Module 6 Flashcards

Question

WHAT ARE CANCER AND CARINOGENS

Answer 1

* Large number of diseases but shares certain characteristics 1. Cell growth and division- aboloty to proliferate indeifnitely the cell cycle is not faster but division does not stop 2. Invasions - Ability to invasde surrounding normal tissues 3. Metastasis - Ability to spread throughout the body * Long latent period between time of exposure and development of diseases * Carinogensis is initation of cancer * Carinogens are called procaringogens that undergo metabolic activation and become ultimate carinogens that damage DNA * If the damage is repaired normally nothing happens but if repaired incorrectly or not at all permanent damage may occur ****

Answer 2

* Initiation ○ Initiators are chemical agents that alter genes involved in control of cell divisuon ○ And the proliferation of cells ○ Cancer arises when a single cell accumulates a number of mutations and escapes restraints on cell division * Promotion ○ Secod dtage ○ Accumulation of initiated cells * Progression ○ Final step where the precouros of cancer are further modified and phenotypically ○ Chemicals acting at this stage allow rapid growth of tumour once established * Initiation ○ Initiators are chemical agents that alter genes involved in control of cell divisuon ○ And the proliferation of cells ○ Cancer arises when a single cell accumulates a number of mutations and escapes restraints on cell division * Promotion ○ Secod dtage ○ Accumulation of initiated cells * Progression ○ Final step where the precouros of cancer are further modified and phenotypically ○ Chemicals acting at this stage allow rapid growth of tumour once established

Answer 3

* Genetics ○ Genetic makeup can contribute to varition in repsonse to carcinogens ○ People who have Xeroderma pigmentosum have a genetic deficency in DNA repair ○ And have high incidences of skin cancer ○ BRCA genes are a tumour supressive gene. Women who have it are at risk of developing breast cancer * Environmental factors ○ Non genetic elements ○ Diet , chemiclas, infections * Tobacco use * Diet/obesity Infections

Answer 4

* Smoking causes cancer * Smoking increase with increased tar content of cigarettes * 8x morel ikely to develop cancer in non smokers Passive smoking whioch is inhaling smokje from the environment is a risk facto

Answer 5

* Saturated animal fat and red meat are strongly linked to cancer of the colon, rectum and prostate * High intake of salt has been linked as well * Skimping on fresh fruit and vegetables can contribute to this development of many different cancers Fruits and vegetables contain constituents that block cancer inducing chemicals produced in our own body

Answer 6

* Viruses ○ Hepatitis B and Hepatitis C cause liver cancer ○ 80% of liver cancer globally is caused by hepatitis ○ HPV which is sexually transmitted can cause cerival cancer ○ HIV can cause Kaposi sarcoma a systemic disease that can often present with red to violet skin lesions * Bacteria ○ Helicobacter Pylori Causes stomach ucler associated with stomach cancer

Answer 7

* Marked difference between major cancer that affects different countries based on factors such as food consumed acess to vaccines and regulatory measures * Central africa has a high incidence of Hep B and contamination of food by aflatoxin NA and EU Colorectal cancer is more prevalent due to shitty diets

Answer 8

* Ames test ○ Mutant of bacteria salmonella that lost ability to make histidine ○ When maintained in a histidine free culture it cannot grow ○ Bacterium regains ability to grow when exposed to mutagenuc chemicals that initiate DNA repair mechanisms and fix the original defect When 174 known carinogens are tested by the Ames test 90% caused mutations

Answer 9

1. Detect cancer or precancerous conditions 2. Improve chance of sucessful treatment Decrease cancer death rates

Answer 10

* Get vaccinated ○ Hep B can cause liver cancer nad HPV cervical there are vax for both of these * Eliminate tobacco products ○ Reduce risk factor by 8x * Eat healthy ○ Maintain adequate diet of vegetables and moderate consumption of saturated fats and red meats * Avoid excessive exposure to sunlight ○ Decrease risk of skin cancer * Moderate alcohol intake ○ Associated with risk in cancer * Improve exercise habits Maintaining healthy life style will ensure body has best form to combat carcinogens

Answer 11

* Surgery * Chemotherapy * Radiotherapy * Targeted therapy Immunotherapy

Answer 12

* Alkylating agents ○ Directly bind to DNA lead to cross linked DNA strands result in DNA damage and consequently cell death ○ Cisplastin is example * Antimetabolities ○ Disrupt cellular metabolism ○ Halt cell growth and division ○ Folic acid antagonist methorexate * Mitotic inhibitors ○ Isolated from plants and affect microtubules fimction and formation of mitotic spindle ○ Example is vinsctistine * Topiosomerase inhibitors ○ Interfere with Enzymes responsible for super coiling DNA during DNA replication ○ Introduce DNA double stranded breaks and lead to cell death * Antitumour antibiotics ○ Agents that are natural products produced from strptomyces bacteria that work by various mechanisms to damage DNA * Hormone antagonists ○ Used to treat hromone sensitive tumours by supressing division ○ Anti estrogen tamoxifen is used to prevent breast cancer in some women at high risk * Biologicals ○ Number of drugs deruved throygh molecular biological techniques inhibit cell replication by blocking cytokines * Anti-angiogenic agents ○ Drugs interefere with process of angio gensis Without blood supply the tumour cells are not able to obtain sufficent growth and die

Answer 13

* Rapidly divideing normal cells in the body are also harmed by drugs employed in cancer chemotherapy * Bone marrow cell toxocitu occurs * Leading to decrease in white blood cells and platelets resulting in anemia decreased ability to fight infections * Cells lining the GI tract are harmed causing Diarrhea, nausea, vomiting and ulceration * Hair follicles are also harmed and cause hair loss * Primary goal of chemo is for antineoplastics to be selectively toxic meaning they damage cancer cells but leave non cancerous cells untouched * Biological different between cancer and non cancerous is still not known * Adverse effects often require therapeutic intervention * Such as srthypoietin - increase RBC and therombopoeitin - increase platelets Vomiting can be controlled by antiemetic agents and pain by opioids

Answer 14

* Rational is that cancer cells are less able to defend when attacked by variety of drugs which act in different ways. Chemo drugs can be additive or synergistic * Second reason to use antineoplastic agents is that 1 can select drugs that have different toxictie. If a single drug is used may not be possible to increase dose beyond certain level because of toxicities would be too great * Each individual drug can be decreasedw hich translates to decrease in toxicties * Finally combination decreases development of resistance cancer cells Treatment has improved with combination therapy

Answer 15

* Decreased drug accumulation ○ Small pumps on surface of cancer sells that move antineoplacti agents from sinside cancer cells to the outside ○ One is the multi-drug resistance protein 1 MRP-1 * Increase DNA repair ○ Mechanism of acquired resisatcne to alkylating agents may involve increase in the cancer cells ability to repair damaged DNA * Increased drug target ○ Cancer cells can adapt to chemo agents by increasing specific target of drug or by altering the senstivity of the drug target ○ In the case of anti estrogen agents such as tamoxifen cancer cells may increase number of estrogen receptiors Diminish effect of the drug as endogenous estrogen can now bind to the extra receptors

Answer 16

* Progressive destruction and regenration of liver leading to fibrosis and cirrhosis * Many causes exist like hep B and alcoholic liver diseasse * Ability to handle medication is altered * Absorption ○ Chronic liver disease does not have direct effect on absorption of drugs in the body but can affect oral bioavailability * Distribution ○ Chronic liver disease also associated wit hincrease ine ECF peripheral edema and ascites ○ Affecting distribution ○ Apparent volume of distribution and hydrophillic drugs is increased * Metabolism ○ Decline in liver function associated wit hchronic hepatic disease accompanied by delcine ie xodiative activity of the liver * Excretion ○ Drugs that depend on primary liver for systemic clearance are excreted by the billary system are likely to have reduced elimionation in patients with chronic liver disease ○ Can lead to drug accumulation ○ 3 drugs are perscribed § Drugs that primaryily eliminated by renal excretion § Drugs that are metabolized by PhaseII condjugation § Drugs that have a high orla bioavilability ## Footnote `

Answer 17

* Kidney is the primary organ for elimination drugs and metabolites * Decreases the function and ability of the kidney * Major impact on pharmacokinetics of many drugs * AS kidney function declines * ECF increases and increases the Vd of Hydrophillic drugs * Patients with Chronic kidney disease need to be perscribed dosages of drugs Especially true for drugs that are primarily elimninated by glomerular filtration of the parent compound

Answer 18

* Any disease that affects heart of blood vessels * Atherosclerosis and hypertension are most common * Can lead to chronic heart failure * Progressigve decline in the ability of the heart to adequately pump blood throughout the body * Many effects on function of other organs in the body * As a result can have reduction on cardiac output * Results in impaired organ perfusion and compensatory changes lead to sodium and water retention * Causing peripheral edema and viscerla congestion * These changes lead to decreased volume of distribution for drugs * Recommended dosages will need to be reduced by 50% for patienst with Cardiovascular disease * This reduction is dosage is to compsensate for the reduced VD * In chronic therapy reduction is dosage is to compensate for imapred metabolic and renal clearance Intravenous administration may be preffered where oral or intramuscakr will be severely imapired

Answer 19

* BMI greater than 30 * Morbid is greater than 33 * Increase in fat lean body mass 20-40%, cardiac output and GFR in the kidney * Because of the changes in physiology pharmaokinetics of the drug should be altered * Absorption ○ Accomapnied by increased gastric emptying as well as increased gut perfusion ○ Both associatedw ith increase in the rate and extent of drugs oral absorption * Distribution ○ Increase in body fat associated with increased Vd for lipophillic drugs ○ Fat can store lipophillic drugs ○ Decreasing amount of an acute drug dose that is avilable * Metabolism ○ Fat is not metabolically active ○ Metabolism of drugs is dependent on lead body mass ○ Vd is increasedw ith lipophillic drugs which requires increasei nd ose for an acute dose and for drug requiring chronic dosing ○ Lean body mass is used to calculate the dose * Excretion ○ Effect of obesity on drug remains controversial ○ GFR may be increased in obese patients ○ Increase rate of renal cleareance of drugs Also associated with numerous diseases that may have an impact on the drug excretion

Answer 20

* Older alduts often perscribed multiple medications which complicates things * Absorption ○ No major effect on absorption * Distribution ○ Increasing age associatedw tih decrease in total body water ○ Increase in fat which is not accomapnied by increase in body weight * Metabolism ○ Reduced activities of cytochrome P450 enzymes ○ Little change in phase 2 reactions ○ Cardiac output generally declines by 50% from age 20 to 80 ○ Decreased blood flow to the liver these can lead to increased half lide of numerous drugs as well as reduced hepatic clearance * Excretion ○ Renal elimination is also reduced ○ Decrease GFR ○ 50-60% ○ Reduced active tubular secretion and reduced reabsorptive capacity * Geriatic patients hae reduced compensatory reserved * They are unable to compensate for compromised function as well as dimionished homeostatic resposnse * Memonry has a cholinergic basis and elderly have reduced cholinergic fuinction and antocholinergic medications can cause confusion and disorientation * Such as antihistamines and over the counter sedatives * Benzos often produce increase sedation and confuse the elderly * Bp medication is typically med with compensatory effects

Answer 21

* Baby ass people * Absorptions ○ Newborns have slower gastric emptying time ○ Resulys in more complete absorption of some orially administered drugs ○ Also results in delayed therapeutic effect of drugs that are absorbed primarily from the intestine * Distribution ○ 70-75% of a newborn is water ○ 50-60 of an adult is water ○ Hydrophillic drugs will have a greater VD compared to adultys ○ Plasma binding proyteins are also found at lower levels in the neonate ○ Reuslting in reduced bound to free ration of the drug ○ Young also have a poorly developped blood brain barrier * Metabolism ○ Both phase I and II generally reduced in the neonate ○ Resulting in prolonged elimination of half lives of the drug in early months of life * Excretion ○ Renal excretion and GFR is reduced 30-40% ○ Reaching adult values by 6 to 12 months of age ○ Half life of some drugs in toddlers is actually shroter than in adults

Answer 22

* 90% of pregnants take 1 or more drugs * Following changes are in pregants ○ Metabolism ○ Blood volume ○ Cardiac output ○ Fat - Increased Vd for lipophillic drugs * Obvious consideration is tetragenic effects * Since lots of shit passes through the placenta * Some are more readily able to cross than others * Liphillic drugs and small dreugs readily diffuse acriss * Effect on a feetus is in 2 categories ○ Unpredicatble teratogenic effects § Unecpected effecst that occur following exposure to a drug § Happen with little as a single exposure § To a drug during a crtical window of development § Thalidomide exposure during the 4th to 7th week of gestation § Limbs are developing can result in phocomelia ○ Predictable toxic effects § Effecst that we can anticipate will occur in the fetus or neonate upon exposure to certain drugs for example withdrawal syndrom in neonates * If a woman is continuing drug therapy that was initiated pre pregancny it may be unwise to chance the perscription during pregancny - seizure medication of antidepressant * Less known risk may be outweighed by the benefit of controlled symptoms in the patient

Answer 23

* Drugs taken by lactating individuals are detectable in breast milk * Concentrations un breakmilks are typically levels too low to cause adverse effects in the infant * Due to this misconcetpion breast feeding individuals tend not to take medication duing this time * Some drugs to reach levels in the breastmilk to cause a pharmacological effect in the ifnant ○ Sedatives/hypnotics ○ Some antibiotics ○ Opioids * Large number of drugs are compatibkle with breastfeeding * If a person must talke these medications It is best to take medication 30-60 minutes after nysing and 3-4 before the next feeding * Whenver possible in some cases this may allow for time for drugs to be partially cleared from the blood and concentrations in breast milk to be low

Module 6 Flashcards

(48 cards)