Pharm 2

Which of the following statements regarding calcitonin is LEAST accurate? A.It can help relieve postmenopausal symptoms like hot flushes. B.It may reduce acute bone pain. C.It is destroyed quickly in the GI tract. D.Salmon calcitonin is commonly used. E.It may cause development of drug tolerance.

A.It can help relieve postmenopausal symptoms like hot flushes. Calcitonin is leess critical for calcium homeostasis, but in pharmacologic concentrations can reduce serum calcium and phosphorus by promoting bone deposition and stimulating renal excretion. • A32 amino acids single chain polypeptide produced by the parafollicular C cells of the thyroid gland. • Inhibits bone resorption by directly blocking osteoclast. - May increases bone density, decreases fractures by 20-30%, and reduces acute pain due to fractures or bone metastasis. - Available in injectable form and as an intranasal spray since calcitonin is destroyed quickly in GI tract. - Prescribed for osteoporosis in women who do not tolerate or who do not want to take estrogens or who do not tolerate bisphosphonate medications. - Can worsen postmenopausal symptoms like hot flushes. Only for women more than 5 years past menopause. - Injected calcitonin is also for treatment of symptomatic Paget's disease of bone. - Development of tolerance to its effects is common, due to calcitonin-induced loss of calcitonin receptors or development of anti-calcitonin antibodies.

All the following are false for naltrexone EXCEPT: A.It precipitates withdrawal in methadone tolerant patients. B.It is a kappa agonist and weak mu antagonist. C.It exhibits cross-dependence with naloxone. D.It exhibits ceiling effects for analgesia and respiratory depression. E.It produces analgesia spinally.

A.It precipitates withdrawal in methadone tolerant patients. Naloxone, Naltrexone and Nalmefene - Antagonists at MOP, KOP & DOP Reversibility of a drug's effects by naloxone often defines an opiate No pharmacological utility when used alone Reverse all pharmacological effects mediated by mu and kappa receptors Reverses respiratory depression from overdose or in neonates whose mothers received opiates during labor Precipitates withdrawal syndrome in patients physically dependent Naloxone and Nalmefene not absorbed orally (high first pass effect); Naltrexone is Naloxone has short half-life ~45 minutes; repeated doses may be needed Naltrexone and Nalmefene have longer half-lives (10-14 h)

Which of the following agents is most likely the best choice to treat Jessie's thyroid problem? A.Levothyroxine (T4) B.Iodide salts C.Liothyronine (T3) D.Methimazole E.Propylthiouracil

A.Levothyroxine (T4) Levothyroxine (L-thyroxine, L-T4) is a synthetic natural hormone, has a long half-life, and is the best choice for thyroid replacement. Medical uses: Hypothyroidism (i.e. hashimoto), Thyroid cancer, Goiter by lowering TSH, (Graves'disease.?? not sure why) Side effects: Cardiac side-effects; long-term use may contribute to osteoporosis; Hyperthyroidism-like effects: heart palpitations, abdominal pain, nausea, anxiousness, etc.; Allergic reactions; Fever, hypoglycemia, heart failure, coma, adrenal insufficiency, and increased sympathetic activity. Interactions: Food may interfere with absorption: e.g. calcium, iron, soy products.; Grapefruit juice may delay the absorption. Reduce absorption: aluminium and magnesium containing antacids, simethicone or sucralfate, cholestryramine, colestipol, Kayexalate. Coffee and bran interfere with absorption as well. Ketamine may cause hypertension and tachycardia. Some antidepressants may increase its toxicity. Lithium affects iodine metabolism.

A 28-year old male complains of a burning sensation on urination with a yellow discharge. Lab tests confirm a chlamydial infection. His physician decides to treat him with a "Z-pack," which is a 5-day course of azithromycin. Which of the following antibiotics target the same macromolecule as azithromycin? _____ A.Linezolid B.TMP-SMX C. Bacitracin D.Ciprofloxacin E.Vancomycin

A.Linezolid Inhibitors of the 50S ribosomal subunit: macrolides (end in -thromycin), lincoasamide-clindamycin, streptogramins-quinupristin/dalfopristin and oxazolidinone-linezolid. Both the macrolides and linezolid target the 50S subunit of bacterial ribosomes. None of the other antibiotics target protein synthesis. TMP-SMX is an antifolate. Bacitracin effects cell wall synthesis. It is an inhibitor of peptidoglycan precursors by inhibiting lipid phosphatase that dephosphorylates lipid carrier of peptidoglycan subunits. Bacitracin is a cyclic polypeptide active against Gram(+) organisms. Ciprofloxacin is a fluoroquinolone. Fluoroquinolones end in "-floxacin". They block DNA synthesis by inhibiting DNA gyrase (topoisomerase II) in Gram negative bacteria and topoisomerase IV in Gram-positive bacteria

A drug with a slow onset of action that should be added to DD's drug regimen to treat her Grave's disease, and which acts by selectively inactivating the thyroid peroxidase enzyme is: A.Methimazole B.Levothyroxine C.Liothyronine D.Radioiodide E.Amiodarone

A.Methimazole Methimazole (MMI) and PTU are thioamides that inhibit hormone production Management of Graves' Disease Antithyroid Drug Therapy:Most useful in young patients with mild disease. • MMI or PTU is administered until the disease undergoes spontaneous remission. • Begun with divided doses of MMI, shift to maintenance daily dose. • PTU brings hormone levels down more quickly. • Adverse reactions: minor rash controlled by antihistamine, hepatitis and agranulocytosis by discontinuing the drug. Like PTU, may cause agranulocytosis- a severe and dangerous form of leukopenia, causing serious infections. • For hyperthyroidism, before thyroid surgery to lower hormone levels. • Inhibits TPO, not iodide transporter, does not block peripheral T4-T3 conversion. • longer half-life (5-6 hr), concentrated in thyroid, so taken once daily. • first-line agent in non-pregnant patients.

Alteplase exerts its fibrinolytic activity through activation of: _____ A.Plasminogen B.COX-1 C.cAMP D.Thrombin E.Factor X

A.Plasminogen

What hormone directly stimulates thyroid glands to synthesize and secrete thyroid hormones? A.TSH B.TRH C.GnRH D.T4 E.T3

A.TSH

Serotonin Syndrome

Adverse effect of combining an MAOI with either an SSRI, SNRI or TCA. Also may result from combining an SSRI plus drug with MAOI like activity (i.e.linezolid which is an antibiotic) com or combining an SSRI plus serotonergic drug s.a. dextromethorphan, sumatriptan, tramadol or St. Joh's wort Characterized by altered mental status, fever, tachycardia, hypertension, agitation, tremor, myoclonus, hyperreflexia, ataxia, incoordinatioon, diaphoresis, shivering, GI symptoms

What would you give a patient to rapidly lyse thrombi when a clot has inappropriately formed or has broken free into general circulation i.e. following a heart attack? HINT: ACUTE Situation drug

A fibrinolytic drug like alteplase (activase) which is a recombinant t-PA or tissue plasminogen activator. Alteplase is an immediate clot buster.

Poly (ADP-ribose) polymerase (PARP) inhibitors can effectively target breast and ovarian cancers with DNA repair defects caused by mutation of ____ genes. A.BRCA B.EGFR C.MEK D.BRAF E.VEGF-R

A.BRCA Can also target BRCA cancers with platinum compounds (type of chemo)

Which of the followings is the key molecular target of methotrexate in cancer therapy? A.Dihydrofolate reductase (DHFR) B.Aerobic metabolism C.Cyclin kinases D.Multidrug resistance pump E.Voltage-gated sodium channel

A.Dihydrofolate reductase (DHFR) Methotextrate is an antifolate which is under the grouping of antimetabolites. Antimetabolites inhibit cell division by limiting availability of DNA or RNA precursors. Antifolates prevent DNA synthesis upstream in the process. Folate metabolism is involved in our body's production of the bases that are incorporated into our DNA and RNA.Folate is really a cofactor of the synthesis of pyridines and purines. Aminopterin is a precursor of methotextrate. Nothing is better than methotextrate as a folate antagonist. Aminopterin and methotrexate look very similar to folic acid. They just take away some of the things that make them work properly. They get bound to the enzymes that use folic acid as a substrate but prevent those enzymes from working properly. And thus prevent our bodies from being about to make DNA and RNA building blocks.

Fondaparinux is a synthetic analog of a pentasaccharide sequence found in: _____ A.Heparin B.Protein C C.Plasmin D.Prostacyclin E.Thrombin

A.Heparin

Which of the following signalling pathways is most important in the differentiation and activation of osteoclast precursors into mature osteoclasts? A.Vitamin D receptor. B.Activation of RANK by RANK ligand (RANKL). C.The JAK_STAT pathway. D.Activation of vitamin D. E.Activation of cAMP

B.Activation of RANK by RANK ligand (RANKL).

Acute promyelocytic leukemia (APL) APL is characterized by a chromosomal translocation involving the retinoic acid receptor alpha gene. Which of the following agents is best known to induce differentiation of these leukemic cells, leading to remission? A.Vitamin D B.All-trans retinoic acid C.Fatty acid D.Vitamin K E.Arachidonic acid

B.All-trans retinoic acid

H.K. is a 25-year-old female graduate student who complains of "attacks" of chest pain, difficulty breathing, dizziness and extreme nausea. She says she has been under extreme stress with examinations, working too much, and fighting with her roommate. She is not taking any other medications, has no history of drug abuse, and has no apparent physical abnormalities. You diagnose panic disorder. Which of the following agents is the most appropriate for initial treatment of this type of anxiety disorder? _____ A.Suvorexant B.Alprazolam C.Flumazenil D.Buspirone E.Eszopiclone

B.Alprazolam She could take any benzodiazepine which all end in "-am". BZs are widely used for the management of acute anxiety states and for rapid control of panic attacks. Lorazepam (Ativan®) Clonazepam (Klonopin®) Chlordiazepoxide (Librium®) Oxazepam (Generic) Clorazepate (Tranxene®) Diazepam (Valium®) Alprazolam (Xanax®) Midazolam (Versed®

A 6-year old boy with a fever and severe cough is diagnosed with community-acquired pneumonia of bacterial origin. Which of the following is an antibiotic that his doctor would consider a good option for his treatment? ____ A.Tobramycin B.Azithromycin C.Clindamycin D.TMP-SMX E.Doxycycline

B.Azithromycin The tetracyclines and macrolides are both effective for treatment of community-acquired pneumonia. However the tetracyclines are contraindicated for use in this patient due to their impact on teeth and bones in pediatric patients. Tobramycin is an aminoglycoside (-end in mycin). Aminoglycosides are rapidly bactericidal against many aerobic Gram-negative bacteria. Tobramycin and Gentamicin are mainly used in cases of severe infection (e.g., sepsis and pneumonia) caused by aerobic Gram-negative bacteria. They are often used in combination with a b-lactam antibiotic to take advantage of synergistic effects. Azithromycin is a macrolide (end in -thromycin). Clinical uses of macrolides are Useful as a penicillin-substitute in penicillin-allergic individuals • Respiratory tract infections - community-acquired pneumonia, bronchitis • Skin and soft-tissue infections • Acute otitis media (middle ear infection) • Streptococcal pharyngitis ("strep throat") • Chlamydial infections • Diptheria (Corynebacterium diphtheriae) • Pertussis - whooping cough (Bordetella pertussis) Clindamycin is a lincoasamide. Clindamycin is used for the treatment of skin and soft-tissue infections caused by aerobic and anaerobic Gram-positive bacteria. (NOT MRSA) TMP-SMX is an antifolate. Clinical uses: Uncomplicated UTIs • Skin and soft tissue infections (MSSA); MRSA treatment in combination with other drugs only • Pneumocystis jiroveci pneumonia (PCP) - treatment and prophylaxis • Nocardia infections (Gram-positive rods that are opportunistic pathogen) • Back-up choice for Salmonella infections, Shigellosis, cholera Doxycycline is a tetracycline. Bacteriostatic for many aerobic and anaerobic Gram-positive and Gram-negative bacteria, including rickettsiae, chlamydiae, and mycoplasmas. Rickettsial Infections: Rocky Mountain spotted fever, typhus, and Q fever. • Sexually Transmitted Infections: Chlamydia, urethritis, cervicitis, and epididymititis. • Respiratory Infections: Community-acquired pneumonia. • Skin and Soft-Tissue Infections: Community-acquired Staph and acne. • Infections Caused by MDR Bacteria: (IV only) is used for MDR intraabdominal, skin, and soft-tissue infections, and communityacquired pneumonia. • Other Infections: Doxycycline is used in the treatment of anthrax, malaria, and Lyme disease.

The sulfonamides class of antibiotics block folic acid synthesis in bacteria. What is the basis for the selective toxicity of this class of drugs? _____ A.Humans do not need folic acid while bacteria do. B.Bacteria must synthesize folic acid, while humans acquire it from their diet. C.The prokaryotic enzyme that is the target of the sulfonamides is very different from its human homolog. D.Human cells have different ribosomal subunits than bacterial cells. E.The receptors for such metabolic analogs are present only on the cell surface of prokaryotic cells.

B.Bacteria must synthesize folic acid, while humans acquire it from their diet. All cells require folic acid. It is acquired through the diet for humans, but bacterial cells must make their own. The sulfonamides target a key bacterial enzyme in folic acid synthesis in bacteria, dihydropteroate synthase, which is absent in human cells. Note that trimethoprim (the synergistic partner of the sulfonamides) inhibits the enzyme dihydrofolate reductase, which catalyzes a downstream biochemical step that occurs in both bacteria and human cells. However trimethoprim is ~50,000 times less efficient at inhibiting mammalian dihydrofolate reductase than its bacterial homolog.

All of following are pharmacological properties of levodopa, EXCEPT: ____ A.Metabolized in peripheral tissues to 3-O-methyl-dopa. B.Bind to dopamine receptors in peripheral tissues. C.Contraindicated in psychotic patients. D.Absorbed in the small intestine by active transport. E.A precursor of dopamine.

B.Bind to dopamine receptors in peripheral tissues. The most effective drug for treatment of PD is levodopa, a precursor of dopamine that can enter the CNS and metabolized into dopamine (dopamine itself cannot penetrate the blood brain barrier). Levodopa is usually used in combination with carbidopa, which inhibits conversion of levodopa to dopamine by amino acid decarboxylase in peripheral tissues, thus increasing the amount of levodopa that can enter CNS and decrease peripheral side effects of dopamine. • The single most effective agent in treatment of PD • Levodopa (3,4-dihydroxyphenylalanine) normally synthesized from L-tyrosine • Largely inert, but decarboxylation converts to dopamine • Unlike dopamine, levodopa penetrates the blood brain barrier • Absorbed rapidly from small intestine by active transport system - Competitive with aromatic amino acids - High protein meal will delay absorption and reduce peak plasma concentration • Transported into the brain by active transport system - Competitive with dietary protein - Transport is reduced with high protein diet Metabolized in peripheral tissues by L-aromatic amino acid decarboxylase (L-AAD, 60%) to dopamine (does NOT enter the CNS) and by catechol-O-methyltransferase (COMT, 10%) to 3-O-methyl-dopa (15 hr half-life) which competes with levodopa for transport into the brain

Which of the following agents is a direct orally available thrombin inhibitor? _____ A.Eptifibatide B.Dabigatran C.Heparin D.Bivalirudin E.Alteplase

B.Dabigatran

Which of the following side effects is LEAST likely to be associated with use of an SSRI anti-depressant? _____ A.Sleep disturbances. B.Increased heart rate. C.Sexual dysfunction. D.Diarrhea E.Nausea

B.Increased heart rate.

All of the following statements are true regarding selegiline used for Parkinson's desease, EXCEPT: _____ A.It is a monoamine oxidase B inhibitor. B.It inhibits decarboxylation of levodopa in peripheral tissues. C.It exhibits an antioxidative effect similar to rasagiline. D.Adverse effects include insomnia and anxiety. E.It should not be administered to patients receiving meperidine

B.It inhibits decarboxylation of levodopa in peripheral tissues. Selegiline is an irreversible MAO-B inhibitor => B selective at 10 mg/day or less (at higher doses also inhibits MAO-A). It retards breakdown of dopamine in striatum without inhibiting peripheral metabolism of catecholamines.Has a modest beneficial effects when used alone; also used in combination with levodopa/carbidopa to decrease response fluctuations in late PD patients. Adverse effects: May accentuate the adverse motor and cognitive effects of levodopa therapy; Insomnia, anxiety (metabolites include amphetamine and methamphetamine); Should not be taken together with analgesic meperidine - stupor, rigidity, agitation, and hyperthermia (mechanism is unknown), tramadol, methadone, cyclobenzaprine, St. John's wort.;Concomitant use with tricyclic antidepressants or serotonin-reuptake inhibitors should be done with caution - risk of acute serotonin syndrome (rarely encountered in practice) Rasailine decreases the synthesis of toxic metabolites and thus may provide neuroprotection by reducing oxidation of dopamine

The newer non-GABAergic anxiolytic drug buspirone has all of the following properties, EXCEPT: _____ A.It is thought to activate brain 5-HT1A receptors. B.It is useful to treat acute anxiety states. C.It does not bind to nor activate the GABA receptor. D.It is less effective in panic disorders. E.It causes less psychomotor impairement than benzodiazepines.

B.It is useful to treat acute anxiety states. The anxiolytic effects of buspirone may take >1 week to become established, making the drug unsuitable for acute anxiety states. Buspirone has selective anxiolytic effects without causing marked sedative, hypnotic, or euphoric effects. It is thought to exert its anxiolytic effects by acting as a partial agonist at brain 5-HT1A receptors, though it also has affinity for brain dopamine D2 receptors.It does not interact directly with GABAergic systems. Buspirone-treated patients show no rebound anxiety or withdrawal signs on abrupt discontinuance. The drug is not effective in blocking the acute withdrawal syndrome resulting from abrupt cessation of the use of BZs. It is used in generalized anxiety states, but is less effective in panic disorders

Clopidogrel exerts its antithrombotic effect by irreversible inhibition of: _____ A.Thrombin (Factor IIa) B.Platelet ADP receptors. C.Cyclooxygenase 2 D.Plasmin E.Platelet glycoprotein IIb/IIIa receptors

B.Platelet ADP receptors.

Paget's diesease of the bones causes enlarged and deformed bones due to uncontrolled bone remodelling. Which of the following agents is most suitable for treating this disease? A.Teriparatide B.Risedronate C.Ergocalciferol D.Estradiol E.Denosumab

B.Risedronate Risedronate is a bisphosphonate. Bisphosphonates are analogs of pyrophosphate with a P-C-P bond. P-C-P bond is non- hydrolyzable and binds to calcium. Bisphosphonates sccumulate at bone & prevent bone dissolution. R1 side chain enhances affinity for bone mineral. R2 side chain enhances anti- resorptive potency. MOA: • Bind calcium, accumulate at remodeling sites; incorporated into bone matrix; prevent hydroxyapatite dissolution. • Prevent differentiation of macrophages into osteoclasts; endocytosed by osteoclasts and inhibit osteoclast activity and cause apoptosis. • Simple bisphosphonates like etidronate and clodronate are converted to toxic ATP analogues and may induce apoptosis of osteoclasts. • Nitrogen-containing bisphosphonates inhibit farnesyl pyrophosphate (FPP) synthase, inhibiting osteoclast activity and induce apoptosis. • Also have anticancer activity by inducing cancer cell apoptosis. • May stimulate osteoblasts to produce an inhibitor of osteoclast. • Suppress remodeling rates and reduce numbers of remodeling units.

As compared to TCAs, why are SNRIs typically preferred for treatment of depression? _____ A.SNRIs act more quickly. B.SNRIs interact less with other receptors. C.SNRIs are less likely to cause serotonin syndrome. D.SNRIs do not have effects on blood pressure or heart rate. E.SNRIs are metabolized more efficiently.

B.SNRIs interact less with other receptors. The SNRI's (Serotonin and Norepinephrine Reuptake Inhibitors) inhibit both those serotonin reuptake transporters as well as reuptake transporters that are found on noradrenergic neurons (the ones that produce norepinephrine). In either case we elevate the amount of serotonin and norepinephrine available to bind to target cells. Like the SNRI's, Tricyclics (TCA's) are reuptake inhibitors of serotonin and norepinephrine transporters. But the major difference between the TCA's and SNRI's is that the TCA's have a lot more side effects because these agents tend to bind to other drug targets/other receptors in the body that are not useful for treating depression.

All of the following are true of clinically used opiates EXCEPT: A.They constrict pupils by action on oculomotor nerve. B.The reduce sensitivity of medullary control center to pO2. C.They are more effective against continuous dull pain than sharp, intermittent pain. D.They cause drowsiness and clouding of mentation. E.They decrease motility throughout GI tract via inhibition of the myenteric plexus.

B.The reduce sensitivity of medullary control center to pO2. Actions of opiates: Analgesia: Reduce reactive component of pain (anxiety, fear, suffering): pain still present, but less aversive, Reduce sensory threshold, More effective against continuous dull pain than sharp, intermittent pain; Pupils: constriction by action on oculomotor nerve (miosis); valuable in the diagnosis of opiate overdose; Respiration: Reduce sensitivity of medullary control center to pCO2, Primary action on respiratory rate (<3,4 / minute, progressing to death); Cough: antitussive, Receptors are not stereospecific Dextromethorphan is antitussive, but produces no respiratory depression Euphoria: Generally seen with a patient in pain or an addict, Occasionally dysphoric; Sedation: Drowsiness and clouding of mentation, Impairment of reasoning abilities; Nausea: Stimulate CTZ in the medulla, Rare in recumbent: 40% nausea, 15% vomiting in ambulatory GI tract:↓ motility throughout (stomach, small and large intestine) via inhibition of the myenteric plexus,↑ tone with periodic spasms, particularly in small intestine, Leads to constipation and dessication of stool Biliary tract: Pressure ↑ more than 10-fold - constricts the sphincter of Oddi (seen with 10 mg morphine), May lead to biliary colic Bladder: ↑ sphincter tone and may precipitate urinary retention

All of the following statements are true about how SSRI antidepressants work, EXCEPT: _____ A.They inhibit the reuptake of serotonin. B.They inhibit the reuptake of norepinephrine. C.They selectively inhibit 5-HT receptor. D.Adverse effects are limited to 5-HT mediated responses. E.They inhibit metabolism of TCA.

B.They inhibit the reuptake of norepinephrine. SNRI (NOT SSRI's) inhibit the reuptake of both serotonin and norepinephrine. SSRI's are relatively selective for 5HT-transporter, thus side effects effects are limited to 5-HT mediated responses.Serotonin is also known as 5-HT or 5-hydroxytryptamine.

Which of the followings is a major adverse effect of trastuzumab? A.Pulmonary toxicity B.Nephrotoxicity C.Cardiac toxicity D.Diarrhea E.Hepatotoxicity

C.Cardiac toxicity Cardiac toxicity is an unusual side effect of trastuzumab. We think that HER2 signaling and HER2 mediated expression may be on the cells that normally regenerate the heart. In a small subset of patients, trastuzumab can reduce the pumping function of the heart and cause congestive heart failure. It usually reverses when the drug is stopped but is an important side effect for this drug which is unusual in the drug that is otherwise very well tolerated. The combination of trastuzumab with an anthracycline (a chemo agent), which also gives cardiac toxicity really massively gives patients cardiac toxicity.

Inhibition of which of the following pathways is not associated with anti-depressant effects? _____ A.Serotonin reuptake B.Norepinephrine reuptake C.Dopamine reuptake D.Serotonin degradation E.5-HT2A receptor

C.Dopamine reuptake Dopamine has not been implicated in depression. The major classes of clinically useful anti-depressant drugs increase monamine neurotransmissions by limiting the reuptake of monoamine neurotransmitters or by preventing their breakdown. The SSRI's (Selective Serotonin Reuptake Inhibitors) target serotonin reuptake transporters on the surface of serotonergic neurons. The SNRI's (Serotonin and Norepinephrine Reuptake Inhibitors) target both those serotonin reuptake transporters as well as transporters that are found on noradrenergic neurons (the ones that produce norepinephrine). In either case we elevate the amount of serotonin and norepinephrine available to bind to target cells. Like the SNRI's, Tricyclics (TCA's) are reuptake inhibitors of serotonin and norepinephrine transporters. But the major difference between the TCA's and SNRI's is that the TCA's have a lot more side effects because these agents tend to bind to other drug targets/other receptors in the body that are not useful for treating depression. 5-HT2 (aka 5-hydroxytryptamine aka serotonin) antagonists are 5-HT2 receptor blockades. It binds to the subtype 2 of the serotonin receptors. This should be counterintuitive to you at this point if you understand that what we want to do it to elevate the amount of serotonin and norepinephrine signaling. So why is it that blocking a particular subtype of a serotonin receptor should have antidepressant activity?Again that is a mystery. It presumably has something to do with the particular location of this particular subclass of serotonin receptor. It may have to do with whether there are 5-HT2 autoreceptors for example on the surface of presynaptic cells. But the observation is that the agent is effective. Trazodone is an antagonist at the 5-HT2 receptor. MAOI's prevent the breakdown of monoamines in presynaptic cell when they are present in the cytoplasm before being packages into vesicles. MAOI=monoamine oxidase inhibitors.

All of the following strategies may be helpful in the management of response fluctuation (wearing off) effects associated with levodopa therapy in late stage Parkinson's disease, EXCEPT: _____ A.Adding amantadine. B.Adding pramipexole. C.Increasing levodopa dose. D.Adding Apomorphine. E.Adding Tolcapone

C.Increasing levodopa dose.

A patient presents to his primary care physician on multiple occasions with a chronic cough that has not been managed well with dextromethorphan. The physician decides that a stronger antitussive may be required. Codeine also can be used to manage chronic cough when dextromethorphan is not effective enough. One of the key properties of codeine in the context of cough suppression is: A.It acts as a strong mu agonist. B.It acts as delta receptor antagonist. C.Its antitussive effects do not require metabolism of the parent drug. D.It requires co-formulation with atropine. E.It can lead to the accumulation of a toxic, hyperpyrexic convulsant metabolite.

C.Its antitussive effects do not require metabolism of the parent drug. Antitussives help your cough by deterring your cough reflex. Antitussive is sometimes used in combination with an expectorant that helps to thin mucus. Antitussive drug names include dextromethorphan and codeine. Cough receptors are not stereospecific. Dextromethorphan is antitussive, but produces no respiratory depression. Codeine - 3-methylmorphine; constituent of opium (0.5%). 60% oral bioavailability Largely a prodrug: shows weak mu affinity in vitro. Small percentage converted to morphine in vivo (10%) by CYP2D6: largely responsible for analgesic activity. Commonly used as antitussive (10-20 mg): does not require metabolism. Mild analgesic in combination with aspirin, etc. (60 mg). Low abuse potential Dextromethorphan: isomer of levomethorphan (potent, stereospecific mu agonist). Does not bind to the mu receptor. Does bind to the receptor that mediates cough suppression Available OTC. No abuse potential; no other pharmacological actions. Large TI: safest antitussive available

All the following are true of meperidine EXCEPT: A.It exhibits cross tolerance with morphine. B.It is metabolized by N-demethylation. C.Its withdrawal symptoms after abrupt discontinuation are milder, though more prolonged, than with morphine. D.It has high abuse potential. E.Its oral bioavailability is higher than that of morphine

C.Its withdrawal symptoms after abrupt discontinuation are milder, though more prolonged, than with morphine. Severity depends on the degree of physical dependence, and the rate at which it is unmasked - how rapidly the agonist leaves Meperidine (Demerol) - synthetic mu agonist 50% oral bioavailability; t½ ~3 h Pharmacological actions similar, but not identical, to morphine Metabolized by N-demethylation to normeperidine (convulsant) → renal considerations High abuse potential MORPHINE: Low oral bioavailability (<20%); high first pass effect; usually administered parenterally Enters CNS slowly compared to heroin or methadone Elimination almost entirely metabolic; excreted via the kidney, Half-life 2-3 hours 3-glucuronide major metabolite; 6-glucuronide minor metabolite → retains activity Cross-Dependence: Drug B suppresses withdrawal syndrome after abrupt discontinuance of chronic Drug A use

Compared to morphine, buprenorphine would be expected to: A.Show more profound analgesia in a methdone-tolerant patient. B.Activate the mu opioid receptor to a greater extent. C.Precipitate withdrawal in a heroin addict. D.Have its activity blocked by a therapeutic dose of naloxone more effectively. E.Be used in the hospital setting to elicit profound analgesia in combination with nitrous oxide

C.Precipitate withdrawal in a heroin addict. Because buprenorphine is a partial agonist compared to morphine, it would activate the mu receptor to a lesser extent. Buprenorphine is now used as a maintenance therapy for addicts, like methadone, but b/c of the nature of its partial agonism, patients needs to be slowly tapered from heroin or methadone before switching to buprenorphine, or else withdrawal will be precipitated.

Which of the following chemotherapeutic agents in cancer therapy binds to and inhibits the activity of DNA topoisomerase II? A.Dactinomycin B.MTX C.Teniposide D.Ifosphamide E.Vinblastine

C.Teniposide Anthracyclines(the -rubicins drrugs), intercalate into DNA and inhibit Topoisomerase II. They also cause oxidative damage. Actinomycin D (Dactinomycin) intercalates into DNA & inhibits transcription, resulting in cell death. MTX is methotextrate is an antifolate. Ifosphamide is an alkylating agent. Vinblastine is a vinca alkaloid which inhibit microtubule polymerization.

A 68-year-old woman was being treated with Sinemet® (carbidopa-levodopa) for Parkinson's disease. A secondary medication was later added to address the wearing off effects that she was experiencing. After several months on the new drug, laboratory tests indicated an increase in alanine aminotransferase levels from a baseline of 20 units/L to 110 units/L. Which of the following drugs most likely produced this effect? _____ A.Benztropine B.Entacapone C.Tolcapone D.Amantadine E.Ropinirole

C.Tolcapone A COMT inhibitor with hepatotoxicity. Think "TOlcapone is TOxic" Tolcapone is a COMT Inhibitor =Catechol O-Methyl Transferase Inhibitors. COMT is an enzyme that metabolizes/degrades levodopa and dopamine in both the periphery and the brain. •Given as an adjunct to levodopa/carbidopa allowing reduction of levodopa dose - Inhibition of COMT prolongs plasma half-life of levodopa and increases availability of levodopa to brain • Approved for patients with late PD who have developed response fluctuations. Tplcapone is associated with Hepatotoxicity: Can cause an increase in aminotransferase and transaminase activity - an indicator of liver damage. (stop drug if increase > 5x) => rarely associated with death; use in US requires signed patient consent

Imatinib (Gleevec®) is remarkably effective in treating CML as a single agent mainly through its ability to bind to and inhibit the activtiy of _______. A.Retinoic acid receptor B.BRCA1 C.Tyrosine kinase ABL D.MEK kinase E.PI3K

C.Tyrosine kinase ABL

Which of the followings most strongly binds to and activates vitamin D receptor? A.cholecalciferol B.calcium C.calcitriol D.ergocalciferol E.calcidiol

C.calcitriol Calcitriol aka 1α,25-dihydroxyvitamin D is the active form of Vitamin D, water soluble. Ergocalciferl and Cholecalciferol are inactive, fat soluble prodrugs of Vitamin D Vitamin D2 (ergocalciferol) or vitamin D3 (cholecalciferol): given orally to prevent vitamin D deficiency; to treat familial hypophosphatemia, hypoparathyroidism, and hereditary vitamin D- resistant rickets. • Calcitriol: water soluble, may be given orally or intravenously. Calcitriol-induced hypercalcemia resolves quickly once it is stopped.

Macrolide antibiotic ____ A.include azithromycin and doxycycline. B.are rarely used except for serious infections because they can only be administered IV. C.inhibit the 50S ribosomal subunit. D.are bactericidal. E.must not be taken after eating as oral bioavailability is impaired by food.

C.inhibit the 50S ribosomal subunit.

Bacteriostatic drugs _____ A.rapidly kill bacterial cells. B.have no impact on bacterial growth. C.slow or stop bacterial growth. D.stimulate bacterial growth. E.can only be used topically.

C.slow or stop bacterial growth.

What are the antiplatelet agents that inhibit ADP receptors?

Clopidrogrel, Prasugrel, and Ticagrelor

Advantages of benzodiazepines for the treatment of anxiety states include all of the following, EXCEPT: _____ A.Rapid onset of action. B.Minimal effects on cardiovascular and autonomic function. C.The availability of flumazenil for treatment of overdose. D.Minimal risk of amnesic effects. E.Minimal risk of drug interactions based on liver enzyme induction or inhibition.

D. Minimal risk of amnesic effects. Advantages of benzodiazepines: i. A rapid onset of action ii. A relatively high therapeutic index and availability of flumazenil for treatment of overdose (discussed later) iii. A low risk of drug interactions based on liver enzyme induction: BZ's do not induce or inhibit any liver enzymes. They do not have a lot of drug interactions. You can often take them when you are taking other drugs. BZ's do not have any serious life threatening side effects. iv. Minimal effects on cardiovascular and autonomic functions Disadvantages of benzodiazepines: i. Risk of dependence: These drugs tend to be abused because they make you feel relaxed and kind of euphoric. They are drugs on the most common overdosed list. BZ's are addictive. That ALONE is a reason to not use it chronically. ii. Depression of CNS functions (additive when administered with other drugs, including antihistamines, anticholinergics, and ethanol). Although BZ's do not have metabolic interactions via liver enzymes, it is a CNS depressant and if you take if with anything else that has CNS depressing activities it will add to it and cause some real serious harm. Cannot drink if you are taking BZ's. iii. Amnesic effects People who take BZ's often cannot remember anything that they did while they were under the influence of a BZ. BZ's induce retrograde amnesia and you lose recollection of periods of your life. BZ's also give you extended periods of disinhibition where you feel like you could do anything. Your judgement becomes impaired. You can make bad decisions and not recall you made them. These effects do not happen to everyone. It is idiosyncratic. Some patients may have these adverse side effects. Some may not. But it can definitely happen at a normal dose. The adverse side effects are NOT related to the dosage.

One of the fundamental problem in cancer chemotherapy is the development of drug resistance. Which of the followings BEST describes known reasons for the drug resistance? A.Mutation in p53 tumor suppressor gene. B.Defects or loss in DNA mismatch repair activity. C.Expression of multidrug resistance MDR1 gene. D.All of the above. E.None of the above.

D.All of the above.

Which of the following agents exerts its anticoagulant activity by binding to and activating antithrombin III? _____ A.Bivalirudin B.Eptifibatide C.Aspirin D.Enoxaparin E.Vitamin K

D.Enoxaparin Enoxaparin is a low molecular weight indirect thrombin inhibitor. Thrombin= factor IIa Enoxaparin like heparain is a highly sulfated, very acidic mucopolysaccharide. It is not as good at inhibiting thrombin (factor IIa) as heparin is. It is better at inhibiting factor Xa activity. Typically used in - Prevention of deep venous thrombosis in the postoperative period - Treatment of acute venous thromboembolic disease & acute coronary syndromes

For a patient with non-small cell lung cancer with bronchoalveolar histology, liver metastasis, and overexpression of EGF-R, which of the followings is a potential therapy for this patient? A.Trastuzumab B.All-trans retinoic acid C.Poly ADP ribose polymerase (PARP) inhibitors D.Erlotinib E.Crizotinib

D.Erlotinib Human Epidermal Growth Factor Receptor 1 (aka EGFR aka HER1) is highly expressed in many cancers including lung, breast, colon; activating mutations in a small subset (<10% of NSCLC). Gefitinib and Erlotinib are small molecule tyrosine kinase inhibitors specific to EGF-R.

Trastuzumab (Herceptin®) is most effective in treating breast cancer with amplification and overexpression of which of the following genes? A.VDR B.RARα C.ERα D.HER2 E.PR

D.HER2 Trastuzumab (Herceptin) mechanism of action: 1, Interfering with HER2-dependent signaling 2. Antibody-dependent cellular cytotoxicity (immune mediated) Now every women with HER2 amplified breast cancer gets treated with chemo plus trastuzumab. Trastuzumab binds to the extracellular part of the HER2 molecules. It prevents the dimerization of HER2 which prevents HER2 dependent signaling from occurring. Trastuzumab is also an immune modulating drug. Andtibody dependent cellular cytotoxicity: Once an antibody is bound, a phagocyte can recognize the Fc receptor on the antibody and attacks the target cell it is bound to.

Jessie D is a 50 yr old 145 lb women who arrives at your clinc with the chief complaint of feeling poorly for the past few months. When asked for more details, she complains of a list of symptoms including fatigue, cold intolerance, weight gain and constipation. Her physical appearance is normal except for a noticeable yellow tint to her skin and puffiness of her face. Her thyroid gland appears firm and enlarged. Her laboratory data includes free thyroxine (FT4) = 0.5 ng/dL (normal: 0.7-1.9), TSH = 70 iU/ml (normal: 0.5-4.7), and thyroperoxidase antibodies = 140 IU/L (normal <100). These symptoms and lab data are most consistent with: A.Hyperthyroidism B.Euthyroidism C.Thyroid storm D.Hypothyroidism

D.Hypothyroidism This is a case consistent with Hashimoto's thyroiditis, the most common cause of hypothyroidism. The presence of antibodies for thyroid peroxidase indicates an autoimmune reaction. Approximately 95% of patients with Hashimoto's are Ab positive. These circulating Abs interfere with the intrathyroid binding of iodine to thyroglobulin, which then prevents the synthesis of thyroid hormones T3 & T4. TPO is an enzyme that can conjugate/add the activated iodine into a protein molecule called thyroglobulin. Hashimoto's Thyroiditis is caused by autoantibodies that block Tg, TPO, or TSH-R (TSH-receptor) on thyroid glands

All of the following are true regarding modifications to the phenanthrene core structure of opiates EXCEPT: A.They can result in changes to the oral:parenteral potency. B.They can result in changes to the rate and extent of CNS penetration. C.They can lead to reduced susceptibility to first pass hepatic clearance. D.They can lead to the requirement for coformulation with aspirin or acetaminophen. E.They can affect the binding and functional activity at different opioid receptors.

D.They can lead to the requirement for coformulation with aspirin or acetaminophen.

All of the following statements are true regarding how MAOIs work as antidepressants, EXCEPT: _____ A.MAOIs are monoamine oxidase inhibitors. B.They block degradation of certain neurotransmitters. C.They increase serotonin and norepinephrine levels in the brain. D.They decrease dopamine levels in the brain. E.They can promote serotonin syndrome when combined with SSRI or SNRI.

D.They decrease dopamine levels in the brain. All monoamines are subject to oxidation. That is part of their normal metabolic breakdown pathway. MAOI's act to reduce the frequency of which the monoamines are broken down. One of them acts irreversibly. Their sides effects are due to an excess of ALL types of monoamines, not just serotonin and norepinephrine. Remember that dopamine is also a monoamine. so MAOI essentially elevate the levels of all monoamines.

The anticoagulant activity of warfarin can be competitively inhibited by: ____ A.Protein S B.Vitamin A C.Prothrombin D.Vitamin K E.Vitamin C

D.Vitamin K

PTH (parathyroid hormone) raises blood calcium levels directly and indirectly from the following three sources: A.liver, kidney, and intestine. B.bones, liver, and skin. C.intestines, liver, and kidney. D.bones, kidney, and intestines. E.kidney, muscle, and bones.

D.bones, kidney, and intestines. Low calcium causes parathyroid glands to make more PTH. -->PTH raises calcium levels from bone, kidney, and intestine (PTH increases active Vitamin D levels to promote calcium reabsorption in the intestine).

Teriparatide is an N-terminus 34 amino acids fragment of human PTH. Its use in combination with calcium and vitamin D has been shown to have all of the following effects, EXCEPT: A.increase bone mineral density. B.decrase risk of bone fractures. C.stimulate proliferation of osteoblasts. D.decrease 1,25-dihydroxyvitamin D levels. E.transiently increase serum calcium levels

D.decrease 1,25-dihydroxyvitamin D levels. Teriparatide is indicated for postmenopausal osteoporosis and senile osteoporosis, and for glucocorticoid-induced osteoporosis. It is reserved for the patients at high risk for fractures, or those patients intolerant or unresponsive to other available therapies. Increases bone mineral density. PTH is a double-edged sword on bone: A chronic increase in PTH in secondary HPT causes a decrease in BMD. However, intermittent increases in PTH once a day increases BMD. Teriparatide is thought to bind to PTH-R on osteoblasts but not on osteoclasts, stimulates osteoblast proliferation and inhibit apoptosis, increasing the number of remodeling units. These properties underlie the usefulness of teriparatide for the treatment of osteoporosis. Affects calcium and phosphorus in a pattern consistent with endogenous PTH: transiently increases serum calcium, transiently decreases serum phosphorus, transient phosphaturia, increase 1,25 dihydroxyvitamin D. Initially stimulates bone formation directly, followed by stimulation of both bone resorption and formation.

A physician intends to prescribe buspirone to a 24-year-old patient suffering from Generalized Anxiety Disorder (GAD). The physician should inform the patient to anticipate: _____ A.a need to continually increase drug dosage because of tolerance. B.a significant effect of the drug on memory. C.additive CNS depression with alcoholic beverages. D.that the drug will take a week or so to begin working. E.that if he stops taking the drug abruptly, he will experience withdrawal signs.

D.that the drug will take a week or so to begin working. Buspirone was developed to avoid all of the effects of the GABA pathway. It bypasses GABA and avoids all of the tolerance, dependence and other adverse side effects of GABAergic drugs. Buspirone is used to treat anxiety. It can be taken chronically. It does not cause marked sedation aka sleepiness. It doesn't seem to have the euphoric effects and even at a high does it will never promote sleep. Not exactly sure how it works but what is known is that it is a partial agonist at serotonin receptors 5-HT1A and also has some affinity for dopamine D2 receptors. Buspirone can be taken without risk of dependence. It is not on the controlled substance list like the BZ's are.

What is the main contraindication for fibrinolytic therapy i.e. alteplase?

DO NOT give to patients with hemorrhagic strokes are any situation where patient is already bleeding.

TCAs and SNRIs exert their antidepressant effects by blocking the reuptake of which neurotransmitters? _____ A.Serotonin B.Dopamine C.Norepinephrine D.A and B E.A and C

E.A and C

Which of the following statements is TRUE of BOTH rasagiline and selegiline? _____ A.Both are MAO-B inhibitors. B.May increase the risk of serotonin syndrome when used together with TCA or SSRI C.May be used together with levodopa/carbidopa to decrease wearing off effects. D.May accentuate the adverse motor and cognitive effects of levodopa therapy. E.All of the above are true.

E.All of the above are true. The "-giline" are MAO-B inhibitors= Monoamine Oxidase B Inhibitors. MAO-B metabolizes dopamine selectively. MAO-A metabolizes norepinephrine, serotonin, and dopamine; also found in liver and GI tract.

DJ is a 60 yrs old male with a history of atrial fibrillation, insulin-dependent diabetes and hypertension that presents with signs of hypothyroidism. DJ's drug regimen includes: insulin, amiodarone, losartan, hydrochlorothiazide, lipitor and metoprolol. Which of NJ's medications might be a likely cause for his hypothyroid symptoms? A.Losartan B.Insulin C.Hydrochlorothiazide D.Metoprolol E.Amiodarone

E.Amiodarone Amiodarone is an anti-arrhythmia heart drug. It contains a high content of iodine. Because of this, amiodarone can induce hypothyroidism. This drug has a very long half life. In amiodarone-induced hypothyroidism, T4 therapy may be necessary even after discontinuance of amiodarone. Metabolism of Amiodarone: High iodide content (37.3%), similar to thyroxine. Causes both hypo- (~6%) and hyperthyroidism (~2%).

The key mechanism of action of paclitexal (taxol) in cancer chemotherapy is mediated through: A.DNA crosslinking. B.Inhibiting unwinding of double stranded DNA. C.Intercalating DNA. D.Inhibiting production of DNA building blocks. E.Binding to and retarting disassembly of tubulin, causing mitotic arrest.

E.Binding to and retarting disassembly of tubulin, causing mitotic arrest. Taxanes (paclitaxel, docetaxel) inhibits microtubule de-polymerization Toxicity: 1. Peripheral Neuropathy: 2. Allergic reaction..mostly to solvent cremaphore ***FOR EXAMS: allergic reaction associated with taxanes not due to the drug but due to the solvent. The taxanes are not soluble in water. To give them intravenously, you have to put them in this oily solvent called cremaphore. Cremaphore is what people have allergic reactions to. One way to get rid of this problem is to give taxanes directly conjugated to albumin. 3. Alopecia, myelosupression

All of the following drugs used in the therapy of Parkinson's disease cross the blood-brain barrier, EXCEPT: _____ A.Levodopa B.Tolcapone C.Selegiline D.Pramipexole E.Carbidopa

E.Carbidopa Carbidopa is an L-aromatic amino acid decarboxylase inhibitor, which Increases the fraction of levodopa that remains unmetabolized and available to enter the CNS Cabidopa Does not itself penetrate the blood-brain barrier. The Plasma half-life of levodopa is longer and the plasma concentration of levodopa is higher Carbidopa allows reduced dosage of levodopa which reduces peripheral side effects

Which of the following is a best description regarding how the alkylating agent cyclophosphamide is used clinically as a cytotoxic chemotherapeutic agent? A.It blocks cell cycle by directly inhibiting checkpoint proteins. B.It is an antibiotic. C.It inhibits DHFR. D.It directly inhibits mitosis. E.It crosslinks DNA and inhibits DNA synthesis.

E.It crosslinks DNA and inhibits DNA synthesis. Mechanism of alkylators: Covalent bonding to proteins, RNA, DNA. DNA binding most critical to cytotoxicity, by limiting cell replication and leading to strand breaks. Selectivity derives from diminished repair capacity (They make cross links in DNA which is a form of DNA damage which normal cells can recover from but cancer cells cannot). Cyclophosphamide and Ifosfamide are the most commonly used alkylating agents. They are prodrugs, requiring activation by cytochrome P450 system to active metabolites. One metabolite, acrolein, is particularly toxic to the bladder. The reason the metabolite acrolein is toxic to the bladder is because it is concentrated in the bladder. Drugs either are gotten rid of through the bile and they go out in our feces or the kidneys and go out in the urine. These acrolein compounds go through the urine, are concentrated in the bladder and sit there. Cause bladder irritation. Examples: busulfan, dacarbazine, Procarbazine, Temozolomide, cyclophosphamide, melphalan, Ifosfamide; Thiotepa, Nitrosoureas: BCNU (carmustine) and CCNU (lomustine)

The benzodiazepines class of anxiolytic drugs depresses CNS activity by which of the following mechanisms? _____ A.It competes with γ-aminobutyric acid (GABA) for binding to its receptor. B.It blocks the activation of GABAA receptor. C.It reduces Cl- ion channel activity in the CNS. D.It stimulates β2-adrenergic receptor. E.It increases the frequency of GABA-gated ion channel opening events

E.It increases the frequency of GABA-gated ion channel opening events Benzodiazepines act by binding to the γ-aminobutyric acid (GABA) receptor in neuronal membranes and potentiating the Cl- ion channel effects of GABA, thereby inhibiting all levels of the neuraxis. (GABA is a major inhibitory neurotransmitter in the CNS). This potentiation takes the form of an increase in frequency of GABA-gated channel opening events. • The GABAA receptor is a heteropentameric glycoprotein assembled from 5 subunits (designated as a, b, g, d, e, etc.) GABA interacts at 2 sites between the a and b subunits, triggering Cl- ion channel opening with resulting membrane hyperpolarization. While the binding of the BZs occurs at a single site between the a and gamma subunits, a site also targeted by the BZ antagonist flumazenil (discussed later) and the hypnotics zolpidem, zaleplon, and eszopiclone, but not by the barbiturates.

DD is a 56 yrs old women who arrives at the RWJUH ED with the chief complaint of chest pain unrelieved by nitroglycerin. After giving her a chewable aspirin and beginning an evaluation for a possible MI, you begin taking her history and learn that she has been experiencing bouts of heat intolerance, nervousness, palpitations, and weight loss (despite having an increased appetite). Her vital signs include a blood pressure of 170/90 m Hg, pulse 120/min, and 37.4oC temperature. Her ECG appears normal, with no signs of ST segment changes. You suspect that DD's symptoms may be caused by hyperthyroidism. You take a blood sample and order a series of lab tests. When considering an appropriate durg regimen for treating DD's thyroid problem, you decide to include a drug that can act quickly to inhibit thyroid hormone release. This drug is: A.Levothyroxine B.Liothyronine C.Methimazole D.Propylthiouracil E.Potassium iodide

E.Potassium iodide TPO blocked by high iodide and thioamides. Proteolysis blocked by high iodide.Block TPO, colloid resorption, proteolysis of Tg. • Hyperthyroid begin to subside in 1-2 days. • Body adapts to iodide levels eventually. • Leaves thyroid loaded w/ iodide, problematic for RAI and thioamide therapy. • Used to reduce size and vascularity of thyroid gland prior to surgery. • Used during thyrotoxic crisis. • Untoward effects rare: sore throat, rashes, ulcerations of mucous membranes, and metallic taste. Induces fetal goiter.

Which of the following sedative-hypnotic agents is NOT classified as a controlled substance with a risk of dependence? _____ A.Diazepam B.Zolpidem C.Suvorexant D.Eszopiclone E.Ramelteon

E.Ramelteon Ramelteon is a new Non-GABAergic hypnotic. Ramelteon acts as an agonist at MT1 and MT2 receptors in the brain and has no GABAergic effects in the CNS. Melatonin (MT) receptors are thought to be involved in maintaining circadian rhythms underlying the sleep-wake cycle. The drug decreases sleep latency and increases sleep periods, with no rebound insomnia or risk of dependence (i.e., not a controlled substance). It is metabolized mainly by CYP1A2 and should not be taken in combination with inhibitors of this isozyme. Adverse effects include dizziness, fatigue, and endocrine changes, such as decreases in testosterone and increases in prolactin.

Which of the following might be a serious toxicity observed in a tuberculosis patient who has been receiving daily intramuscular injections of streptomycin as part of his treatment? ____ A.depression B.steatorrhea (presence of excess fat in feces) C.increased serum albumin levels. D.photosensitivity E.deafness

E.deafness Ototoxicity and nephrotoxicity are serious toxicities associated with aminoglycosides.

Name the HIV protease inhibitors

End in "-navir" darunavir, atazanavir, ritonavir

What are all of the indirect thrombin inhibitors?

HePARIN EnoxaPARIN FondaPARINux

Why is it important to overlap Warfarin with another anti-coagulant until a therapeutic dose is reached?

In the early phase of warfarin therapy (before achievement of therapeutic levels), it is selective for inhibition of the anticoagulant Protein C. This is because protein C has a short half life in comparison to the procoagulant factors. If you only give the patient warfarin, you will be inhibiting this anticoagulant Protein C and thus go into a procoagulant state i.e. you are at more risk for clotting because you are inhibiting one of the natural clotting factors. Warfarin does not effect already produced clotting factors. It affects only new synthesis. It would be common to start a patient on a heparin derivative and then transfer them over to warfarin after a few days.

Clopidrogrel, Prasugrel, and Ticagrelor

Mechanism of action: Anti-platelet agents that inhibit ADP receptors and thus inhibit platelet aggregation. ADP is released from degranulating platelets and is a strong stimulater of platelet activation and aggregation. Uses: in dual anti-platelet therapy (e.g. coronary artery stenting)= ADP inhibitor + aspirin in triple therapy (e.g. coronary artery stenting plus atrial fibrillation)= oral anticoagulant+ADP inhibitor + aspirin Most Common adverse effect: bleeding

The major most serious adverse effects of the cancer chemotherapeutic agent etoposide are: A.Diarrhea and abdominal pain. B.GERD C.Headache D.Hepatotoxicity E.Myelosuppression and alopecia

Myelosuppression and alopecia Myelosupression is a condition in which bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells, and platelets. Alopecia is patchy hair loss.

Does Warfarin inhibit already produced clotting factors?

No It affects only new synthesis.

What are the oral anticoagulants which are direct Factor Xa inhibitors?

RivaroXABAN, EdoXABAN and ApiXABAN

Warfarin

Vitamin K antagonist Mechanism of action: Inhibits synthesis of Vit K dependent zymogens including both procoagulant factors (prothrombin(factor2), factor 7, 9 and 10) and anticoagulants (protein C and protein S). It does this by blocking the enzyme Vitamin K reductase (VKORC1 gene), which is required to recycle oxidized Vit K to reduced Vit K. Reduced Vit K is required to carboxylate non-functional pro-zymogens and turn them into functional/active zymogens containing GLA residues. Adverse effects: Narrow therapeutic index. Bleeding, birth defects and abortion, skin necrosis Indications for usage: prevention of valve thrombosis and embolism in patients with mechanical heart valves, prevention of stroke in atrial fibrillation, lowering risk of complications and recurrent in deep vein thrombosis and pulmonary embolism