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88 Cards in this Set
- Front
- Back
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What is the MOA of glucocorticoids?
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enter the cell and bind to cytostolic receptors that transport the steroid into the nucleus
The steroid-receptor complex alters gene expression by binding to glucocorticoid response elements (GREs) or mineralocorticoid-specific elements |
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What are the metabolic effects of glucocorticoids?
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stimulate gluconeogenesis --> blood glucose rises, muscle protein is catabolized, and insulin secretion is stimulated
stimulates lypolysis and lipogenesis --> fat deposits in face, shoulders and back |
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What are the catabolic effects of glucocorticoids?
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cause muscle protein catabolism
osteoporosis in children, growth is inhibited lymphoid and CT, fat and skin undergo wasting with high doses of glucocorticoids |
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What the immunosuppressive effects of glucocorticoids?
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inhibit cell-mediated immunologic functions (especially lymphocytes)
actively lymphotoxic = important in treatment of hematologic cancers delay rejection reactions in transplant patients |
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What are the anti-inflammatory effects of glucocorticoids?
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increased neutrophils and decrease lymphocytes, eosinophils, basophils and monocytes
migration of leukocytes is inhibited induce phospholipase A2 decrease mRNA for COX-2 decrease interleukin-2 and IL-3 decrease platelet activating factor (PAF) = inflammatory cytokine |
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What are the effects of glucocorticoids on the kidneys, CNS and GI?
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kidneys = cortisol is required for normal renal excretion of water
CNS = profound behavioral changes when given in large doses GI = stimulate gastric acid secretion and decrease resistance to ulcer formation |
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What regulates the physiologic secretion of cortisol?
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ACTH
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To what is 95% of cortisol bound in the cytoplasm?
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corticosteroid-binding globulin (CBG)
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Which organ clears cortisol when given orally?
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absorbed in GI tract
cleared by the liver |
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Why is hypertension a significant concern with cortisol?
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cortisol has small but significant salt-retaining effects
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List common synthetic glucocorticoids
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predinsone
prednisolone dexamethasone triamcinolone beclomethasone budesonide |
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How do synthetic glucocorticoids compare to cortisol?
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longer half-life and duration of action
reduced salt-retaining effect better penetration of lipid barriers for topical use |
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Which synthetic glucocorticoids readily penetrate the airway mucosa and have short half lives once they enter the blood stream?
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beclomethasone
budesonide |
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Clinical uses of glucocorticoids
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Adrenal disorders
- Addison's disease - acute adrenal insufficiency - congenital adrenal hyperplasia Nonadrenal disorders: - inflammatory or immunologic disorders - tx of hematopoietic cancers - neurologic disorders - chemo-induced vomiting - hypercalcemia - mountain sickness |
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Which glucocorticoid can be safely given to pregnant women in premature labor to hasten maturation of the fetal lungs?
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betamethasone
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What are the toxicities of glucocorticoids?
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Metabolic effects = growth inhibition, diabetes, muscle wasting, osteoporosis
salt retention pyschosis |
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Which substance controls aldosterone secretion?
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angiotensin II which is regulated by ACTH and the renin-angiotensin system
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What is the naturally occurring precursor of aldosterone?
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deoxycorticosterone
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Which glucocorticoid is favored for replacement therapy after adrenalectomy and why?
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fludrocortisone
because it has a long duration of action |
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List some corticosteroid antagonist
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spironolactone and eplerenone = antagonists of aldosterone (diuretics)
mifepristone (RU-486) = competitive inhibitor of glucocorticoid and progesterone receptors (used to treat Cushing's syndrome) |
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Addison's disease
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Partial or complete loss of adrenocortical function, including loss of glucocorticoid and mineralcorticoid function
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Cushing's syndrome
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A metabolic disorder caused by excess secretion of adrenocorticoid steroids, which is most commonly due to increased amounts of ACTH
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Antiemetic
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a drug that reduces nausea and vomiting
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Gastroparesis
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paralysis of the muscles of the stomach and possibly other other parts of the GI tract due to damage to gastrointestinal nerves or muscle
common in advanced diabetes and advanced Parkinson disease |
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Prokinetic
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a drug that promotes gastrointestinal motility
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Proton pump
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parietal cell H+/K+ ATPase that uses the energy of ATP to secrete protons into the stomach; final common target of drugs that suppress acid secretion
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What is the MOA of antacids?
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neutralize stomach acid by reacting with protons in the lumen of the gut and may also stimulate protective functions of the gastric mucosa
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Magnesium hydroxide
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antacid
has strong laxative effect not readily absorbed from the gut |
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Aluminum hydroxide
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antacid
has strong constipating effect not readily absorbed from the gut |
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Calcium carbonate
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antacid
weak base are absorbed from the gut--therefore are less popular as antacids |
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bicarbonate salts
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antacid
weak base are absorbed from the gut--therefore are less popular as antacids |
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Cimetidine
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H2 antagonist
used for acid-peptic disease = reduce symptoms, accelerate healing and prevent recurrences Can be used in GERD and Zollinger-Elllison syndrome |
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What is the MOA of H2 antagonists?
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produce a surmountable pharmacologic blockade of histamine H2 receptors
relatively selective and have no effect on H1 receptors |
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Toxicity of H2 blockers
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cimetidine:
- potent inhibitor of hepatic drug-metabolizing enzymes and may reduce hepatic blood flow - has significant antiandrogen effects Ranitidine = has weaker effect on hepatic drug metabolism no endocrine effects |
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Rantidine
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Histamine H2 blocker
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Famotidine
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Histamine H2 blocker
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Nizatidine
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Histamine H2 blocker
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What is the MOA of proton-pump inhibitors?
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they are lipophilic weak bases that diffuse into the parietal cell canaliculi, where they become pronated and concentrated more than 1000 fold
they undergo conversion to compounds that irreversibly inactive the parietal cell H+/K+ ATPase --> decrease stomach acid |
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Where are proton-pump inhibitors absorbed?
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in the intestine
**they are enteric coated to prevent acid inactivation in the stomach |
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Where are proton-pump inhibitors metabolized?
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liver
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Which drugs are effective in treating Zollinger-Ellison syndrome?
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proton-pump inhibitors (mainly)
also H2 antagonists |
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Toxicity of proton-pump inhibitors
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adverse side effects occur infrequently, they include:
diarrhea abdominal pain headache chronic use can lead to hypergastrinemia decrease the oral bioavailability of vitamin B12 and certain drugs that require gastrointestinal absorption small increase in the risk of respiratory and enteric infections |
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Which drugs may show decreased bioavailability when taken with proton-pump inhibitors?
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drugs that require acidity in the stomach to be absorbed by the GI tract:
digoxin ketoconazole |
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Sucralfate
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alumnium sucrose sulfate
environment of the stomach accelerates the healing of peptic ulcers and reduces the recurrence rate |
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MOA of sucralfate
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it is a small, poorly soluble molecule that polymerizes the acid environment of the stomach
This polymer binds to injured tissue and forms a protective coating over ulcer beds **must be taken 4 times per day |
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toxicity of sucralfate
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it is too insoluble to have significant systemic effects when taken by oral route, toxicity is low
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Misoprostol
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analog of PGE1
reduces the risk of ulcers in users of NSAIDs **has to be taken several times a day and is poorly tolerated |
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MOA of misoprostol
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it is an analog of PGE1 and thus, increases the mucosal protection and inhibits acid secretion
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MOA of Colloidal bismuth
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formation of a protective coating on ulcerated tissue
stimulation of mucosal protective mechanisms direct antimicrobial effects sequestration of enterotoxins |
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Bismuth subsalicylate
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OTC version of colloidal bismuth
reduces stool frequency and liquidity in infectious diarrhea |
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Adverse effects of bismuth
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causes black stool
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neostagmine
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achetycholinesterase inhibitor used for tx of hospitalized patients with acute bowl distention
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metoclopramide
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D2 dopamine receptor antagonist that promotes GI motility
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domperidone
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D2 dopamine receptor antagonist that promotes GI motility
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Toxicities of D2 receptor anatagonists
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Metoclopramide = can cross the blood brain barrier and can cause symptoms of Parkisonism and hyperporlactinemia
domperidone has less CNS toxicity because it cannot cross the BBB |
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Which antibiotic promotes motility of the GI tract? How?
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erythromycin
stimulates motilin receptors |
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Which laxatives have a bulk-forming action on the stool that evokes reflex contraction of the bowl?
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psyllium
methylcellulose polycarbophil |
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Which laxatives have a stool-softening action on hard or impacted stool?
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docusate
glycerine mineral oil |
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Which laxatives have an osmotic effect on the stool that allows for lubrication of the stool?
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magnesium oxide
sorbitol lactulose magnesium citrate sodium phosphate polyethylene glycol |
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Which laxative is a Cl-channel blockers?
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lubiprostone
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Which laxatives have a stimulant effect on bowel movements?
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aloe
senna cascara castor oil bisacodyl |
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Which laxative are opioid receptor antagonists?
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methylnatrexone
avimopan |
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Which laxative is a 5HT4-receptor agonist?
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Tegaserod
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What are the most effective antidiarrheal drugs?
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opioids or derivative of opioids
diphenoxylate loperamide |
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MOA of anticholinergic drugs in IBS
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used as antispasmodics to relieve abdominal pain
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Dicyclomine
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anticholinergic drug used in IBS as an antispasmodic
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hyoscyamine
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anticholinergic drug used in IBS as an antispasmodic
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Alosetron
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potent 5HT3 antagonist
approved for women with IBS and severe diarrhea |
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toxicity of alosetron
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can cause constipation that on rare occasions can be so bad that it calls for hospitalization or surgery
can rarely cause ischemic colitis |
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Diphenhydramine
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H1 histamine blocker
antiemetic |
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phenothiazines
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H1 histamine blockers
antiemetics |
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scopolamine
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antimuscarinic drug that is an antiemetic
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how is dexamethasone used in treating GI symtoms?
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it is a corticosteriod that is used as an antiemetic
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dronabinol
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cannabinoid receptor agonist that is used as an antiemetic
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ondansetron
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5HT3 antagonist
used to prevent nausea and vomiting after general anesthesia and in patients who are receiving chemo |
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ganisetron
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5HT3 antagonist
used to prevent nausea and vomiting after general anesthesia and in patients who are receiving chemo |
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dolasetron
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5HT3 antagonist
used to prevent nausea and vomiting after general anesthesia and in patients who are receiving chemo |
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palonosetron
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5HT3 antagonist
used to prevent nausea and vomiting after general anesthesia and in patients who are receiving chemo |
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Aprepitant
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NK1 receptor antagonist; receptor is located in the area postrema of the CNS that is normally activated by substance P and other tachykinins
used in combination for pts receiving chemo to prevent nausea and vomiting |
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toxicities of aprepitant
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fatigue
dizziness diarrhea |
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5-aminosalicylic acid (5-ASA) or mesalamine
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an aminosalcylate
used in topical therapy for IBD |
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Where is mesalamine readily absorbed?
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in the small intestine
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Sulfasalazine
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combo of 5-ASA and sulfapyridine
used for tx of IBD |
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toxicities of sulfasalazine
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higher incidence of side effects than just 5-ASA because of systemic absorption of the sulfapyridine, include:
nausea GI upset headaches arthralgias myalgias bone marrow suppression malaise severe hypersensitivity rxn |
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Natalizumab
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humanized monoclonal antibody that blocks integrins on circulating leukocytes
used for Crohn's disease |
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toxicities of natalizumab
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possible association with multifocal leukoencephalopathy
**has restricted use |
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Pancreatin
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oral administration of pancreatic lipase that is obtained from pigs
drug should be enteric coated because pancreatic lipase is inactivated at a pH lower than 4.0 |
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ursodiol
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decreases the cholesterol content of bile by decreasing hepatic cholesterol secretion
inhibits the formation of cholesterol gallstones toxicity is uncommon |
