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FA 2015 High Yields > Pharmacology High Yields > Flashcards

Pharmacology High Yields Flashcards

1
Q

Azathioprine, 6-MP, G-TG

A

Mechanism: purine analog; activated by HGPRT; AZ –> 6-MP
Use: preventing organ rejection, RA, IBD, SLE, ALL
Toxicity: Myelosuppression, GI, liver (Jaundice)
AZ and 6-MP are metabolized by xanthine oxidase (and TPMT in liver), thus both have increased toxicity with allopurinol or febuxostat
Works during S phase

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2
Q

Cladribine (2-CDA)

A

Mechanism: purine analog; resistant to degradation by adenosine deaminase
Use: Hairy cell leukemia
Toxicity: myelosuppression, nephrotoxicity and neurotoxicity

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3
Q

Cytarabine (arabinofuranosyl cytidine)

A

Mechanism: pyrimidine analog –> inhibition of DNA polymerase
Uses: AML, lymphomas
Toxicity: leukopenia, thrombocytopenia, megaloblastic anemia
“CYTarabine causes panCYTopenia”

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4
Q

5-FU

A

Mechanism: pyrimidine analogue, bioactivated to 5F-dUMP, which covalently complexed with folic acid and inhibits thymidylate synthase -> decreased DNA synthesis
Uses: colon cancer, pancreatic cancer, basal cell carcinoma
Toxicity: mylosuppression NOT reversed by leucovorin (folinic acid)

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5
Q

MTX

A

Mechanism: Folic acid analog that competitively inhibits dihydrofolate reductase –> decreased DNA synthesis
Uses: ALL, lymphoma, ectopic pregnancy, medical abortion, RA, psoriasis, IBD, vasculitis
Toxicity: myelosuppression which IS reversible with leucovorin “rescue” ; hepatoxocity, mucositis (mouth ulcers), pulmonary fibrosis, teratogen, nephrotoxicity

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6
Q

Bleomycin

A

Mechanism: Induces free radical formation –> breaks in DNA strands
Use: testicular cancer, Hodgkin lymphoma
Toxicity: pulmonary fibrosis, skin hyperpigmentation, mucositis, minimal myelosuppression
Acts during G2 phase

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7
Q

Dactinomycin

A

Mechanism: intercalates in DNA –> inhibition of DNA-dep. RNA pol.
Use: Wilms tumor, Ewing sarcoma, rhabdomyosarcoma - tumors of childhood (“children ACT out”)
Toxicity: myelosuppression, radiation recall

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8
Q

Doxorubicin/Daunorubicin

A

Mechanism: generate free radicals; intercalate in DNA –> breaks in DNA
Use: solid tumors, leukemia, lymphoma
Toxicity: dilated cardiomyopathy, myelosuppression, alopecia

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9
Q

Dexrazoxane

A

Iron chelating agent used to prevent cardio toxicity from doxorubicin and daunorubicin

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10
Q

Leucovorin

A

Folinic acid - N5-formyl-THF; used to overcome myelosuppression in Methotrexate usage NOT 5-FU usage

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11
Q

Busulfan

A

Mechanism: cross-links DNA
Use: CML, bone marrow ablation
Toxicity: myelosuppression severe, pulmonary fibrosis, hyperpigmentation, seizures

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12
Q

Cyclophosphamide/Ifosfamide

A

Mechanism: Cross-link DNA at guanine N-7; requires bioactivation by P450 in liver
Use: Solid tumors, leukemia, lymphoma, immunosuppression
Toxicity: hemorrhagic cystitis (partially prevented with MESNA)

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13
Q

MESNA

A

thiol group of mesna binds toxic metabolites and helps to reduce hemorrhagic cystitis when using cyclophosphamide

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14
Q

Nitrosoureas

A

Carmustine, Lomustine, Semustine, Streptozocin
Mechanism: requires bioactivation; cross blood brain barrier (lipid soluble); cross link DNA; effective in CNS
Use: brain tumors
Toxicity: CNS - convulsions, dizziness, ataxia, nephrotoxicity

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15
Q

Paclitaxel/Taxols

A

Mechanism: hyperstabilize polymerized microtubules in M phase so that mitotic spindle cannot break down and anaphase cannot occur
Use: Ovarian and breast cancer; coat stents
Toxicity: myelosuppression, alopecia, hypersensitivity

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16
Q

Vincristine/Vinblastine

A

Mechanism: vinca alkaloids that bind beta-tubulin and inhibit polymerazation into microtubules –> prevent mitotic spindle formation (M phase)
Use: solid tumors - testicular breast - NSCLC - Hodgkin (vinblastine) and non-Hodgkin (vincristine), ALL
Toxicity: Neurotoxicity - peripheral neuritis (Vincristine), paralytic ileus (Vincristine), Marros suppression (Vinblastin - Blasts bone)

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17
Q

Cisplatin/Carboplatin

A

Mechanism: cross-link DNA
Use: testicular, bladder, ovary and lung carcinoma
Toxicity: nephrotoxicity (prevent with amifostine and chloride diuresis), ototoxicity

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18
Q

Amifostine

A

Free radical scavenger used to treat cisplatin nephrotoxicity

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19
Q

Etoposide/Teniposide

A

Mechanism: inhibit topoisomerase II –> DNA degradation
*S–>G2 phase
Use: solid tumors - testicular and SCLC - leukemia, lymphoma
Toxicity: myelosuppression, GI upset alopecia

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20
Q

Irinotecan/Topotecan

A

Mechanism: inhibit topoisomerase I and prevent DNA unwinding and replication
*S –> G2 phase
Use: colon cancer, ovarian and SCLC
Toxicity: myelosuppression, diarrhea

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21
Q

Hydroxyurea

A

Mechanism: inhibit ribonucleotide reductase –> decreased DNA synthesis (S phase specific)
Use: melanoma, CML, sickle cell (increases HbF)
Toxicity: severe myelosuppression, GI upset

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22
Q

Bevacizumab

A

Mechanism: monoclonal antibody against VEGF –> inhibit angiogenesis
Use: solid tumors - colorectal and renal cell
Toxicity: hemorrhage, blood clots, impaired wound healing

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23
Q

Erlotinib

A

Mechanism: EGFR tyrosine kinase inhibitor
Use: NSCLC
Toxicity: rash

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24
Q

Imatinib

A

Mechanism: tyrosine kinase inhibitor of BCR-ABL and c-kit
Use: CML, GI stromal tumors
Toxicity: fluid retention, heart failure

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25
Q

Rituximab

A

Mechanism: monoclonal antibody against CD20, found on most B cell neoplasms
Use: Non-Hodgkins, CLL, IBD, RA
Toxicity: increased risk of progressive multifocal leukoencephalopathy, infusion rxn, tumor lysis sydrome

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26
Q

Tamoxifen/ Raloxifene

A

Mechanism: selective estrogen receptor modulator (SERM) - block the bind of estrogen to ER+ cells
Use: breast cancer (Tamoxifen) Osteoporosis prevention (Raloxifen)
Toxicity: increased risk of endometrial cancer; hot flashes (tamoxifen)

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27
Q

Trastuzumab (Herceptin)

A

Mechanism: monoclonal antibody against HER-2 (c-erbB2) - a tyrosine kinase inhibitor; through inhibition of HER-2-initiated cellular signaling and antibody-dependent cytotoxicity
Use: Her2+ breast canse and gastric cancer
Toxicity: cardiotoxicity - “HEARTceptin”

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28
Q

Vemurafenib

A

Mechanism: small molecule inhibitor of BRAF oncogene + melanoma
Use: metastatic melanoma

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29
Q

Vemurafenib

A

Mechanism: small molecule inhibitor of BRAF oncogene + melanoma
Use: metastatic melanoma

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30
Q

Alpha 1

A

Gq

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31
Q

Gq

A

PLC –> DAG/IPS –> Ca2+/Calmodulin/PKC –> Phosphorylation

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32
Q

Gs

A

ATP–> cAMP –> PKA

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33
Q

Alpha 2

A

Gi

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34
Q

Beta1 & Beta2

A

Gs

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35
Q

M1 & M3

A

Gq

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36
Q

M2

A

Gi

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37
Q

D1

A

Gs

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38
Q

D2

A

Gi

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39
Q

H1

A

Gq

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40
Q

H2

A

Gs

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41
Q

V1

A

Gq

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42
Q

V2

A

Gs

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43
Q

Bethanechol

A

Muscarinic agonist; Tx of Ileus and urinary retention (resistant to esterase)

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44
Q

Carbachol

A

Muscarinic/nicotinic agonist; Causes contraction of ciliary muscle for open-angle glaucoma; constricts pupil

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45
Q

Pilocarpine

A

Muscarinic agonist; stimulates tears, sweat and saliva; Constricts pupil and ciliary muscle - acute glaucoma tx.

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46
Q

Clonidine

A

Agonist of central alpha2 adrenergic receptors –> decreased sympathetic outflow

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47
Q

Nonselective Alpha Blockers

A

Phenoxybenzamine (irreversible)

Phentolamine (reversible)

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48
Q

Alpha 1 Selective Blockers

A

Prazosin, Terazosin, Doxazosin (longest acting)

Tx. of HTN and BPH; may cause orthostatic hypotension so take at bedtime

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49
Q

Alpha 2 Selective Blockers

A

Mirtazapine - treatment of depression; can cause sedation, increased cholesterol and increased appetite

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50
Q

Alpha 2 Selective Blockers

A

Mirtazapine - treatment of depression; can cause sedation, increased cholesterol and increased appetite

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51
Q

Mixed Alpha and Beta Blockers

A

Carvedilol

Labetalol

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52
Q

Partial Beta Agonists

A

Pindolol

Acebutolol

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53
Q

Acetaminophen Antidote

A

N-acetylcysteine helps regenerate glutathione

54
Q

Salicylates Antidote

A

sodium bicarb to alkalinize urine; dialysis

55
Q

Anticholinesterases

Organophosphate Toxicity Antidote

A

Atropine; 2-PAM

56
Q 
Anticholinergics Antidote
(eg. Scopolamine, Atropine)
A

Physostigmine

57
Q

Beta Blocker Antidote

A

Glucagon to increase inotropy and chronotrophy

58
Q

Digitalis Antidote

A

Anti-digitalis Fab fragments; Normalize serum electrolytes, esp. K+; then lidocaine, magnesium

59
Q

Iron Antidote

A

Deferoxamine

60
Q

Lead Antidote

A

Ca-EDTA; Dimercaprol, Succimer, Penicillamine

61
Q

Arsenic, Mercury, Gold Antidote

A

Dimercaperol, Succimer

62
Q

Copper, Arsenic, Gold Antidote

A

Penicillamine

63
Q

Cyanide Antidote

A

Nitrite, Hydroxocobalamin, Thiosulfate

64
Q

Methemoglobin Antidote

A

Methylene Blue, Vit. C

65
Q

Heparin Antidote

A

Protamine

66
Q

tPA, Streptokinase Antidote

A

Aminocaproic acid

67
Q

Theophylline Antidote

A

Beta-blocker

68
Q

Atropine-Like (anticholinergic) SE

A

TCAs, Anti-histamines

69
Q

Dilated Cardiomyopathy SE

A

Doxorubicin, Danorubicin

70
Q

Coronary Vasospasm SE

A

Cocaine, Sumitriptan

71
Q

Cutaneous Flushing SE

A

Vancomycin, Adenosine, Niacin, Ca-channel blockers

72
Q

Torsades De Pointes SE

A 
Class III (sotalol), Class IA (quinidine), Cispride; 
Tx. with magnesium
73
Q

Agranulocytosis SE

A

Clozapine, Carbamazepine, Colchicine, Propylthiouracil, Dapsone, Methimazole

74
Q

Aplastic Anemia SE

A

Cholramphenicol, Benzene, NSAIDs, Felbamate

75
Q

Hemolytic Anemia (Coombs +) SE

A

Methyldopa

76
Q

G-6-PD deficiency Hemolytic Anemia

A

Isoniazid, Sulfa drugs, Asprin, Ibuprofen, Nitrofurantoin, Primaquin

77
Q

Megaloblastic Anemia SE

A

Methotrexate, Sulfa Drugs, Phenytoin

78
Q

Thrombosis SE

A

OCPs

79
Q

Thrombosis SE

A

OCPs

80
Q

Pulmonary Fibrosis SE

A

Bleomycin, Amiodarone, Busulfan

81
Q

Pulmonary Fibrosis SE

A

Bleomycin, Amiodarone, Busulfan

82
Q

Hepatitis SE

A

Isoniazid

83
Q

Cholestatic Hepatitis SE

A

Macrolides (azithro, clarithro)

84
Q

Hepatic Necrosis SE

A

Halothane, Valproic Acid, Acetaminophen, Amanita phalloides (mushroom)

85
Q

Pseudomembranous Colitis SE

A

Clindamycin, Ampicillin, Cephalosporins

86
Q

Pancreatitis SE

A

Azathioprine, Sulfonamides, Valproic acid, methyldopa, furosemide, corticosteroids, sulindac, tetracycline, didanosine, estrogens, 6-MP, pentamide, 5-ASA, Ocreotide

87
Q

Adrenocortical Insufficiency SE

A

Glucocorticoid withdrawal, Etomidate

88
Q

Gynecomastia SE

A

Spironolactone, Digitalis, Cimetidine, Alcohol, Estrogens, Ketoconazole

89
Q

Hot Flashes SE

A

Tamixoifen, Clomiphene

90
Q

Hypothyroidism SE

A

Lithium, Amiodarone

91
Q

Gingival Hyperplasia SE

A

Phenytoin

92
Q

Gout SE

A

Furosemide, Thiazides

93
Q

Osteoporosis SE

A

Corticosteroids, Heparin, H2 Blockers

94
Q

Photosensitivity SE

A

Sulfonamides, Amiodarone, Tetracytlines, Fluoroquinolones

95
Q

Rash (steven-johnson)

A

Sulfa Drugs, Penicillin, Carbamazepine, Allopurinol

96
Q

Tendon Rupture SE

A

Fluoroquinolones

97
Q

Lupus-Like Syndrome SE

A

Hydralazine, INH, Procainamide, Phenytoin

98
Q

Fanconi’s Syndrome SE

A

Expired tetracylcines

99
Q

Interstitial Nephritis SE

A

Methicillin, NSAIDs

100
Q

Hemorrhagic Cystitis SE

A

Cyclophosphamide

101
Q

Cinchonism SE

A

Quinidine, Quinine

102
Q

Diabetes Insipidus SE

A

Lithium, Demeclocycline (tx. for SIADH)

103
Q

Seizures SE

A

Buproprion, Imipenem/Cilastatin, INH

104
Q

Parkinson-Like Syndrome SE

A

Haloperidol, Chlorpromazine, Reserpine, Metoclopramide

105
Q

Tardive Dyskinesia SE

A

Typical antipsychotics

106
Q

Disulfiram-Like Reaction

A

Metro, Procarbazine, Sulfonylureas, Cephalosporins

107
Q

Nephrotoxicity/Neurotoxicity

A

Polymxyins

108
Q

Nephrotoxicity/Ototoxicity

A

Aminoglycosides, Vanco, Loop diuretics, Cisplatin

109
Q

P450 Inducers

A 
Chronic Alcohol
Modafinil
St. Johns Word
Phenytoin
Pehnobarbital
Nevirapine
Rifampin
Griseofulvin
Carbamazepine
"Chronic Alcoholic Mona Steals Phen-Phen and Never Refuses Greasy Carbs"
110
Q

P450 Inducers

A 
Chronic Alcohol
Modafinil
St. Johns Word
Phenytoin
Pehnobarbital
Nevirapine
Rifampin
Griseofulvin
Carbamazepine
"Chronic Alcoholic Mona Steals Phen-Phen and Never Refuses Greasy Carbs"
Also Quinidine and Glucocorticoids
111
Q

P450 Substrates

A 
Anti-epileptics
Antidepressants
Antipsychotics 
Anesthetics
Theophylline
Warfarin
Statins
OCPs
"Always, always, always, always think when starting others"
112
Q

P450 Inhibitors

A 
Acute alcohol abuse
Gemfibrozil (fibrate)
Ciprofloxacin
Isoniazid
Grapefruit juice
Quinidine
Amiodarone
Ketoconazole
Macrolides
Sulfonamides
Cimetidine
Ritonavir
"A cute gentleman 'cipped' iced grapefruit juice quickly and kept munching on soft cinnamon rolls"
113
Q

Sulfa Drugs

A 
Probenecid
Furosemide
Acetazolamide
Celecoxib
Thiazides
Sulfonamides
Sulfasalazine
Sulfonylureas
"Popular FACTSSS"
May develop fever, UTI, Steven-Johnson, hemolytic anemia, thrombocytopenia, agranulocytosis, and urticaria
114
Q

Sulfa Drugs

A 
Probenecid
Furosemide
Acetazolamide
Celecoxib
Thiazides
Sulfonamides
Sulfasalazine
Sulfonylureas
"Popular FACTSSS"
May develop fever, UTI, Steven-Johnson, hemolytic anemia, thrombocytopenia, agranulocytosis, and urticaria
115
Q

Sulfa Drugs

A 
Probenecid
Furosemide
Acetazolamide
Celecoxib
Thiazides
Sulfonamides
Sulfasalazine
Sulfonylureas
"Popular FACTSSS"
May develop fever, UTI, Steven-Johnson, hemolytic anemia, thrombocytopenia, agranulocytosis, and urticaria
116
Q

Vd

A

= Total amount of drug in body / [drug] plasma

117
Q

Clearance

A

= Rate of drug elimination / plasma drug concentration = Vd x Ke

118
Q

Half Life

A 
= 0.7 x Vd / Clearance 
1 Half Life - 50%
2 Half Lives - 75%
3 Half Lives - 87.5%
4 Half Lives - 93.8%
5 Half Lives - 96.9%
119
Q

Loading Dose

A

= Vd x blood plasm concentration / bioavailability

120
Q

Maintenance Dose

A

= Clearance x Css / bioavailability

121
Q

Bioavailability

A

= 1 for IV infusions

122
Q

Low Vd

A

Mostly in blood

123
Q

Mid Vd

A

Mostly in extracellular fluid

124
Q

High Vd

A

In all tissues

125
Q

Metformin SE

A

Lactic Acidosis

126
Q

Prednisone Electrolyte Abnormalities

A

H2O retention, hypokalemia, hypernatremia, hypocalcemia, hyperglycemia

127
Q

Therapeutic Index

A

= LD50/ ED50 = median dose that produces toxic effect / median does required to produce therapeutic effect

128
Q

Priapism SE

A

Hydralazine, Prazosin, Chlorpromazine, Sildafil, Trazodone

129
Q

Phenylephrine

A

Pupillary dilation

130
Q

ACh

A

miosis

FA 2015 High Yields (10 decks)

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