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Flashcards in Pharmacology Deck (41)
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1
Q

Heparin

A

MECHANISM Cofactor for the activation of antithrombin, decr thrombin, and decr factor Xa. Short half-life.
CLINICAL USE Immediate anticoagulation for PE, acute coronary syndrome, MI, DVT. Used during pregnancy (does not cross placenta). Follow PTT.
TOXICITY Bleeding, thrombocytopenia (HIT), osteoporosis, drug-drug interactions. For rapid reversal (antidote), use protamine sulfate (positively charged molecule that binds negatively charged heparin).
NOTES Low-molecular-weight heparins (e.g., enoxaparin, dalteparin) act more on factor Xa, have better bioavailability and 2–4 times longer half-life. Can be administered subcutaneously and without laboratory monitoring. Not easily reversible.

Heparin-induced thrombocytopenia (HIT)—development of IgG antibodies against heparin bound to platelet factor 4 (PF4). Antibody-heparin-PF4 complex activates platelets–> thrombosis and thrombocytopenia.

2
Q

Argatroban, bivalirudin

A

Derivatives of hirudin, the anticoagulant used by leeches; inhibit thrombin directly. Used instead of heparin for anticoagulating patients with HIT.

3
Q

Warfarin (Coumadin)

A

MECHANISM Interferes with normal synthesis and
γ-carboxylation of vitamin K–dependent clotting factors II, VII, IX, and X and proteins C and S. Metabolized by the cytochrome P-450 pathway. In laboratory assay, has effect
on EXtrinsic pathway and incr PT. Long half-life.
The EX-PresidenT went to war(farin).

CLINICAL USE Chronic anticoagulation (after STEMI, venous
thromboembolism prophylaxis, and prevention of stroke in atrial fibrillation). Not used in pregnant women (because warfarin, unlike heparin, can cross the placenta).
Follow PT/INR values.
TOXICITY Bleeding, teratogenic, skin/tissue necrosis,
drug-drug interactions.
For reversal of warfarin overdose, give vitamin K. For rapid reversal of severe warfarin overdose, give fresh frozen plasma.

4
Q

Warfarin (Coumadin)

A

MECHANISM Interferes with normal synthesis and
γ-carboxylation of vitamin K–dependent clotting factors II, VII, IX, and X and proteins C and S. Metabolized by the cytochrome P-450 pathway. In laboratory assay, has effect
on EXtrinsic pathway and incr PT. Long half-life.
The EX-PresidenT went to war(farin).

CLINICAL USE Chronic anticoagulation (after STEMI, venous
thromboembolism prophylaxis, and prevention of stroke in atrial fibrillation). Not used in pregnant women (because warfarin, unlike heparin, can cross the placenta).
Follow PT/INR values.
TOXICITY Bleeding, teratogenic, skin/tissue necrosis,
drug-drug interactions.
For reversal of warfarin overdose, give vitamin K. For rapid reversal of severe warfarin overdose, give fresh frozen plasma.

5
Q

Direct factor Xa inhibitors

A

Apixaban, rivaroxaban.
MECHANISM Bind and directly inhibit the activity of factor Xa.
CLINICAL USE Treatment and prophylaxis of DVT and PE (rivaroxaban), stroke prophylaxis in patients with atrial
fibrillation.
Oral agents do not usually require coagulation monitoring.
TOXICITY Bleeding (no specific reversal agent available).

6
Q

Heparin

A

Heparin
STRUCTURE Large anionic, acidic polymer
ROUTE OF ADMINISTRATION Parenteral (IV, SC)
SITE OF ACTION Blood
ONSET OF ACTION Rapid (seconds)
MECHANISM OF ACTION Activates antithrombin, which decr the action of IIa (thrombin) and factor Xa.
DURATION OF ACTION Acute (hours)
INHIBITS COAGULATION IN VITRO Yes
TREATMENT OF ACUTE OVERDOSE Protamine sulfate
MONITORING PTT (intrinsic pathway)
CROSSES PLACENTA No

7
Q

Warfarin

A
Heparin
STRUCTURE Small lipid-soluble molecule
ROUTE OF ADMINISTRATION Oral
SITE OF ACTION Liver
ONSET OF ACTION Slow, limited by half-lives of normal clotting factors 
MECHANISM OF ACTION Impairs the synthesis of vitamin K–dependent clotting factors II, VII, IX, and X (vitamin K
antagonist)
DURATION OF ACTION Chronic (days)
INHIBITS COAGULATION IN VITRO No
TREATMENT OF ACUTE OVERDOSE IV vitamin K and fresh frozen plasma
MONITORING PT/INR (extrinsic pathway)
CROSSES PLACENTA Yes (teratogenic)
8
Q

Thrombolytics

A

Alteplase (tPA), reteplase (rPA), tenecteplase (TNK-tPA).

MECHANISM Directly or indirectly aid conversion of plasminogen to plasmin, which cleaves thrombin and fibrin
clots. Incr PT, incr PTT, no change in platelet count.
CLINICAL USE Early MI, early ischemic stroke, direct thrombolysis of severe PE.
TOXICITY 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. Fresh frozen plasma and cryoprecipitate can also be used to correct factor deficiencies.

9
Q

Thrombolytics

A

Alteplase (tPA), reteplase (rPA), tenecteplase (TNK-tPA).

MECHANISM Directly or indirectly aid conversion of plasminogen to plasmin, which cleaves thrombin and fibrin
clots. Incr PT, incr PTT, no change in platelet count.
CLINICAL USE Early MI, early ischemic stroke, direct thrombolysis of severe PE.
TOXICITY 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. Fresh frozen plasma and cryoprecipitate can also be used to correct factor deficiencies.

10
Q

Aspirin (asa)

A

MECHANISM Irreversibly inhibits cyclooxygenase (both COX-1 and COX-2) enzyme by covalent acetylation.
Platelets cannot synthesize new enzyme, so effect lasts until new platelets are produced: incr bleeding time, decr TXA2 and prostaglandins. No effect on PT or PTT.
CLINICAL USE Antipyretic, analgesic, anti-inflammatory, antiplatelet (decr aggregation).
TOXICITY Gastric ulceration, tinnitus (CN VIII). Chronic use can lead to acute renal failure, interstitial nephritis, and upper GI bleeding. Reye syndrome in children with viral infection.
Overdose causes respiratory alkalosis initially, which is then superimposed by metabolic acidosis.

11
Q

ADP receptor inhibitors

A

Clopidogrel, ticlopidine, prasugrel, ticagrelor.
MECHANISM Inhibit platelet aggregation by irreversibly blocking ADP receptors. Inhibit fibrinogen binding by preventing glycoprotein IIb/IIIa from binding to fibrinogen.
CLINICAL USE Acute coronary syndrome; coronary stenting. decr incidence or recurrence of thrombotic stroke.
TOXICITY Neutropenia (ticlopidine). TTP/HUS may be seen.

12
Q

Cilostazol, dipyridamole

A

MECHANISM Phosphodiesterase III inhibitor; Incr cAMP in platelets, thus inhibiting platelet aggregation; vasodilators.
CLINICAL USE Intermittent claudication, coronary vasodilation, prevention of stroke or TIAs (combined with
aspirin), angina prophylaxis.
TOXICITY Nausea, headache, facial flushing, hypotension, abdominal pain.

13
Q

GP IIb/IIIa inhibitors

A

Abciximab, eptifibatide, tirofiban.
MECHANISM Bind to the glycoprotein receptor IIb/IIIa on activated platelets, preventing aggregation. Abciximab
is made from monoclonal antibody Fab fragments.
CLINICAL USE Unstable angina, percutaneous transluminal coronary angioplasty.
TOXICITY Bleeding, thrombocytopenia.

14
Q

Methotrexate (MTX) - antimetabolite

A

MECHANISM
Folic acid analog that inhibits dihidrofolate reductase –> decr dTMP –> decr DNA and decr protein synthesis.
CLINICAL USE
Cancers: leukemias, lymphomas, choriocarcinoma, sarcomas.
Non-neoplastic: abortion, ectopic pregnancy, rheumatoid arthritis, psoriasis, IBD.
TOXICITY
Myelosuppression, which is reversible with leucovorin (folinic acid) “rescue.”
Macrovesicular fatty change in liver.
Mucositis.
Teratogenic.

15
Q

5-fluorouracil (5-FU)

A

MECHANISM
Pyrimidine analog bioactivated to 5F-dUMP, which covalently complexes folic acid.
This complex inhibits thymidylate synthase–> decr dTMP –> decr DNA and decr protein synthesis.
CLINICAL USE
Colon cancer, pancreatic cancer, basal cell carcinoma (topical).
TOXICITY
Myelosuppression, which is not reversible with leucovorin.
Overdose: “rescue” with uridine.
Photosensitivity.

16
Q

Methotrexate (MTX)

A

Antimetabolite, S-phase specific
MECHANISM
Folic acid analog that inhibits dihidrofolate reductase –> decr dTMP –> decr DNA and decr protein synthesis.
CLINICAL USE
Cancers: leukemias, lymphomas, choriocarcinoma, sarcomas.
Non-neoplastic: abortion, ectopic pregnancy, rheumatoid arthritis, psoriasis, IBD.
TOXICITY
Myelosuppression, which is reversible with leucovorin (folinic acid) “rescue.”
Macrovesicular fatty change in liver.
Mucositis.
Teratogenic.

17
Q

5-fluorouracil (5-FU)

A

Antimetabolite, S-phase specific
MECHANISM
Pyrimidine analog bioactivated to 5F-dUMP, which covalently complexes folic acid.
This complex inhibits thymidylate synthase–> decr dTMP –> decr DNA and decr protein synthesis.
CLINICAL USE
Colon cancer, pancreatic cancer, basal cell carcinoma (topical).
TOXICITY
Myelosuppression, which is not reversible with leucovorin.
Overdose: “rescue” with uridine.
Photosensitivity.

18
Q

Cytarabine (arabinofuranosyl cytidine)

A

Antimetabolite, S-phase specific
MECHANISM
Pyrimidine analog –> inhibition of DNA polymerase.
CLINICAL USE
Leukemias, lymphomas.
TOXICITY
Leukopenia, thrombocytopenia, megaloblastic anemia.

CYTarabine causes panCYTopenia.

19
Q

Azathioprine
6-mercaptopurine (6-MP)
6-thioguanine (6-TG)

A

Antimetabolite, S-phase specific
MECHANISM
Purine (thiol) analogs –> decr de novo purine synthesis.
Activated by HGPRT.
CLINICAL USE
Preventing organ rejection, RA, SLE (azathioprine).
Leukemia, IBD (6-MP, 6-TG).
TOXICITY
Bone marrow, GI, liver.
Azathioprine and 6-MP are metabolized by xanthine
oxidase; thus both have incr toxicity with allopurinol,
which inhibits their metabolism.

20
Q

Azathioprine
6-mercaptopurine (6-MP)
6-thioguanine (6-TG)

A

Antimetabolite, S-phase specific
MECHANISM
Purine (thiol) analogs –> decr de novo purine synthesis.
Activated by HGPRT.
CLINICAL USE
Preventing organ rejection, RA, SLE (azathioprine).
Leukemia, IBD (6-MP, 6-TG).
TOXICITY
Bone marrow, GI, liver.
Azathioprine and 6-MP are metabolized by xanthine
oxidase; thus both have incr toxicity with allopurinol,
which inhibits their metabolism.

21
Q

Dactinomycin (actinomycin D)

A
Antitumor antibiotic
MECHANISM
Intercalates in DNA
CLINICAL USE
Wilms tumor, Ewing sarcoma, rhabdomyosarcoma. Used for
childhood tumors (“children act out”).
TOXICITY
Myelosuppression.
22
Q

Doxorubicin (Adriamycin), daunorubicin

A

Antitumor antibiotic
MECHANISM
Generate free radicals. Intercalate in DNA –> breaks in
DNA –> decr replication.
CLINICAL USE
Solid tumors, leukemias, lymphomas.
TOXICITY
Cardiotoxicity (dilated cardiomyopathy), myelosuppression, alopecia.
Toxic to tissues following extravasation.
Dexrazoxane (iron chelating agent), used to prevent cardiotoxicity.

23
Q

Bleomycin

A
Antitumor antibiotic
MECHANISM
Induces free radical formation, which causes breaks in DNA
strands.
CLINICAL USE
Testicular cancer, Hodgkin lymphoma.
TOXICITY
Pulmonary fibrosis, skin changes, mucositis. Minimal myelosuppression.
24
Q

Bleomycin

A
Antitumor antibiotic
MECHANISM
Induces free radical formation, which causes breaks in DNA
strands.
CLINICAL USE
Testicular cancer, Hodgkin lymphoma.
TOXICITY
Pulmonary fibrosis, skin changes, mucositis. Minimal myelosuppression.
25
Q

Cyclophosphamide, ifosfamide

A

Alkylating agent.
MECHANISM
Covalently X-link (inter strand) DNA at guanine N-7. Require
bioactivation by liver.
CLINCIAL USE
Solid tumors, leukemia, lymphomas, and some brain cancers.
TOXICITY
Myelosuppression; hemorrhagic cystitis, partially
prevented with mesna (thiol group of mesna binds toxic
metabolites).

26
Q

Nitrosoureas

carmustine, lomustine, semustine, streptozocin

A

Alkylating agent.
MECHANISM
Require bioactivation.
Cross blood-brain barrier–> CNS. Cross-links DNA.
CLINICAL USE
Brain tumors (including glioblastoma multiforme).
TOXICITY
CNS toxicity (convulsions, dizziness, ataxia).

27
Q

Busulfan

A
Alkylating agent.
MECHANISM
Cross-links DNA. 
CLINICAL USE
CML. Also used to ablate patient’s bone marrow before bone marrow transplantation.
TOXICITY
Severe myelosuppression (in almost all cases), pulmonary
fibrosis, hyperpigmentation.
28
Q

Vincristine, vinblastine

A

Microtubule inhibitor.
MECHANISM
Vinca alkaloids that bind β-tubulin, inhibit its polymerization into microtubules, thereby preventing mitotic spindle formation (M-phase arrest).
CLINICAL USE
Solid tumors, leukemias, and lymphomas.
TOXICITY
Vincristine—neurotoxicity (areflexia, peripheral neuritis), paralytic ileus.
Vinblastine blasts bone marrow (suppression).

29
Q

Vincristine, vinblastine

A

Microtubule inhibitor.
MECHANISM
Vinca alkaloids that bind β-tubulin, inhibit its polymerization into microtubules, thereby preventing mitotic spindle formation (M-phase arrest).
CLINICAL USE
Solid tumors, leukemias, and lymphomas.
TOXICITY
Vincristine—neurotoxicity (areflexia, peripheral neuritis), paralytic ileus.
Vinblastine blasts bone marrow (suppression).

30
Q

Paclitaxel, other taxols

A
Microtubule inhibitor.
MECHANISM
Hyperstabilize polymerized microtubules in M phase so that mitotic spindle cannot break down(anaphase cannot occur).
“It is taxing to stay polymerized.”
CLINICAL USE
Ovarian and breast carcinomas. 
TOXICITY
Myelosuppression, alopecia, hypersensitivity.
31
Q

Cisplatin, carboplatin

A

MECHANISM Cross-link DNA.
CLINICAL USE Testicular, bladder, ovary, and lung carcinomas.
TOXICITY Nephrotoxicity and acoustic nerve damage. Prevent nephrotoxicity with amifostine (free radical scavenger) and chloride diuresis.

32
Q

Etoposide, teniposide

A

MECHANISM Etoposide inhibits topoisomerase II–> incr DNA degradation.
CLINICAL USE Solid tumors (particularly testicular and small cell lung cancer), leukemias, lymphomas.
TOXICITY Myelosuppression, GI irritation, alopecia.

33
Q

Irinotecan, topotecan

A

MECHANISM Inhibit topoisomerase I and prevent DNA unwinding and replication.
CLINICAL USE Colon cancer (irinotecan); ovarian and small cell lung cancers (topotecan).
TOXICITY Severe myelosuppression, diarrhea.

34
Q

Hydroxyurea

A

MECHANISM
Inhibits ribonucleotide reductase –> decr DNA Synthesis
(S-phase specific).
CLINICAL USE
Melanoma, CML, sickle cell disease (incr HbF).
TOXICITY
Bone marrow suppression, GI upset.

35
Q

Prednisone, prednisolone

A

MECHANISM May trigger apoptosis. May even work on nondividing cells.
CLINICAL USE Most commonly used glucocorticoids in cancer chemotherapy. Used in CLL, non-Hodgkin lymphomas (part of combination chemotherapy regimen). Also used as immunosuppressants (e.g., autoimmune diseases).
TOXICITY Cushing-like symptoms; weight gain, central obesity, muscle breakdown, cataracts, acne, osteoporosis, hypertension, peptic ulcers, hyperglycemia, psychosis.

36
Q

Tamoxifen, raloxifene

A

MECHANISM Selective estrogen receptor modulators (SERMs)—receptor antagonists in breast and agonists in
bone. Block the binding of estrogen to ER+ cells.
CLINICAL USE Breast cancer treatment (tamoxifen only) and prevention. Raloxifene also useful to prevent
osteoporosis.
TOXICITY Tamoxifen—partial agonist in endometrium, which incr the risk of endometrial cancer; “hot flashes.”
Raloxifene—no incr in endometrial carcinoma because it is an endometrial antagonist.

37
Q

Trastuzumab (Herceptin)

A

MECHANISM Monoclonal antibody against HER-2 (c-erbB2), a tyrosine kinase receptor. Helps kill breast cancer
cells that overexpress HER-2, through inhibition of HER2-initiated cellular signaling and antibody-dependent cytotoxicity.
CLINICAL USE HER-2+ breast cancer and gastric cancer (tras2zumab).
TOXICITY Cardiotoxicity. “HEARTceptin” damages the HEART.

38
Q

Imatinib (Gleevec)

A

MECHANISM Tyrosine kinase inhibitor of bcr-abl (Philadelphia chromosome fusion gene in CML) and c-Kit
(common in GI stromal tumors).
CLINICAL USE CML, GI stromal tumors.
TOXICITY Fluid retention.

39
Q

Rituximab

A

MECHANISM Monoclonal antibody against CD20, which is found on most B-cell neoplasms.
CLINICAL USE Non-Hodgkin lymphoma, rheumatoid arthritis (with MTX), ITP.
TOXICITY incr risk of progressive multifocal leukoencephalopathy.

40
Q

Vemurafenib

A

MECHANISM Small molecule inhibitor of forms of the B-Raf kinase with the V600E mutation.
CLINICAL USE Metastatic melanoma.

41
Q

Bevacizumab

A

MECHANISM Monoclonal antibody against VEGF. Inhibits angiogenesis.
CLINICAL USE Solid tumors (colorectal cancer, renal cell carcinoma).
TOXICITY Hemorrhage and impaired wound healing.