Z5. Pharmacology p329
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- Thrombolytics
- p. 329
- questions from diagram at bottom of page
- plasmin is the major ___________ enzyme. It breaks down both _______ and _______
- fibrinolytic enzyme. It accelerates breaks down of both fribin and fibrinogen yielding fibrin splip products and degradation products, respectively.
- Fibrinogen is converted to fibrin by _________
- thrombin
- tPA and urokinase promote the converson of ______ to ________ thereby increasing fibrinolysis.
- plasminogen to plasmin
- Various stimuli activate a blood proactivator to a blood activator that promotes conversion of _________ to blank thereby increasing fibrinolysis
- plasminogen to plasmin
- Streptokinase and anistreplase both activate and Activator that increases convesion of plasminogen to plasmin.
- Aminocaproic acid:____________ fibrinolysis.
- inhibits fibrinolysis by inhibition of plasminogen conversion to plasmin.
- 4 examples of thrombolytics include: ________, _________, _____________, and ___________
- Streptokinase, urokinase, tPA(altepalse), APSAC (anistreplase)
- work by directly or indirectly aiding the conversion of ___________ to __________, which cleaves ______ and ________ clots. tPA specifically coverts _______________ to plasmin
- Directly or indirectly aid conversion of plaminogen to plasmin, which cleaves thrombin and fribrin clots. It is claimed that tPA specifically coverts fribrin-bound plasminogen to plasmin.
- T/F: clinical use is for DVTs
- False: used for early MI
- pts. receiving this medication are at most risk for: ______
- bleeding
- Hematologic Drugs
- p. 330
- mechanism of antiplatelet interaction
- questions from diagram at top of page
- When a break in the endothelium occurs _________ and _________ are exposed.
- collagen and vWF
- Platelets are activated by binding to the above macromolecules. The two structures expressed by the platelets involved in this process are __________ and _________ and they bind to _________ and __________, repectively
- Platelets bind to collagen and vWF. The two structures expressed by platelets that are involved in this process are GP 1a and GP 1b. GP 1a and GP 1b bind to collagen and vWF, respectively.
- After platelet activation _________ is expressed on their surface. What is the role of this structure?
- after platelets are activated they express GP IIb/IIIa. This molecule is important in platlelet-platelet aggregation.
- _________ and _________ interaction is needed in order for platelet aggregation to occur.
- GP IIb/IIIa and fribinogen
- 5-HT, _______, and ________ are molecules that play a role in the glycoprotein expression of activated platelets.
- 5-HT, ADP, and TxA2 are molecules that play a role in the glycoprotein expression of activated platelets.
- Aspirin acts by inhibiting production of ________ that in turn inhibits glycoprotein expression in activated platelets.
- TxA2
- ADP production is inhibited by the drug _________.
- ticlopidine
- This antibody drug targets the _______ on platelets.
- Abciximab
- Copidogrel, ticlopidine
- p. 330
- T/F: inhibits platele aggregation by irreversibly inhibiting the ADP pathway involved in the binding of fibrinogen
- TRUE
- It is used for ______ ________ syndrome, coronary _______, and it has been shown to decrease the incidence or recurrence of___ ____.
- it is used for acute coronary syndrome, coronary stenting. Decreases incidence or recurrence of thrombotic stroke
- Ticlopidine is associated with_________ as a side effect.
- Ticlopidine causes neutropenia and it is reserved for those who cannot tolerate aspirin.
- Abciximab
- p. 330
- This Abciximab binds to __________ on activated platelets.
- gp IIb/Iia
- Abciximab is used for ___________ and ________ _________ ___________ ___________
- acute coronary syndromes and percutanous transluminal coronary angioplasty
- Abciximab toxiciites are _______ and ________
- bleeding and thrombocytopenia
- Aspirin
- p 330
- It ________ and (reversibly/irreversibly) inhibits COX1 and COX2 to prevent the conversion of _______ to prostaglandins.
- acetilates and irreversably inhibits COX-1 and COX-2
- T/F: aspirin has an effect of PT, PTT
- false it has no effect
- What are the 4 A's of aspirin and NSAIDS in general
- Antipyretic, Analgesic, Anti-inflam, antiplatelet
- Important toxicities include _________, bleeding, hyperventilation, __________- in children, and CN ____ toxicity
- gastric ulceration, bleeding, hyperventilation, Reyes syndrome and tinnitus (CNVIII).
- Endocrine Drugs
- pg 332
- diabetes drugs
- p331
- AUTHOR
- Marc Waase
- Hydrocortisone, prednisone, triamcinolone, dexamtasone, bleclomethasone are examples of what kind of drugs?
- Glucocorticoid
- Glucocorticoids decrease the production of ___ and ____
- Leukotrienes and prostanglandins
- To treat Addison's disease, inflammation, immune suppression, asthma, use ____
- Glucocorticoids
- An important side-effect of Glucocortioid usage is ____
- Iatrogenic Cushing's Syndrome
- Buffalo hump, moon facies, truncal obesity, muscles wasting, thin skin, easy bruisability, osteoporosis, adrenocortical atrophy, peptic ulcers characterize what syndrome?
- Cushing's Syndrome
- Reproductive Drugs
- pg 332
- Which two drugs inhibit cGMP phosphodiesterase, leading to smooth muscle relaxation in the corpus cavernosum and penile erection?
- Sildenafil and Verdenafil --they fill the penis
- What class of drugs are used tto treat erectile dysfunction
- cGMP Inhibitors
- CGMP inibitors taken with ____have a high risk of liofe-threeatening hypotension
- nitrates
- Which drugs is a partial agonist of estrogen recpetors in the pituitary gland, stimulating increase in LH and FSH, which stimulates ovulation to treat infertility
- clomiphene
- Clomiphene's side effects include:
- Hotflashes, ovarian enlargment, multiple simultaneous pregnancies, visual disturbances
- What abortifacient is a competitite inhibitor of preogestins at progesterone recpetor and may lead to heavy menstrual-like bleeding?
- Mifepristone (RU486)
- The advantage of this drug is that it is reliable, decreases incidence of ectopic pregnancy, decreases risk of pelvic infections, and regulates menses; however it also puts you in a hypercoagulable stat and may increase your trigylcerides, weight, and bl
- Oral Contracpetices - syntheitc progestins/estrogen
- Rheumatologic Drugs
- pg 333
- ____is converted to uric acid which leads to gout
- Xanthine (converted from excess purines)
- This drug depolymerizes microtubules, impairing leukocyte chemotaxis and degranulation, and used to treat acute gout
- Colchicine
- This drugs inhibits reabsorption of uric acid and used to treat chronic gout
- Probenecid
- This drug is used to treat chronic gout, but also inhbits secretion of penicillin
- Probenecid
- This drugs inhibits xanthine oxidase decreasing the conversion fo xanthine to uric acid
- Allopurinol
- Oncologic Drugs
- pg 333-336
- What are the cell cycle specific oncologic drugs
- antimetabolites, plant alkaloids, stroid hormones, bleomycin, paclitaxel, etoposide
- What are the cell cycle Nonspecific oncologic drugs?
- alkylating agents and antibiotics
- ____is an S-phase-specific anti-metabolite that is an folic acid analog that inhibits dihydrofolate reducate decreasing dTMP(thymidine and purines) and decreaing DNA/prtein synthesis.
- Methotrexate
- ____is an S-phase-specific anti-metabolite that is a pyrmidine analog which complexed to folic acid, inhibiting thymidylate synthase, decreasing dTMP and decreasing DNA/protein synthesis
- 5-Fluorouracil (5-FU)
- Myelosuppression by methotrxate is reversible with ____
- leucovorin (folinic acid) rescue
- Which drug blocks purine synthesis and is used to treat leukemias, lymphomas (not CLL or Hodgkins)
- 6-mercaptopurine (6-MP)
- Which drug alkylates DNA and is used to treat CML?
- Busulfan
- Which drug inhibits DNA polymerase and is used to treat AML?
- cytarabine
- This drug used to treat Leukemias and Lymphomas is metaboilized by xanthine oxidase
- 6-mercaptopurine (6-MP)
- Used to treat leukemias, lymphomas, choricarcinoma, sacromas, rheumatoid arthritis, psoriasis, and can be an abortifacient; it may lead to myelosuppression
- Methotrexate
- Used to treat colon cancer and other solid tumors, basal cell carcinoma (topically)
- 5-Fluorouracil (5-FU)
- Myelosuppression by 5-FU is ______
- Not reversible
- This drug used to treat AML may lead to leukopenia, thrombocytopenia, megaloblastic anemia?
- cytarabine
- This drugs used to treat CML may lead to pulmonary fibrosis and hyperpigmentation?
- Busulfan
- ____is an alkylating agent acivated by liver that covalently x-links DNA at guanine N-7, and is used to treat non-hodgkin's lymphoma, breast/ovarian carcinomas
- cyclophosphamides
- ____ alkylates DNA after bioactivation and can cross the BBB and treats brain tumors (glioblastoma multiforme)
- Nitrosoureas (Carmustine, lomustine, semustine, streptozocin)
- ____acts like an alkylating agent, x-linking via hyrdolysis of Cl and platinum; used to treat testicular, bladder, lung carcinomas
- Cisplatin
- This alkylating agent can cause myelosuppression and hemorhagic cystitis
- cyclophosphamides
- This combination of drugs is used to treat Hodgkin's and myelomas, sarcomas, and solid tumors (breast, ovary, lung)
- ABVD: Adriamycin, Bleomycin, Vinblastine, Dacarbazine
- ____noncovalently intercalates in DNA, creating breaks to decrease replication and transcription
- Doxorubicin (adriamycin)
- ____intercalates DNA strands and induces free radical fromation which causes strand breaks
- Bleomycin, Dactinomycin
- Which drugs causes cardiotoxicity, alopecia, and myelosuppression?
- Doxorubicin (adriamycin)
- Which drug is used to trat oat cell carcinoma of the lung and prostate/testicular carcinoma?
- Etoposide
- This combination of drugs is used to treat lymphoma, CLL, Hodgkin's, Wilm's tumor, choriocarcinoma
- MOPP (Mustargen, Oncovin (Vincristine), Procarbazine (Matulane), Prednisone)
- Which glucocorticoid may trigger apoptosis and may even work on nondividing cells
- Prednisone
- This drug is a G2-phase specific inhibitor of Topisiomerase II, leaving double strand breaks in DNA following DNA replication
- Etoposide
- This drug used to treat testicular cancer and lymphomas may cayse pulmonary fibrosis, skin chnages, and myelosuppression
- Bleomycin, Dactinomycin
- This drugs used as an immunosuppressant and in lymphomas may cause acne, osteoporosis, hypertension, peptic ulcers, hyperglycemia, psychosis?
- Prednisone
- ____is an estrogen receptor mixed agonist/antagonist that blocks the binding of estrogen to ER+ cells.
- Tomoxifen/Raloxifene
- ____is n M-phase-specific alkaloid that binds to tubulin and blocks polymerization of microtubules, preventing spindle formation
- Vincristine and Vinblastine
- ____is an M-phase-specific agen that binds to tubulin and hyperstabilizes the polymerized microtubules, so that the mitotic spindle cannot break down
- Paclitaxel
- What drugs is used to treat breast cancer, but may increas the risk of endometrial carcinomas and hot flashes
- Tomoxifen
- Side-effects of Vinblastine includeÂ….
- VinBASTine BLASTs Bone Morraow, causing myelosuppression, as well as neurotoxicity and paralutic ileus.
- Side effects of Paclitaxel includeÂ….
- Myelosuppression and hypersensitivity
- Immunosuppressants and Cytokine Therapy
- pg 336-337
- This drug binds to cyclophilins, blocking differentiation and activation of T cells mainly by inhibiting IL2 production
- cyclosporine
- This antimetabolite derivative of 6-mercaptopurine interferes with the metabolism and synthesis of nucleic acid, therefore toxic to proliferating lymphocytes
- azathioprine
- This potent immunosuppressive drug binds to the FK-binding protein and inhibits secretion of IL2 and other cytokines
- tacrolimus (FK506)
- This drug is used to suppress organ rejection after transplantation, but may predispose patient to viral infections and lymphoma
- cyclosporine
- Azaothioprine is used to in what setting?
- Kidney transplants, autoimmune disorders (glomerulonephritis, hemolytic anemia)
- Recombinant Cytokine- Aldesleukin (interleukin-2) is used for?
- Renal cell carcinoma, metastatic melanoma
- Recombinant Cytokine- Erythropoietin (epoetin) is used for?
- anemia
- Recombinant Cytokine- Filgrastim is used for?
- Recovery of Bone Marrow; it is a granulocyte colony stimulating factor
- Recombinant Cytokine- alpha interferon is used for?
- Hep B/C, Kaposi's sarcoma, leukemia, malgnant melanoma
- Recombinant Cytokine- beta interferon is used for?
- Multiple Sclerosis
- Recombinant Cytokine- gamma interferon is used for?
- Chronic Granulomatous disease
- Recombinant Cytokine- oprelvekin (interleukin2) is used for?
- Thrombocytopenia
- Recombinant Cytokine- sargamostim is used for?
- Recovery of Bone Marrow (it is a granulocyte-macrophage colony stimulating factor)
- Recombinant Cytokine- thrombopoietin is used for?
- Thrombocytopenia
- Toxicology
- pg 338
- What is the antidote for acetaminophen toxicity/overdose
- N-acetylcysteine
- What is the antidote for salicylates toxicity/overdose
- Alkanize urine/dialysis
- What is the antidote for antichoinesterase toxicity/overdose
- Atropine, pralidoxime
- What is the antidote for antimuscarinic/anticholinergic agents toxicity/overdose
- physostigimine salicylate
- What is the antidote for Beta-blockers toxicity/overdose
- glucagon
- What is the antidote fordigitalis toxicity/overdose
- Stop digitalis, Normalize K+, lodpcaine, anti-digitialis Fab Fragments, Magnesium
- What is the antidote for lead toxicity/overdose
- CaEDTA, dimercaprol, succimer, penicillamine
- What is the antidote for iron toxicity/overdose
- Deferoxamine
- What is the antidote for aresnic/mercury/gold toxicity/overdose
- Dimercaprol (BAL), succimer
- What is the antidote for copper, arsenic, gold toxicity/overdose
- Penicillamine
- What is the antidote N-acetylcysteine used to treat?
- Acetaminophen toxicity/overdose
- What is the antidote for cyanide toxicity/overdose
- nitrite, hydroxocobalamin, thiosoulfate
- What is the antidote for methemoglobin toxicity/overdose
- methylene blue
- What is the antidote glucagon used to treat?
- Beta-blocker toxicity/overdose
- What is the antidote for carbon monoxide toxicity/overdose
- 100% oxygen, hyperbaric oxygen
- What is the antidote atropine used to treat?
- anticholinesterase toxicity/overdose
- What is the antidote for methanol toxicity/overdose
- Ethanol, dialusis, fomepizole
- What is the antidote for opiods toxicity/overdose
- Nalozone/naltrexone
- What is the antidote for ethylene glycol toxicity/overdose
- Ethanol, dialusis, fomepizole
- What is the antidote for benzodiazepines toxicity/overdose
- Flumazenil
- What is the antidote for (TCA) Tricyclic Antidepressants toxicity/overdose
- NaHCO3
- What is the antidote for Heparin toxicity/overdose
- Protamine
- What is the antidote Deferoxamine used to treat?
- Iron toxicity/overdose
- What is the antidote for warfarin toxicity/overdose
- vitamin K, fresh frozen plasma
- What is the antidote Naloxone/naltrexone used to treat?
- opioid toxicity/overdose
- What is the antidote for tPA/streptokinase toxicity/overdose
- aminocaproic acid
- What is the antidote Physostigmine salicylate used to treat?
- Antimuscarinic/anticholinergic agents toxicity/overdose
- What is the antidote Flumazenil used to treat?
- Benzodiazepine toxicity/overdose
- What is the antidote Protamine used to treat
- Heparin toxicity/overdose
- Children living in old houses might eat the paint chips which could cause ____
- Lead Poisoning
- Signs of Lead poisoning include:
- Lead Lines on gingivae and epiphyses of Long bones, Encephalopathy and Erythrocyte Basophilic stippling, Abdominal colic and sideroblastic Anemia, Wrist and Foot Drop
- 1st line of Treatment for Lead Poisoning include
- Dimercaprol and EDTA
- Weak acids, such as phenobarbitol, methotreaxate, aspirin, alkanize urine with ____ to increase clearance
- bicarbonate
- Weak bases, such as amphetamines, acidify urine with NH4Cl to ____ clearance
- increase
- Drug reactions
- p. 339
- For each drug reaction, give the pharmacological agents responsible. The number of drugs you should list are given in parentheses. You could also quiz yourself in reverse by going down the list of drugs on the right.
- Pulmonary fibrosis (3)
- bleomycin, amiodarone, busulfan
- Hepatitis (2)
- isoniazid, halothane
- Focal to massive hepatic necrosis (4)
- halothane, valproic acid, acetaminophen, amanita phalloides
- Anaphylaxis (1)
- penicillin
- SLE-like syndrome (4). [mnemonic: it's not HIPP to have lupus]
- hydralazine, INH, procainamide, phenytoin
- Hemolysis in G6PD-deficient patients (8)
- sulfonamides, INH, aspirin, ibuprofen, primaquine, nitrofurantoin, pyrimethamine, chloramphenicol
- Thrombotic complications (1 class)
- OCPs (e.g. estrogens and progestins)
- Adrenocortical insufficiency (withdrawal of what class of drugs causes adrenocortical insufficiency?)
- withdrawal of glucocorticoids causes hypothalamic-pituitary-axis suppression
- Photosensitivity reactions (3) [mnemonic: SAT for a photo]
- Sulfonamides, amiodarone, tetracycline
- Induce P-450 system (6)
- barbiturates, phenytoin, carbamazepine, rifampin, griseofulvin, quinidine
- Inhibit P-450 system (6, including one fruit)
- cimetidine, ketoconazole, grapefruit, erythromycin, INH, sulfonamides
- Tubulointerstitial nephritis (5)
- sulfonamides, furosemide, methicillin, rifampin, NSAIDs (except aspirin)
- Hot flashes (1)
- Tamoxifen
- Cutaneous flushing (4)
- niacin, Ca++ channel blockers, adenosine, vancomycin
- Cardiac toxicity (2)
- doxorubicin (adriamycin), daunorubicin
- Agranulocytosis (3, all start with letter C)
- clozapine, carbamazepine, colchicine
- Stevens-Johnson syndrome (3)
- ethosuximide, sulfonamides, lamotrigine
- Cinchonism (2)
- quinidine, quinine
- Tendonitis, tendon rupture and cartilage damage (kids) (1)
- fluoroquinolones
- Disulfiram-like reaction (4)
- metronidazole, certain cephalosporins, procarbazine, sulfonylureas
- Otoxicity and nephrotoxicity (3)
- aminoglycosides, loop diuretics, cisplatin
- Drug-induced Parkinson's (4)
- haloperidol, chlorpromazine, resperine, MPTP
- Torsades de pointes (two subclasses of antiarrhythmics)
- Class III (sotalol), class IA (quinidine) antiarrhythmics
- Aplastic anemia (3)
- chloramphenicol, benzene, NSAIDs
- Neuro/nephrotoxicity (1)
- polymyxins
- Pseudomembranous colitis (2)
- clindamycin, ampicillin
- Gynecomastia (5) [mnemonic: Some Drugs Create Awesome Knockers]
- spironolactone, digitalis, cimetidine, chronic Alcohol use, estrogens, ketoconazole
- Atropine-like side effects (1)
- tricyclics
- Cough (1)
- ACE inhibitors (losartan --> no cough)
- Gingival hyperplasia (1)
- phenytoin
- Diabetes insipidus (1)
- lithium
- Tardive dyskinesia (1)
- antipsychotics
- Fanconi's syndrome (1)
- tetracycline
- Gray baby syndrome (1)
- chloramphenicol
- Extrapyramidal side effects (3)
- chlorpromazine, thioridazine, haloperidol
- Osteoporosis (2)
- corticosteroids, heparin
- Alcohol toxicity
- p. 340
- Ethylene glycol is converted to ------- ------ by alcohol dehydrogenase. This product can lead to acidosis and nephrotoxicity.
- oxalic acid.
- Alcohol dehyrogenase also converts methanol to formaldehyde and formic acid, which can cause severe ----- and damage to the -------.
- acidosis. retina
- Ethanol competes with ethylene glycol and methanol (if present) for alcohol dehydrogenase. ADH action on EtOH produces -------.
- acetaldehyde
- What symptoms does acetaldehyde cause?
- nausea, vomiting, headache, hypotension
- Acetaldehyde itself can be metabolized by acetaldehyde dehydrogenase to ----- -----.
- acetic acid.
- Acetaldehyde dehydrogenase is inhibited by what drug?
- disulfiram.
- Herbal agents
- p. 341
- Give the clinical uses for the following herbal agents.
- echinacea
- GI distress, dizziness, and headache
- ephedra
- CNS and cardiovascular stimulation; arrhythmias, stroke and seizures at high doses.
- feverfew
- GI distress, mouth ulcers, antiplatelet actions
- ginko
- GI distress, anxiety, insomnia, headache, and antiplatelet actions
- kava
- GI distress, sedation, ataxia, hepatotoxicity, phototoxicity, dermatotoxicity
- milk thistle
- loose stools
- saw palmetto
- GI distress, decreased libido, hypertension
- St. John's wort
- GI distress and phototoxicity; serotonin syndrome with SSRIs
- dehyroepiandrosterone
- Androgenization (premenopausal women), estrogenic effects (postmenopausal), feminization (young men)
- Melatonin
- Sedation, suppresses midcycle LH, hypoprolactinemia
- Give the toxicities for the following herbal agents.
- Drug name
- p. 341
- For each drug name ending, give the general category of drug it indicates and an example of a drug in that category.
- -ane
- inhalational general anesthetic. Halothane
- -azepam
- benzodiazepine. Diazepam
- -azine
- phenothiazine (neuroleptic, antiemetic). Chlorpromazine
- -azole
- antifungal. Ketoconazole
- -barbital
- barbiturate. Phenobarbital
- -caine
- local anesthetic. Lidocaine
- -cillin
- penicillin. Methicillin
- -cycline
- antibiotic, protein synthesis inhibitor. Tetracycline
- -ipramine
- tricyclic antidepressant. Imipramine
- -navir
- protease inhibitor. Saquinavir
- -olol
- beta antagonist. Propranolol
- -operidol
- butyrophenone (neuroleptic). Haloperidol
- -oxin
- cardiac glycoside (inotropic agent). Digoxin
- -phylline
- methylxanthine. Theophylline
- -pril
- ACE inhibitor. Captopril
- -terol
- beta-2 agonist. Albuterol
- -tidine
- H2 antagonist. Cimetidine
- -triptyline
- tricyclic antidepressant. Amitriptyline
- -tropin
- pituitary hormone. Somatotropin
- -zosin
- alpha-1 antagonist. Prazosin