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460 Cards in this Set

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  • Back
What is phenacetin?
the prodrug that quickly metabolizes to acetaminophen…no longer used in the U.S.
What is the half-life of acetaminophen?
1-3 hours
What happens when over 7 grams of acetaminophine (or greater are ingested?
liver damage --> irreversitble hepatic necrosis
The formation of what metabolite deactivates glutathione?
a) N-acetylimidoquinone
How can N-acetylimidoquinone be neutralized?
administer N-acetylcysteine
What is the optimum pH range for the absorption of aspirin?
pH 2.5 - 4
When do plasma levels of aspirin peak?
2 hours
what is the half-life of aspirin?
15 minutes
What causes aspirins duel effects?
1) aspirin itself… 2) liberated salicylate
What causes the half-lfe of aspirin to increase
increased dose
With respect to plasma proteins, what effect do the (aspirin) salycylates have?
They can displace other drugs from plasma proteins
How would you increase renal clearance of free salycylates (aspirin)?
increasing the urine pH from a few % of clearance at pH 5 -to- 80% clearance at pH 8
At what ranges does asprin have an a) analgesic effect and b) anti-inflammatory effect?
a) 10-15 mg -> analgesic… b) 20 mg -> anti-inflammatory effect
Which are aspirin and salycylate, COX 1 or a COX 2 inhibitor?
a) Aspirin is a nonselective COX 1 inhibitor (which is constituitively expressed) and COX 2 inhibitor at the site of inflammation… b) salicylate is less effective for inhibiting either form.
What is the pathway for COX that ends with pain?
COX catalyzes the conversion of arachidonic acid to PGG2 --> converted to protaglandins (by prostaglandin synthase) --> inflammation, redness vasodilation.
What effect does aspirin have on platelet aggregation?
by inhibiting COX, aspirin irreversibly inhibits platelet aggregation for 72 hours, which is the lifetime of a platelet
What effect does aspirin have on body temperature and bleeding time?
anti-pyretic and increases bleeding time
What effects does aspirin toxicity cause? (5 each)
1) gastritis with acute and chronic blood loss, 2) gastric and duodenal ulcers, 3) dose dependent tinnitus with hearing loss, 4) mild and reversible hepatotoxicity, 5) Aspirin hypersensitivity.
What is codeine synthesized from?
How do codeine and morphine differ?
Morphine is a complete opioid receptor agonist in the CNS, while codeine is a partial agonist.
Which is potentially more addicting, morphine or codeine?
morphine is more addictive… this is because codeine is a prodrug which will go directly to the brain, only to be sent back to the liver to be metabolized to morphine by P450
Does codeine have a large first pass metabolism?
No, small
What are the organ system effects of morphine and surrogate?
anagesia, euphoria, sedation and respiratory depression.
How does codeine cause respiratory depression?
it depresses respiratory by inhibiting brain stem respiratory mechanism, cough suppression.
what other effects does codeine have due to brainstem activity? And how?
codeine causes nausea and vomiting by activating the brainstem chemoreceptor trigger zone
When does ethanol peak in the blood?
30 min in fasted state
How does food in the stomach delay absorption of ethanol?
ethanol delays absorption by delaying gastric emptying
What does the volume of distribution (Vd) of ethanol approximate and why do women have a higher peak concentration?
a) total body water… b) women have a higher peak concentration of ethanol because they have smaller water content compared to men
why does the brain receive a higher concentration of ethanol?
greater perfusion to the brain and ethanol easily crosses the BBB
where is ethanol metabolized (oxidized)?
90% in the liver, the rest is excreted thru the lungs and urine
a) What order of kinetics does the rate of ethanol oxidation follow? b) What consequences does this have?
a) zero order kinetics… b) ethanol metabolism is independent of time and concentration
what is the average adult capacity to metabolize ethanol per hour? (grams)
7-10 g ethanol / hr
What is the pathway for ethanol metabolism? (include metabolites and necessary enzymes)
ethanol --(alcohol dehydrogenase)--> acetldehyde --(aldehyde dehyrogenase)--> aldehyde
What types of interactions does ethanol have?
increased P450 for ethanol metabolism can increase drug metabolism… i.e., acetaminophine
a) What is flurosemide (Lasix)? b) what is its mechanism of action?
a) a loop diuretic… b) it selectively inhibits NaCl absorption in the TAL of the loop of Henly… specifically, it the inhibits Na/K/2Cl transporter at the lumen side, which contributes to excess K+ accumulation --> this drives Mg and Ca reabsorption --> thus urinary excretion is increased (increased delivery of salt and water to the collectin duct and thus enhanced secretion of K+ and H+ causes hypokalemic metabolic alkalosis)
a) What is the duration of effect of flurosemide and b) what does its half-life depend upon?
a) flurosemide duration of effect is about 2-3 hours and b) it half-life is dependent upon renal function
What pulmonary and cardiac effects does flurosemide have?
reduces pulmonary conggestion and left ventricle filling prssures in the heart before increased urinary output are seen
what is the bioavailability of flurosemide?
about 70%
What is the relative therapeutic index of flurosemide?
very wide
What are the indications for propranolol and its mechanism of action?
high blood pressure… b) ß-blocker… decreased heart rate => decreased cardiac output… plus it inhibits renin secretion
a) What is the bioavailability of propranolol after first pass? b) What can cause the bioavailability to increase?
a) ~20%… b) increase dose
What are the indications for digoxin (digitalis) and its mechanism of action?
a) Rx: heart failure and atrial fibrillation… b) 1) Digoxin (digitalis) binds to and inhibits the Na/K ATPase pump, which will cause an increase in intracellular Na and Ca --> resulting in increased contractility, stroke volume and thus an increase in cardiac output... 2) digoxin (digitalis) also decrease conduction of velocity through the AV node, which will cause a decrease in ventricular rate... it does this by stimulation of the vagal response
What are the possible toxic side effects of digoxin (digitalis)? (3 each)
Premature ventricular contractions, bigeminal rhythm, 2nd degree blockade.
Does digoxin (digitalis) have an effect on CNS?
yes… (discussed earlier, increased vagal response) but digoxin (digitalis) will effect Na/K ATPase pumps in neurons and smooth muscle, which will increase neuronal and smooth muscle activity.
Besides the possible side effects discussed earlier, what other possible risks are there with digoxin (digitalis)?
digoxin (digitalis) carries the possible risk of cardiac arrhythmias if hypokalemia develops.
a) What is the loading (and maintenance) dose of digoxin (digitalis)… b) what is the toxic plasma concentration?
a) loading and maintenance does = .25 mg digoxin (digitalis)… b) toxic [plasma] = 2 ng/mL
What three things should be monitored during digoxin (digitalis) therapy?
1) serum digoxin (digitalis), 2) K+ levels, 3) ECG
What are the indications for Gentamicin and its mechanism of action?
a) Gentamicin indications: both gram (+) and (-) infection (bacterial antibiotic)… Amionoglycosides are useful against gram (-) enteric bacteria esp. bacteremia and sepsis. b) inhibits protein synthesis in bacterial cell.
Which types of bacteria are resistant to Gentamicin?
streptococci and enterococci are resistant because Gentamicin can't penetrate the cell.
What are the indications for Chloroquine? What does it do? Is Chloropquine well tolerated?
a) Chloroquine is indicated as a chemoprophylaxis of malaria… however, due to drug resistance, its use against P falciparum is compromised. b) it is an anti-parasite, terminates fever and clears parasitemia… c) yes it is well tolerated
What are the indications for Isonizid?
Mycobacterial infection (TB), which is slow growing, dormant, and resistant to drugs.
What are the indications for Meperidine?
a) What is Meperidine? b) How long does it take to build a tolerance to Meperidine?
a) strong opioid agonist… b) two weeks, requiring a larger dose
What are the toxic consequences of Meperidine and how is it caused?
Meperidine is metabolized in the liver to Normeperidine and this metabolite can cause seizure at high plasma levels
What are the indications for Phenytoin (Dilantin) and its mechanism of action?
a) Seizures both partial and generalized (it's an anti-seizure drug) b) it blocks voltaged-gated Na Channels in neuronal membranes and thus prolongs inactive state of Na channela and refractory period of the neuron… Overall it blocks the repetitive firing of action potentials
How is Phenytoin (Dilantin) cleared?
hepatic enzymes and it binds extensively to plasma proteins (97-98%)
What order kinetics does Phenytoin (Dilantin) exhibit?
At therapeutic levels elimination is first order kinetics… Zero order kinetics are seen when the liver's maximum capacity to metabolize Phenytoin (Dilantin) are reached and plasma protein become saturated.
What happens when Phenytoin (Dilantin) concentrations increase due to zero-order kinetics?
half-life is prolonged --> followed by toxicity sedation and seizure
A) What is propofol used for? B) Why is this a good____(answer to A)___?
a) It is an IV anesthetic… b) rapid onset and rapid recovery.
Why does proporol diffuse to the brains first? What causes rapid recovery?
perfusion… redistribution to other fatty areas of the body and other areas.
What is the distribution half-life of Propofol? What is the elimination half-life of Propofol?
distribution t1/2 = 2-8 min… elimination t1/2 = 30-60 minutes.
What are thiazides? What is their mechanism of action? What are indications of thazides?
a) diuretics… b) Inhibits NaCl transport in DCT and enhances Ca reabsorption… (THUS IT IS DIFFER FROM LOOP DIURETICS)… c) heart failure and hypertension
What the indications of Warfarin (Coumadin)? What are Warfarin (Coumadin) mechanism of action?
a) indications: people with increased of thrombosis, e.g., artificial heart valves, deep vein thrombosis, pulmonary embolism… b) inhibits effective synthesis of clotting factors by sequestration of Vitamin K.
What is the Bioavailability of Warfarin (Coumadin)? Where is Warfarin (Coumadin) distributed? What effect does this have on volume distribution?
a) BA = 100%… b) bound to albumin… c) it has a small volume of distribution
what are concerns for preganant women taking Warfarin (Coumadin)?
Warfarin (Coumadin) crosses the placenta --> leading to hemorrhagic disorder in the fetus
Name the 4 general classes of chemotherapeutic agents used in the Rx of cancer
Alylating Agents... Antimetabolites… Natural products… Biologicals
Name 2 sub-classes of Alkylating Agents used as chemotherapeutics agents in the Rx of cancer
Nitrogen mustards… Platinum Based Compounds
What is the general mechanism of action for nitrogen mustards?
Rxn of chloromethyl group with water that forms a aziridine ring that forms a covalent bond with nucleic acids or proteins, which CROSS-LINKS DNA (@7-nitrogen of guanine)
Name 2 specific Nitrogen-mustards (alkylatign agents) and the major cancers they are used to Rx.
Cyclophosphamide (cytoxan): Broad general activity…

Ifosfamide: Testis and sarcomas

NOTE: Ifosfamide is use in combination with Vinblastin and Cisplantin to Rx testicular cancer (VIC)
Which alkylating chemotherapeutic agent is a prodrug?
Cyclophosphamide (cytoxan)
What does cyclophosphamide get metabolized to and what considerations must be made?
Acrolein; it turns whatever it comes in contact with into plastic… b) do not administer at night or the bladder will turn to plastic… also give with MESNA to convert acrolein into a non-toxic metabolite.
Compare and contrast Cyclophosphamide and Ifosfamide in terms of a) Dose and acrolein and b) BBB & myelosuppressive
both produce acrolein, but you need higher dose of Ifosfamide, thus it needs more MESNA… also Ifosfamide crosses the BBB and is myelosuppressive.
What is the mechanism of action of Platinum-based agents?
Covalently binds to DNA and cross-links via N-7 and/or O6 of DNA guanine
Name 2 specific Platinum Based Compounds (alkylating agents) and the major cancers they are used to Rx.
Cisplatin: Lung, TESTIS, ovarian, bladder…

Carboplatin: Ovarian, LUNG (Bext Rx when used with Taxol small cell lung cancer... sometimes curative) , bladder

NOTE: Taxanes are better for ovarian cancer

NOTE: Cisplatin is used in combination: BEP and VIC for testicular cancer

NOTE: Best Rx for non-mall Cell Lung cancer is carboplatin and Taxol... sometimes curatuve.
Is there cross-resistance between cisplatin an dcarboplatin?
What are associated toxicities of cisplatin?
a) renal insufficiency with Mg2+ wasting hypokalemia is a very IMPORTANT toxic effect--> NEPHROTIC RENAL INSUFFICIENCY… b) nausea and vomiting… c) peripheral neuropathy… d) auditory impairment… e) thrombocytopenia (mild compared to carboplatin)
What some precautions for cisplatin?
monitor Mg, K and Ca levels… b) don't use with other nephrotoxic drugs… c) AGGRESSIVE use of antiemetics is helprul… d) maintain high urine flow… VIGOROUS HYDRATION (FLUSHING)… creatinine should > 60 ml/hr… if not use carboplatin.
What are associated toxicities of carboplatin?
a) IMPORTANT adverse effect is THROMBOCYTOPENIA…b) nausea and vomiting… c) less nephrotoxicity than cisplatin
a) Define: Antimetabolite (in terms of antineoplastic drugs)

b) Name three sub-classes of antimetabolites chemotherapeutic agents used to Rx cancer
a) an antineoplastic drug that inhibits the utilization of a metabolite

b) Folic acid analogs… Pyrmidine analogs… Purine analogs
Name a specific folic acid analog and the major cancers its used to Rx
Methotrexate: bladder cancer and lymphoma
What is the mechanism of action of methotrexate?
Inhibition of DIHYDROFOLATE --> leading to depletion of folates (FH4) --> Polyglutamates of methotrexate lead to the inhibition of purine and thymidylate (dTMP) synthesis
What are the associated toxicities for methotrexate?
MYELOSUPPRESSION, RENAL TUBULAR OBSTRUCTION & INJURY, Neurotoxicty (interthecal), pneumonitis, mucositis,
What is necessary for methotrexate to be retained cells?
Metabolism: converted to polygutamates
How do you rescue normal tissue from methotrexate toxicity?
Administer Leucovorin
a) What special considerations are there for Methotrexate? (hint:3 things)

b) Can Methotrexate cross the BBB?
a) i. Requires normal renal function…
ii. Reduce dose proportionally to creatinine…

ii. monitor [drug] and keep patient hydrated.

b) No, it can't cross the BBB, it's a large polar molecule
Name 2 specific pyrimidine analogs and the major cancers they are used to Rx.
5-flurouracil: Breast, all GI-especially colon, urinary bladder, premalignant cancer (topical)… Gemcitibine: bladder, pancreas, and lung cancer
What is the mechanism of action gemcitibine
dFdCMP --(phosphorylated)--> dFdCTP, which competes with dCTP as DNA pol inhibitor also, dFdCDP is an inhibitor of ribonucleotide reductase, lastly, once incorporated into DNA it causes leading strand termination
What must happen to 5-fluorouracil (5-FU) for activity to occur?
Converted to nucleotide (F-dUMP)
What are the likely toxicities of Gemcitibine? (2 each)
1) myelosuppression (but mild at low doses… 2) mild flu-like symptoms…
What is the mechanism of action for 5-FU?
5-FU is an analog of dUMP… --(inhibition of thymidylate synthetase, which is the enzyme required for dTMP synthesis) -> consequently DNA synthesis is inhibited
What should 5-FU be administered with in adjuvant Rx of the colon?
Name a specific purine analogs and the major cancers they are used to Rx.
Mercaptopurine: acute myelogenous leukemia (rarely given)
What is the mechanism (6-MP) of action for mercaptopurine?
first converted to nucleotide 6-MP is an analog of IMP --> inhibits rxns by inhibiting adenylosuccinate enzymes --> impaired purine biosynthesis
a) What drug interaction should you be careful with when administering 6-MP? b) what should you do if 6-MP and drug-X from question "a" (above) must be given together?
a) Allopurinol, which inhibits xanthine oxidase (which normally serves to oxidize 6-MP… b) give less 6-MP when given with allopurinol
Name 5 the two sub-classes of Natural product chemotherapeutic agents used to Rx cancer
Vinca alkaloids… Taxanes… Epipodophylotoxin… Camptothecins… Antibiotics
Name 2 Vinca Alkaloids and the major cancers they are used to Rx.
Vinblastine: Hodgekin's and non-Hodgekin's lymphoma and breast cancer…

NOTE: V in VIC is =Vinbastin... ifosfamide, Cisplatin

Note: it's the "V" in ABVD: Hodgkin's Lymphoma: Adriamycin, Bleomycin, Vinbastin, Dacarbazine

Vincristine: acute lymphocytic leukemia, Hodgekin's and non-Hodgekin's lymphoma

Note: it's the "O" in MOPP: Hodgkin's Lymphoma: MOPP: Mustard, Vincristin, Procarbazine, Prednisone
What is the mechanism of action for Vinca Alkyloids?
Both Vinblastin and Vincristin bind with tubulin (needed protein in the mitotic spindle) and arrest the cell in metaphase.
Of Vinblastin and Vincristin, which myelosuppressive?
Vinblastin is myelosuppresive… NOT Vincristin
Does cross-resistance occur between Vinblastin and Vincristin?
a) Between Vincristin and Vinblastin, a) which is highly neurotoxic?

b) which is used in the treatment of Hodgekin's as ABVD?

c) which is used in the treatment of Hodgekin's as part of MOPP (which is letter does it represent?)
a) Vincristine…

b) Vinblasatin

c) Vincristin... "O"
Name 2 Taxanes and the major cancers they are used to Rx.
Paclitaxol (Taxol): ovary, breast, bladder and prostate… Doxitaxel (Taxotere): Breast and prostate
What is the mechanism of action for Taxanes?
Bind to tubulin, which renders microtubules less suseptible to depolymerization --> may affect p53 dependent and independent apoptosis
Between Taxol and Taxotere, which stay in the cell longer and what is the consequence?
Taxotere: increased response rate
Is there cross-resistance between taxol and taxotere?
What is the mechanism for cross-resistance for Taxanes?
presence of P-glycoprotein --> leading to mutations of ∂ and ß tubulin subunits
What is the cause of anaphylaxis (along with hypothension and dyspnea and flushing) in taxanes? b) what can be done to resolve this?
a) the vehicle: cremophor E1 + alcohol… b) premedicate with antihistamine and hydrocortisone
Taxanes are used as first-line defense in what type of cancer… b) which two drugs do taxane out-perform for the above type of cancer?
a) ovarian… b) cisplatin/cyclophosphamide (cytoxan)
Which type of cancer is the combination of Carboplatin and Taxol seen to be curative?
non-small cell lung cancer
Which type of cancer is the combination of cytoxan and Taxol a better advanced disease Rx over Cytoxan and Adriamycin?
Breast cancer
Taxanes are used with Estramustine in the treatment of what disease?
Prostate cancer
Are taxanes myelosuppressive?
What two types of myelosuppression are seen with taxanes?
neutropenia and thrombocytopenia
Besides myelosuppression, what possible toxicities are seen with taxanes?
sensory neuropathy; alopecia; nausea, and vomiting (relatively mild)
Match the Taxane (Taxol & Taxotere) with the Toxicity: a) major neurologic toxicity, peripheral neuropathy b) capillary leak syndrome leading to pleural effusion and peripheral edema
a)Taxol: major neurologic toxicity, peripheral neuropathy… b) Taxotere: capillary leak syndrome leading to pleural effusion and peripheral edema
Name one Epipodophylotoxin (Natural Product chemotherapeutic agents) and the major cancers it is used to Rx.
Etoposide: Lung, testis, lymphomas
What is Etoposide? What is its mechanism of action?
It is an plant derived chemotherapeutic… it mechanism of action is it inhibits topoisomerase II (which normally unwinds DNA during replication)
Name one Camptothecins (Natural Product chemotherapeutic agents) and the major cancers they are used to Rx.
Irinotecan: colon
What is Irinotecan and what is its mechanism of action?
It is an plant derived antineoplastic… it targets topoisomerase I, it relaxes DNA by making single strand nicks --> resulting in double stranded DNA damage…
Name 2 Antibiotic (Natural Product chemotherapeutic agents) and the major cancers they are used to Rx.
Doxorubicin: Broad general activity BUT NOT: colon or lung cancers… also Bleomycin is an antibiotics
Is Irinotecan a prodrug? What are some toxicities seen with Irinotecan?
a) yes, it's a prodrug… b) delayed onset diarrhea (Rx with anti-diarrhial) also myelosuppression
a) What is the primary mechanism of action for Doxorubicin (adriamycin)… b) what are the three remaining mechanisms of action?
Inhibits function of topoisomerase-II-dependent causing DNA damage… b) intercalation (where base pairs are moved apart), Free Radical Formation, and increases BAX in some cell lines
Which antineoplasitc drug(s) are dose dependent?
a) Which of the four mechanisms of action for Doxorubicin is responsible for cardiotoxicity? b) Doxorubicin toxicity is ____ dependent… c) why is cardiotoxicity occuring? d) what can be done to avoid cardiotoxicity?
a) Free radical formation… b) dose dependent… c) myocytes do not have catalase to detoxify H2O2… d) give a drug with an iron chelator that has a higher affinity for iron than adriamycin.
What are 3 things to consider for patients using doxorubicin?
1) acute and chronic decompensation can occur… people with hypertension, heart disease and those receiving high doses of radiation are at increased risk… 2) Lasting (16 yrs) radiation sensitivity… 3) can lead to loss of limbs
a)What is the major route of clearance for Doxorubicin…

b) What are the precautions needed for treating patients with depressed liver function with Doxorubicin?

c) What is the mechansim of action of Bleomycin?

d) What is Bleomycin used to Rx?

e) Why is Bleomycin used so often in combination with other drugs?

f) Bleomycin toxicities?
a) liver, biliary excretion and aglycone formation…

b) no modification of dose is needed for depressed liver function when Rx w/ Doxorubicin.

c) Antibiotic (fermentation of streptomycin), nicks DNA and inhibits ligase enzymes

d) active against squamous cacinomas and lymphomas

NOTE: Bleomycyin is used in ABVD to treat Hodgkin's lymphona
NOTE: Bleomycin is used in combination with Etoposide and Crisplatin in the Rx of testicular cancer.

e) little myelosuppression allows it to be used with other myelosuppressive drugs.

f) pulmonary
Name 4 sub-classes of Biologicals (chemotherapeutic agents) used as Rx for cancer.
Hormones, Enzymes, hematopoietic growth factors, interleukins
Name 4 specific Hormones (Biologicals - chemotherapeutics agents) and the major cancers they are used to Rx.
Tamoxifen: Breast… Leuprolide: Prostate (LHRH antagonist)… Flutamide: prostate (non-steroidal antiandrogen)… Prednisone: acute and chronic lymphoctytic leudemia, non-Hodgekin's lymphoma, Hodgekin's disease, and breast cancer
What is the mechanism of action of Platinum-based agents?
Covalently binds to DNA and cross-links via N-7 and/or O6 of DNA guanine
What is the mechanism of acdtion for Tamoxifen?
a) (Anti-Estrogen) Tamoxifen depletes estrogen stimulated progesterone receptor synthesis, b) Tamoxifen has cytotoxicity activity: blocks 52K protein synthesis, blocks DNA polymerase activity and blocks tritiated thymidine incorporation and… c) traps cell in mid G1 phase... d) forms tight association with estrogen receptor and nucleus... e) stimulates TGFß
What are the toxicities of Tamoxifen? (hint: 7 each)
a) hot flashes… b) risk of endometrial cancer… c) retinal and paramacular issues… d) thrombocytopenia (myelosuppression)… e) anovulation… f) liver cancer… g) cataracts
What is the mechanism of action of Flutamide?
It is an antiandrogen. Like others in this sub-class it blocks cytoplasmic receptor for dihyrotestosterone.
a) Which antineoplastic drug is a antibiotic? (2 each)… b) Which of these is known as a anthracycline?
a) Doxorubicin (adriamycin), Bleomycin, … b) Doxorubicin
Which drug is given to reduce cardiotoxicity caused by Doxorubicin?
an Fe chelator
a) Which antineoplastic drug give bone pain? b) Why?
Taxoxifen… b) Tamoxifen retards normal bone density loss.
What is the mechanism of action for Leuprolide?
It is a LHRH (lutenizing hormone releasing hormone) analogue that blocks the signals from the pituitary to the testes to produce Testosterone… thus LH and FSH levels drop because the number of LHRH receptors in the pituitary decline.
For a weak base, which gives more neutral drug, a negative or a positive value? (Hint: pka-pH)
A negative value (pH > pka) thus more drug in the unprotonated form, which for weak bases are neutral.
For lipid solubility, do you want a more acid or more basic environment to neutralize a weak base? (Hint: pka-pH)
More basic
For a weak acid, which gives more neutral drug, a negative or a positive value? (Hint: pka-pH)
A positive value (pka > pH) thus more drug is in the protonated form, which for weak acids are neutral.
For lipid solubility, do you want a more acid or more basic environment to neutralize a weak acid? (Hint: pka-pH)
More acid
For a weak acid, which is lipid soluble, protonated or unprotonated form?
For a weak base, which is lipid soluble, protonated or unprotonated form?
For a weak acid (pka = 3) in an acid environment (pH = 2), what percentage will be lipid soluble?
The value will be = 1… thus 1:10 protonated (neutral) : unprotonated giving 10% lipid soluble.
For a weak acid (pka = 2.5) in an acid environment (pH = 3.5) what percentage will be lipid soluble?
The value will be = -1… thus 10:1 protonated (neutral) :unprotonated giving 90% lipid soluble
For a weak base (pka = 7.5) in a basic environment (pH = 8.5), what percentage will be lipid soluble?
The value will be = -1… thus 10:1 protonated :unprotonated (neutral) giving 10% lipid soluble
For a weak base (pka = 8.5) in a basic environment (pH = 7.5), what percentage will be lipid soluble?
The value will be = 1… thus 1:10 protonated: unprotonated (neutral) giving 90% lipid soluble.
For receptor time-response, place the following in order of response: G-protein, Ion channel, Enzyme linked , DNA transcriptional contol (milisec, sec, min, hours)
milisec: ion channel… Seconds: G-protein… Minutes: Enzyme Linked… Hours: DNA transcriptional control
If Kd is low, what is the receptor/drug affinity?
If the Kd is high, what is the receptor/drug affinity?
Give the formula for determining the amount of bound drug to receptors
B=(Bmax X [D])÷(Kd + [D])
When does the Kd = [D]?
when 50% of the receptors are bound to drug
What does EC50 represent?
ED50= [D] when 50% of the max effect (Emax) is seen
Are Kd and EC50 the same?
not necessarily
What does Kd represent?
it determines the fraction of receptors bound to Drug at a given [D], independent of the [B], such that the affinity is absolute, but even with the Kd the proportion of Drug bound to receptors can be still changed by other competing agonist or antagonists of varying Kd values
Which cannot be saturated by drug, specific binding or non-specific binding?
non-specific binding
How do you determine the number of specific binding, given the total number of binding and the total number of non-specific binding?
Specific Binding = total binding - non-specific binding
What does cell sensitivity to drug dependent upon?
Affinity (Kd) and degree of spareness
What are two factors that determine the degree of spareness?
1. Temporal: Drug at regulatory receptor, where effect last beyond binding… 2. "Spare in number": full biologic effect is seen when only a few receptors are bound.
What is an antagonist?
binds to receptor but does not produce a response
What is a competitive antagonist?
A compound that binds to a receptor and inhibits an agonist's effect proportional to it's concentration. ALSO defined by the ability to reverse the inhibitory effect by adding a greater concentration of agonist
What is a non-competitive antagonist?
a compound that can inhibit the activity of an agonist. but annot be reversed by any concentration of agonist
Is an irreversible antagonist always non-competitive?
Is a non-competitive antagonist always irreversible?
In an effect/[agonist] curve what does a) a competitive antagonist graph show at increased [agonist] and b) a non-competitive antagonist at increased [agonist] show?
a) competitive: increased [agonist] can give Emax = without antagonist… b) non-competitive: no amount of increase in [agonist] can give Emax of agonist alone
what is a partial agonist?
a) bind and produces response , but not = in response to full agonist, b) it can also be described as having a partial competitive-antagonist effect, since in the presence of a partial agonist the agonist must compete with an agonist the does not elicit a full response
What does a partial agonist look like on a graph?
like an agonist combined with an antagonist
what affect does a partial agonist have on a full agonist?
act somewhat like an antagonist, such that the agonist can over-come the competitive nature of the partial agonist and eventually reach Emax
What is an inverse agonist?
it binds to a receptor and produces a response that is opposite to an agonist
Of the following, (parial agonist, antagonist, inverse agonist)which will have the greatest NEGATIVE affect on a circuit that is on (due to an agonist)? (Hint: place in order)
Greatest to lowest negative effect: inverse agonist > antagonist > partial agonist
Of the following, (partial agonist, agonist, inverse agonist), which will have the most POSITIVE affect on the circuit that is off (due to an antagonist)? (Hint: place in order from greatest to lowest positive effect:
Greatest to lowest positive affect: Agonist > partial agonist > inverse (no positive effect)
On a drug response curve how is a) greater potency demontrated… b) greater efficacy demonstrated?
a) more potent the curve is to the left… b) greater efficacy goes higher in reponse
a) On a curve that show 3 drugs, one has NO cooperativity and the other two have either positive cooperativity and negative cooperativity, how is it demontrated graphically?

b) Does cooperativity effect Emax?

c) Do positive and negative cooperativities demonstrate the Michaelis-Mentis relationship?
a) Postive cooperativity has a steeper curve… where negative cooperativity is a shallower curve relative to the "no cooperativity" curve

b) no

c) no
When are quantal dose-effect reponse curves used?
When it is all-or-none, thus it shows the fraction of individuals that resond at a given dose.
What is the usefulness of quantal dose curves?
They are useful in determining therapeutic indices.
What are the posible interactions determining the actions/effects of a drugs?
a) One drug/receptor --> one effector --> can give toxic or beneficial reponse… b) one drug/receptor --> two effectors --> either toxic or beneficial… c) one drug/2 receptors --> one receptor is toxic the other is beneficial.
What 3 things done in in vitro drug studies? (Hint: If I... want to make a new drug?)
1) IIdentify molecular targets, 2) find lead compound, 3) Improve selectivity
Which 8 things animal testing of a drug hope to determine?
1) Metabolism, 2) ED50, 3) LD50, 4) (TD50), 5) Chronic Toxicity, 6) teratogenicity, 7) carcinogenicity, 8) mutagenicity, 9) Adverse Side Reaction by Organ Systems
When is an investigational New Drug application to the FDA filed? (IND)
after animal testing and before human clinical trials
a)What is the population size in phase I of clinical trials? b) What is the health of the typical phase I participant? c) Are there any blind studies in phase I? d) what is being looked at in phase I?
a) 25-50… b) healthy… c) no everyone knows what's given… no controls… d) Drug safety and pharmacokinetics
a)What is the population size in phase II of clinical trials? b) What is the health of the typical phase II participant? c) Are there any blind studies in phase II? d) what is being looked at in phase II?
a) 100-200… b) they have the disease the drug treats… c) single-blind with controls… d) drug efficacy and safety
a)What is the population size in phase III of clinical trials? b) What is the health of the typical phase II participant? c) Are there any blind studies in phase II? d) what is being looked at in phase II?
Phase III: a) 1000-5000… b) diseased… c) double-blind… d) safety and efficacy
When is a New Drug Application filed?
after phase III clinical trials
What is phase IV of clinical trials?
What is the usual % for people that do better due to the placebo effect?
30% , but as high as 75% in antidepressnts
What is the Herbal Kava used for? What toxic side effects can Kava cause?
liver damage… b) as effective as benzodiazepines in the Rx of anxiety disorder
What is the herbal Comfry used for? What toxic side effects can Comfry cause?
a) used for Rx of inflammation and constipation… b) liver failure and cancer
Glomerular filtration is an example of what?
passive diffusion
Is carrier-mediated transport active or passive?
can be either
Can facilitated diffusion move againt a concentration gradient?
a) Show Flick's equation. b) Flick's law show that flux (passive movement) is dependent on which variables?

b) What variable is not mentioned here but plays a big part in passive transport across a lipid bilayer?
a) Flux = (C1-C2 X area X permeability coefficient) ÷ thickness… b) [drug] across membrane (C1-C2) and lipid solubility (permeability coefficient)…

b) not addressed in Flick's law is the pH along the membrane and drug pka, but they play a big role in passive diffuse
What are the 6 factors that determine absorption? (Hint: SAD CAB for cutie)
Solubility, Administration route, Dissolution, Concentration at site, Area at site of absorption, Blood circulation at site
For oral administration, what type of drug do you want lipid or aqueous soluble?
it's a balance, since it must be lipid soluble to pass through the membrane, however, if its too lipid soluble it will be unstable in the aqueous environment in the intestine and therefore be unstable and eratically absorbed.
Besides Flick's law and pH an pka, what other factors are important in absorption of an orally administerd drug?
Intestinal blood flow and gastric emptying (food mental state, diseases, other drugs, and endocrine status)
What does "extraction ratio" (a.k.a., Intrinsic clearance) mean?
the extent of removal of a drug form the circulation by the liver
What is the difference between "high" and "low" extraction drugs?
High Extraction = drug extensively removed by the liver… Low Extraction: little drug removal by the liver
Which does hepatic blood effect more High or Low extraction drugs?
T/F Rectal administration of drugs is 100% absorbed into the system circulation
False, drug that travels up the intestine is subject to first pass
Why are gaseous and volitale drugs ideal for rapid absorption through the pulmonary administration?
they are lipid soluble
Which types (targets) of drugs are used in transdermal administration? Why?
cardiac, CNS and endocrine drugs… because of their slow and sustained release
What limits absorption of hydrophilic drugs via transdermal administration?
Stratum Corneum
List 6 advantages of transdermal administration.
1. Sustained release --> Stable blood levels… 2. Avoid first pass (no hepatotoxic effects)… 3. Pt compliance… 4. No injection risks… 5. No variability as seen in oral absorption… 6. Better control of drugs with short half-lives.
List 3 Disadvantages of transdermal administration.
1. Too slow for therapeutic efficacy of some drugs… 2. Toxicity and disease to skin… 3. Metabolism by skin
What is the criteria for transdermal drugs? (hint: potency, lipid soluble, water soluble, irritating, stability)
high potency, lipid sol to penetrate skin, water sol to enter systemic circulation, non-irritating to skin, stable in reservoir.
What percentage of IV drugs enter the liver during one circulation time?
30%, vs. 100% for orally administered drugs
What type of absorption is seen in IV drugs?
none… it's directly in to the systemic circulation
What are two of the dangers of IV administration of drugs?
overdose and toxicity
What are two of the advantages of IV administration of drugs?
rapid access to systemic circulation and accuracy in dosage
What factors determine the aborption of intramuscular and subcutaneous administration of drugs?
lipid solubility and blood flow at site
What is the definition of bioavailability?
1. the % of drug that enters the systemic circulation after first pass… 2. Relative amount received in the systemic circulation from different modes of administration (other than IV)
a) What is represented in AUC (area under the curve)? (hint: Y/X coordinates)... b) What does the AUC reflect? c) What is the AUC used for?
a) plama levels/time… b) it reflects total amount of blood entering the systemic circulation… c) calculate bioavailability (comparing different modes of administration)
Define Pharmaceutical equivalence
Drug content identical, but inactive ingredience and manufacturing may not be the same.
Define biological equivalence
provides the same [drug] to blood and tissues
Define therapeutic equivalence
provides equal therapeutic benefit
In which types of drugs is bioavailability a big factor?
drugs with a narrow therapeutic index
What does bioavailability measured by AUC NOT reflect?
rate of absorption… thus even though a rapid absorption demonstrates a peak [plasma] faster a slower performing drug can still have the same AUC
Does a "true" equivalent have the same rate of absorption? Are generic drugs necessarily equal in terms of bioavailability? What has the FDA done about BA?
a) yes, they would be the same in all respects… b) no, generic drugs can differ with respect to BA… c) requires that all new generic drug have equal BA
What is the FDA tolerance for a drug to be considered BA (AUC) and peak [plasma]?
The FDA requires (+/-) 20% for first order drugs… and (+/-) 10% for zero order drugs
What does the FDA classification of "A" or "B" indicate?
A=therapeutically equivalent… B=equivalence is doubtful
What is the main determinate of tissue distribution?
organ perfusion
Why is it that a response to a drug like thiopental terminates even though much of the drug remains in the body?
redistribution to lesser perfused areas of the body
What positive effects would a site-specific drug have?
enhance therapeutic value and limited toxic side effects
Name 4 drug reservoirs in the body. (Hint: FIBI)
1) Fat (for lipid sol drugs), 2) Intestinal tract, where extensive enterhepatic circulation increase levels of drug hours or days after administration… 3) Bone and teeth, i.e., tetracycline 4)Intracellular macromolecules (in liver and muscle store Drug for extended periods)…
Which drugs are more likely to be bound by plasma proteins (acidic, basic or neutral)?
Primarily acid and netural, HOWEVER: some basic drugs can bind to 1) ∂1-acid glycoprotein, which is an acute phase reactant protein AND 2) lipoproteins
Is binding to plasma proteins is rarely reversible?
No, it is ALWAYS reversible… lasting miliseconds
How do plasma proteins influence the rate of movement of drug across the membrane?
concentration gradients are based on only the free drug not bound.
Why is the half-life of a drug related to plasma protein binding?
If it's bound it will not be metabolized nor excreted.
Do you have to adjust the dose of a drug if there is more plasma protein binding?
No, you only change dosage if free drug levels change
What can cause the plasma protein levels to change?
age, pregnancy and disease
Besides effecting the ability of the liver and other organs to metabolize or extract drug, what other two things do plasma proteins influence?
1) Solubilizes some drugs for that are often poorly soluble in water, 2) Overall absorption
Is active transport effected by the concentration of plasma proteins?
no, since it's not concentration related
a) What offsets the displacement of drugs plasma proteins in terms of drug effect duration? b) What is the danger in displacement of drug from plasma protens
a) yes, displacement increase the amount of free drug, but it also increase the amount of drug available for metabolism and excretion. b) increasing dosage based on lower plasma concentrations.
a) What can decrease albumin? b) What can decrease the amount of ∂1-acid glycoprotein (basic drug binding protein)?
a) many things… b) aging, oral contraceptives, and pregnancy
Which type of drug binding (basic or acid) is decreased by uremia?
acidic drugs
What is the average volume in liters of the following? A) total body water. B) extracellular water. C) whole blood? D) plasma. E. intracellular water.
A) total body water = 42 L… B) Extracellular water = 14 L… C) Whole Blood = 6 L… D) Plasma = 3 L… E) Intracellular water = 28 L
a) Give the equation for determining the volume of distribution (Vd)… b) when is Vd measured?
a) Vd = Dose ÷ [plasma] (@equilibrium)… b) after a single dose @ equlibrium
What is indicated by Vd = plasma volume?
most of the drug is bound to plasma proteins
What is the clinical value of knowing the Vd?
its value lies in calculating dose
How do you calculate dose for a IV (100% bioavailability)?
Rearrange Vd equation: dose = Vd X [desired plasma]
How do you calculate dose for drugs with less than 100% bioavailability? (give equation)
Dose = (Vd X [desired plasma]) ÷ F… where F= fraction absorbed into systemic circulation: BA
What can alter Vd?
age, sex, disease, changes in skeltal muscle, fat mass, plasma protein synthesis, fat/muscle ratio, and hydration. etc…
a) What is Total Body Clearance? b) Show equation for determining total Clearance.
a) Total Cl: fluid volume (Vd) cleared per unit time… b) Total Cl = K(elim) X Vd, where K(elim) is the elimination constant
a) Give the equation for determining half-life?

a) What does this equation assume?

b) How can this equation be clinically utilized?
a) T1/2= (0.693 X Vd) ÷ Total Cl


T1/2= 0.693/K(elim), where K(elim)=(total CL) ÷ Vd

b) Clearance from a single compartment.

c) While this assume a single compartment, it can be used to calculate the total body clearance.
What effect does increased clearance have on length of half-life?
increased clearance --> decreased half-life
Which organ is the major factor in non-metabolized clearance?
How do you calculate hapatic clearance? (theoretical)
hepatic Cl = (drug in bile + metabolite in hepatic venous blood) ÷ [plasma]
How do you determine hepatic clearance in humans?
Hepatic Cl = Total Cl - renal clearance
When would a log scale plot of half-life be a straight line?
elimination follows first order kinetics, where drug occupies only one compartment
What is the difference between ∂ and ß half-life and which is presumed when discussing half-life?
a) ∂-half-lfe = distribution… ß-half-life is elimination… b) elimination
When would a drug's half-life in the plasma not correlate with the drugs action? (HINT: NIMBsa)
1. Metabolite is an active form of the drug… 2. Drug activates a nuclear steroid receptor… 3. Drug binds irreversibly to receptor… 4. Drug is an ultra-short acting barbituate
a) Is elimination half-life route of administration or dose dependent? Why?
a) It's independent of both administration and dose, elimination half-life is a first order rxn, where the plasma concentration does not saturate the rate-limiting step… thus it's calculated after distribution
a) For maintenance dosing, if the dosing rate is smaller than the T1/2, do you need to change the interval?
a) No, longer dosing intervals (that are shorter than the half-life) produce better patient compliance
What order rxn is seen when the rate limiting step is saturated? b) Give 3 examples of the above-order metabolized drugs
a) zero order… b) aspirin (@ high dose), ethanol (almost always zero order) and phenytoin (plasma disappearance of therapeutic level is zero order)… thus difficulty calculating dose.
What is the time to reach the steady state of a drug dependent upon?
half-life and dosage (NOT dose, nor frequency)
a) What is the time required to reach steady state dependent upon. And what is it not dependent upon?

b) What are steady state levels dependent upon?

c) What will more frequent dosing and/or slower absorptioin result in?
a) half-lfe (NOT on dose or dosing rate)

b) Amount of drug absorbed ÷ (time and clearance)

c) Smaller fluctuations
What two factors are steady state levels dependent upon?
1. amount of drug absorbed/time and 2. Clearance
What two factors result in smaller fluctuation in plasma concentration?
1. Frequent doses… 2. Slower absorption
What percent of steady state is reached given these numbers of half-lives: 1, 2,3, and 4.
1 t1/2= 50%… 2 t1/2= 75%… 3 t1/2= 87.5% … 4 t1/2= 93.75%
What is the difference between average steady state and plateau steady state?
a) The average taking into account all plasma concentration including fluctuation from initial dose to plateau… b) Plateau is the steady state after multiple doses
As stated earlier, average steady state is dependent upon frequency of dose and absorption, what is plateau steady state dependent upon?
Total input and output... such that input = output at steady state, where the quantity cleared is equal to one dose
After drug withdraw, what is percentage of plasma level are reduced by the following half-lives? 1, 2, 3, and 4
same as above, except reduced: 1 t1/2= 50%… 2 t1/2= 75%… 3 t1/2= 87.5% … 4 t1/2= 93.75%
Give the equation for calculating a single does
Single dose = (Vd x desired plasma concentration) ÷ Bioavailability
Is the example of 50 mg/hr, an example of dose of dosage?
Dosage, where in this example dosage = 5 mg/hr (or 120 mg/day), Dose = 40 mg every 3 hours.... (Note: Dose is an absolute quantity and Dose = Dosage X dosing interval)
What is the equation for dose?
dose = dosage (or dosing rate) X dosing interval
At steady state plateau, what is dosage equal to?
Dosage is the replacement of cleared drug… in = out
Show the equation for calculating maintenance dosage.
Dosage = (Clearance X plasma concentration) ÷ Bioavailability (fraction absorbed)
Show the equation used for calculating loading dose.
Loding dose = (Vd x desired plasma concentration) ÷ Bioavailability (fraction aborbed)
When would you want to use a modified loading dose?
When the time it take for steady state plateau is long, e.g., 14 hours
When calculating dose for an obese person, what weight do you use? How do you find this weight?
a) That depends, if the drug enters fat, use total body weight. If not, use ideal Body Weight (IBW)

b) IBW for men = 52 kg +1.9 x inches in height above 5')… IBW for women = 49 kg + 1.7 kg x (inches above 5')
Do you have to adjust loading dose of a drug for a person with impaired renal function?
No, Loading dose = (Vd x desired plasma conc.) ÷ F (Bioavailability)
Do you have to adjust maintenance dose in a person with impaired renal function?
Yes! Maintenance dose = (clearance X desired plasma conc.) ÷ bioavailability (F)
How do you calculate renal function in a) men and b) women
a) For Men: Calculate renal function with creatinine clearance… Creatinine clearance = [(140-age) X (weight in Kg)] ÷ [72 X (Serum creatinine in mg/dL)]

b) For Women: [0.85 X (140-age) X (weight in Kg)] ÷ [72 X (Serum creatinine in mg/dL)]
Why do drug companies care so much about drug metabolism?
1. FDA required… 2. Know which metabolite are toxic, 3. Find out which metabolites are active and get patent
Can one say whether metabolism will lead to activation or inactivation without more information?
No, it can be either, depending on the drug
Why is it important for physician to understand drug metabolism?
a) prediction of drug-drug interaction, genetic variation… b) use alternate drug Rx with knowledge
Why is it important that metabolism make a drug more polar?
so that it will remain excreted after glomerular filtration or secretion into the intestines
What are the two major biotransformation phases in drug metabolism?
Phase I - Non-synthetic: drug remains same size but becomes more polar (hydroxylation)… Phase II - Synthetic: drug has a bulky group attached and becomes even more polar
Does phase I happen before phase II?
Not always
Name the different types of pathways in the Synthetic phase II (Hint: GAS GG)
(GAS GG):glucuronide formation, acetylation, sulfation, glycine congugation, and glutathione conjugation
Name the Major Oxidation and Reductive pathways in Phase I that are catalyzed by mixed function oxidase CYP 450s and the ones that are not catylized by the CYP 450s. (Hint: you cast one)
"Rick's SHaD-OH"CYP: Reduction of Azo and Nitro groups, Sulfoxidation, Hydroxylation, and Dealkylation… non-CYP: O-methylation and Hydrolysis
Which phase I rxn is associated with toxic activation of aromatic amines?
Which dealkylation rxn removes a methyl or ethyl group from a nitrogen atom
Which dealkylation rxn removes a methyl or ethyl group from an oxygen atom
Which phase and rxn adds an oxygen to a sulfur atom?
Phase I (CYP) Sulfoxidation rxn
Which phase and rxn is a common catacholamine pathway?
O-Methylation phase I, non-CYP
Which phase and rxn is associated with non-specific esterases in the plasma and in cells?
Hydrolysis in phase I… non-CYP
Name 4 additional CYP rxns in phase I (comes when everything is over)
D-END: dechlorination, deamination, epoxidation, N-oxidation
Which 3 cofactors are required in the Mixed Function Oxidase (CYP450) System Enzymes?
Fe, O2, and NADPH
CYPs are ____-____ containing proteins.
Fe heme
What is the role of NADPH in mixed function oxidase (CYP450) system enzymes?
Supplies electrons
Where do you find the activities of CYP 450s?
smooth ER
T/F The CYP 450 enzyme have many polymorphisms
What are the 4 generalized steps involved in Mixed Function Oxidase (CYP) system drug rxns?
1. Drug binds to CYP in its oxidized 3+ state… 2. Reduction of the CYP-Drug complex by NADPH…(transferred by Flavoprotein)... 3. Oxygen binds to complex… 4. One atom of oxygen is inserted into drug the other into H2O.
T/F Individual CYP members do not have overlapping specificity.
False, the have low and frequently overlapping specificity… which gives the collective CYPs a wide range of drugs they can metabolize
T/F CYP3A4 is the principle form found in the intestine.
T/F The nasal mucosa have a small but present concentration of CYP
False, it has one of the highest concentration of CYP
Which of the congugation (synthesis) pathways of Phase II is most commonly seen?
Glucuronide formation
Describe the 2 steps in glucuronic formation
Glucose --(UTP added w/ glucuronosyl transferase) --> Glucuronic acid --> added to substrate (Drug)
NAT1 and NAT2 transferases are used in which Phase and pathway in drug metabolism?
Phase II (synthesis): Acetylation
_____ is a common pathway for aliphatic and aromatic primary amines and utilize s acetyl CoA as a co-substrate
Acetylation, in phase II
Steroid hormones are metabolized by which phase II metabolic pathway? What is required in this pathway?
Sulfation… ATP
Which phase and specific metabolic pathway would you find a glycine being added to the substrate (drug)?
Glycine conjugation, in phase II
Which is the major detoxifying (for drugs and toxins) metabolic mechanism found in the body… and which phase?
Glutathione (GSH) conjugation in phase II
Which metabolic pathway is the only one that creates a less polar substrate?
Acetylation in phase II
Mercapturic acid excreted in the urine is a product of which metabolic pathway?
glutathioine in phase II
T/F GSH pathway (glutathione), aside from being the major detoxifying pathway, also activates drugs and some being toxic and carcinogenic
a) which 6 metabolic pathways are seen in gut flora? (hint: HHDDAN)… b) what do all gut flora have in common in terms of metabolism of drugs?
Hyrolysis of conjugates, hyrolysis of amides, dehydroxylation, deamination, azo and nitro reduction… b) none use oxygen because gut flora are obligate anaerobes
What can cause the reversal of phase II conjugation?
Enterohepatic circulation remove conjugate
Elimination occurs by what order of kinetics?
First order and is thus proportional to the amount of drug in the body
How are drugs reabsorbed in the tubules? What criteria must be met for passive diffusion to occur?
a) passive diffusion… b) they must be non-polar… thus the metabolized polar drugs are efficiently excreted
How can renal excretion of drugs be altered?
changing pH
Can renal excretion only be increased in the renal tubules?
No, it can be increased (for toxic compounds) or decreased.
a) How are organic anion and cation, bound to plasma proteins excreted in proximal tubules? b) How does this understanding help maintain desired high plasma levels of given drugs?
a) Non-selective active transport by pumps. b) Inhibit the pumps, e.g., probenecid extends penicilin half-life in to several hours
What types of compounds are excreted by biliary system?
highly polar and high molecular weight
Where was amionopyrine used? What was it replaced by?
a) breath test (involving lung excretion and carbon 14 and 13) of liver function… b) erythromycin
What 4 factors effect drug entry in milk?
a) drug pka, b) pH of milk and plasma, c) binding of drug to plasma and milk proteins, and c) fat composition of milk.
What is the role of saliva in drug excretion?
not a major route, but it may offer a method to monitor drug levels.
After normal dose, which would be the cause of altered drug levels (other than normal), pharmacodynamics or pharmacokinetics?
If there are no changes in dose and plasma levels, and response is changed, what is the cause pharmacodynamics or pharmacokinetics?
Name 7 causes of altered drug disposition in neonates.
1) Prolonged gastric emptying and fluctuation pH. 2) erratic intramuscular absorption (small muscles), 3) greater cutaneous absorption (high surface area ratio), 4) Body water and fat ratio changes in first year of life (they have more water at birth), 5) less plasma proteins, 6) immature CYP in liver, 7) poor renal blood flow, filtration and secretion
Why do neonates of addicted mothers get jaundice?
they are deficient in glucuronyl transferase to metabolis the drug
Give 9 problems associated with aging and metabolism of drugs.
1) Decreased CO, 2) decreased liver blood flow, 3) decreased renal blood flow, 4) increased gastric pH and slowing of gastric emptying intestinal absorption --> slower absorption, 5) decrease in Phase I metabolism, 6) increase fat in organs, 7) decreased muscle mass, 8) decreased water compartment, 9) altered Vd
Because of a greater proportion of fat in elderly, what happens to Vd and plasma concentration in WATER soluble drugs?
decrease in Vd, and increased plasma concentration
Because of a greater proportion of fat in elderly, what happens to Vd and plasma concentration in LIPID soluble drugs?
higher Vd and lower [plasma]
In obese people, drugs that are limited to plasma and/or total body fluid are dosed based on what?
Ideal body weight or idea body weight plus a little extra for increased body fluid
What effect on drug half-life does liver and renal disease have?
increased half-life for many drugs
What is the adverse side effect of antibiotic use with digoxin in some patients? Why?
digoxin intoxication, the antibiotic kills a type of bacteria that inactivates digoxin, so kill it off and overdose occurs… due to polymorphism
What effect does the suppression of gut bacteria (via oral antibiotics) have on half life on drugs that undergo extensive enterohepatic circulation?
Decreases half-life
what drug does grapefruit juice inhibit the metabolism?
What can selectively induce CYPs in phase I and glucuronic acid and glutathioine in phase II?
chronic exposure to drugs, via increased DNA transcription.
What does ketoconazole inhibit?
terfenadine (seldane): drug-drug inhibition interaction
What effect do barbituates and St. Johns wort have on cyclosporin?
induce the metabolism of cyclosporin
What effect do barbequed meat and environmental toxins have on many drugs
induce metabolism
Which CYP does phenobarbital induce?
Which CYP does ethanol/ isoniazid induce?
Which CYP do barbituates and glucocorticoids induce?
A) Slow acetylation of Isoniazid is caused by lower levels of which which enzyme? B) What causes this deficient production? C) Which ethnic group has more slow acetylizers, Europeans or Asians? D) Which ethnics group, in general, requires larger doses of isoniazid? E) Which group would be suseptible to toxicity?
a) NAT2 (in liver), b) single recessive gene, c) Europeans. d) Asians. e) Europeans
a) 5-10% of caucasian fail to synthesize CYP2D6, which drugs are effected in these individuals? B) What consideration must be taken given this deficit?
a) anitdepressants, antihyperglycemic, and beta blockers…b) give less drug to these patients if the drug is inactivated by cYP2D6 -or- realize that some of these drugs will not work at all in some patients because the the active drug is metabolized (i.e., codeine).
codeine --( ?)--> morphine
In terms of ethanol metabolism, which ethnic group is deficient in high affinity isozyme and thus exhibit acetaldehyde toxicity (flushing)
People that are completely deficient for TPMT, which along with xanthine oxidase metabolizes 6-MP to an inactive metabolite are at risk for______?
severe myelosuppression (1 out 300)
What order of kinetics are seen in the killing of tumor cells? What is the net of effect of this?
a) first order, b) elimination is at a constant proportion, so the same dose would be require to kill 1,000 out of 100,000 cells as it would to kill 1 out of 1000 cells.
When is chemotherapy used?
to kill microscopic metases (as an adjuvant therapy with surgery) or for systemic control
Which types of cells are more responsive to cytotoxic chemotherapy?
rapidly dividing cells
What 3 factors influence the response to chemotherapy?
1) Growth fraction and mass doubling time. 2) total tumor burden (where large tumor are not curable w/chemo). 3) Cell cycle phases
Which drugs are effect in Rx cancers in all cycling and non-cycling cells and in all phases of the cell cycle?
anthrcycline antibiotics (doxorubicin), alkylating agents, and nitrosoureas
Which chemotherapeutic agents are more active in cycling cells?
cyclophosphamide and 5-fluorouracil
Which chemotherapeutic agents are more active in cycling cells of the following phases? S-phase, M-phase
S-phase: 6-MP and methotrexate… M-phase: vincristine and vinblastin
In which phase of the cell cycle are taxanes most effective?
G2 (--> M)
What are the 5 principles of cancer chemotherapy?
1) use multiple drugs. 2) use cancer specific drugs to avoid toxicity. 3) Use drugs that have differing mech of action to avoid resistance. 4) Use agents that different toxicities so full dosage can be used without cummulative toxic effect of all drugs. 5) Use maximally tolerated dose to kill the highest fraction of tumor cells
What combination is used to Rx breast cancer?
CAF, CMF: Cyclophosphamide, Doxorubicin (adriamycin), methotrexate, 5-fluorouracil (5-FU)
What combination of drugs is used to Rx Colon cancer?
5-FU and leucovorin
What combination of drugs is used to Rx Hodgekin's disease?
MOPP: Mustard, Vincristine (oncovin), procarbazine, Prednizone… ABVD: Doxorubicin (adriamycin), bleomycin, vinblastin, and dacarbazine
What combination of drugs is used to Rx testicular cancer?
BEP: Bleomycin, etoposide, cisplatin… VIC: Vinblastin, Ifosfamide, cisplatin
Give three general mechanisms of drug resistance
1) Multiple drug resistance phenotype. 2) Gene amplification. 3) Resistance to alkylating agents
What is the mechanism and drugs that exhibit resistance with MDR (multiple drug resistance). (Hint: TAVE)
protein pumps drug out of the cell. 2) anthracyclines, etoposide, taxol and vinca alkaloids
What is the mechanism and drugs that exhibit resistance with Gene aMplification.
1) overproduction of enzyme. 2) methatrexate
What is the mechanism and drugs that exhibit resistance with alkylating agents.
Glutathione… 2) take your pick of alkylating agents
What are the 3 mechanism of resistance for alkylating agents?
1. Decreased drug uptake, 2) increased DNA repair, 3) high cytoplastic sulfhydryl levels (glutathione)
What are the 3 mechanism of resistance for methotrexate?
1) increased dihyrofolate (DHF) reductase (amplification). 2) decreased drug affinity. 3) decreased drug uptake
What are the 2 mechanism of resistance for 5-FU?
1) decreased uridine kinase. 2) decrease affinity of thymidylate synthase for 5-FU.
What is the mechanism of resistance for Vinca alkaloids and doxorubicin?
decreased uptake
Bone marrow suppress in chemotherapeutic agents is cause for careful consideration of what increased risk?
bleeding and infection
What toxic side effect can tumor lysis cause?
tumor lysis syndrome: increased uric acid release resulting in renal damage
What consideration must be given to pregnant women receiving antimetabolites?
teratogenic effects and spontaneous abortion in the first trimeseter
What increased risk occurs with the use of doxorubicin and cyclophosphamide (in bone marrow transplant)?
heart failure
What increased risk occurs with the use of bleomycin?
Lung damage
What increased risk occurs with the use of cisplatin?
bladder damage
What increased risk occurs with the use of cyclophosphamde and ifosfamide?
(acrolein) Give MESNA
What increased risk occurs with the use of Vinca Alkaloids?
hearing loss (reversible), and neurotoxicity (numbness and tingling)
Name 5 immunosuppressive agents
Corticosteroids, Cytotoxic drugs, T-cell specific drugs, Antibody therapy, Cytokine/receptor antagonist
What is the major glucocorticoid and which is the major mineralocorticoid?
glucocorticoid: cortisol… mineralocorticoid: aldosterone
What induces cortisol?
Hypothalamus-CRF stimulate pituitary ACTH secretion --> cortisol in adrenal gland
What are the effect of cortisol? Which is the major effect?
Na + glucose homeostasis. B) glucose homeostasis is the major effect by providing increased energy in the form of glucose
How does cortisol maintain glucose homeostasis?
cortisol increases glycogen storage in the liver, increasing gluconeogenosis, and decreasing peripheral use of glucose
What effect does cortisol have on Na?
Increases Na and water reabsorption (but not as much as aldosterone)
What other effects does cortisol have?
renal loss of calcium and redistribution of body fat
How does cortisol effect inflammatory cytokines and growth factors?
via gene transcription/nuclear receptors
What is the major therapeutic use of corticosteroids?
a) anti-inflammatory... cases of excessive immune response; WIDELY used for Rx of delayed hypersensitivity skin rxns, immediate hypersensitivity, and skin graft… b) decrease function and number of leukocytes and lymphocytes ALSO the inhibit cytokine synthesis and decrease vascular permeability… ALSO they increase annexins and lipocortins which block phospholipase A2 --> leading to a decrease in arachidonic acid --> leading to a decrease in protaglandins and leukotrienes
Which lymphocyte response do glucocorticoids inhibit?
T cell, due to the need for macrophage APC.
What effect do glucocorticoids have on neutrophils and eosinophils?
the block phagocytosis and granulation
List the natural and synthetic corticosteroids from highest to lowest anti-inflammatory activity (Hint: Date of Birth… Tueday Monday PHalicia)
Dexamethasone > Betamethasone > Tramcinolone > Methylprednisone > Prednisone > Hydrocortisone (cortisol)
Name some glucocorticoid adverse side effects.
Peptic ulcer, growth failure, hirsutism, Cataract, glucoma, psychosis, thining of skin, acne… there are other obvious ASE not named here
Name 4 cytotoxic drugs used to mediate the immune system (Hint: CLAMM)
Azathioprine, Cyclophosphamide, Methotrexate, Lefluonomide, and Mycophenolate mofetil.
What is azothioprine converted to? What is it's mechanism of action? What are the indications for azothioprine?
a) 6-MP.. b) blocks purine synthesis… c) transplant rejection, rheumatoid arthritis, SLE, Wegener's granulomatosis or polyarteritis (excessive inflammation)
Does azothioprine have an effect on lymphocytes?
yes, both cell mediated T and humoral B cells
What are the ASE of azothioprine?
GI, leukopenia, infection and malignancy
What is the mechanism of action for cyclophosphamide in its use as a immunomodulator? B) Besides cancer, what are the indications for cyclophosphamide
B and T cell… b) Wegener's granulomatosis and nephrotic syndrome and polyarteritis (all chronic inflammation diseases)
a) What are the indiccation for methotrexate? b) What accounts for it anti-inflammatory action? c) what are the major ASE of Methotrexate
a) Inflammatory diseases such as rheumatoid arthritis, psoriasis, Crohn's disease. b) impairs neutrophil chemotaxis… c) Liver tox, GI tox, pneumonitis (allergic), bone marrow suppression.
Name the 3 T-cell specific immunosuppressing drugs.
Cyclosporine, Tacrolimus/ Picrolimus, Sirolimus (Rapamycin)
a) What are the indication for cyclosporine? b) What accounts for its anti-inflammatory action? c) what are the major ASE of cyclosporine… d) what should be monitored when giving cyclosporin?
a) transplant rejection and aplastic anemia. b) T cell specific. c) nephrotoxicity… also hypertrichosis, encephalopathy and liver tox… d) low serum cholesterol, which is associated with increase in tox
a) What are the indication for Tacrolimus? b) What accounts for it anti-inflammatory action? c) what are the major ASE of Tacrolimus? d) Where is Tacrolimus derived?
a) Graft rejection and atopic dermatitis b) decreased T-cell synthesis, c) Like cyclosporine but also increase in headaches, d) Bacteria
Name 4 Antibody therapy treatments used as immunemodulators. (Hint: MAIN)
ATGAM, Muromonab-CD3, Rho (D) Immune globulin (rhogam), New Humanized monoclonal antibodies.
a) What are the indication for Infliximab? b) What accounts for it anti-inflammatory action? c) what are the major ASE of Infliximab?
a) rheumatoid arthritis and Chrohn's disease, b) antibodies against tumor necrosis factor-∂ (TNF-∂), c) Increased infection (TB), lymphoma and exacerbationof MS
Name 3 Cytokine receptor antagonists.
Etanercept, Alefaept and Kineret
a) What are the indication for Etanercept? b) What accounts for it anti-inflammatory action? c) what are the major ASE of Etanercept?
a) adult and childhood heumatoid arthritis as well as psoriatic arthritis, b) This is a unique antagonist, it's essentially a free floating receptor that binds TNF and the other binds phagocytic cells. c) worsening of inffections and sepsis
Name 7 immunopotentiators
1) Gamma globulin, 2) BCG, 3) Levamisole, 4) Pegademase, 5) Cytokines, 6) Lymphokines, 7Hematopoietic Growth Factors
a) What are the indication for Gamma Globulin? b) What is the mechanism of action of Gamma Globulin? c) what are the major ASE of Gamma Globulin
a) Hypogammaglobulinemia, idopathic autoimmune thrombocytopenia, Prevention of infection in B cell malignancies, Kawasaki disease, b) Passive immunization, c) anaphylactic rxn (give slowly), do not treat IgA deficient patiens because they have anti-IgA antibodies --> rxn
a) What are the indication for BCG? b) What is the mechanism of action of BCG?
a) TB vaccine and stimulates macrophage and T cell function, (intravesical BCG is used to Rx bladder malignancies b) non-pathological mycobacterium
a) What are the indication for Levamisole? b) What is the mechanism of action of Levamisole?
a) Anti-helminthic (anti-parasitic) drug, and can be used as a adjuvant Rx of colon cancer, b) augments T cell and macrophage activation
a) What are the indication for Interleukin-2 (IL-2)? b) What accounts for its mechanism of action? c) what are the major ASE of IL-2
a) renal cell carcinoma, b) directly affect immune system, c) hypothyroidism, capilary leak syndrome --> leading to pulmonary edema
a) What are the indication for Interferon-∂? b) What accounts for its mechanism of action? c) what are the major ASE of Interferon-∂
a) hairy cell leukemia and other malignancies, other viral condition as well as kaposi's sarcoma, b) interfere with viral replication, c) autoimmune thryoiditis and hepititis
a) What are the indication for Interferon-ß? b) What accounts for its mechanism of action?
a) MS, b) anti-viral and immunomodulatory activity
a) What are the indication for Gamma Interferon? b) What accounts for it anti-inflammatory action?
a) chronic granulomatous diease and visceral leishmaniasis, b) induces macrophage activation (it is produced endogenously only by activated T cells)
What is the mechanism of action for NSAIDs?
cyclooxygenase enzyme inhibition, which catalyzes Arachidonic acid to PGG2
Why are the intestinal tract, kidney and uterus affected by NSAIDs?
COX inhibitors reduce levels of all mediators causing physiological function changes in these organs
Which COX, 1 or 2 is constituitively on and which is turned on primarily at sites of inflammation?
COX1 is always on, COX2 is turned on at inflammation sites.
What are the adverse side effects of NSAIDs?
GI: due to changes in permeability of mucosa and sloughing off of mucosal cells… b) Renal papillary necrosis… c) Fetal: increased gestation and parturition, ASE to fetal cardiovascular syst… d) Increased bleeding… e) Drug-drug interaction: displacement from plasma proteins
Where are salicylates (aspirin) absorbed and which is the major route of absorption?
Stomach and small intestine (major route)
How are salicylates (aspirin) absorbed in the intestines?
Passive diffusion of the undissociated molecule
What is the optimal pH range for salicylate (aspirin) absorption in the stomach?
pH 2.5 to 4
How many stages of effects does aspirin have? Describe them.
Two, the short term effect is from the aspirin itself, the long term effect is from the liberated salicylate.
How and where is aspirin metabolized?
In the liver, mainly by glycine conjugation
What order of kinetics is the metabolism of aspirn? Describe the kinetics of aspirin.
First order at low dose. Second order at low dose.
Why is the order of kinetics for the metabolism of aspirin dose dependent?
The rate limiting step for the metabolism of aspirin is catalyzed through the glycine pathway, when it is saturated any small increase in aspirin concentration will cause a large increase in serum salicylate
What effect does the change in the order of kinetics for the metabolism of Aspirin have on the length of its serum half-life? What's rationale?
a) Aspirin dose increases -> zero order kinetics -> increase in serum concentration -> increase in half-life, b) As serum concentration increases clearance decreases -> and half-life increases (T1/2= (0.693 X Vd) ÷ Total Cl)
a) How are salicylates excreted and b) what is the rate of excretion dependent upon? Why?
a) Kidneys, b) Salicylates excretion rate is pH dependent, the higher the pH, the higher rate of excretion, c) Salicylates are weak acids, thus at high pH Salicylate is deprotonated and charged, thus no reabsorption into tubules.
What is the % rate of kidney excretion of aspirin at pH 5, and at pH 8?
Excretion: pH 5 -> few %… pH 8 -> 80%
What is the therapeutic dose of aspirn that gives a moderately analgesic effect?
10-15 mg
What is the therapeutic dose of aspirn that gives an anti-inflammatory effect?
20 mg
What are the 5 main toxicities of aspirin?
1) Gastritis with acute and chronic blood loss, 2) reduced platelet aggregation, 3) Reversible hepatotoxicty in pts with SLE and juvenile rheumatoid arthritis (dose dep), 4) Dose dependent tinitis and hearing loss, 5) Aspirin hypersensitivity: uticaria, asthma, rhinitis
When is aspirin contraindicated?
Pts w/: Hemophiliia, peptic ulcer or allergy
What benefits do the following forms of Salicylated render? a) non-acetylated salicylate, b) cation salicylates.
a) non-acetylated salicylate : reversible inhibition of platelet aggregation b) cation salicylates: fewer GI side effects
Give 3 examples of cation salicylates.
Magnesium salicylate, Choline salicylate and Choline magnesium salicylate
Name 3 Carbo and Heterocyclic Acetic Acid NSAIDs
Indomethacin, Tometin, Sulindac
What are the indication for Carbo and Heterocyclic Acetic Acids?
a) rheumatoid disorders, e.g., gout, ankylosig spondylitis, tendonitis, bursitis, rheumatoid arthritis
Give the 3 mechanisms of action of Carbo and Heterocyclic Acetic Acids that account for its anti-inflammatory/analgesic properties.
1) inhibits prostaglandin biosynthesis, 2) inhibits motility of polymorphonuclear leukocytes, 3) uncouples oxidative phosphorylation in hepatic mitochondria: NOTE that this can lead to fever
How do the Carbo and Heterocyclic Acetic Acids differ? Campare and contrast them.
a) Pharmacokinetics and dynamics (adverse side effects) 1) Indomethacin is serotonin-like drug -> CNS toxicity, headaches, depersonaliztion, depression, lightheadedness, 2) Tometin Hais not a serotonin-like drug -> fewer CNS and GI adverse side effects, ALSO 60 minute half-life, 3) Sulinadac is a prodrug with a 16 hour half-life, ALSO fewer side effects than aspirin
Name 2 Propionic Acid NSAIDs
Ibuprofen and Naproxen
What are 2 ways Ibuprofen and Naproxen differ?
1) Naproxen has a longer half-life of 14 hours, Ibuprofen's half-life is 2 hours 2) Naproxen has fewer adverse side effects, although there has been report of GI bleeding with Naproxen
How are Ibuprofen and Naproxen similar?
Peak plasma concentration in about 1-2 hours and both well tolerated.
What are the adverse side effects of Ibuprofen?
epigastric discomfort, nausea, indigestion and blurred vision
How does 1/2-life effect dosage?
shorter half-lfe --> increased dosage to maintain steady state
Name 2 Oxicams (Benzothiazines).
Sudoxican and Piroxicam
For Sudoxicam: a) What is the benefit? b) What is the toxicty? c) What is its relative half-life?
a) superior anti-inflammatory action, exceeding other NSAID in this capacity, b) Hepatotoxicty (removed from trials on this basis), c) long half-life
For Piroxicam: a) indications, b) half-life
a) indications: rheumatoid arthritis, b) 48 hours
What is the main feature of the NSAID sub-class COXIBs?
They are selectively inhibit COX-2 enzymes and NOT COX1, which would account for fewer adverse side effects, esp. gastric epithelium where COX-1 is cytoprotective.
a) Why were COXIBs initially removed from the market by the FDA? b) Once COXIBs were return to the market, what were 2 the warnings?
a) Increased risk of thromboembolic events, b) cardiovascular disease and life-threatening GI bleeding.
What were the 3 reasons the COXIB, Valdecoxib, removed from the market by Pfizer?
1) lack of data on cardiovascular safety with long-term use, 2) serious and life-threatening skin reaction, 3) lack of demonstrated advantage over other NSAIDs
a) What are the indications for Acetaminophen? b) What is its mechanism of action? c) What the the adverse side effects of acetaminophen?
a) analgesic and antipyretic NOT anti-inflammatory, b) Similar to aspirin, but not fully understood, c) renal papillary necrosis and liver damage if over 7 g/day and @ large regular dosage --> irreversible hepatic necrosis (also overdose)
How and where is acetominophen metabolized?
Liver, glucuronic (60%) and sulfate (35%) phase II pathways.
What is the name of the toxic metabolite of acetaminophen? What pathway converts this toxic metabolite into a non-toxic metabolite?
a) N-acetylimidoquinone, b) glutathione
What is a method of Rx for acetaminophen overdose?
In terms of indicated use: a) How is aspirin widely used? b) What is its action at low dose? c) what is its action at high dose?
a) analgesic and antipyretic, b) analgesic, c) anti-inflammatory
In terms of half-life, how do new NSAIDs compare with older ones?
longer half-life
Do COXIBs (COX-2 inhibitors) inhibit platelet aggregation?
Rank the MYELOSUPPRESIVE nature of the neoplastic chemotherapeutic drugs.
Ifosfamide = √

Crisplatin = √√ Trombocytopenia

Carboplatin = √√√ THROMBOCYTOPENIA

Methotrexate = √

Gemcitibine = Mild

Vinblastin = √√


Doxorubicin = √√


Etoposide = √

Irinotecan = √

Tamoxifen = √ Thrombocytopenia
Rank the NEPHROTOXIC nature of the neoplastic chemotherapeutic drugs.
Cisplatin = √√√ MONITOR

Carboplatin = √√ Dose Dependent

Methotrexate = √√√ Need full renal function. (Obstruction & injury)
Give the drug that causes the following Toxicities:

a) Bladder

b) Capillary Leak

c) Cardiotoxicity

d) Hot Flashes, Endrometrial Cancer, Venous Thrombosis

e) Hepatic

f) Psychosis

g) Highly Emetogenic

h) Pulmonary Toxicity

i) Diarrhea

j) Eye

k) Auditory
a) Bladder: Ifosfamid >>> Cyclophosphamide

b) Capillary Leak = Taxotere

c) Cardiotoxicity = Doxorubicin

d) Hot Flashes, Endrometrial Cancer, Venous Thrombosis = Tamoxifen

e) Hepatic = Flutamide

f) Psychosis = Thiazenes

g) Highly Emetogenic = Cisplatin

h) Pulmonary Toxicity = BLEOMYCIN, BCNU & Methotrexate

i) Diarrhea = Irinotecan

j) Eye = Tamoxiphen

k) Auditory = cisplatin
Rank the NEUROTOXIC nature of the neoplastic chemotherapeutic drugs.
Cisplatin = √√√ Peripheral

Vincristin = √√√ cummulative discontinue w/ "pins & needles"

Methotrexate = √ Intrathecal

5-FU = (Rare)

Vincristin = √√√ cummulative discontinue w/ "pins & needles"

Taxol = √√√ Major + peripheral

Triazenes = √√√ --> CSF --> Psychosis
a) Which neoplastic drug(s) is/are indicated for BREAST cancer? (which is best choice?) (Hint: 5TT VP)

b) Which 2 neoplastic drug combinations are best for LATE STAGE BREAST cancer? (Which combination is best?)
a) Breast: TAMOXIFEN (best), Taxotere, 5-FU, Vinblastin, Prednisone

b) Late Stage Breast: (CYCLOPHOSPHAMIDE + TAXOL) >>> (Doxorubicin + Taxol)
Which neoplastic drug combination(s) is/are indicated for Testicular cancer?
Testicular: BEP (bleomycin, etoposin, cisplatin), VIC (Vinbastine, Ifosfamide, cisplastin)
Which neoplastic drug combination(s) is/are indicated for OVARIAN cancer

b) Ovarian: (CARBOPLATIN + TAXOL) >>> (Cisplatin + Taxol)
Which neoplastic drug combination(s) is/are indicated for HODGKIN'S LYMPHOMA?
MOPP: (Mustards, Vincristine, Procarbazine, Prednisone

ABVD: (Doxorubicin, Bleomycin, Vinblastine, Dacarbazine)

NOTE: Etoposide is used for lymphomas
Which neoplastic drug(s) is/are indicated for BLADDER cancer?
Blader: Cisplatin, Carboplatin, Methotrexate, 5-FU, Gemcitibine, Taxol,
a) Which neoplastic drug combination is the best Rx indicated for LUNG cancer (curable in some)?

b) Which neoplastic drug(s) is/are indicated for LUNG cancer?

c) Which drug should not be used for LUNG cancer?
a) Lung Drug Combination: (CARBOPLATIN + TAXOL) best Rx... curative in some patients

b) Lung single drug: Cisplatin, Etoposide

c) DON'T USE for LUNG or COLON: Doxorubicin!!!
a) Which neoplastic drug(s) is/are indicated for COLON cancer?

b) Which neoplastic drug combination is indicated for COLON cancer?

c) Which neoplastic drug is not recommended for COLON cancer?
a) Colon: Irinotecan

b) Colon Drug Combination: (5-FU + Leucovorin)

c) DON'T USE for COLON or LUNG cancers: Doxorubicin!!!
Which neoplastic drug(s) is/are indicated for PANCREAS cancer?
Pancreas: Gemcitbine
a) Which neoplastic drug(s) is/are indicated for PROSTATE cancer?

b) Which neoplastic drug combination is indicated for PROSTATE cancer?
a) Prostate: Leuprolide, Flutamide

b) Prostate Drug Combination: (Taxotere + Estramustine)
a) Which neoplastic drug(s) is/are indicated for LEUKEMIAS?

b)a) Which neoplastic drug is indicated for Sarcomas?
a) Leukemia: Prednisone, 6-MP (rarely used)

b) Sarcoma: Ifosfamide
a) Which are broad range neoplastic drugs?
a) Broad Range: Cyclophosphamide, Doxorubicin (don't use on COLON or LUNG cancers)