and erythropoietin), peripheral neuropathy, lactic acidosis (nucleosides), rash (non-nucleosides), megaloblastic anemia (ZDV)

195

HIV therapy: Protease inhibitors

Saquinvir, Ritonavir, Indinavir, Nelfinavir, Amprenavir (-navir) Mechanism: Assembly of virions depends on HIV-1 protease (pol gene), which cleaves the polypeptide products of HIV mRNA into their functional parts. Thus, protease inhibitors prevent maturation of new viruses Toxicity: Hyperglycemia, GI intolerance (nausea, diarrhea), lipodystrophy (Cushingoid), thrombocytopenia (indinavir)

196

HMG-Coa reductase inhibitors (-statin)

Mechanism: Inhibit cholesterol percursor, mevalonate Toxicity: Hepatotoxicity (↑LFTs), rhabdomyolysis LDL↓↓↓; HDL↑; TG↓

197

Hydralazine

Mechanism: ↑ cGMP → smooth muscle relaxation. Vasodilates arterioles > veins; afterload reduction. Clinical use: Severe hypertension, CHF. First-line therapy for hypertension in pregnancy, with methyldopa. Frequently coadministered with a β-blocker to prevent reflex tachycardia. Toxicity: Compensatory tachycardia, fluid retention, nausea, headache, angina, Lupus-like syndrome.

198

Hydroxyurea

Mechanism: Inhibits ribonucleotide reductase → ↓ DNA synthesis (S-phase specific) Clinical use: Melanoma, CML, sickle cell disease (↑ HbF) Toxicity: Bone marrow suppression, GI upset.

199

Hypothalamic / pituitary drugs - Clinical use: ADH (desmopressin)

Pituitary (central, not nephrogenic) DI

200

Hypothalamic / pituitary drugs - Clinical use: GH

GH deficiency, Turner syndrome

201

Hypothalamic / pituitary drugs - Clinical use: Oxytocin

Stimulates labor, uterine contractions, milk let-down; controls uterine hemorrhage

202

Hypothalamic / pituitary drugs - Clinical use: Somatostatin (octreotide)

Acromegaly, carcinoid, gastrinoma, glucagonoma

203

Imatinib (Gleevec)

Mechanism: Philadelphia chromosome bcr-abl tyrosine kinase inhibitor. Clinical use: CML, GI stromal tumors Toxicity: Fluid retention

204

Infliximab

Mechanism: A monoclonal antibody to TNF, proinflammatory cytokine. Clincal use: Crohn's disease, rheumatoid arthritis Toxicity: Respiratory infection (including reactivation of latent TB), fever, hypotension

205

Insulin

Mechanism: Bind insulin receptor (tyrosine kinase activity). Liver - ↑glucose stored as glycogen. Muscle - ↑ glycogen and protein synthesis, K+ uptake. Fat - aids TG storage Clincal use: Type 1 DM, type 2 DM, gestational diabetes, life-threatening hyperkalemia, and stress-induced hyperglycemia. Toxicity: Hypoglycemia, hypersensitivity reaction (very rare)

206

Isoproterenol

Mechanism: β1 = β2 (isolated to β) Clinical use: AV block (rare)

207

Ketorolac

NSAID often used as an analgesic, indicated for short-term management of moderate to severe pain

208

Lepirudin, bivalirudin

Hirudin derivatives; directly inhibit thrombin. Used as an alternative to heparin for anticoagulating patients with HIT

209

Leucovorin

Folinic acid, rescue methotrexate (MTX) myelosuppression

210

Levothyroxine, triiodothyronine

Mechanism: Thyroxine replacement Clinical use: Hypothyroidism, myxedema Toxicity: Tachycardia, heat intolerance, tremors, arrhythmias

211

Low-molecular-weight-heparins (e.g., enoxaparin)

act more on Xa, have better bioavailability and 2-4 times longer half-life. Can be administered subcutaneously and without laboratory monitoring. Not easily reversible.

212

Malignant hypertension treatment: Diazoxide

K+ channel opener - hyperpolarizes and relaxes vascular smooth muscle. Can cause hyperglycemia (reduces insulin release)

213

Malignant hypertension treatment: Fenoldopam

Dopamine D1 receptor agonist - relaxes renal vascular smooth muscle

214

Malignant hypertension treatment: Nitroprusside

Short acting; ↑ cGMP via direct release of NO. Can cause cyanide toxicity (releases CN)

215

Mechanism of resistance: Acyclovir, famciclovir

Lack of viral thymidine kinase

216

Mechanism of resistance: Amantadine

Mutated M2 protein. 90% of all influenza A strains are resistant to amantadine, so not used.

217

Mechanism of resistance: Foscarnet

Mutated DNA polymerase

218

Mechanism of resistance: Ganciclovir

Mutated CMV DNA polymerase or lack of viral kinase

219

Mechanism: Atropine

Eye: ↑pupil dilation, cycloplegia Airway: ↓secretion Stomach: ↓acid secretion Gut: ↓motility Bladder: ↓urgency in cystitis

220

Mechanism: Calcium channel blockers

Block voltage-dependent L-type calcium channels of cardiac and smooth muscle and thereby reducing muscle contractility.

221

Mechanism: Cardiac glycosides - Digoxin

75% bioavailability, 20-40% protein bond, t1/2 = 40 hours, urinary excretion Directly inhibition of Na+/K+ ATPase leads to indirect inhibition of Na+/Ca2+ exchanger/antiport. ↑[Ca2+]i → positive inotropy. Stimulates vagus nerve.

222

Mechanism: Glucocorticoids

↓ the production of leukotrienes and prostaglandins by inhibiting phospholipase A2 and expression of COX-2

223

Mechanism: H2 blockers

Reversible block of histamine H2 receptors → ↓ H+ secretion by parietal cells

224

Mechanism: Heparin

Cofactor for the activation of antithrombin, ↓ thrombin, and Xa. Short half life.

225

Mechanism: Sorafenib

↓ serine / threonine kinase activity

226

Mechanism: Thrombolytics

Directly or indirectly aid conversion of plasminogen to plasmin, which cleaves thrombin and fibrin clots. ↑ PT, ↑ PTT, no change in platelet count.

227

Mechanism: Warfarin (Coumadin)

Interferes with normal synthesis and γ-carboxylation of vitamin K-dependent clotting factors II, VII, IX, and X and protein C and S. Metabolized by the cytochrome P-450 pathway. In laboratory essay, has effect on extrinsic pathway and ↑ PT. Long half-life.

228

Metaproterenol (albuterol, sameterol, terbutaline)

Mechanism: Selective β2-agonists (β2>β1) Clinical use: MAST: Metaproterenol and Albuterol for acute asthma; Salmeterol for long-term treatment; Terbutaline to reduce premature uterine contractions

229

Methacholine

Direct cholinomimetic agents Clinical use: Challenge test for diagnosis of asthma Action: Stimulates muscarinic receptors in airway when inhaled

230

Methimazole

Mechanism: Inhibit organification of iodide and coupling of thyroid hormone synthesis. Clinical use: Hyperthyroidism Toxicity: Skin rash, agranulocytosis (rare), aplastic anemia, a possible teratogen.

231

Methotrexate (MTX)

Mechanism: Folic acid analog that inhibits dihydrofolate reductase → ↓ dTMP → ↓ DNA and ↓ protein synthesis Clinical use: Cancers: Leukemias, lymphomas, choriocarcinoma, sarcomas. Non-neoplastic: Abortion, ectopic pregnancy, rheumatoid arthritis, psoriasis Toxicity: 1. Myelosuppression, which is reversible with leucovorin (folinic acid) "rescue" 2. Macrovesicular fatty change in liver 3. Mucositis 4. Teratogenic

232

Metoclopramide

Mechanism: D2 receptor antagonist. ↑ resting tone, contractility, LES tone, motility. Does not influence colon transport time. Clinical use: Diabetic and post-surgery gastroparesis Toxicity: ↑ parkinsonian effects. Restlessness, drowsiness, fatigue, depression, nausea, diarrhea. Drug interaction with digoxin and diabetic agents.

233

Mimetics (first name them)

Pramlintide Mechanism: ↓ glucagon Clinical use: Type 2 DM Toxicity: Hypoglycemia, nausea, diarrhea

234

Misoprostol

Mechanism: A PGE1 analog. ↑ production and secretion of gastric mucous barrier. ↓ acid production. Clinical use: Prevention of NSAID-induced peptic ulcers; maintenance of a patent ductus arteriosus. Also used to induce labor. Toxicity: Diarrhea

235

Muromonab-CD3 (OKT3)

Mechanism: Monoclonal antibody that binds to CD3 (epsilon chain) on the surface of T cells. Blocks cellular interaction with CD3 protein responsible for T-cell signal transduction. Clinical use: Immunosuppression after kidney transplantation. Toxicity: Cytokine release syndrome, hypersensitivity reaction

236

Muscarinic antagonists (GI): Names

Pirenzepine, propantheline

237

Muscarinic antagonists: Atropine, homatropine, tropicamide

Organ system: Eye Clinical use: Produces mydriasis and cycloplegia

238

Muscarinic antagonists: Benztropine

Organ system: CNS Clinical use: Parkinson's disease

239

Muscarinic antagonists: Ipratropium

Organ system: Respiratory Clinical use: Asthma, COPD

240

Muscarinic antagonists: Methscopolamine, pirenzepine, propantheline

Organ system: Gastrointestinal Clinical use: Peptic ulcer treatment

241

Muscarinic antagonists: Oxybutynin, glycopyrrolate

Organ system: Genitourinary Clinical use: Reduce urgency in mild cystitis and reduce bladder spasms

242

Muscarinic antagonists: Scopolamine

Organ system: CNS Clinical use: Motion sickness

243

Neostigmine

Indirect cholinomimetic agents Clinical use: Postoperative and neurogenic ileus and urinary retention, myasthenia gravis, reversal of neuromuscular junction blockade (postoperative) Action: ↑endogenous ACh; no CNS penetration

244

Niacin

Mechanism: Inhibits lipolysis in adipose tissue; reduces hepatic VLDL secretion into circulation Toxicity: Red, flushed face (↓ by aspirin in long-term use), hyperglycemia (acanthosis nigricans), hyperuricemia (exacerbates gout) LDL↓↓; HDL↑↑; TG↓

245

Nitroglycerin, isosorbide dinitrate

Mechanism: Vasodilate by releasing nitric oxide in smooth muscle, causing ↑ in cGMP and smooth muscle relaxation. Dilate veins >> arteries. ↓ preload Clinical use: Angina, pulmonary edema. Also used as an aphrodisiac and erection enhancer. Toxicity: Reflex tachycardia, hypotension, flushing, headache, "Monday disease".

246

Nitrosoureas (carmustine, lomustine, semustine, streptozocin)

Mechanism: Require bioactivator. Cross blood-brain barrier → CNS. Clinical use: Brain tumors (including glioblastoma multiforme) Toxicity: CNS toxicity (dizziness, ataxia)

247

Nonselective α-blockers (2)

Phenoxybenzamine (irreversible), phentolamine (reversible) Clinical use: Pheochromocytoma (use before removing tumor, since high levels of released catecholamines will not be able to overcome blockage) Toxicity: Orthostatic hypotension, reflex tachycardia

248

Norepinephrine

Mechanism: α > β Clinical use: Hypotension (but ↓ renal perfusion)

249

Octreotide

Mechanism: Somatostatin analog Clinical use: Acute variceal bleeds, acromegaly, VIPoma, and carcinoid tumors. Toxicity: Nausea, cramps, steatorrhea

250

Ondansetron

Mechanism: 5-HT3 antagonist. Powerful central-acting antiemetic. Clinical use: Control vomiting postoperatively and in patients undergoing cancer therapy. Toxicity: Headache, constipation

251

P-450 Inducers (+)

Quinidine; Barbiturates; Phenytoin; Rifampin; Griseofulvin; Carbamazepine; Chronic alcohol use

252

P-450 Inhibitors (-)

HIV protease inhibitors; Ketoconazole; Erythromycin; Sulfonamides; Isoniazid; Cimetidine; Grapefruit juice; Acute alcohol use

253

Paclitaxel / Other -taxols

Mechanism: Hyperstabilize polymerized microtubules in M-phase so that mitotic spindle cannot break down (anaphase cannot occur) Clinical use: Ovarian and breast carcinomas Toxicity: Myelosuppression and hypersensitivity

254

Phenylephrine

Mechanism: α1 > α2 Clinical use: Pupillary dilation, vasoconstriction, nasal decongestion

255

Physostigmine

Indirect cholinomimetic agents Clinical use: Glaucoma (crosses blood-brain barrier → CNS) and atropine overdose Action: ↑endogenous ACh

256

Pilocarpine

Direct cholinomimetic agents Clinical use: Potent stimulator of sweat, tears, saliva Action: Contracts ciliary muscle of eye (open angle), pupillary sphincter (narrow angle); resistant to AChE.

257

Pirenzepine, propantheline

Mechanism: Block M1 receptors on ECL cells (↓ histamine secretion) and M3 receptors on parietal cells (↓ H+ secretion). Clinical use: Peptic ulcer (rarely used) Toxicity: Tachycardia, dry mouth, difficulty focusing eyes

258

Prednisone

Mechanism: May trigger apoptosis. May even work on nondividing cells. Clinical use: Most commonly used glucocorticoid in cancer therapy. Used in CLL, Hodgkin's lymphomas (part of the MOPP regimen). Also an immunosuppressant used in autoimmune diseases. Toxicity: Cushing-like symptoms; immunosuppression, catarcts, acne, osteoporosis, hypertension, peptic ulcers, hyperglycemia, psychosis

259

Propylthiouracil

Mechanism: Inhibit organification of iodide and coupling of thyroid hormone synthesis, also ↓ peripheral conversion of T4 to T3. Clinical use: Hyperthyroidism Toxicity: Skin rash, agranulocytosis (rare), aplastic anemia, hepatotoxicity.

260

Proton pump inhibitors

Omeprazole, lansoprazole (-prazole) Mechanism: Irreversibly inhibit H+/K+-ATPase in stomach parietal cells. Clinical use: Peptic ulcer, gastritis, esophageal reflux, Zollinger-Ellison syndrome

261

Pyridostigmine

Indirect cholinomimetic agents Clinical use: Myasthenia gravis (long acting); does not penetrate CNS Action: ↑endogenous ACh; ↑strength

262

Raloxifene

Mechanisms: SERMs - receptor antagonists in breast and agonists in bone. Block the binding of estrogen to estrogen receptor positive cells. Clinical use: Breast cancer. Also useful to prevent osteoporosis. Toxicity: No ↑ in endomerial carcinoma because it is an endometrial antagonist

263

Recombinant cytokines: Aldeleukin

interleukin-2 for Renal cell carcinoma, metastatic melanoma

264

Recombinant cytokines: Erythropoietin (epoetin)

Anemias (especially in renal failure)

265

Recombinant cytokines: Filgrastim

granulocyte colony-stimulating factor for Recovery of bone marrow

266

Recombinant cytokines: Oprelvekin

interleukin-11 for Thrombocytopenia

267

Recombinant cytokines: Sargramostim

granulocyte-macrophage colony-stimulating factor for Recovery of bone marrow

268

Recombinant cytokines: Thrombopoietin

Thrombocytopenia

269

Recombinant cytokines: α-interferon

Hepatitis B and C, Kaposi's sarcoma, leukemias, malignant melanoma

270

Recombinant cytokines: β-interferon

Multiple sclerosis

271

Recombinant cytokines: γ-interferon

Chronic granulomatous disease

272

Ritodrine

Mechanism: β2 Clincal use: Reduces premature uterine contractions

273

Rituximab

Mechanism: Monoclonal antibody against CD20, which is found on most B-cell neoplasms. Clinical use: Non-Hodgkin's lymphoma, rheumatoid arthritis (with methotrexate)

274

Second generation Sulfonylureas (first name them)

Glyburide, Glimepiride, Glipizide Mechanism: Close K+ channel in β-cell membrane, so cell depolarizes → triggering of insulin release via ↑ Ca2+ influx Clinical use: Stimulate release of endogenous insulin in type 2 DM. Require some islet function, so useless in type I DM. Toxicity: Hypoglycemia

275

Selective α1-blockers

Prazosin, terazosin, doxazosin (-zosin) Clinical use: Hypertension, urinary retention in BPH Toxicity: 1st-dose orthostatic hypotension, dizziness, headache

276

Selective α2-blockers

Mirtazapine Clinical use: Depression Toxicity: Sedation, ↑serum cholesterol, ↑appetite

277

Selectivity: Nonselective α- & β- antagonists

Carvedilol, labetalol

278

Selectivity: Nonselective β antagonists (β1 = β2)

Propranolol, timolol, nadolol, pindolol (>N)

279

Selectivity: Partial β agonists

Pindolol, Acebutolol

280

Selectivity: Selective β1 antagonists (β1 > β2)

Acebutolol, Betaxolol, Esmolol (short acting), Atenolol, Metoprolol (

281

Sirolimus (rapamycin)

Mechanism: Inhibits mTOR. Inhibits T-cell proliferation in response to IL-2 Clinical use: Immunosuppression after kidney transplantation in combination with cyclosporine and corticosteroids. Toxicity: Hyperlipidemia, thrombocytopenia, leukopenia

282

Sulfa drugs

Celecoxib, furosemide, probenecid, thiazides, TMP-SMX, sulfasalazine, sulfonylureas, acetazolamide, sulfonamide antibiotics

283

Sulfasalazine

Mechanism: A combination of sulfapyridine (antibacterial) and 5-aminosalicylic acid (anti-inflammatory). Activated by colonic bacteria. Clinical use: Ulcerative colitis, Crohn's disease Toxicity: Malaise, nausea, sulfonamide toxicity, reversible oligospermia

284

Sympathoplegics (2)

Clonidine, α-methyldopa Mechanism: Centrally acting α2-agonist, ↓central adrenergic outflow Clinical use: Hypertension, especially with renal disease (no ↓ in blood flow to kidney)

285

Tacrolimus (FK506)

Mechanism: Similar to cyclosporine; binds to FK-binding protein, inhibiting secretion of IL-2 and other cytokines. Clinical use: Potent immunosuppressive used in organ transplant recepients Toxicity: Significant - nephrotoxicity, peripheral neuropathy, hypertension, pleural effusion, hyperglycemia

286

Tamoxifen

Mechanisms: SERMs - receptor antagonists in breast and agonists in bone. Block the binding of estrogen to estrogen receptor positive cells. Clinical use: Breast cancer. Also useful to prevent osteoporosis. Toxicity: May ↑ the risk of endometrial carcinoma via partial agonist effects; "hot flashes"

287

Therapeutic antibodies: Abciximab

Target: Glycoprotein IIb/IIIa Clinical use: Prevent cardiac ischemia in unstable angina and in patients treated with percutaneous coronary intervention

288

Therapeutic antibodies: Adalimumab

Target: TNF-α Clinical use: Crohn's disease, rheumatoid arthritis, psoriatic arthritis

289

Therapeutic antibodies: Daclizumab

Target: IL-2 receptor Clinical use: Prevent acute rejection of renal transplant

290

Therapeutic antibodies: Digoxin Immune Fab

Target: Digoxin Clinical use: Antidote for digoxin intoxication

291

Therapeutic antibodies: Infliximab

Target: TNF-α Clinical use: Crohn's disease, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis

292

Therapeutic antibodies: Muromonab-CD3 (OKT3)

Target: CD3 Clinical use: Prevent acute transplant rejection

293

Therapeutic antibodies: Rituximab

Target: CD20 Clinical use: B-cell non-Hodgkin's lymphoma

294

Therapeutic antibodies: Trastuzumab (Herceptin)

Target: erb-B2 Clinical use: HER-2 overexpressing breast cancer

295

Thrombolytics: Names

Streptokinase, urokinase, tPA (alteplase), APSAC (anistreplase)

296

Toxicity: Amiodarone

Pulmonary fibrosis, hepatotoxicity, hypothyroidism / hyperthyroidism (amiodarone is 40% iodine by weight), corneal deposits, skin deposits (blue/gray) resulting in photodermatitis, neurologic effects, constipation, cardiovascular effects (bradycardia, heart block, CHF)

297

Toxicity: Antiarrhythmics - Na+ channel blockers (Class IA)

thrombocytopenia; torsades de pointes due to ↑QT interval

298

Toxicity: Antiarrhythmics - Na+ channel blockers (Class IB)

local anesthetic. CNS stimulation / depression, cardiovascular depression

299

Toxicity: Antiarrhythmics - Na+ channel blockers (Class IC)

Proarrhythmic, especially post-MI. Significantly prolongs refractory period in AV node.

300

Toxicity: Atropine

↑body temperature (due to sweating); rapid pulse; dry mouth; dry, flushed skin; cycloplegia; constipation; disorientation Can cause acute angle-closure glaucoma in elderly, urinary retention in men with prostatic hyperplasia, and hyperthermia in infants

301

Toxicity: Bretylium

New arrhythmias, hypertension

302

Toxicity: Calcium channel blockers

Cardiac depression, AV block, peripheral edema, flushing, dizziness, and constipation

303

Toxicity: Cardiac glycosides - Digoxin

Cholinergic - nausea, vomiting, diarrhea, blurry yellow vision (think Van Gogh). ECG - ↑PR, ↓QT, scooping, T-wave inversion, arrhythmia, hyperkalemia Worsened renal failure (↓ excretion), hypokalemia (permissive for digoxin binding at K+-binding site on Na+/K+ ATPase), quinidine (↓ digoxin clearance, displaces digoxin from tissue-binding sites)

304

Toxicity: Cimetidine

a potent inhibitor of P-450, it also has antiandrogenic effects (prolactin release, gynecomastia, impotence, ↓ libido in males); can cross blood-brain barrier (confusion, dizziness, headaches) and placenta, ↓ renal excretion of creatinine

305

Toxicity: Glucocorticoids

Iatrogenic Cushing's syndrome - buffalo hump, moon facies, truncal obesity, muscle wasting, thin skin, easy bruisability, osteoporosis, adrenocortical atrophy, peptic ulcers, diabetes (if chronic) Adrenal insufficiency when drug stopped after chronic use.

306

Toxicity: Heparin

Bleeding thrombocytopenia (HIT), osteoporosis, drug-drug interactions. For rapid reversal (antidote), use protamine sulfate (positively charged molecule that binds negatively charged heparin)

307

Toxicity: Ibutilide

Torsades de pointes

308

Toxicity: Metoprolol

Dyslipidemia

309

Toxicity: Procainamide

Reversible SLE-like syndrome

310

Toxicity: Quinidine

chichonism - headache, tinnitus;

311

Toxicity: Ranitidine

↓ renal excretion of creatinine

312

Toxicity: Sotalol

torsades de pointes, excessive β block

313

Toxicity: Thrombolytics

Bleeding. Contraindicated in patients with active bleeding, history of intracranial bleeding, recent surgery, known bleeding diatheses, or severe hypertension. Treat toxicity with aminocaproic acid, an inhibitor of fibrinolysis

314

Toxicity: Warfarin (Coumadin)

Bleeding, teratogenic, skin/tissue necrosis, drug-drug interactions.

315

Toxicity: β-blockers

Impotence, exacerbation of asthma, cardiovascular adverse effects (bradycardia, AV block, CHF), CNS adverse effects (sedation, sleep alterations); use with caution in diabetics

316

Trastuzumab (Herceptin)

Mechanism: Monoclonal antibody against HER-2 (erb-B2). Helps kill breast cancer cells that overexpress HER-2, possibly through antibody-dependent cytotoxicity. Clinical use: Metastatic breast cancer Toxicity: Cardiotoxicity

317

Triple therapy of H. pylori ulcers

Metronidazole, amoxicillin (or tetracycline), bismuth. Can also use PPI.

318

Types of Insulin

Rapid-acting: Lispro, Aspart, Regular Intermediate: NPH Long-acting: Glargine, Detemir

319

Vinblastine

Mechanism: Alkaloids that bind to tubulin in M-phase and block polymerization of microtubules so that mitotic spindle cannot form. Clinical use: Hodgkin's lymphoma, Wilm's tumor, choriocarcinoma. Toxicity: Myelosuppression

320

Vincristine

Mechanism: Alkaloids that bind to tubulin in M-phase and block polymerization of microtubules so that mitotic spindle cannot form. Clinical use: Hodgkin's lymphoma, Wilm's tumor, choriocarcinoma. Toxicity: Neurotoxicity (areflexia, peripheral neuritis), paralytic ileus

321

α-glucosidase inhibitors (first name them)

Acarbose, Miglitol Mechanism: Inhibit intestinal brush border α-glucosidases. Delayed sugar hydrolysis and glucose absorption lead to ↓ postprandial hyperglycemia Clinical use: Used as monotherapy in type 2 DM or in combination with above agents. Toxicity: GI disturbances