Muma Drugs Flashcards

Question

Abx for the Tx of H. Pylori only need to know 2

Answer 1

Clarithromycin and Metronidazole

Answer 2

Psyllium- Indigestible hydrophobic colloid that absorb water to form a bulky gel that distends the colon and advances peristalsis, bacteria in colon can cause bloating and fart from nat product

Answer 3

Docusate Surfactants allowing water and lipids to penetrate stool

Answer 4

should not be used in pts with renal insufficiency due to hypermagnesemia

Answer 5

Inert non-absorbable sugar balanced with isotonic solution of sodium sulfate, sodium chloride, sodium bicarbonate, potassium chloride No change in intravascular volume or electrolyte balance Not associated with cramps or flatus Used for colonic cleansing before GI endoscopic procedures and chronically for constipation at lower doses

Answer 6

used for acute and chronic constipation, and in conjunction with PEG for colonic cleansing prior to endoscopy

Answer 7

Lubiprostone

Answer 8

Stimulates type 2 chloride channels in small intestine. Used for the tx of chronic constipation and IBS with constipation

Answer 9

Methylnaltrexone

Answer 10

alvimopan and naloxegol are selective mu opioid antagonists that do not cross the blood brain barrier. Used for the treatment of opioid-induced constipation and post-operatively.

Answer 11

Loperamide

Answer 12

cross the BBB

Answer 13

Cholestryamine

Answer 14

Conjugated bile salts are absorbed in the terminal ileum. Diseases of terminal ileum such as Crohn’s disease or surgical resection disturb bile salt absorption and may cause colonic secretory diarrhea. Bile salt binding resins bind bile salts to decrease diarrhea due to excess fecal bile acids.

Answer 15

Bloating, flatulence, constipation, fecal impaction Further removal of bile acids may cause fat malabsorption

Answer 16

Cholestryanine and colestipol may bind other drugs and decrease their absorption, so do not take other drugs within 2 hrs. Colesevelam does not alter absorption of other drugs.

Answer 17

Palonosetron

Answer 18

Anti-emetic actions through blockade of 5-HT3 receptors on extrinsic intestinal vagal and spinal afferent nerves and perhaps on the vomiting center and chemoreceptor trigger zone.

Answer 19

longer t1/2 and higher binding affinity Selective- no antagonism at dopamine or cholinergic muscarinic receptors May slow colon transport but no effect on esophageal or gastric motility.

Answer 20

Anti-emetic effects for emesis due to vagal stimulation such as post-operative or chemotherapy. Chemotherapy induced emesis- primary agents for use alone but can also be used in combination with dexamethasone or NK1 antagonist Used for nausea and vomiting induced by radiation therapy to the abdomen or whole body and post-operatively.

Answer 21

Well-tolerated and generally safe Most common side effects are headache, dizziness and constipation.

Answer 22

Dexmethasone

Answer 23

Aprepitant _Pharmacokinetics_ Aprepitant has 65% oral bioavailability. Fosaprepitant is an iv infusion formulation that is rapidly converted to aprepitant. Rolapitant- long half-life prolongs therapeutic effects _Pharmacodynamics_ Selective neurokinin 1 receptor antagonist with antiemetic properties via central blockade of receptors in the area postrema. _Uses_ Prevent and treat post-operative and chemotherapy-related nausea & vomiting Less effective for motion sickness related nausea & vomiting Used alone or in combination with 5-HT₃receptor antagonist and dexamethasone (corticosteroid). _Adverse effects_ Safe, well tolerated, few adverse effects reported but include fatigue, dizziness and diarrhea. _Drug interactions_ Inhibit P450 metabolism (CYP3A4) and metabolism of drugs including some chemotherapeutic agents.

Answer 24

Prochlorperazine

Answer 25

_Pharmacodynamics_ Antipsychotics with antiemetic effects via dopamine & muscarinic receptor antagonism (phenothiazines) or for butyronphenones via central dopaminergic antagonism. Sedative effects via antihistamine activity _Uses_ In the past, used extensively for post-operative antiemetic and sedative effects. _Adverse effects_ Extrapyramidal effects and hypotension

Answer 26

Metoclopramide

Answer 27

_Pharmacodynamics_ Mechanism of antiemetic effect- dopamine receptor antagonisms Trimethobenzamide also has weak antihistamine effects _Adverse effects_ Via central dopaminergic antagonism- restlessness, dystonia, parkinsonism

Answer 28

Diphenhydramine ## Footnote **Hyoscine (scopolamine**) _Pharmacodynamics_ Diphenhydramine and dimenhydramine have both antihistamine and anticholinergic properties Meclizine has antihistamine effects but limited anticholinergic effects so less sedating. Hyoscine is a muscarinic antagonist. _Uses_ Used to prevent and treat motion sickness. Diphenhydramine and dimenhydramine used in combination with other agents for treatment of chemotherapy caused emesis. Meclizine is used for preventing motion sickness and treatment of vertigo caused by labrynth dysfunction. Hyoscine in a transdermal patch used extensively for motion sickness. _Adverse effects_ Use limited by side effects- sedation, dizziness, confusion, dry mouth, cycloplegia, urinary retention

Answer 29

Lorazepam ## Footnote Enhance GABAergic neurotransmission Used to reduce vomiting associated with anxiety or anticipatory vomiting related to chemotherapy

Answer 30

Dronabinol _Uses_ Used as an appetite stimulant and antiemetic Used with other antiemetics, synergistic with phenothiazines and decrease adverse effects of both drugs. _Adverse effects_ Euphoria, dysphoria, sedation, hallucination, dry mouth, increased appetite, tachycardia, orthostatic hypotension

Answer 31

1. Anti-diarrheal agents especially loperamide 1. Mu and kappa opioid agonist, delta opioid antagonist Eluxadoline Decreases abdominal pain and diarrhea Adverse effects: constipation, nausea, abdominal pain 1. Tricyclic anti-depressants at low doses Reduce pain Normalize GI motility and secretions to reduce frequency and volume No effects on mood 1. 5-HT₃ receptor antagonists **Alosetron** approved for treatment of women with severe IBS with diarrhea Efficacy of other 5-HT₃ antagonists not examined 5-HT₃ receptors in GI modulate visceral pain and intestinal motility Alosetron- rare but serious GI toxicity limits use to women refractory to other therapies 1. Bile salt binding resins About 1/3 of people with IBS-D have bile acid malabsorption and can be treated with bile salt binding resins 1. Antispasmodics Hyoscine Used to reduce colon muscle spasms and pain 1. Antibiotic Rifaximin- GI specific broad spectrum antibiotic

Answer 32

1. Polyethylene glycol and osmotic laxatives used to soften stools and increase frequency, but no impact on pain. 1. Guanylate cyclase agonist **Linaclotide** _Adverse effects_ diarrhea, upper respiratory tract infection, abdominal pain or distention, flatulence, headache 1. Chloride channel activators **Lubiprostone** Stimulates type 2 chloride channels in small intestine, low systemic absorption Used for the treatment of chronic constipation and women with IBS with constipation _Adverse effects_ Nausea (29%),\< 12 % headache, diarrhea, stomach pain or bloating, gas, vomiting, dizziness, swelling of the hands, feet, ankles, or lower legs, discomfort in chest, tiredness

Answer 33

1. _Aminosalicylates_ 5-aminosalicylic acid differs from salicylic acid by addition of an amino group at the 5 position Mechanism of action uncertain but thought to alter inflammation and immune responses. Thought to work topically in the GI mucosa so several formulations used to limit absorption and aid in delivery to small bowel or colon. Azo compounds Sulfasalazine Olsalazine **Balsalazide** An aza bond to another 5-aminosalicylate or inert compound reduces absorption until drug reaches the terminal ileum and colon where an azoreductase cleaves the azo bond to achieve high concentrations of active compound at site of action. Mesalamine compounds Pentasa Asacol Lialda Rowasa Canasa Formulations designed to deliver 5-aminosalicylic acid to various segments of the small and large bowel. _Uses_ Mild to moderate ulcerative colitis and Crohn’s disease. _Adverse effects_ Sulfasalazine has high incidence of adverse effects especially in slow acetylators due to sulfapyridine, up to 40% cannot tolerate. Olsalazine causes stimulatory diarrhea in 10% of pts. Some of the common side effects of aminosalicylates include abdominal pain, diarrhea, headaches, heartburn, nausea and vomiting. 1. _Glucocorticoids_ _Pharmacokinetics_ **Prednisone** and prednisolone are the most commonly used oral glucocorticoids. Hydrocortisone enemas, foam and suppositories used to maximize colon effects and diminish systemic absorption. **Budesonide** is a high affinity synthetic prednisolone analog with high first pass effect, available in controlled release formulation for delivery to distal ileum and colon. _Pharmacodynamics_ Via interaction with glucocorticoid receptors: Decrease production of inflammatory cytokines and chemokines. Decrease inflammatory cell adhesion molecules. Decrease transcription of nitric oxide synthase, phospholipase A₂, cyclooxygenase-2 and NFB. _Uses_ Treatment of moderate to severe IBD. Budesonide for mild to moderate Crohn’s disease since slightly less effective but with significantly fewer adverse effects. _Adverse effects_ For treatment less than 2 weeks, very well tolerated, occasional peptic ulcer, and rare pancreatitis. Extensive adverse effects for treatment lasting longer than 2 weeks 1. _Immune Modulators_ Purine analogs **Azathioprine** 6-mercaptopurine (6-MP) _Pharmacokinetics_ Bioavailability of azathioprine better than 6-MP, azathioprine converted to 6-MP Short half-life but active 6-thioguanine nucleotide metabolites have a long half-life and are concentrated in cells _Pharmacodynamics_ Immunosuppressive properties through an unknown mechanism 6-thioguanine inhibits purine nucleotide metabolism and DNA synthesis and repair leading to decreased cell division and proliferation _Uses_ Induction & maintenance of remission of ulcerative colitis and Crohn’s disease Help maintain remission in up to 80% of pts Used to reduce dose or eliminate glucocorticoid treatment _Adverse effects_ Nausea, vomiting, hepatotoxicity, bone marrow suppression Monitoring of complete blood count and liver function tests needed Leukopenia and liver dysfunction usually reverse with dose reduction Hypersensitivity characterized by fever, rash, pancreatitis, diarrhea & hepatitis in 5% _Drug interactions_ Reduce the dose of azathioprine and 6-MP by half in patients taking allopurinol because allopurinol reduces purine analog catabolism. **Methotrexate** Anti-metabolite used for a number of chronic inflammatory diseases. _Pharmacodynamics_ Primary mechanism of action is inhibition of dihydrofolate reductase, an enzyme important in production thymidine and purines. _Uses_ Induce and maintain remission of IBD _Adverse effects_ At high doses- bone marrow suppression, megaloblastic anemia, alopecia and mucositis. At doses used for IBD, uncommon but if occur, reduce dose Folate supplements reduce the risk of adverse effects without reducing anti-inflammatory effects. 1. Anti-Tumor Necrosis Factor (TNF) therapy **Infliximab** Adalimumab Certolizumab Golimumab _Pharmacokinetics_ Due to a long half-life, these drugs are given at bi-weekly or longer intervals for induction and maintenance of remission. _Pharmacodynamics_ Monoclonal antibodies to human TNF approved for the treatment of IBD. TNF is a pro-inflammatory cytokine dysregulated via TH1 T cell response in IBD, esp. Crohn’s disease. _Uses_ Acute and chronic treatment of moderate to severe Crohn’s disease with inadequate response to other therapies. Infliximab approved for acute and chronic ulcerative colitis with inadequate response to other therapies. Median clinical response time is 2 weeks. _Adverse effects_ Serious adverse effects occur in 6% of pts Infection due to suppression of TH1 inflammatory response such as pneumonia & sepsis, fungal infections, viral infections, reactivation of latent TB and other opportunistic infections. Acute adverse infusion reactions in ~10% characterized by fever, chills, pruritis, urticaria, cardiopulmonary symptoms, dyspnea or hemodynamic instability Antibody production against the antibodies which eliminate the clinical response and increase the risk for infusion reactions. Delayed(1-2 wks) infusion reaction in 1% characterized by myalgia, arthralgia, fever, rash, urticaria and edema. Usually requires discontinuation of therapy. Rare adverse effects include hepatic failure, demyelinating disorders, hematological reactions congestive heart failure in pts with heart disease and lymphoma 1. Anti-Integrin therapy **Natalizumab** **Vedolizumab** _Pharmacodynamics_ Integrins are adhesion molecules that allow circulating leukocytes to enter tissue Natalizumab is a monoclonal antibody against α4 integrin that prevents circulating leukocytes from entering tissues targeting brain and gut. Vedolizumab humanized monoclonal antibody directed against α4β7 integrin. The α4ß7 integrin is expressed on the surface of a discrete subset of memory T-lymphocytes that preferentially migrate into the GI tract providing increased selectivity. _Uses_ Approved for the treatment of moderate to severe Crohn’s refractory to other treatments. _Adverse effects_ Natalizumab Acute infusion reactions and opportunistic infections. Progressive multifocal leukoencephalopathy a rare infection of the brain that cannot be treated, prevented, or cured and that usually causes death or severe disability. The risk for PML is higher with one or more of the following risk factors: treatment for longer than 2 years, previous treatment with immunosupressants (azathioprine, cyclophosphamide, methotrexate, mitoxantrone, and mycophenolate mofetil), exposure to JC virus. Hepatotoxicity with jaundice in 0.1% -discontinue if occurs Vedolizumab- no PML reported 1. Antibiotics Metronidazole Ciprofloxacin Used to treat infections resulting from IBD

Answer 34

Life-long gluten-free diet accomplished by excluding wheat, rye and barely from the diet, oats should also be excluded due to contamination issues. Initial supplements with iron, calcium, phosphorous, folate, B12 and fat-soluble vitamins as needed. Refractory disease can be treated with corticosteroids such as budesonide or anti-inflammatory drugs such as azathioprine. Untreated celiac disease damages the small intestine and interferes with nutrient absorption. Without treatment, people with celiac disease can develop complications such as osteoporosis, anemia, and cancer.