Term
| In congenital adrenal hyperplasia, there is a deficiency of what? |
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Definition
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Term
| This is a major site of steroid hormone production during fetal and adult life and is more active in fetal life? |
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Definition
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Term
| The adrenal cortex may produce ____ mg of _______ per day in comparison to _____ mg in the nonstressed adult adrenal gland? |
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Definition
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Term
| T/F: Enzyme deficiencies are reported at only certain steps of cortisol production? |
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Definition
| False: Enzyme deficiencies have been reported at all steps of cortisol production. |
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Term
| Diseases associated with insufficient cortisol production are referred to as __________________? |
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Definition
| Congenital Adrenal Hyperplasias (CAH) |
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Term
| The most common enzyme deficiency in congenital adrenal hyperplasias is? |
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Definition
| 17alpha-hydroxyprogesterone to 11-deoxycortisol, which is converted by CYP11B1 to cortisol |
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Term
| What is the pituitary hormone that regulates production of cortisol? |
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Definition
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Term
| Because there is not enough _____, secretion of ACTH increases. |
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Definition
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Term
| Prolonged periods of elevated ACTH levels cause ______ and an increased production of the adrogenic hormones, _______ and ________. |
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Definition
| adrenal hyperplasia; DHEA; androstenedione |
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Term
| The additional production of ________ steroids causes virilization in females, preocious sex organ develoment in prepubertal males, or disease related to salt imbalance because of decreased levels of ________. |
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Definition
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Term
| Clinical consequences of severe _______ deficiency may be recognizable at birth, particularly in females, because the excessive buildup of androgenic steroids may cause obvious irregular development of _____? |
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Definition
| 21-hydroxylase; genitalia |
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Term
| In male newborns, a deficiency of 21-hydroxylase activity may be overlooked because male _____ appear normal, but there will be _________ and physical development later on. |
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Definition
| genitalia; preocious masculinization |
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Term
| In late onset congenital adrenal hyperplasias include early development of _____, early fusion of ______ causing premature cessation of growth, male _____ patterns in females. |
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Definition
| pubic hair; epiphyseal growth plates; baldness |
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Term
| CYP450 plays a major role in ______ synthesis? |
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Definition
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Term
| During _______, a unique interaction among CYP450 in different organs is needed to synthesize the large quantities of steroids that are required. |
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Definition
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Term
| Steroid hormone production increases dramatically and, at term, reaches ____ mg of estradiol, ____ mg of estriol, and ____ mg of progesterone per day, amounts that are a _____ times greater than those produced by premenopausal, nonpregnant women. |
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Definition
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Term
| The major site for estrogen production in the first few weeks of pregnancy is? |
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Definition
| The corpus luteum of the ovary |
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Term
| At approximately __ weeks of gestation, the _____ begins synthesizing and secreting progesterone and estrogens. |
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Definition
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Term
| After __ weeks of gestation, the _____ becomes the dominant source of progesterone? |
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Definition
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Term
| The human placenta lacks ____, which catalyzes both the 17alpha-hydroxylation reaction and the cleavage of the C17-C20 bond and thus cannot synthesize _____ from cholesterol? |
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Definition
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Term
| The placenta can catalyze the side-chain cleavage reaction to form _____ from cholesterol and oxidizes that to ______, which is secreted into the maternal circulation. |
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Definition
| pregnenolone; progesterone |
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Term
| Since the placenta cannot synthesize DHEA or androstenedione from progesterone, The fetal _____ gland catalyzes the synthesis of ____ from cholesterol and releases it into the fetal circulation. |
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Definition
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Term
| A large proportion of fetal DHEA is metabolized by the fetal adrenal and liver to 16alpha-hydroxy-DHEA, which is converted by _____ in the placenta to the estrogen _____. This is example of the cooperativity of the CYP450-mediated _____ systems leading to the formation of ______ during gestational development |
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Definition
| CYP19; estriol; hydroxylating; estrogens |
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Term
| The role that CYP450 play in drug metabolism and the serious consequences of drug-drug interaction were clearly shown for two drugs: _____(Seldane) and ____ (Propulsid), when their metabolism was inhibited by other drugs. |
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Definition
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Term
| A small percentage of terfenadine and cisapride users experienced severe adverse effects that forced the manufacturers and FDA to issue warning that the drugs should not be taken with other drugs that inhibit ____ and had to be taken off the market. |
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Definition
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Term
| Tefenadine, a second generation ______ was approved in 1985 to treat _____. |
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Definition
| H1 anti-histamine; seasonal allergies |
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Term
| Terfenadine is rapidly metabolized in the liver by CYP3A4 to ______, resulting in low levels of the parent drug soon after ingestion, but the therapeutic effects of terfenadine are actually caused by ______. |
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Definition
| fexofenadine; fexofenadine |
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Term
| Because many other drgs are substances or inhibitors of CYP3A4, the metabolism of ______ is potentially inhibitable. |
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Definition
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Term
| Those who took terfenadine with the macrolide antibiotic ______ or the anti-fungal agent, ______, both strong inhibitors of _______, had significantly elevated plasma levels of terfenadine. |
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Definition
| erythromycin; ketoconazole |
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Term
| In a small % of terfenadine users, serious ________ problems developed because the parent drug caused alteration in in cardiac _____ channels and increased the risk of a rare ventricular tachycardia called _________. |
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Definition
| cardiac; potassium; Torsades de Pointes |
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Term
| T/F: Some individuals died from cardiac problems that developed after taking terfenadine with erythromycin or fexofenadine? |
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Definition
| False; erythromycin or ketoconazole NOT fexofenadine. |
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Term
| Since the therapeutic properties of terfenadine were associated with its nontoxic ______, fexofenadine, the manufacturer tested fexofenadine as a new medication and sought FDA approval, now marketed as _______. |
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Definition
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Term
| Cisapride was approved in 1993 for patients who suffer _____ as a result of gastroesophageal reflux disease (GERD). |
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Definition
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Term
| The elimination of Cisapride from the body is dependent on _____ metabolism, and when administered alone or with drugs that do not inhibit the above blank, the parent drug does not accumulate in the ___. |
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Definition
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Term
| When taken with drugs that are substrates or inhibitors of ______, cisapride metabolism is ______, and it accumulates with subsequent intake. |
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Definition
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Term
| In some individuals, increased cisapride levels cause _______ and by the end of 1999, _____ abnormalities were reported in 341 patients, resulting in 80 deaths. Cisapride marketing was stopped after 2000. |
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Definition
| cardiac arrythmias; heart rhythm |
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Term
| Acetaminophen is one of the most commonly used ____ (pain-relieving) and _____ (fever-reducing) OTC medication. |
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Definition
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Term
| Acetaminophen is available alone or as a component of more than ______ other nonprescription medications. |
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Definition
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Term
| The consumption of ____, an induced and substrate of _____, has a profound effect on acetaminophen. |
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Definition
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Term
| Drinking a 750-mL bottle of wine, six 12-oz. beers, or 9 oz. 80-proof liquor, over a 6-7 hour period causes a 22% increase in ____-mediated metabolism of acetaminophen that manifests several hours post alcohol intake. |
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Definition
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Term
| T/F: Timing is very critical between alcohol consumption and intake of acetaminophen in the development of acetaminophen-induced liver injury. |
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Definition
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Term
| In a person drinking alcohol, metabolism of acetaminophen taken shortly after cessation of drinking is delayed because ____, like acetaminophen is a substrate for CYP2E1, and therefore competes for binding. |
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Definition
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Term
| In chronic alcohol consumption, CYP2E1 is induced and greater amounts of _______ are produced; however, alcohol may actually ____ the liver from acetaminophen-induced injury, if taken at the same or shortly before. |
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Definition
| N-acetyl-p-benzoquinoneimine (NAPQI); protect |
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Term
| If acetaminophen is taken several hours post alcohol intake, the alcohol has already been metabolized and increased levels of ____ are then available to metabolize acetaminophen to _____, increasing the risk of ____ damage. |
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Definition
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Term
| The length of time and amount of alcohol consumed daily affect the amount of CYP2E1 expressed in ________. |
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Definition
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Term
| T/F: The amount of acetaminophen consumed is also a major determining factor for risk, as normally recommended doses usually generate sufficient NAPQI to produce liver cell damage. |
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Definition
| False - recommended dosages do NOT usually generate sufficient NAPQI to produce liver cell damage. |
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Term
| Why does higher doses of acetaminophen increase the risk of liver cell injury? |
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Definition
| More drug will be metabolized through the CYP2E1 pathway |
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Term
| Both the ______ and ______ pathways are essential in determining the amount of acetaminophen that will be metabolized by CYP2E1 |
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Definition
| Sulfation; glucuronidation |
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Term
| The levels of intracellular _____ are critical as it forms conjugates with NAPQI to protect the liver from this reactive metabolite. |
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Definition
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Term
| In the present of high levels of ____, the glutathione is rapidly depleted and can no longer protect against damage. |
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Definition
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Term
| Induction of CYP450 may decrease the therapeutic effects of drugs, because increases in liver P450 levels increase rates of ____, and, therefore, _____ and/or excretion of drugs. |
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Definition
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Term
| Induction of the P450 system may also have adverse effects due to the increased formation of toxic ________. |
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Definition
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Term
| Induction of CYP3A4 by the anti-tuberculosis drug, __________, may greatly increase elimination of the oral contraceptive ethinyl _____, causing subeffective plasma levels of the drug, which increases the risk of ______. |
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Definition
| rifampin; estradiol; pregnancy |
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Term
| Treatment with the anticonvulsant drugs, ______ and ___________, may also induce CYP3A4 and reduce the ________ potency of ethinyl estradiol. |
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Definition
| Phenytoin; carbamazepine; contraceptive |
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Term
| It is imperative that a women taking ethinyl ________ as an oral contraceptive simultaneously with a CYP3A4 inducer _______ (increase/decrease) the dose of the contraceptive or use an alternative contraceptive method or drug. |
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Definition
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Term
| The herbal agent, ____, also induces CYP3A4 activity, raising concerns who those who ingest the herb may not receive the therapeutic benefits of drugs that are CYP3A4 substrates. |
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Definition
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Term
| A reduction in _____ levels of oral contraceptives, HIV anti-protease drugs, the immunosuppressive drug ______, or certain _____ drugs, used to lower cholesterol levels, can occur because each of these drugs is a ______ for CYP3A4. |
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Definition
| plasma; cyclosporine; statin; substrate |
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Term
| Because ____ is considered a natural substance, individuals may take this agent without notifying their physician or knowing its effects. |
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Definition
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Term
| Multiple alleles have been demonstrated for approximately ___% of human P450 genes. These genetic polymorphisms may produce defective _______. |
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Definition
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Term
| Why would the absence of CYP450 activity cause many problems? |
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Definition
| Due to the accumulation of therapeutic drugs that cannot be metabolized |
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Term
| The discovery of exaggerated hypotensive effects with the antihypertensie drug, ______, led to the characterization of individuals who inefficiently metabolized ______ substrates. |
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Definition
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Term
| About 4-50% of caucasion, 8% of african and african-american, and 1% of asian polulations are deficient in catalytically active ______. |
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Definition
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Term
| The drugs sparteine, amitriptyline, dextromethorphan, and codein are metabolized by? |
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Definition
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Term
| In the case of codein, CYP2D6 in normal individuals catalyzes the ______ of approximately 10% of the codein to morphine, so individuals who lack function CYP2D6 are unstable and do not achive the _____ effects of codein. |
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Definition
| O-demethylation; analgesic |
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Term
| A genetic polymorphism associated with CYP2C19 has been demonstrated in individuals who are poor metabolizers of _____, a drug used in the treatment of epilepsy. CYP2C19 hydroxylates C4 of the S-enantiomer of mephenytoin to inactive the phsyiological effort. |
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Definition
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Term
| Approximately 14-22% of Asian, 4-7% of the African and African-American, and 3% of the Caucasion populations lack the active form of _____. |
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Definition
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Term
| CYP2C9 is rear in all ethnic groups, and its absence may have serious consequences in the metabolism of ____, an orally administered drug used to inhibit blood coagulation in patients who have suffered a heart attack or stroke to prevent clots. |
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Definition
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Term
| Warfarin is metabolized by ____ for elimination and excess amounts can cause uncontrollable bleeding and possibly death. |
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Definition
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Term
| CYP2C9*3 is an allilic variant in which ___ is substituted for leucine at residue 359, resulting in substantial loss of enzymatic activity. |
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Definition
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Term
| Individuals deficient in CYp2C9 may require only 0.5-1 mg of warfarin per week in contrast to the _____ mg/day for those with normal CYP2C9; If that dose of warfarin was taken by someone lacking functional CYP2C9, uncontrollable bleeding could result. |
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Definition
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Term
| The levels of cyclic nucleotides (____ and ___) present in the cell are dependent not only on their formation by adenylate or guanylate cyclase, but also on their degradation by ____, which hydrolzye them to 5'-nucleotides and so play a critical role in the modulation of these second messenger signaling pathways. |
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Definition
| cGMP; cAMP; phosphodiesters (PDEs) |
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Term
| The inhibition of ____ destruction of cyclic nucleotides would thus prolong the physiological response elicited by the cyclic nucleotides. |
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Definition
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Term
| _____, a drug prescribed for erectile dysfunction is a potent inhibitor in the human _____ and in vascular and GI smooth muscle. |
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Definition
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Term
| In the penis, ___ produces erection via a ___-dependent pathway, as the cGMP is degraded by ____, the vasodilatory signal attenuates and the erection subsides. |
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Definition
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Term
| ____ inhibits PDE5, delaying cGMP degradation and thus prolonging erection. It is highly selective for PDE5 over PDE3, a cAMP-specified PDE involved in the regulation of ______. |
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Definition
| Sildenafil; cardiac contracility |
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Term
| Inhibition of ___ increases the incidence of cardiac arrythmias and decreases long-term mortality in heart failure patients. |
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Definition
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Term
| Sildenafil also inhibits, to a lesser extent, PDE6, which is localized to photoreceptors in the _____, and one of the side effects sometimes reported with Sildenafil use is a ________ tint in the patient's vision. |
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Definition
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Term
| Because PDE5 is present in _________, Sildenafil causes a mild, clinically insignificant, reduction in blood pressure due to ____, but more importantly, it greatly exacerbates the effects of nitrates and external NO donors such as _____, taken for angina, causing potentially fatal ______. |
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Definition
| vascular smooth muscle; vasodilation; nitroglycerin; hypotension |
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Term
| Sildenafil is contraindicated in patients using ____ in any form. In addition, it is metabolized by both the ___ and ____ pathways. Inhibition of these pathways by other drugs may increase the plasma concentration of Sildenafil, intensifying ______. |
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Definition
| Nitrates; CYP2C9 and 3A4; side effects |
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Term
| Although NO is essential in tumoricidal and bactericidal functions of ____, overproduction of NO (by NOSII) has been implicated in septic/cytokine-induced circulatory ____ in humans through the activation of _______. |
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Definition
| macrophages; shock; guanylate cyclase |
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Term
| Overproduction of NO is responsible for profound _____ in postoperative patients complicated by _________ infections that produce endotoxins; this hypotension is often refractory to treatment with conventional vasoconstriction drugs. |
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Definition
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Term
| Therapeutic intervention by ______ inhibitors is being investigated for treatment of septic shock, inflammatory diseases of the GI tract (such as pancreatitie and ulcerative colitis), and ____. |
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Definition
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Term
| ____ plays a critical role in maintaining a base vasotonus in hemodynamic regulation such that a decrease in the production of NO could result in hypertension, ________, or atherosclerosis |
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Definition
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Term
| Direct application of NO gas may be beneficial in the treatment of _________. |
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Definition
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Term
| T/F: In selected patients, NO improved arterial oxygenation and increased pulmonary arterial hypertension. |
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Definition
| False: DECREASED pulmonary arterial hypertension |
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Term
| T/F: Inhales NO can reduce the need for extracorpeal membrane oxygenation in newborn patients with hypoxic respiratory failure, which was both expensive and invasive. |
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Definition
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Term
| T/F: Inhaled NO has been used to treate ARDS, inducing vasodilation, decreasing MPAP, and increasing cardiac index? |
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Definition
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Term
| When the gene for ___ has been knocked out in mice, the animals have distended stomachs due to constriction of the ____, which is relaxed via signaling by ____ (line 1) located in the neurons that innervate the myenteric plexus. |
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Definition
| NOSI; pyloric sphincter; NOSI |
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Term
| The NOSI-deficient mice are also resistant to _____ damage as a result of ischemic injury, suggesting involvement of NOSI, in the injurious process. Thus, specific inhibition or induction of the isoforms of ______ synthase is an ideal goal for therapeutic intervention. |
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Definition
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Term
| ____, more correctly called glyceryl trinitrate, was first synthsized by A. Sobrero ins 1847. It was extremely ___ and many fatal accidents occurred. |
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Definition
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Term
| Alfred Nobel developed a procedure in 1846 to stabilize nitroglycerine by mixing it with _________ which became known as dynamite and the bases of the Nobel prizes. |
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Definition
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Term
| In 1867, Sir Thomas Lauder Brunton first reported the use of inhaled ____ in his patients with chest pains and in 1879, William Murrell published an article describing the use of the longer-lasting and more convenient compound nitroglycerin to better alleviate the pain of ______. |
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Definition
| amyl nitrate; angina pectoris |
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Term
| Nitroglycerin worked by dilating ________ of the heart, thus allowing more ____ of the tissue. |
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Definition
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Term
| Not until 1987, over a century after Murrell's publication that ______ gas released from nitroglycerin metabolism was postulated to be the active agent in the ____ of the coronary blood vessels. Even today the actual ____ of the NO release from nitroglycerin is unclear. |
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Definition
| nitric-oxide; dilation; mechanism |
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