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349 Cards in this Set
- Front
- Back
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Vincristine
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Vinca alkaloid natural product against cancer. Terminates mitotic spindle assembly by binding to tubulin.
Toxicity: constipation, orthostatic hypertension, urinary retention, CNS problems. Resistance: alteration in tubulin bind, upregulation of P-glycoprotein which sends drug out of cell. Pneumonics: C-CNS |
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Vinblastine
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Vinca alkaloid natural product against cancer. Terminates mitotic spindle assembly by binding to tubulin.
Toxicity: constipation, orthostatic hypertension, urinary retention, Bone Marror problems. Resistance: alteration in tubulin bind, upregulation of P-glycoprotein which sends drug out of cell. Pneumonics: B-Bone Marrow |
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Paclitaxel
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bind to tubulin and promote ASSEMBLY to mititoc spindle. (Beta Site) (AGAINST CANCER)
Toxicity: neuronal and Bone Marrow Resistance: alteration in tubulin bind, upregulation of P-glycoprotein which sends drug out of cell. |
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Which Vince Alkaloids (1)Inhibit mitotic spindle and Which ones (2) Promote mitotic spindle?
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1) Vincristine/Vinblastine
2) Paclitaxel |
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Epipodophylotoxins
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Block stage G2 for Cancer (Plant Alkaloid) and Inibit TOPOISOMERAS 2
Resistance: P-glycoprotein |
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Commonalities of antibiotics used for cancer
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all products of streptomyces
Mechanisms: 1) large molecules which intercalate in DNA and bind to GUANINE 2) Block RNA Polymerase 3) decrease topoisomerase activity 4) increase Free Radical Production |
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Major Base that the Antibiotics for cancer bind to
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Guanine
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Only Antibiotic to be cell-cycle specific and block phase G2
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Bleomycins
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Patient has a skin or lung cancer (epithelial origin), give them whAT ANTIBIOTIC?
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Bleomycins
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Bleomycins Specific facts
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adverse effect to the lung - pulmonary fibrosis
No overlap of toxicities with other drugs |
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Used for squamous cell or testicular tumors - Antibiotic
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Bleomycins
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Anthracyclines
What are they? Whats their problem |
Non-cell cycle specific Cancer Antibiotic
Interact with P450 causing increase in free radicals leading to cardiomyopthy (Daunorubicin, Doxorubicin, Mitoxantrone) Mito does not cause free radicals and the adverse effect They can also cause alopecia |
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Which anthracyclins does not cause the adverse effect?
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Adverse effect = cardiomyopthy
Which one does not? - Mitoxantrone) |
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Dactinomycin
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Antibiotic cancer. used for sarcomas, it is most potent. It is bad with use of radiation
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What is the most potent Anti-tumor agent and what is it used for?
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Dactinomycin is used for Sarcomas and is?
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What is dactinomycin synergistic with?
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Radiation
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What do u use for advanced testicular tumor?
How does it work? |
Plicamycin/Mithramycin (antibiotic cancer)
Impairs clotting factors |
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antibiotic to reduce calcium secreting tumors
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plicamycin
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hypoxic tumors you use what?
How does it work? What are its side effects? |
Mitomycin C
it is an alkylating agent ANEMIA, renal, interstitial pneumonitis |
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Only active agent n Acute Lymphoblastic Leukemia?
Side effects? |
Asparaginase
S.E.: anaphylactic type reactions |
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A person had a MELANOMA or a HAIRY CELL LEUKEMIA and then on treatment got a FLU, what drug?
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Cytokines such as interferons/interleukins augment T-cell cytotoxicity
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TX for Non-Hodgkins lymphoma
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Rituximab
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Rituximab method for killing and adverse effects
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binds to CD20 to help with nonhodgkins lymphoma. Can cause hypersensitivity and circulatory problems if used too soon.
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Used for Adrenal corticoid tumors
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Mitotane
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After you have treated with mitotane, what do you give and what type of patient needs it?
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Patient with adrenal corticoid tumor...after TX give them replacement hydrocortison because drug can cause side effects of LETHARGY and SKIN ERUPTIONS
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Amsacrine
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Used for Cancer...Binds to topoisomerase 2 in DNA and can cause cardiac arrest
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Adrenocorticosteroids (Prednisone)
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For cancer.
1) inhibit Tumor Growth 2) Improve physical health 3) Reduce calcium levels in advanced breast cancer Cause nausea and vomiting |
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Aminoglutetimide
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1st generation aromatase inhibitor used for breast cancer. it inhibits all adrenal steroidsogenesis, so you need to have a hydrocortisone therapy with it
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Anastrozole
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3rd gen aromatase inhibitor used for breast cancer. Selectively effects the aromatase enzyme converting androstenedione to estrogen.
Basically it inhibits the prodcution of estrogen in post menauausal women in order to reduce estrogen levels which is proven to prevent breast cancer. |
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Better breast cancer treatment...Aromatase or a Tamoxifen?
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Aromatase like anastrozole is a better initial therapy
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Antiestrogen: tamoxifen
Side effects: |
binds to estrogen and inhibits transcription
Side effects: increase endometrial cancer, thromboembolic events, hot flashes, nausea |
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delays onset of osteoperosis
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Tamoxifen
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Raloxifen
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antiestrogen that is safer than tamoxifen
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Used in treatment of premenapausal people with high susceptibility to breast cancer
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Tamoxifen
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treatment of prostate cancer
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leuprolide
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leuprolide
Side effects: |
stimulates release of FSH and LH in pituitary, and initially a flare reaction of increase of testosterone which can be subdued by giving FLUTAMIDE to reduce amount of steroid receptors.
Used for prostate Cancer SE: gynecomastia, thromboembolism, edema, nausea, vomiting. |
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Needed to give with leuprolide to reduce initial "Flare up"
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Flutamide
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mOst Important T-cell growth factor
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IL-2
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Helper T-cells make these cytokines
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IL-4, IL-5, IL-6
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Macrophages make these cytokines.
What is 1 of them responsible for? |
The first make TNF-a which then makes IL-1 and then IL-6.
TNF-a is responsible for Rheumatoid Arthritis |
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Cyclosporine
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Targets calcineurin in T-cells and does not allow NFAT to go into the nucleus and increase IL-2 transcription.
Needs to be given before the inflammation. Does not cause bone marrow problems S.E.: liver problems, nephrotoxicity. |
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FK506
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Targets calcineurin in T-cells and does not allow NFAT to go into the nucleus and increase IL-2 transcription. Does not cause bone marrow problems
Needs to be given before the inflammation. |
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Rapamycin
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Targets mTOR (FKBP) and blocks the RESPONSE TO IL-2. Prevents progression from G1 to S. You can give this drug later in the inflammation episode
less nephrotoxicity |
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Rapamycin combonation
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Can take it with Cyclosporin but not with FK506
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Azathioprine
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anti-metabolite that is a 6-mercaptopurine derivative. Inhibits DNA synthesis on rapidly proliferating cells. needs to be taken with other agents
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Corticosteroids in immunotherapy do what 3 things?
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1) neutrophillia (increase)/lyphopenia(decrease)/monocytopenia(decrease)
2)functional changes on leukocytes 3)inhibit leukotriens/COX2/IL-1. IL-8, TNF-a |
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Anti-CD3 Anitbody
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used prophylactically to prevent an immune response before organ transplantation
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IgG-Anti-Rh(D) (Rhogam)
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used for passive immunization and for pregnancy when a child has a different RF factor than the mother
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Common feature of NSAIDs
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(-) Cox-1 and/or COX-2.
AlL have analgesic, anti-pyretic, anti-inflammatory effects, used to close patent ducturs arteriosus. |
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Only NSAID not to have an inflammatory effect
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Tylenol (Acitomenaphen)
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Similar Side effects of NSAIDs (4)
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1) GI irratation moreso with COX-1 inhibitors
2) Renal toxicity 3) Sodium and water retention 4) Decreased platlet aggregation with COX-1 inhibition |
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Aspirin mechanism and Uses
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Blocks COX 1 and COX 2 but more selective for COX1 for low doses and equally selective at high doses
IRREVERSIBLE block of COX1 which is needed to convert arachidonic acid intro prostaglandin. So it BLOCKS PLATELET AGGREGATION and reduces COLON CANCER |
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Aspirin Side Effects
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GI tract irritation and ulceration, hemorrhage, and renal toxicity, tinnitus(ringing in ears)
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Moderate stage of aspirin overdose
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It is an acid so it lowers blood pH which causes a reflex exretion of CO2
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Severe Aspirin Overdose
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Aspirin is an Acid so pH gets too low and inhibits the respiration center causing metabolic acidoses and low levels of bicarbonate causing HEART FAILUER
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Celecoxib
Side Effects |
COX-2 inhibitor so they do not affect platelet function. Less GI distress
Increased cardiovascular thrombotic event and renal toxicity |
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Taken with (this) COX-2 inhibitors to reduce their chances of thrombotic event
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COX-2 inhibitor - Celecoxib
Taken with it - Baby aspirin |
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Acetaminophen location of action
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only works in CNS and Spinal Cord and not periphery so do not have gastric problems.
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Acitomenaphen side efffect and who should not take them
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Liver toxicity
Alcoholics should not take them |
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What acitomenaphen turns into if it is metabolized by CYP450 instead of glucaronic/sulfuric acid
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Benzoquinopomine which can cause cell death
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ibuprofen
what is its contraindication? |
propionic acid derivative which blocks COX1 and COX2 reversibly and should not be used with people with nasal polyps
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Diclofenac
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COX-1/COX-2 inhibitor which accumulates in synovial joints
less complaints of GI ulcers |
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Etodolac
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more COX-2 selective and a good painkiller and used after bypass surgery.
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Ketoroloac
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COX2 inhibitor used for pain killing after surgery especially to reduce use of morphine
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Indomethacin
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Potent analgesic effect and anti-pyritic effects but used for anti-inflammatory
TX: acute gout and hodgkins fever |
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What do you use for Hodgkins disease which has a stubborn fever?
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Indomethacin
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Gout - Cause and Effect
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causes arthritis
You get gout usually by excess uric acid which comes from purine degeneration. so Uric Acid builds up and forms crystals in the joints which cause an inflammatory reaction |
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Tx for gout involves...
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1) relieve inflammation (Colchicine)
2)reduce uric acid concentration (Probenecid and NSAIDs) 3)reduce synthesis of uric acid (Allopurinol and Febuxostat) |
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Colchicine
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TX for gout inflammation.
Should be first treatment because it affects polymerization fo microtubules |
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Reduce Uric Acid absorption in Gout
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Probenecid/indomethacin (NSAIDs)
use at high doses because then it blocks reabsorption, but if you use low doses it promotes reabsorption |
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OAT and URAT
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OAT is used for secretion of Uric acid (dnt want to block this in GOUT)
URAT isused for reabsorption of Uric Acid (want to block this in gout) OAT - blocked by low doses of NSAID OAT/URAT - Blocked by high doses of NSAIDs |
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Allopurinol
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reduce synthesis of Uric Acid for tx of gout
Competitively inhibits xanthine Oxidase |
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Febuxostat and side effects
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directly blocks Xanthine Oxidase in order to reduce amounts of Uric Acid to prevent Gout
Side Effects: Diarrhea, nausea, vomiting |
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chemo drugs usually treat?
but cannot treat? |
they treat sarcomas but can not treat lung cancer
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used to save bone marrow when treating with chemo
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Granulocyte colony-stimulating factor (G-CSF)
Granulocyte/Macrophage colony-stimulating Factor (GM-CSF) Erythropoetin |
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Saves Kidney from Chemo therapy
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Allopurinol
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cell cycle phase attacked by most cell cycle drugs
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G1 or S phase
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easy to treat with chemotherapy because of the high mitotic index
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Burkitt lymphoma
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Cell cycle specific drugs
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Antimetabolites-S phase (methotrexate, 4-flurouracil)
antibiotics-G2 (bleomycin) plant alkaloids-M phase(Vincristine, vinblastine, Paclitaxel) podophyllian alkaloids- G2 (etoposide, teniposide) |
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Cell cycle non-specific drugs
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act on DNA directly
Alkylating agens (cyclophosphamide, nitrosoureas, cisplatin) antibiotics (antracyclins, plicamycin, mitomycin) |
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cancer caused by this 50% of time
Caused by this 33% of time |
1) decreased expression of p53 - apoptotic
2) Increased expression of bcl2 - antiapoptotic |
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pulls drug agents out of the cell...causes and efflux and a common mechanism for resistance
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P-Glycoprotein
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Chemotheraputic agents that do not have vomiting (3)
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Bleomycin, steroids, antimetabolites
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Chemotheraputic agent that causes bad vomiting
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Cisplatin
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chemotheraputic agent that causes severe GI complications
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Anti-metabolites
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Chemotheraputic agent tht causes pulmonary fibrosis
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Bleomycins
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Chemotheraputic agent that causes delayed leukemias
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Alkylating agents
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binds to guanine of DNA
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Mechlorethamine ( alkylating chemo agent)
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Mechlorethamine
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highly electrophilic, take IV with a short half life. and can bind intrastrand or interstrand
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Pathway for cyclophosphamide
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Prodrug activated by cytochrom P450 to aldosphosphamide and then to phophoramide mustard which is good
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Bad version of cyclophosphamide breakdown
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Acrolein which causes hemorrhagic cystitis and bladder cancer
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Too much of this enzyme turns cyclophosphamide into a bad version
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aldehyde dehydrogenase
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Side effects of cyclophosphamide
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GI problems, Alopecia, but has less vomiting and less bone marror effect and spares platlets
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Do not take alkylating agents with this agent because it reduces its effect
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glutathiones (used for OD)
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Alkylating agent that does not cause alopecia
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Melphalan
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alkylating agent that causes secondary leukemia
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chlorambucil
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take allopurinol with this alkylating agent to reduce its nephrotoxic effects
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Busulfan
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alkylating agents that cross the BB and god for CNS tumors
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Procarbazine and Dacarbazine
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alkylating agents that are MAOI so do not take them with anti-depressants
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Procarbazine and dacarbazine
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suffix for nitrosureas
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-mustine or -ocin
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used for brain cancer:
Side effects: |
Notrosoureas (carmustine, Lomustine, Semustine)
Long delay of bone marrow recovery. Cross BBB so bad for nausea |
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Nitrosureas that do not have problem with bone marrow
Side effects: |
Streptozocin and Chlorozotocin
Cause anemia |
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Nitrosureas with less nausea problems
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Chlorozotocin
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Tx pancreatic tumors
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Nitrosurease: Streptozocin and Chlorozotocin
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Cisplatin/Carboplatin
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Cancer agent (platinum) tbat is used for epitheila tumors like ovarian, testicular, lung cancers.
cause anaphylaxis, reversible neuropathy, irreversible hearing loss, nephrotocitiy, and severe nausea |
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Cancer agent that causes irreversible tinnitus (hearing loss)
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Cisplatin/carboplatin
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antimetabolite that acts liek folic acid
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Methotrexate
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Affects synthesis of DNA in the S phase
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Methotrexate
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Do not take this cancer drug with NSAIDs
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Methotreaxate
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blocks Dihydrofolate Reductase thereby inhibiting DNA synthesis on cancer cells
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Methotrexate
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Blocks thymidylate synthetase thereby inhibiting DNA synthesis on Cancer cells
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Flurouracil
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used as a rescue therapy with methotrexate
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leucovorin
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pyrimidine analog to treat Leukemia
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Cytarabine
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Flurouracil/floxuridine
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Pyrimide analog that inhibits thymidylate snthetase and used to stop dna synthesis in cancer patients. you use LEUCOVORIN with it for a synergistic effect.
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Methotrexate Side effects
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interstitial pneumonitis, nephrotoxicity, hepatic toxicity
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Purine analogs
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Mercaptopurine and Thioguanine
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Purine analog of hypoxanthine and blocks hypoxanthine guanine phosphoriboyl transferase
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mercaptourine
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need to reduce dose of this purine analog if given with allopurinol
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mercaptourine
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used to treat leukemia
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mercaptopurine
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purine analog of guanine
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thioguanine
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thioguanine blocks what
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xanthine oxidase
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1)this purine analog goes through deamination first so it is ok to take it with allopurinol.
2)Versus this one which is not safe |
1) thioguanine
2) mercaptourin |
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these Anti-metabolites inhibit DNA polymerase and afffect ribonucleotide reductase reducing CD4 levels
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Fludarabine, cladribine
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This anti-metabolite inhibits diphosphate reducatase
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hydroxyurea
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Hydroxyurea
Side effects: |
inhibits diphosphate reducatse
Side effects: megaloblastic anemia, radiation recall |
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hapten
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a molecule that by itself cannot cause an immune response but combined with something else like a protein can be immunogenic
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TYPE I immune response
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immediate hypersensitivity. IgE mediated and rapid. Comes in through GI, Lung and skin.
Mast cells, basophils, eosinophils Get cross-linking and release of histamine, PGEs, Leukotriens, and cytokines |
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Something that is not IgE mediated response
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anaphylactoid
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Type II immune response
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antibody-dependent cytotoxic hypersensitivity. Ab plus complement mediated lysis of cells.
IgG or IgM |
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Type III immune response
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Immune complex mediated hypersensitivity.
IgG or IgM to get lysis or ongoing inflammation |
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Type IV immune response
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delayed type hypersensitivity, contact sensitivity, tuberculin-type hypersensitivty
Uses Tcells Sensitization phase - langerhans cells Elicitation Phase - clonol expansion of Tcells in lymph nodes |
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Causes a Skin delayed type hypersitivity response
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Toulene and Diisohydrocyonate
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Innocent bystander
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Type II Immune response
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major determinant of a penicillin allergy
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penicillin moeity
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the minor determinants of a penicillin allergy
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Non-enzymes like penicillenate and penicillamine
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if you are allergic to penicillin you might also be allergic to?
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cephalosporins and other B-lactams
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Hemolytics anemia can be cuase by which immune responses?
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Type II direct response (penicllin) or Type II inderect response (Bystander), or an autoimmune reaction
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Agranulocytosis can be caused by?
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1) Ab mediated response (type II/III)
2) when it is metabolized and effects the bone marrow |
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activated myeloperoxidases in neutrophiles to cause agranulocytosis
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procainamide
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causes thrombocytopenia
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type III immune response - QUINIDINE
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cause drug induced Lupus
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Procainamide/hydralazine
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differences between Spontaneous lupus and drug induced lupus
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Drug induced has less pronounced renal effects and is only of the ssDNA sort
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Aspirin-induced Asthma
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not IgE response so it is an anaphylactiod response. has an upper airway response on the nasal polyps. have an allergic response to the inhibition of cyclooxygenase.
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Type of diabetes prone to keotacidosis
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Type 1 Diabetes
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aim of treatment for both type 1 and type 2 diabetes
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Fine Glycemic Control
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Insulin
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synthesized from pro-insulin by endopeptidases. complexed to zinc in a 6:2 ratio
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these stimulate the release of Insulin
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Vagal stimulation, glucagons, GH, ACTH, Beta-2 receptors
Also glucose, amino acids, fat |
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Inhibits release of insulin
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Serotonin, hypoxia, alpha-2 receptors
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Greatest stimulater of insulin release
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ORAL GLUCOSE because when u take sugar orally it causes release of Gastric inhibitory protein (GIP) and secretin
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how glucose signals for insulin release
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It enters the beta cell, changes ATP:ADP ratio which inhibits ATP sensitive K challels and opens Ca channels which stimulates insulin release
Does this through tyrosine kinase and posphotidylinositol-3 kinase. |
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principal action of insulin
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energy utilization and the net synthesis of carbohydrate protein and fat
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where is glucose uptake not mediated by insulin levels?
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Brain, Kidney tubules, Intestinal Mucosa, RBCs, Beta-cells of the islets
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type of insulin compatable with all other insulin types is also the only one that can be administed through IV
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regular insulin
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if you have ketoacidosis then you should look out for this electrolyte loss...
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K loss so if you give insulin it can reduce K+ even more
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rapid acting insulin preparations
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Insulin lispro, and insulin aspart
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Short acting insulin preparation
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regular insulin
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intermediate insulin preparation
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lente and NPH(neutral protamine Hagedorn)
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Long-acting insulin preparation
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Ultralente and insulin Glargine
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the lente insulin preparations and their lengths
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Short - semilente
medium - lente long - ultralente |
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do not take insulin with this because it may mask the effects of hypoglycemia
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beta blockers
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Side effect of insulin that can be treated and what is it treated with
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Insulin edema
TX: thiazide diuretic |
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Contraindicated in type 1 diabetes
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Sulfonylureas (1st gen tolbutamide, chlorpropamide, tolazamide)
(more potent 2nd gen glyburide, glipizide, glimepiride) |
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1st gen sulfonoureas
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(Tolbutamide, Tolazamide, Chlorpropamide)
inhibit ATP sensitive K+ channels in Beta Cells Used for treatment of Type II diabetes mellitus. Contraindicated in Type I and kidney insufficiencues |
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diabetic drug that is an antidiuretic by increasing ADH release
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1st gen sulfonyurea - chlorpropamide
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antaganistic effect on sulfonureas
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sulfonureas are used for diabetics. Do not take with diazoxide, thiazide diuretics or ethanol
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agents that might increase effects of Sulfonureas
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dicoumarol, salicylates, phenylbutazine
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This agent decreases the kidney excretion of sulfonureas
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Probenecid
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sensitive to ATP K+ channels associated with diabetes
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Meglitinides (REPAGLINIDE)
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these are glucose dependent in order to work their release of insulin
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repaglinide
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these inhibit ATP-sensitive K channels
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natiglinide
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Diabetic good for types II who have RESISTANCE to insulin
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Metformin which is a biguanide.
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do not give metformin to people with?
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anyone with a condiction of hypoperfusion because they can develop LACTIC ACIDOSIS
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insulin sensitizers used to help diabetes (2)
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thiazolidinediones (rosiglitazone and pioglitazone)
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rosiglitazone and pioglitazone
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activated receptos called PPAR-y which is highly expressed in adipose tissue and do not cause them to release their free fatty acids.
do not cause hypoglycemia |
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acarbose
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inhibits alpha-glucosidase on interstitial epithelium to delay their absorption in the GI tract
Contraindicated in any bowel disease |
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miglitol
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inhibits alpha-glucosidase on interstitial epithelium to delay their absorption in the GI tract
Contraindicated in any bowel disease |
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Amylin
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an islet amyloid polypeptide which is secreted with insulin. It slows gastric emptying and inhibits glucagon as well as promoting satiety
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Thype of amylin that has a short duration and can be combined with insulin, metphormin, and sulfonoureas
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pramlintide
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Incretin, secreting, GIP
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GI harmone that increases insulin release.
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exenatide
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a type of incretin that is a GLP-1 in order to increase insulin release
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sitagliptin
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inhibits dipeplidy peptidase 4 which degrades amylins and incretin so take it to increase those amounts
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take this to amplify any incretins or amylins by inhibiting that which degrades them
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Sitaglyptin
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polypeptides
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Human GH and prolactin. These things Change in the nucleus and use the JAK STAT pathway
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Glycoprotein hormones
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LH, FSH, TSH and hCG
2 subunits activate Gcoupled proteins to increase cAMP and Ca++ |
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V1 receptor of Vasopressin
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involved in vasoconstriction
|
|
|
V2 receptor of Vasopressin
|
involved in anti-duretic effects as well as pro-coagulant effects (increases vWF)
|
|
|
Desmopressin
|
a V2 agonist where you do not have to worry about high BP because it is an anti-diuretic
|
|
|
Use low doses of desmopressing to
|
fix diabetes insipidus in children and those with bedwetting
|
|
|
use high doses of desmopressin in those with
|
hemophillia A or vWF disease
|
|
|
desmopressin overdose leads to
|
hyponitremia
|
|
|
use vasopressin to treat
|
diabetes insipidus, and works more on V1 receptors. OD could be hypertensive crisis
|
|
|
Oxytocin
Side effects: |
milk ejection reflex and rhythmic contractions of uterus
Side Effects: hemorrhage and increases in BP |
|
|
has a lactogenic effect like prolactin
|
Growth harmone
|
|
|
Method of action for GH
|
increases IGF-1 mostly in the liver
|
|
|
Somatostatin (GH)
|
has some diabetogenic effects causing a decrease in glucose uptake and increased lipolysis
Fixes turners syndrone and treats short stature. Use with an aromatase inhibitor in order to prolong the amount of time before the epiphyseal plates close |
|
|
GH receptor anatagonist
|
pegvisomant used for acromegaly
|
|
|
FSH
|
primarily used for oocyte or follicular MATURATION during reproductive therapy and stimulates spermatogenia for males with low sperm levels. also used to induce estrogen synthase to produce estradiol
|
|
|
LH
|
induces ovulation of ripe follicles and leutalization of granulosa cells to form a copus luteim that produces progesterone in response to LH. In males produces testosterone
|
|
|
differences between FSH and LH
|
FSH - Follicle maturation, and estrogen synthesis
LH - Follicle ovulation and progesterone/testosterone release |
|
|
human Menopausal Gonadotropin (hMG) and type of it
|
LH and FSH mix but mainly used for FSH effects
UROFOLLITROPIN |
|
|
Human Chorionic Gonadotrop (hCG)
|
used for its LH effects and to induce ovulation
|
|
|
Used for cryptorchidism (undropped testies)
|
hCG
|
|
|
adverse effects of over GnRH
|
too much will cause a desensitization that impairs FSH and LH release leading to a chemical CASTRATION
|
|
|
GnRH
|
used for infertility due to hypothalamic dysfunction in women without the multiple birth hyperstimulation with the FSH and LH analogs
|
|
|
leuprolide/nafarelin
|
super-agonist of GnRH. Take advantage of overstimulat of GnRH to inhibit LH and FSH. Used for management of sex hormone therapy as a PALLATIVE care (help quality of life) for things liek prostate cancer and breast cancer.
Side effects include the chemical castration |
|
|
Ganirelix, cetrorelix
|
GnRH ANTAGONISTS. Faster induction fo chemical castration
|
|
|
Octreotide
|
novel synthetic somatostatin analog which inhibit GH release.
TX: acromegaly, carcinoid syndrome, WDHA(watery diarrhea, hypokalemia, achlorhydria |
|
|
Somatostatin
|
inhibit GH, TSH, glucagons and insulin.
|
|
|
Treats WDHA and Carcinoid syndrone pallatively
|
sOMATOSTATIN ANALOG USED to inhibit GH release - OCTREOTIDE
|
|
|
Bromocriptine and cabergoline
|
D2 agonists used to inhibit prolactin release.
Also used for parkinsons. adverse effects: nausea and vomiting |
|
|
estrogens and progesterones produce their major affects by
|
effecting the nuclear hormone receptors
causing CHROMATIN REMODELING |
|
|
binding to level C means
|
highly conserved DNA-binding
|
|
|
required for endometrial development
|
Progestins and estrogens
|
|
|
estrogen effect on pituitary
|
has both a negative and positive feedback effect
|
|
|
mid cycle surge of estrogen on hypothalamus
|
FSH/LH spike for ovulation (POSITIVE FEEDBACK)
|
|
|
Negative feedback of estrogen
|
on post menapausal women to reduce FSH and LH levels
|
|
|
other metabolic effects of estrogen
|
increase in production of clotting factors and also decreases in production of plasminogen-activator inhibitor
GIVES RISK OF THROMBOEMBOLISM |
|
|
High risk of thromboembolism
|
estrogen in post-menapausal women because it is dose dependent
|
|
|
half-life of estrogen
|
less than 30 minutes because of its rapid hepatic metabolism
|
|
|
adding an alkyl group to estrogen
|
makes ethinyl estradiol which has a much longert half life and resist hepatic first pass metabolism for use with once a day treatment
|
|
|
esterfiing the estrogen at the 17 position
|
estradiol cypionate and estradiol valerate
the molecule is now more hydrophobic. So you do not want to give it orally...so give it IM. This is good for long lasting estrogen to induce pubertal changes |
|
|
analogs of estrogen esterfied but for testosterone
|
testosterone enanthate and testosterona cypionate which last long
|
|
|
testosterone propionate
|
less dose required
|
|
|
this is unique to estrogens and required for activity
|
the aromatic first ring
|
|
|
estrone sulfate/equilin sulfate
|
a conjugated estrogen. absorbed in LOWER GI tract. used in ORAL hormone replacement therapy of POST menapausal women. LESS POTENT THAN SYNTHETIC ETHINYL ESTRADIOL
|
|
|
used as a oral contraceptive most popularly
|
ethinyl estradiol which has a 17-alkyl constituent
|
|
|
mestranol
|
another potent estrogen that is used for oral contraceptives but it isa progrugnorethindrone
|
|
|
classic progestin used as an oral contraceptive
and its problesm |
northindrone which can cause troublesome of beneficial effects
have weak androgenic effects and anti-estrogenic effects |
|
|
19-notestosteron derivatives that have minimal androgenic or estrogenic effects
|
desogestrel and norgestimate
|
|
|
reason for combining estrogen and progestin for contraceptives
|
then u can use lower dose of estrogen and u get a predicatable onset of menses and the least chance of fertility impairment
|
|
|
have a lower dose of estrogen but they are not good for ladies who want kids in the future
|
mini-pills which are progestin alone
|
|
|
best contraeptives for those who want future kids
|
combination pills
|
|
|
depot injection of medroxyprogesteron acetate
|
depoprovera which is an oral contraceptive
|
|
|
side effect of these oral contraceptives include increased risk of breast cancer in post-menopausel women
|
progestins
|
|
|
side effects of these oral contraceptives are nausea, cholecystits and darker complexion on what aged women?
|
ESTROGENS
PRE-MENAPAUSAL |
|
|
severe side effects of estrogen
|
Venous thromboembolic disease and some uterine cancers which will not be caused by progestins
|
|
|
sever side effects of combination oral contraceptives
|
myocardial infarction and stroke. Also in post menapausal women you get BREAST CANCER
|
|
|
give this for advanced prostate cancer
|
Estrogens - diethylstilbestrol
|
|
|
tx: for hereditary angioneurotic edema and the side efects of taking this drug
|
DANAZOL
S.E.: benign hepatic tumors |
|
|
flutamide
|
non-steroidal antagonist of androgen receptor that prevent flare reaction associated with GnRH super agonist analogs
|
|
|
bicalutamide
|
non-steroidal antagonist of androgen receptor that prevent flare reaction associated with GnRH super agonist analogs
|
|
|
androgen receptor agonist used to treat hirsuitism in women
|
spironolactone
|
|
|
makes androgens less potent by inhibits 5-a reductase which converst testosterone to dihydrotestosterone
|
finasteride
|
|
|
use this to tx benign prostatic hypertrophy
|
finasteride
|
|
|
tamoxifen
|
a selective estrogen receptor modulator which acts like an antagonist on breast tissue but an agonist on bone and uterus
TX: BREAST CANCER SE: thromboembolism, uterine cancer |
|
|
Raloxifene
|
Seective estrogen receptor modulator. Agonist on some parts, and antagonist on other parts. This one is used for OSTEOPEROSIS
increased risk of thromboembolism |
|
|
Clomiphene
|
Seective estrogen receptor modulator. Agonist on bone and antagonist on breast.
tx: infertility |
|
|
Best things to use for breast cancers
|
Aromatase inhibitors - anastrazole
|
|
|
Main endogenous glucocorticoid in the body and its purpose
|
involved in regulation of internal metabolism
CORTISOL |
|
|
Main mineralcorticoid
|
Aldosteron involved in salt water homeostasis
|
|
|
where are steroids made?
|
adrenal cortex
|
|
|
made in zona glomerulosa
|
aldosterone
|
|
|
zona fasiculata
|
cortisol
|
|
|
zona reticularis
|
sex steroids
|
|
|
main sex steroid and the enzyme necessary for it
|
dihydroepiandrosterone P450
|
|
|
Apposite of transcortin
|
Albumin which has low affinity and high capacity binding. as oppossed to transcortin (corticosteroid-binding globulin) which has high affinity and low capacity binding
|
|
|
which is more widly distributed...Glucocorticoid receptors or mineral corticoid receptors?
|
glucocorticoid receptors
|
|
|
glucocorticoids can bind to which receptors
|
glucocorticoid receptors or mineralcorticoid receptors
|
|
|
Cortisol binds to which receptors? How do you change it?
|
because it is a glucocorticoid it binds to both glucocorticoid and mineralcorticoid receptors. However if you convert it to cortisone it only binds to glucocorticoid receptors
|
|
|
11B-hydroxysteroid dehydrogenase
|
this converts cortisol to cortison so it can only bind to glucocorticoid receptors instead of both gluco and mineral
You get a mineralcorticoid excess when this enzyme is messed up as in a genetic insufficiency or eating black licorice |
|
|
glucocorticoids side effects
|
want to INCREASE levels of glucose so can cause diabetogonic effects
|
|
|
Aldosterone
|
mineralcorticoid that increase ENaC channels to increase sodium reabsorption
|
|
|
increase in sodium levels caused by aldosterone can lead to
|
atherosclerosis, stroke, hypertension
|
|
|
glucocorticoids do what to prostiglandins?
|
they decrease them thereby getting an ELEVATION OF BP
|
|
|
hydrocortisone can be taken?
|
orally or IV right into the joints
|
|
|
cortison negative feedback loop
|
effects the hypothalamus and pituitary in order to inhibit productions of cytokines like IL1/2/6 and TNF-a to stop an acute organ rejection
|
|
|
why would you give hydrocortison IV
|
because then the 11-b hydroxysteroid cnt convert it to cortisone and it can be used to activate mineralcorticoid receptors in the case that someone has hypotension - acute insufficiency of aldosterone
|
|
|
a type of chronic adrenal insufficiency
|
addisons disease
|
|
|
TX for addissons disease
|
it is a chronic adrenal insufficiency. You want to give somethign to increase the levels of mineralcorticoids instead of glucocorticoids so give FLUDROCORTISONE
|
|
|
congenital adrenal hyperplasia
|
can be when the 21beta-hydroxylase enzyme is missing so cortisol can not do negative feedback because it is not created and thus increased ACTH and increased sex hormones
|
|
|
Cushings syndrome
|
instance of producing more cortisol regardless of function. can be due to ACTH or anything
|
|
|
Cushings Disease
|
Tumor in the pituitary that causes an excess of ACTH which increases Cortisol levels
|
|
|
how to distinguish between cushings syndrome and disease
|
Dexamethasone suppression test - if the levels are supressed you have cushing DISEASE
|
|
|
excessive levels of cotrisol by drugs or by cushings can lead to:
|
osteroperosis and cataracts.
|
|
|
mitotane
|
- of adrenocortical steroids
ONLY DIRECT CYTOTOXIC EFFECT to kill cells int he adrenal cortex. |
|
|
aminoglutethimide
|
inhibitor of adrenocortical steroids
blocks the CYP450 or 11B-hydroxylase in order to inhibit levels of cortisol in cushings syndrome |
|
|
Ketoconazole
|
inhibitor of adrenocortical steroids
used as an antifungal but in high doses can block the 17hydroxylase enzyme which blocks pregnenolone to 17 hydroxypregnenelone which is used to make cortisol. This does NOT affect the aldosterone pathway so it is te BEST for Cushings DISEASE |
|
|
Trilostane
|
inhibitor of adrenocortical steroids
inhibits the 3B dehydrogenase to treat cushings syndrome |
|
|
metyrapone
|
inhibitor of adrenocortical steroids
inhibits 11B-hydroxylase but is not as good as the rest to stop production of aldosterone or cortisol |
|
|
restictive lung disease
|
reduction in lung volumes with a normal FEV1/FVC ratio
|
|
|
obstructive lung disease
|
reduction in expiratory flow rates manifested by a reduced FEV1 and FEV1/FVC ratio
|
|
|
what we use to measure airway hyperresponsiveness (asthma)
|
Methacholine challenge test...If FEV1 drops 20% it is considered a hyperresponsive effect
|
|
|
T cell associated with delayed type hypersenesitive
|
TH1, more the people who have been exposed to things in the past (3rd world)
|
|
|
T-cell associated with allergic inflammation
|
TH2, westerners who have all these allergies
|
|
|
Short (fast) acting beta-2 agonists (3)
|
albuterol, metaproterenol, terbutaline
These are used to help with asthma. they are good for rescue |
|
|
Albuterol
|
a Beta 2 agonist that can cause rapid bronchodilation in those who have asthma. But can develop tolerance quickly and inhalation is the best route with teh least side effects
|
|
|
Long-acting beta-2 agonists (2)
|
come from epinephrine and isoproterenol. They are SALMETEROL AND FORMOTEROL
Used for asthma but are not as effective against the inflammation as the short acting. Plus these ones are more life threatening |
|
|
Beta Agonist side effects
|
cardiac problems, tremor, hypokalemia, and HYPOXEMIA - give oxygen to those patients
|
|
|
Levelbuterol
|
used for asthma and it is more specific because it has the R isomer instead of the S isomer which is less effective
|
|
|
theophylline
S.E. |
a bronchodilater that is an antagonist of adenosine.Has anti-inflammatroy effects and also suprresses permeability edema and is ONLY AVAILABLE ORALLY
S.E. LIVER PROBLEM |
|
|
aminophylline
|
a type of theophylline used for asthma but it is not pure but can be given IV
|
|
|
theophylline efects P450 and increases the levels of these drugs (5)
|
cimetidine, erthromycin, ciprofloxicin, allopurinol, propranolol
|
|
|
both theophylline and beta agonists stimulate...
|
cAMP
|
|
|
Most effective in COPD
|
Ipratropium Bromide (Atrovan) which is an anti-cholinergic
|
|
|
Ipratropim Bromide, tiatropium
|
Atrovan. It is a non selective anti-cholinergic agentwith a slow duration fo action and used to reverse bronchoconstriction to help asthma and COPD
|
|
|
Atropine
|
An anticholinergic but is not used as much because it is a tertiary ammonum and rapidly absobered if used for asthma to cause tachycardia
|
|
|
why do you use ipratropium Bromide to help with asthma instead of Atropine if both are anti-cholinergics?
|
Ipratropium Bromide is a quarternary ammonia as oppossed to teh tertiary atropine so it is less absorbed and has less adverse effects
|
|
|
most potent anti-inflammatory agents
|
corticosteroids
|
|
|
if you are giving some1 with status asthmaticus beta agonists, what else should u give to make them more responsive?
|
glucocorticoids such as methyl-prednisolone
|
|
|
method of administration for corticosteroids for use with asthma
|
inhaled or topical because they have less side effects than when given orally
|
|
|
corticosteroids used for asthma (6)
S.E. |
Beclomethasone, triamcinolone, diflusinide, flucticasone, budesonide, mometasone fluroate
local side effects like oral thrush, dysphnoia and worsened asthma |
|
|
problem with corticosteroids in asthma (not side effects)
|
they have a delayed effect so do not use them for rescue therapy
|
|
|
Side effects of taking oral corticosteroids
|
adrenal suppression, cataracts, hip necrosis, glucose intolerance
|
|
|
Side effects of inhaled corticosteroids
|
mostly local, coughing, oral thrust, weight gain, osteoperosis
|
|
|
anti-leukotrien used for asthma (3) in patients who have ASPIRIN SENSITIVITY
|
montelukast and only needs to be taken once a day
Safirlukast, zileutin need to be taken several times a day and are more dangerous |
|
|
Cromolyn
|
used against asthma. is a prophylactic insoluble salt.
It STABILIZES mast cell degranulation and work better on young adults. It is specific for IfE and mast cells. Pre-treat with this and you block both DELAYED AND IMMEDIATE REACTIONS side effects of hoarseness and sore throat |
|
|
Nedocromil
|
used against asthma. is a prophylactic insoluble salt.
It STABILIZES mast cell degranulation and work better on young adults. It is specific for IfE and mast cells. Pre-treat with this and you block both DELAYED AND IMMEDIATE REACTIONS side effects of hoarseness and sore throat |
|
|
Omalizumab
|
monoclonal antibodies used to help astma. an IgG monoclonal antibody, for anti-IgE. not anaphylactogonic and decreases free IgE
Taken SUBCUTANEOUSLY |
|
|
Infleximab
|
a monoclonal antibody that is used for astma becuse it TBF-a reducer
|
|
|
Which thyroid hormone is more avidly bound and thus has a longer 1/2 life
|
T4
|
|
|
which thyroid hormone is moreactive?
|
T3
|
|
|
deficiency of thyroid hormone in fetus is
|
creatinism
|
|
|
hypothyroidism is associated with
|
HASHIMOTOS THYROIDITIS
hypercholesterolemia and cold intolerance and myxedema coma. Can treat with replacement therapy of T4 which is levothyroxine |
|
|
Levothyroxine
|
analog of T4 and used to treat hypothyroidism associated with hashimotos thyrdoiditis
|
|
|
liothyronine
|
analog of T3 and used in more serious hypothyroidism associated with myxedema coma
|
|
|
usual cause of hyperthyroidism
|
graves disease which stimulates TSH and constant stimulation of thyroid hormone synthesis and secretion
|
|
|
tx: for hyperthyroidism/graves
|
the thiourea deriviatives: propylthiouracil and methimazole.
they INHIBIT THYROID PEROXIDASE |
|
|
Which thiourea derivat do you give ina preagnant woman?
|
propylthiouracil because it doesnt cross the placenta as well as methimazole
|
|
|
this thiourea derivated also inhibits 5'-deiodinase as well as thyroid peroxidase
|
propylthiouracil. By inhibiting this enzyme it stops the conversion of T4 to T3
|
|
|
which thiourea is more potent?
|
methimazole is more potent than propylthiouracil
|
|
|
side effects of methimazole and propylthiouracil which are thiourea
|
agranulocytises
|
|
|
high-dose iodide
|
effects take place in 24 hours. it inhibits the release of TSH so you have less thyroid hormone being released
USED FOR THYROID STORM. |
|
|
radioactive iodide
|
corrects hyperthyroidism. allows u to kill thyroid without affecting parahtyroid.
|
|
|
most likely cause of heavy metal toxicity
|
lead
|
|
|
other likely causes of heavy metal toxicity (3)
|
arsenic, iron, mercury
|
|
|
ligands suceptible to heavy metals usually include
|
sulfhydryl groups
|
|
|
chelating agents
|
used against hte heavy metal poisenin
|
|
|
which is more difficult to detect? acute or chronic metal toxicity?
|
chronic
|
|
|
all inorganic forms of heavy metals cause
|
GI Toxicity leading to nausea, vomiting, abdominal pain, diarrhea, MULTI-ORGAN toxicity,
|
|
|
all heavy metals cause nephrotoxicity EXCEPT?
|
Iron
|
|
|
chelating agents dnt hit this part of the body and thus they are ineffective for treatment of?
|
They dnt hit the CNS and ineffective for tx: of organic forms of tetrahydral lead or methyl mercury
|
|
|
chelating therapy is most useful for?
|
acute metal toxicity associated with high blood metal levels
|
|
|
most common form of lead poisoning
|
environmental on children
|
|
|
lead effects which steps of heme synthesis?
|
o-aminolevulinic acid dehydrogenase and ferrochelatase leading to an anemia
|
|
|
blood level of lead to be problem
|
>10
|
|
|
percentage of homes where kids are living that are made before 1950 that require lead screening
|
>27% of homes
|
|
|
if an ADULT has symptoms of lead poisoning or encephalopathy or their pB>100 give them what chelating therapy?
|
dimercaprol + CaNa2EDTA
|
|
|
If a Child has encephalopathy of is symptomatic with a pb>70
|
give them dimercaprol + CaNa2EDTA
|
|
|
if an adult has mild syptoms of pb70-100 or a child has mild symptoms with a pb of 45-69 then give?
|
give succimer
|
|
|
dimercaprol
|
a dithiol used IM which is used for acute lead toxicity with CaNa2-EDTA. it lowers lead levels in CNS. It is also a single agent treatment for arsenic toxicity or mercury
|
|
|
Single agent treatment for ACUTE arsenic poisoning
|
Dimercaprol
|
|
|
Single Agent treatment for Acute mercury Toxicity
|
Dimercaprol
|
|
|
CaNa2-EDTA
|
used for lead poisoning in conjuction with dimercaprol. However it has a higher affinity for lead and helps better with its excretion. It also helps it to be removed from the bone.
|
|
|
good oral analog of dimercaprol
|
succimer
|
|
|
single agent treatment for MILD toxicity of lead poisining at levels of 45-60
|
succimer
|
|
|
single afent therapy for mild arsenic or mercury poisoning
|
succimer
|
|
|
penicillamine
|
used to treat copper poisonnign or prevent copper accumulation in wilsons disease
|
|
|
deferoxamine
|
used to treat iron poisoning
|
|
|
prussian blue (ferric hexacyanoferrate)
|
chelating agent with high affinty for cesium and thallium. NOT ABSORBED ORALLY. TX: radioactive bombs and thallium poisoning
|
