P2

Front 1

Chemotherapy and hematuria

Back 1

1. **Ifosphamide  given in longer infusion; but must be given with Mesna (changes metabolism of drug and helps with toxicity especially in the bladder and not give hematuria)
ifosphamide is an alkyaling agent.
 Nitrogen mustards  very toxic, bone marrow toxic, secondary leukemia  one example is Cyclophosphamide (Cytoxan)  still used very widely. Given oral or IV, mainstay for lymphomas, NH lymphoma, give with G-CSF, ↑ dose, bone marrow toxic, nausea, alopecia  can cause Hemorraghic Cystitis (hematuria: bladder infection) pt needs to drink lots of fluid and keep urine dilute.

Front 2

Chemotherapy and pulmonary side effects

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 Procarbazine  alkylating agent for tx of Hodgkin’s dz  s/e include pulmonary toxicity
 Bleomycin  complexes w/ Fe and O2  used to tx Hodgkin, testicular, head, neck and skin cancer  one s/e is pulmonary fibrosis
 Anti-folic acids  are under the class--Anti-metabolites  these lower folate levels in the S phase  one example is methotrexate which binds to enzyme dihyrofolate reductase  CMFu – long time regiment of breast cancer  Squamous cell of head or neck  Give with Leukovorin with a high dose of Methotrexate, potentially lethatl, and then give Leukovorin  Really large doses are not the key, need a better drug  High doses are good for osteogenic cancer  Highly adverse, pulmonary toxicity and liver toxicity

Front 3

Vincristine

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C. Vincas AKA Oncovin  come form periwinkle. There is a high degree of neural toxicity, peripheral neuropathy, it is reversible, works in Mitosis (M phase) microtubule production and assembly inhibitors, low dose and lose toxicity. It has VERY LOW Bone Marrow toxicity. Used for combinations since they give less toxicity. (Cytoxin, Oncovin, Pretnazone) Adryomycin  non-hodgkins lymphoma. However they do cause reversible peripheral neuropathy and autonomic neuropathy (constipation opposite to others that cause diarrhea).
1. **Vinblastine(Velban)
a. lymphomas
b. combination with other drugs
2. **Vincristine (Oncovin)
a. lymphoma
b. combination with other drugs
c. least bone marrow toxicity, with large doses
can be used with just Adriamycin (Doxorubicin Hydrochloride) for NHL too!!!! REMEMBER DOSE LIMITED NEURO TOXICITY!!

Front 4

Cardiac toxicity

Back 4

A. Anthracyclines
1. Daunorubicin  as all –rubicins, it is used in acute leukemia, but not real important
2. **Doxorubicin (Adriamycin)
a. non cell cycle specific
b. interacts with topisomerase
c. produces free radicals
d. Used for lymphomas. Most effective for Breast Cancer and Small Cell Lung Cancer, but active in all of them
e. Very toxic
1. Cardiomyopathy  cardiac toxicity  leading to Heart Failure, max dose: 450 - 500 mg/l2 (only about 8 doses), need a baseline EKG, symptoms may show up later like 10-20 years
2. Local irritant quality. If it gets out of the IV  severe ulceration to the skin. All drugs will irritant the vein if constantly given in the same one, but this one is a bit nastier.

Front 5

Methotrexate

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III. Anti-metabolites  Cell Cycle Specific. Lowers folate level in the S phase
A. Anti-folic acids
1. **Methotrexate  bind to enzyme dihyrofolate reductance (make reduced folate) and stop it (inhibit). Cancer cells have high levels of this enzyme.
a. CMFu  long time regiment of breast cancer
b. Squamous cell of head or neck
c. Give with Leukovorin with a high dose of Methotrexate. High dose of Methotrexate is potentially lethal so you have to give Leukovorin (rescue therapy of drug toxicity).
d. Really large doses are not the key, need a better drug
e. These High doses are GOOD for  Osteogenic Cancer
f. Highly adverse, pulmonary toxicity, mucocitis and liver toxicity

Front 6

CD20

Back 6

B. other cell-surface antibodies (CD 20 very common)
1. Anti-CD 20  protein cell marker on B-Cells (prematuration of the B cell)
a. **Rituximab (Rituxin)
1. binds to CD20, helps inhibit cell growth
2. part of standard treatment for B-cell lymphomas
3. you want to give H1 & H2 blockers and steroid to prevent  allergic reaction
(2) ibritumomab (yttrium-90), (Zevalin) –analog of Rituximab (very expensive), (3) tostumomab (1-131),Bexxar) analog of Rituximab (very expensive)  give H1 and H2 blocker to prevent allergic rx

Front 7

Allergic reactions and chemo

Back 7

C. Taxanes  come from the bark of pine needles of the Pacific U Tree (now they are semi-synthetic to preserve the trees). Also inhibit microtubular depolarization in mitosis. For: head and neck cancer, ovarian, breast, lung (wide variety), potential to cause a acute allergic reaction, extreme shortness in breath, tachycardia, diphoresis, must give them pretreatment with anti-anaphylasis such as steroids and large doses of diphenhydramine [benadryl] (anti-histamine) because patient can go into anaphylactic shock and die, neurotoxicity (peripheral, reversible).
1. Taxanes  placitaxel (Taxol) and docetaxel (Taxotere)
2. Placitaxel  inhibits MT depolarization in mitosis  causes edema, but less than docetaxel  used for ovarian cancer
Docetaxel  not as neurotoxic  so better for those w/ ovarian ca

Anti CD20 Rixutimib can cause an allergic reaction so much give with H1 and H2 blockers and steroids to prevent this from occurring.

Front 8

Testis tumor therapy

Back 8

3. Cis-platin  very exciting turn-around in testicular cancer (germ cell: 100 % fatal); extremely TOXIC, bone marrow toxicity, extremely nauseating.
a. Nephrotoxic  tubular poisoning that can lead to kidney (renal) failure
b. Neurotoxicity  peripheral toxicity  ototoxicity (hearing loss), reversible, starts in the toes, can progress to muscle weakness
4. **Carboplatin  works like cis-platin, but reduced toxicity. Still causes ototoxicity and BM toxicity. But stays away from Kidney.
5. **Oxalaplatin  ↓ toxicity, very limited
a. colon cancer  second line treatment
b. Side Effect: Cold temperature related neuropathy. Acute neuropathy (numbness and vasospasm) problems with swallowing, very painful.
Bleomycin, vinblastine can be used for testicular cancer

Front 9

Study phases

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Phase I: participants are generally the sickest, they take a big chance, it is thought as a humanitarian effort. There is a very small chance that they will be cured
Phase II: now that the drug is safe it will take on more patients. It is not compared to any drugs that are available.
Phase III: are the most common and involve thousands of patients. This study is used to compare this new drug to the drugs that are already in the market.
Phase IV: This is used to look at the drug post-market. The toxicities and the side effects are monitored.

Front 10

Dose limiting toxicity

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6. Bleomycin  not used very much, causes DNA breaks, dose limit toxicity 300mg/m2 coz it will cause pulmonary toxicity (causes a change in lung tissue)
a. ABVD  Hodgkin’s Lymphoma
1. Andriomyocin
2. Bleomycin
3. Vinblastin
4. DTIC  alkylating-like drug

7. **Doxorubicin (Adriamycin)
Cardiomyopathy  cardiac toxicity  leading to Heart Failure, max dose: 450 - 500 mg/l2 (only about 8 doses), need a baseline EKG, symptoms may show up later like 10-20 years

Front 11

Anti-angiogenesis

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8. anti-angiogenesis agents
a. **Thalidomide  1960 anti nausea
1. pheocomelia  mal-development of limbs
2. anti-angiogenesis drug aka anti-growth factors
3. now used as an anti-cancer
4. third line drug for  Multiple Myeloma and Lymphoma

Front 12

Neutropenia prevention

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1. seen with adjunct therapy drugs  aim to address the BM suppression
 bone marrow growth factors  used with cytotoxic doses to decrease the toxicities, especially in BM toxicity
i. **G-CSF (Neupogen, Neulasta)
1. Don’t give with the drugs coz you could make the problem worse
2. Pancytopenia
ii. **Erythropoiten (Epogen, Procrit,Aranesp)

Front 13

Cis-platin (dose limited renal toxicity!!)

Back 13

IV. Alkvlating-like Agents  NON cell cycle specific. They cross link with DNA and interfere with DNA replication, similar to Alkylating Agents. There major toxicity is Bone Marrow.
A. Platins  involve the metal platin
1. **Cis-platin  very exciting turn-around in testicular cancer (germ cell: 100 % fatal); extremely TOXIC, bone marrow toxicity, extremely nauseating.
a. Nephrotoxic  tubular poisoning that can lead to kidney (renal) failure
b. Neurotoxicity  peripheral toxicity  ototoxicity (hearing loss), reversible, starts in the toes, can progress to muscle weakness
2. **Carboplatin  works like cis-platin, but reduced toxicity. Still causes ototoxicity and BM toxicity. But stays away from Kidney.
3. **Oxalaplatin  ↓ toxicity, very limited
a. colon cancer  second line treatment
b. Side Effect: Cold temperature related neuropathy. Acute neuropathy (numbness and vasospasm) problems with swallowing, very painful.

Front 14

Prostate Ca

Back 14

In the beginning all prostate cancers are hormone receptive because they grow off of the androgens or testosterone products. So if you deprive the androgen/testosterone levels you can actually kill off the cancer. But as it gets resistant you give other treatments.
 anti-androgens  bind to androgen receptors  useful in treating prostate cancer  used with GnRH  2 drugs: (1) flutamide (Eulixen) and (2) bicalutamide (Casodex)
 Estrogens such as estrogens (estradiol, DES)  very rarely used  in the past was used to tx prostate cancer
 gonadotrophin releasing hormones (GnRH)  used most in Prostate cancer  inhibit the pituitary LH and FSH (BUT FIRST YOU WILL GET PEAK OF TEST then it will decrease estrogen and androgens)  utltimately reduce estrogen and androgen  not much more you can do for Prostate Cancer other than hormones  given as an IM shot, given once every four months  2 drugs: (1) Leupride (Lupron) and (2) Goserelin (Zoladex)
1.
4. Anti-androgens  bind to androgen receptors, useful in treating prostate cancer, used with GnRH. OR LHRH (leuprolide and goserelin)
a. Flutamide (Eulixen)
b. Bicalutamide (Casodex)

Hormonal treatment reduces bone pains up to 70-80% and reduce psa level. Over period of time because refractory though and must switch up. Give mitoxantrone and prednisone in harmone refractory patients.

anti-adrenal agents
5. non-specific anti-adrenal drugs
a. mitotane
b. amingutethemide

Front 15

Cromolyn

Back 15

Cromolyn and Nedocromil
MOA: they inhibit mast cell degranulation
1) may decrease airway hyperresponsiveness
2) not used as acute bronchodilators

Cromolyn ***
- mild anti-inflammatory effect
- not as effective as inhaled corticosteroids for asthma control
- not for acute bronchospasm
- It is a powder inhaler poorly absorbed with almost no systemic toxicity
- It needs to be used for at least 4 weeks to see if effective in asthma
- Uses:
o In children with mild persistent asthma when we need to avoid steroid inhaler
o Has been used in pregnant women with mild persistent asthma
Side Effects:
- bitter taste
- irritation of pharynx or larynx
- mouth dryness

Front 16

Muscarinic M1 receptor antagonism

Back 16

 Competes with Ach  will see dry mouth, constipation, decreasd sweating, mydriasis, urinary retention, tachycardia, decreased lacrimation, decreased respiratory secretions

Front 17

Pilocarpine

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Muscarinic agonist  is a tertiary amine  Topically applied to the eye  produces rapid miosis and contraction of the cilliary muscles  used for emergency lowering of intraocular pressure of wide angle and closed angle glaucoma  Toxic effects: can enter CNS , profuse sweating and salivation  is a natural plant alkaloid that exhibits primarily muscarinic receptor agonist actions  as it is not a choline ester, it is not a substrate for cholinesterases and has a 2-3 hr duration of action  often used topically in the eye for management of glaucoma  produces contraction of the constrictor muscle and facilitates outflow of aqueous humor

Front 18

Clonidine

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antihypertensive  is a selective Alpha 2 receptor agonist used primarily as an antihypertensive drug  acts at presynaptic receptors to inhibit release of neural norepinephrine  IV form acts on postjunctional alpha 2 receptors to induce direct vasoconstriction  Oral form: its peripheral and antihypertensive effects result primarily from action at alpha-2 receptors in the CNS resulting in decreased sympathetic outflow to the heart and blood vessels