Pharmacology 2, Final Exam Study Guide PDF

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Pharmacology 2, Final Exam

Jamie-Dong Viet Nguyen, ID: 0154151 Doctor of Pharmacy Candidate, MCP Class

of 2017 Dr. Dan Kiel ANTI-EMETICS -Vomiting is a protective mechanism a. Unpleasant sensation -Chemotrigger zone monitors bloodstream for various substances that should be expelled from the body  initiates vomiting reflex Ex: Drugs (Opioids, Dopamine), hormonal changes during pregnancy, motion sickness -Motion sickness from inner ear: Vestibular apparatus a. Muscarinic and H1 receptor blockers are good for motion sickness -Other receptors: Mu, D2, NK1, CB1, 5HT3 a. Activating 5HT3 receptors increases secretion of fluids from glands  increase GI movements (NOT DOWNWARD MOTILITY)  increase N/V i. CINV b. Activating D2 receptors and 5HT3 receptors along GI tract decrease GI motility i. Inhibiting D2 receptors = increase GI motility  prevents upward movement  increase antiemetic effect -ALL DRUGS ARE FOR SHORT TERM, INTERMITTENT USE 1. D2 RECEPTOR ANTAGONISTS ***Drugs: Prochlorperazine (Compazine), Trimethobenzamide (Tigan), Promethazine (Phenergan) -Old 1st line drugs, also available as suppositories -Drugs are nonselective traditional antipsychotics  can also block H1 and muscarinic receptors 1A. Prochlorperazine (Compazine) -More antiemetic than antipsychotic -Can block M1 and H1 and increase GI motility **Use: Motion sickness, antiemetic **ADRs: Xerostomia, blurred vision, sedation i. If prolonged use, may cause tardive dyskinesia 1B. Trimethobenzamide (Tigan), Promethazine (Phenergan) -Also have some H1 antagonistic activity 2. 5HT3 RECEPTOR ANTAGONISTS ***Drugs: Ondansetron (Zofran), Granisetron (Kytril), Dolasetron (Anzemet), Palonosetron (Aloxi) -5HT3 receptors are in stomach and GI tract peripherally a. CINV (Chemoinduced N/V) to due killing of cells in GI  release 5HT and activates 5HT3 in GI/brain  N/V effect *MOA: Blocks 5HT3 receptors  decrease secretions and movement  decrease N/V -More effective than D2 antagonists, NOW 1st line 3. Metoclopramide (Reglan) *MOA: D2 AND 5HT3 antagonist, BUT not well (not as effective as D2/5HT3)  long term use may lead to movement disorders and tardive dyskinesia 4. Cisapride -Similar to Metoclopramide, but NOT for human use anymore *MOA: May block potassium in heart  increase in arrhythmias 5. NK1 RECEPTOR ANTAGONIST ***Drugs: Aprepitant/Fosaprepitant (Emend) Page 1

Pharmacology 2, Final Exam

Jamie-Dong Viet Nguyen, ID: 0154151 Doctor of Pharmacy Candidate, MCP Class

of 2017 -NK1 is found in chemotrigger zone and is a neurokinin peptide normally activated by Substance P  promotes vomiting **Use: CINV a. MUST take BEFORE chemotherapy (high dose few hours before) and some after **ADR: Loss of appetite, fatigue 6. CB1 RECEPTOR AGONISTS ***Drugs: Dronabinol (Marinol), Nabilone (Cesamet) -Cannabinoid receptor found in brain *MOA: Activates CB1 receptor in brain  decrease N/V **Use: CINV **ADRs: Increase SANS  tachycardia, palpitations, increase appetite and CNS depression  somnolence, detachment from reality, euphoria a. CB1 antagonists are for obesity by decreasing appetite **ADR: Increase suicidal thoughts -Controlled substances IBS (IRRITABLE BOWEL SYNDROME) -Spasms of GI with intermittent pain: 3 types a. IBS-C, IBS-D, IBS-C/D -Predominantly affects women and is diagnosed when everything else has been ruled out -Relapse and remission is involved -Some people will use laxatives/fiber for IBS-C, others will use antidiarrheals for IBS-D -Most IBS has spasms and pain, so antimuscarinic drugs may be good for rapid relief Ex: Oxybutynin, Ditropan, Hyacyamine -Some antidepressants (TCAs) may be used for IBS by blocking muscarinic receptors in IBS-D  slow GI tract -SSRIs may also block 5HT to increase GI tract and movement for IBS-C -When used chronically, UroG is secreted by epithelial cells  activates Gc-C  increase secretion of chloride ***Drugs: Alosetron (Lotronex), Lubiprostone (Amitiza), Linaclotide (Linzess) 1. Alosetron (Lotronex) **Use: IBS-D *MOA: Like 5HT3 antagonist, but not antiemetic  decrease secretions and movement of GI -When used long term can cause **ADR: Ischemic colitis i. Limited distribution system 2. Lubiprostone (Amitiza) **Use: IBS-C *MOA: Activates C2Cl channel  Increase secretion of chloride and water into lumen of intestine  increase evacuation 3. Linaclotide (Linzess) **Use: IBS-C *MOA: Activates membrane-bound guanylate cyclase  increase intracellular GMP  increase PKG  activates C2Cl channel and CTFR  increase release of chloride and water into intestine -PO peptide

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Pharmacology 2, Final Exam

Jamie-Dong Viet Nguyen, ID: 0154151 Doctor of Pharmacy Candidate, MCP Class

of 2017 STOMACH ULCER PHYSIOLOGY -Sphincter separates esophagus from stomach  moves in forward direction normally a. With old age, muscles weaken and stomach contents may move backwards into esophagus  lying down may cause leaking upwards  heartburn I. Drugs that may provoke GERD, heartburn, dyspepsia: Muscle relaxants (ex: PDE-5 inhibitors) -Reducing stomach acid can treat peptic ulcer disease  imbalance between acid and mucus is present a. Imbalance causes gastric/duodenal ulcer leading to pain after eating and possible blood loss to anemia -G-CELLS release Gastrin (cholecystokinin) from dietary peptides and when stomach is stretched from food: 1. Activates gastric receptors on ECL cells to release histamine  activate H2 receptor on parietal cells  increase activity of proton pump 2. Directly activate same receptor on parietal cell  increase activity of proton pump 3. Activate PANS  increase gland secretion including stomach acids i. ACh is release onto M3 receptors on parietal cells  drives proton pump to increase acid activity and secretions -PARIETAL CELLS release acid into stomach via H+/K+ ATPase proton pump response to ingestion of food -Another receptor for PGE2 is on parietal cells in stomach  decrease activity of proton pump  decrease acid i. Can also increase release of mucus and bicarbonate -Protective effect on stomach -Regulation of production of hydrogen ions on stomach is controlled by Dcells a. When high = D cells release somatostatin and activate receptor on G cells  reduce gastrin  less histamine, less activity of pump, less acid -H.Pylori bacteria is responsible for ulcers by killing off D cells  no feedback, acid continues  ulcers become worse *Treatment: 14 days of Tetracyclines, Metronidazole, Clarithromycin, Amoxicillin ANTI-ULCER DRUGS **MAIN USE: Ulcers, GERD, peptic ulcers 1. PGE2 AGONIST ***Drugs: Misoprostol (Cytotec) *MOA: Agonize PGE2  increase release of mucus, decrease acid release  increase bicarbonate to neutralize -Q6H **ADR: Uterine contractions, diarrhea **Contraindicated: Pregnancy -Can be combined with Diclofenac (NSAID) to decrease PGE2 -Does not worsen inflammation 2. SUCRALFATE **Use: Protect stomach *MOA: Repeating units of sucrose  exposed to acid turns into viscous polymer  adhere to exposed proteins in stomach  helps heal ulceration Page 3

Pharmacology 2, Final Exam

Jamie-Dong Viet Nguyen, ID: 0154151 Doctor of Pharmacy Candidate, MCP Class

of 2017 -Does NOT get absorbed and is charged **DI: Binds to other drugs/substances (Digoxin, Levothyroxine) -Stagger dosing with other drugs! 3. H2 RECEPTOR ANTAGONIST -Anti-secretory agents by decreasing secretion of stomach acid ***Drugs: Cimetidine (Tagamet), Ranitidine (Zyrtec), Nizatidine (Axid), Famotidine (Pepcid) *MOA: SELECTIVELY Antagonizes H2 receptor  decrease binding and 70% decrease secretion of stomach acid -Not reduced completely due to other receptors (M3, Gastrin) -All are OTC **ADRs: Headaches, constipation -Tolerance development: Body responds by increase gastrin release (Hypergastrinemia) a. Increase histamine to compete for H2 with antagonist  increase dose/frequency is needed to work again b. If stop using drugs, increase histamine and gastrin will cause REBOUND ACIDITY  worse than before due to gastrin build up *Must SLOWLY taper dose 3A. Cimetidine (Tagamet) -Inhibits P450  DI a. Slow metabolism = increase toxicity b. Prodrugs = ineffective -Can antagonize androgen receptors  decrease libido/sperm 4. PPIs ***Drugs: Omeprazole (Prilosec/Zegerid), Esomeprazole (Nexium), Lansoprazole (Prevacid), Dexlansoprazole (Kapidex), Rabeprazole (Aciphex), Pantoprazole (Protonix) *MOA: Blocks proton pump -Prodrugs are in inactive form and need to be activated by acid in parietal cells  passing to intestine a. Active drug irreversibly inactivates proton pump -Acid in stomach, so must prevent the drug from being broken down in stomach vs. intestines  ENTERIC COATING or SPECIAL CAPSULES, possible administration with NaHCO3 -Oral suspension is in NaHCO3 base 1 . Omeprazole (Prilosec/Zegerid) -Most notorious for inhibiting P450  increase active drug amount and keeps prodrugs ineffective -ALL are PO **ADRs: Headache, constipation, diarrhea -Better reduction of stomach acid than H2 antagonist, BUT may be TOO effective a. Acid is needed for absorption of SOME nutrients  decrease Calcium from diet but also kills bacteria **Other ADRs: Osteoporosis, Community-acquired pneumonia (longterm use) CANCER: Dr. Khaled Elsaid

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Pharmacology 2, Final Exam

Jamie-Dong Viet Nguyen, ID: 0154151 Doctor of Pharmacy Candidate, MCP Class

of 2017 -Cancer starts with damage to DNA  permanent mutation in cell genome leading to imbalance of cell division and cell arrest pathways  activating oncogenes to cause proliferation a. Tumor suppressive genes do not work anymore i. Some cancers may be from direct activation of certain pathways A) Cytotoxic Agents/Conventional -Cell death and apoptosis initiated, very toxic, no differentiation between cells *MOA: Inhibits cell cycle a. Phase nonspecific OR phase specific (S phase = no DNA synthesis, M phase = mitotic arrest) B) Targeted -Targets the different areas in a cancer cell -More specific and differentiated a. In mutations, relay molecules mutate = no more function = imbalance b. Stimulatory pathway turned on constitutively without signals = imbalance -All leads to favor growth stimulation and loss of function of suppressor gene

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