BIOP211 Pharmacology Tutorial Session 8 Drugs Affecting the Blood, Lipid-lowering Drugs and Drugs Affecting the Gastro-intestinal Tract, GIT

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1 BIOP211 Pharmaclgy Tutrial Sessin 8 Drugs Affecting the Bld, Lipid-lwering Drugs and Drugs Affecting the Gastr-intestinal Tract, GIT Students practise the use f MIMS nline and ther Online Drug / Herb mngraphs fr activities n Drugs Affecting the Bld, Gastr-intestinal Tract, GIT and Lipidlwering drugs Drug-herb interactins research Case study Herbs and Drugs used in peptic ulcer disease PUD Handut n PUD and GORD is included belw in yur Tutrial Handut Discus the fllwing drugs/ drug classes Lipid lwering drugs: hydrxymethylglutarylca reductase inhibitrs (Statins) Lipid lwering drugs: fibrates,bile acid binding resins and Nictinic acid Warfarin and its antidte (antagnist in verdse) Prtn pump inhibitrs H2 antagnists Cytprtective agents and antacids Yur answer shuld cver the fllwing Examples and indicatins. Mechanism f actin. Efficacy and limitatins r cautins / cntra-indicatins. Adverse effects and drug interactins with nutrients and herbs. Fr warfarin use the LibGuides ebk by Veitch, Barnes, Smith, Phillipsn and Andersn (2014) t find ther cumarins. Use peer review t mark yur respnses ut f 10 marks each T assist yu with yur revisin f Pharmacdynamics and Pharmackinetics fr the final assessment, answer these questins. Feedback is available thrugh the Review Quizzes 8 and 13 (Endeavur LMS). Use Online resurces r the Appendix in yur text (Herb-, Nutrient- and Fd-Drug Interactins) t list fur (4) absrptive (r ther pharmackinetic) drug interactins that are drug-herb r drug-nutrient interactins. Use nline resurces r the Appendix in yur text (Herb-, Nutrient- and Fd-Drug Interactins) t list sme pharmacdynamics drug interactins that are drug-herb r drug-nutrient interactins. Endeavur Cllege f Natural Health c885995ba47d4cd68cac1908b0b8e7dc Last updated n 12-Jul-17 Page 1 f 11

2 8.2 Frm subject website, review diseases Peptic Ulcer Disease, PUD, GORD, in Handut n PUD & GORD, Practice using Drug Mngraphs and Herbal Medicines Mngraphs frm Medicines Cmplete (LibGuides link n Endeavur Library Website). Then reflect n the case study and answer the Quiz n Mr U belw. Answers are available in Endeavur LMS Sessin 8 Review Quiz Mr U, a 45 year ld man, is currently nt n anti-hypertensive therapy. Mr U is abut t start triple therapy with antibitics and a prtn pump inhibitr. This is t eradicate Helicbacter pylri fllwing a psitive 13 C urea breath test and endscpy, which revealed tw dudenal ulcers. He asks yu as his cmplementary health practitiner if he can use ginger t relieve pain in his gut area. What wuld yu recmmend fr Mr U? Check n Martindale (Brayfield, 2014) r Herbal sectin f Medicines Cmplete (Veitch et al, 2014) (see LibGuides link n the Endeavur Library site). Alternatively, see Cmplementary and Alternative Medicine cntent with crsswrd puzzles and chse <Case Studies> As Mr U s cmplementary health practitiner, yu warn him that ginger imprves gastr-intestinal mtility but that ginger als a) lwers bld pressure and s wuld aggravate Mr U s hypertensin b) stimulates gastric acid secretin which wuld aggravate Mr U s dudenal pain c) stimulates the grwth f nrmal flra rganisms in the bwel d) inhibits metablizing enzymes fr his antibitic As his cmplementary health practitiner, yu recmmend that Mr U try prbitics t a) decrease the adverse effects f antibitic therapy b) cunteract the antibitic induced diarrhea c) stimulate the grwth f nrmal flra rganisms in the bwel d) all f the abve What mucprtective herbs culd be recmmended fr Mr U? a) ginger and acetyl salicylic acid (ASA) frm willw bark b) marshmallw and liqurice c) peppermint il d) there are n mucprtective herbal remedies Of the herbal remedies given in the previus questin, ginger, ASA (a salicylate) frm willw bark, marshmallw, liqurice, which ne is als anti-inflammatry and antibacterial, making it a valuable herbal medicine fr peptic ulcer disease? a) Ginger b) Acetylsalicylic acid, ASA, frm willw bark c) Marshmallw d) Liqurice What further advice r management strategies wuld yu suggest fr Mr U? a) Check his bld pressure and if needed, encurage him t see a general practitiner regarding anti-hypertensive medicatin b) Check fr herb-drug interactins nce the anti-hypertensive medicatin is knwn t yu c) Get Mr U t infrm his general practitiner abut herbal medicines that he is currently taking d) All f the abve Endeavur Cllege f Natural Health c885995ba47d4cd68cac1908b0b8e7dc Last updated n 12-Jul-17 Page 2 f 11

3 8.3 Review Quiz. Use yur textbk. Feedback is available in Review Quiz 8 (Endeavur LMS) Anti-cagulant and Antiplatelet drugs Review (true / false). Use yur textbk and lecture ntes. Feedback n the subject website: 1. Ciprflxacin, metrnidazle and erythrmycin are all antibitics that increase the anticagulant effect (increased INR) f warfarin. 2. Internatinal nrmalised rati (INR) measures the verall activity f the extrinsic cagulatin pathway. 3. An antidte fr excess warfarin therapy is vitamin K. Antidte is an antagnist drug given when a substance has been taken in excess. Answers fr the fllwing are given fr discussin: 4. Ticlpidine is an antiplatelet agent. True 5. A patient n warfarin therapy shuld be mnitred by use f the activated partial thrmbplastin time (APTT) False, the internatinal nrmalized rati (INR) is used t mnitr warfarin therapy. 6. It is imprtant t keep irn tablets well away frm children because irn has almst n mechanism fr excretin frm the bdy and verdses may be fatal True, review the physilgy 7. The intake f green, leafy vegetables can result in decreased anticagulant effectiveness f warfarin: True, green leafy vegetables are a surce f an imprtant vitamin which antagnizes the effects f warfarin. 8. Fibrinlytic drugs (e.g. alteplase, reteplase and tenecteplase) disslve clts by activatin f plasmingen t plasmin and this digests r disslves fibrin clts. True, review the physilgy 9. Dipyridamle is an anti-cagulant. False, agents which target platelets are mre crrectly called anti-platelet agents. 10. Sdium bicarbnate NaHCO3 shuld be avided in peple with heart failure r hypertensin because it increases the likelihd f fluid retentin. True, review the physilgy f Na +, because it is imprtant fr yu t be able t synthesize yur knwledge abut Drugs Used t Treat Cardivascular Disrders (Sessin 13) and Drugs used t Treat Gastr-intestinal disrders (Sessin 8) and their mechanisms f drug-drug interactin Endeavur Cllege f Natural Health c885995ba47d4cd68cac1908b0b8e7dc Last updated n 12-Jul-17 Page 3 f 11

4 8.4 Handut Peptic Ulcer Disease PUD and Gastr-esphageal Disease GORD Peptic Ulcer Disease, PUD The gals f peptic ulcer disease treatment are t: Relieve ulcer pain Encurage ulcer healing Prevent ulcer recurrence Avid ulcer-related cmplicatins The treatment f PUD fcuses mainly n shrt-term drug therapy f ulcers and eradicatin f H.pylri infectin. Nn-pharmaclgical management PUD: Avidance f unnecessary NSAID and aspirin use One f the main causes f PUD Address underlying scial / lifestyle factrs that may exacerbate ulcer e.g. stress Nte that the rle f stress in PUD is cnsidered cntrversial. Psychlgical factrs appear mre significant in sme patients than thers As a grup ulcer patients have been characterized as having a tendency t repress emtins Cessatin f smking Impairs the healing rate f ulcers Decreases pancreatic bicarbnate secretin (gastric acid neutralizer) Increase in reflux f bile salts int the stmach Acceleratin f gastric emptying time int the dudenum Avid fds that may exacerbate symptms E.g. cffee, carbnated drinks, alchl, spices, chillies, sugar, allergenic fds Increase intake f fds that may prmte healing Cabbage (glutamine) Raw cabbage juice is well dcumented as an effective treatment in PUD 1 litre fresh juice/day in divided dses has resulted in ttal ulcer healing in 10 days n average Fibre (especially dudenal ulcers) Plant based dietary fibre appears t ffer better results than supplemental fibres (pectin, guar gum, psyllium) (Pizzrn et al, 2006) PUD eliminatin f Helicbacter pylri as an pprtunistic pathgen in the stmach mucsa: Helicbacter pylri (H. pylri) is a gram negative bacteria that is well adapted t living belw the layer f gastric mucsa. It is generally cnsidered t be part f the nrmal r indigenus flra that mst humans acquire in childhd and carry fr life in their stmachs. Mst patients carry H. pylri withut develping any symptms but ccasinally, hwever, a small number f H. pylri carriers (15-20%) g n t develp peptic ulcer disease. Virtually all patients with PUD (where NSAID use has been excluded) have evidence f H. pylri infectin. H. pylri has als been assciated with an increase in gastric cancer (it has been classified as a class I carcingen by the WHO) althugh a causal relatinship has nt yet been established. Endeavur Cllege f Natural Health c885995ba47d4cd68cac1908b0b8e7dc Last updated n 12-Jul-17 Page 4 f 11

5 The evidence fr the imprtant rle f H. pylri in PUD is indicated in the facts that: Over 90% f patients with dudenal ulcer and mre than 70% f patients with gastric ulcer are infected with H. pylri. The recurrence f dudenal and gastric ulcers is dramatically reduced fllwing the eradicatin f H. pylri infectin There are varius treatment prtcls available fr H.pylri eradicatin, mst f which include 2 antibitics and a prtn-pump-inhibitr ( triple therapy ). Intense drug treatment is usually prescribed fr a perid f 7 days Susceptibility f H.pylri t antibitics majr factr in success f therapy (antibitic resistance des ccur therefre, patient educatin t maintain crrect regimen fr the whle treatment perid, avids natural selectin f resistant strains) Over 90% f patients with dudenal ulcer and mre than 70% f patients with gastric ulcer are infected with H. pylri. The recurrence f dudenal and gastric ulcers is dramatically reduced fllwing the eradicatin f H. pylri infectin Relapse rate f PUD after H.pylri eradicatin (in infected individuals) 15% Relapse rate after treatment with H2antagnists and prtn pump inhibitrs (PPIs) 80% t 100% Furthermre, H. pylri eradicatin therapy may lead t a permanent cure and therefre eliminates the need fr cstly, lng-term treatment with ther anti-ulcer drugs. Gastr-esphageal Reflux Disrder (GORD) Gastric reflux (the retrgrade mvement f gastric cntents frm the stmach t the esphagus) is a nrmal physilgical event and many patients Up t 40% in Westernised sciety may experience symptms f heartburn at least nce a mnth. Gastr-esphageal reflux disease (GORD) ccurs when symptms and mucsal injury develp as a result f excessive esphageal expsure t gastric reflux. GORD is a chrnic cnditin that may have lng-term cmplicatins if left untreated and has a high rate f relapse fllwing discntinuatin f treatment. GORD is frequently self-treated with antacids and many patients with mild r spradic symptms d nt seek help frm a medical dctr. A number f patients d nt experience typical symptms f GORD (e.g. heartburn, regurgitatin) and may present with atypical symptms such as chest pain, sre thrat, harseness r pulmnary symptms. The incidence f mrtality due t GORD is lw (apprximately 1: ), hwever it can severely limit the quality f a patient s life, especially if symptms are severe and persistent. Severe cases f GORD may lead t cmplicatins such as esphageal ulceratin, bleeding, perfratin, esphageal stricture and Barrett s esphagus (replacement f nrmal epithelium with clumnar epithelium that has a high risk f becming malignant). Risk factrs: Reduced sphincter tne: Fds (e.g. chclate, fatty meals, carminative such as spearmint r peppermint) Drugs (e.g. calcium channel blckers, diazepam, thephylline) Smking Alchl Hrmnes (e.g. estrgen, prgesterne) Physilgic factrs (e.g. prstaglandin, glucagn, vasactive intestinal peptide) Reduced swallwing capacity: Neurlgical disrders (e.g. strke) Decreased saliva prductin (e.g. elderly, antichlinergics) Endeavur Cllege f Natural Health c885995ba47d4cd68cac1908b0b8e7dc Last updated n 12-Jul-17 Page 5 f 11

6 Nn-pharmaclgical Management, GORD: Aviding large meals (eat smaller meals mre frequently) Elevating the head f the bed (increase esphageal clearance) Aviding fds that may reduce LOS tne (e.g. chclate) r that have a direct irritant effect n the esphageal mucsa (e.g. citrus fds, tmates) Reducing high fat cntent in diet (lwers LOS tne and delays gastric mtility) and including mre prtein-rich meals (increases LOS tne) Weight reductin in verweight patients Cessatin f smking (reduced gastric acid and spntaneus LOS relaxatin) Reducing alchl cnsumptin Aviding drugs which may reduce LOS tne (e.g. calcium channel blckers, nitrates) r increase gastric acidity (e.g. aspirin, NSAIDs) Drug Therapies in GORD & PUD Antacids The antacids have been used fr many years in the management f PUD and are available in a variety f cmbinatins f the fllwing antacid ingredients: Aluminum hydrxide / xide (Mylanta, Gaviscn ) Calcium carbnate (Andrews Tums ) Magnesium carbnate/ hydrxide / xide / trisilicate (Mylanta, Gaviscn ) Antacids may als be cmbined with anti-flatulants (e.g. simethicne), antispasmdics (e.g. dicyclmine) r anti-regurgitants (e.g. alginic acid), hwever these frmulatins d nt cnfer any additinal efficacy in the healing f ulcers Mst tablets require chewing befre swallwing t ensure cmplete disslutin f the antacid in the stmach Mechanism f Actin - Antacids The antacids act by neutralizing r buffering hydrchlric acid thereby raising the gastric ph They are thught t have an additinal effect f prtecting the gastric epithelial cells by: increasing bicarbnate and mucus secretins inactivating pepsin binding bile salts enhancing gastric micrcirculatin The efficacy f the antacids is dependent n their acid-neutralizing capacity. Magnesium and aluminum cntaining prducts are the mst widely used antacids. Magnesium hydrxide is the mst ptent acid neutralizing cmpund and has a mre prlnged neutralizing effect than the ther antacids. Regular dsing is required which limits use f these prducts as lng term therapies, r mntherapy in many patients Adverse Effects - Antacids The mst cmmn adverse effects f the antacids are gastrintestinal and include: Diarrhea (caused by magnesium) Cnstipatin (caused by aluminum) Magnesium and aluminum are ften used tgether t minimize these side effects. Aluminium has als be assciated with an increased risk f Alzheimer s disease Drug Interactins- Antacids Can affect the absrptin (reduce r delay) and affect biavailability f sme drugs s needs t be taken at least 2 hurs befre r after (sme antibacterials e.g. tetracyclines quinlnes antibacterial; aledrnate bisphsphnate used t treat steprsis; amprenavir antiviral; digxin interact with Al 3+ & Mg 2+ treats heart failure; gluccrticids immunsuppressive; phenytin anticnvulsant Endeavur Cllege f Natural Health c885995ba47d4cd68cac1908b0b8e7dc Last updated n 12-Jul-17 Page 6 f 11

7 Can affect the binding f certain drugs e.g. sucrulfate binding t the ulcer crater cytprtectant see discussin later ) Hypglycaemic (Oral) drugs (Mg 2+ can increase the absrptin) Amphetamines, ephidrine, pseudephidrine (enhance the effect f these drugs) Histamine H 2 Receptr antagnists Cimetidine (e.g. Tagamet ) Ranitidine (e.g. Zantac ) Famtidine (e.g. Pepcidine ) Nizatidine (e.g. Nizac ) Indicatins H 2 antagnists They are indicated fr shrt-term use in the treatment f active PUD as well as fr gastresphageal reflux disease (GORD). Mechanism f Actin Histamine binds t the parietal cells and stimulates the secretin f HCl (aggressive factr) The H2-antagnists inhibit the secretin f gastric acid by blcking f the H2-receptrs n the parietal cells. Bth basal- and meal-stimulated acid secretin is reduced. Althugh the cncentratin f pepsin is nt reduced, the ttal amunt f pepsin sectin is decreased because the amunt f gastric juice is reduced with the use f the H2- antagnists. Furthermre, an increase in gastric ph leads t a reductin in the activity f pepsin. Adverse Effects - H 2-antagnists The mst cmmn adverse effects f the H2-antagnists are gastrintestinal r central nervus system-related and include: Diarrhea (uncmmn with cimetidine) Nausea Cnstipatin Headache Dizziness Skin rash (rare) Cimetidine has a incidence f adverse effects. It has a weak antiandrgenic activity and may, rarely, cause gynaecmastia r imptence. The elderly are particularly susceptible t the central nervus system effects f cimetidine that may lead t cnfusin, restlessness, lethargy r disrientatin. Therefre the use f cimetidine in the elderly shuld be avided. Prtn Pump Inhibitrs (PPI) Examples: Omeprazle (e.g. Lsec ) Lansprazle (e.g. Ztn ) Pantprazle (e.g. Smac ) Esmeprazle (e.g. Nexium ) Rabeprazle (e.g. Pariet ) Indicatins PPIs PUD, severe ersive esphagitis frm GORD, lng term treatment f hypersecretry cnditins (Zllinger Ellisn syndrme) Endeavur Cllege f Natural Health c885995ba47d4cd68cac1908b0b8e7dc Last updated n 12-Jul-17 Page 7 f 11

8 Mechanism f Actin PPIs The cell surface f the parietal cell cntains a H+/K+ ATPase pump (prtn pump) which is respnsible fr the active secretin f acid (H+) ut f the parietal cell int the gastric lumen. This is the final step in secretin f gastric acid and therefre blcking f the prtn pump may prduce ttal inhibitin f gastric acid secretin. The prtn pump inhibitrs (PPIs) act by inhibiting the enzyme H+/K+ - ATPase (the prtn pump) at the secretry surface f the gastric parietal cells The PPIs frm a nn-cmpetitive and irreversible bnd with the enzyme which prduces a prfund reductin in gastric acid utput that lasts fr several days after discntinuatin f the drug. By reducing gastric acid secretin, the PPIs decrease the irritant and ersive quality f the refluxate, thereby minimising esphageal damage and thus this drug class is highly indicated fr GORD, as well as fr PUD The PPIs are cmmnly used as part f the treatment regimen fr H.pylri eradicatin therapy as they have been shwn t suppress H. pylri infectin. In additin, treatment with PPIs ver a 4-week perid prduces rapid relief f symptms and healing f esphagitis in patients with GORD, hwever relapse ccurs frequently and therefre prlnged therapy may be required in patients t maintain remissin. Efficacy f PPIs They are mre effective than the H2-antagnists in treating peptic ulcers, althugh this is mre apparent in dudenal ulcers. In additin t greater efficacy, the PPIs als prvide a mre rapid reslutin f symptms (e.g. within 2-4 weeks) than the H2-antagnists (8-12 weeks). The PPIs are generally effective in patients wh are prly respnsive t H2-antagnist therapy. The healing rates f the PPIs are impaired by smking and cntinued use f NSAIDs. Adverse Effects PPIs The mst cmmn side effects f the PPIs include: Diarrhea Headache Nausea, vmiting, flatulence Abdminal pain Sustained reductin in hydrchlric acid prductin (hyp- r achlrhydria) causes a prprtinal increase in release f gastrin (hypergastrinaemia) int the circulatin. The prlnged use f PPIs in rats has shwn an increased risk in gastric carcinid tumurs due t hypergastrinaemia, hwever extensive and widespread use in humans has failed t prvide evidence t supprt this. The use f PPIs in PUD is generally nt recmmended fr perids exceeding 8-12 weeks. Cytprtective agents prstaglandin analgues Example Misprstl (Cyttec ) Prstaglandin is ne f the defensive factrs and plays an imprtant rle in prtecting the gastric mucsa frm injury. Misprstl is a synthetic prstaglandin E1 cytprtective agent. Indicatins Prstaglandin analgues Treatment f peptic ulcers and the preventin f gastric ulcers assciated with NSAID use Mechanism f Actin Prstaglandin analgues At lw dses misprstl has a cytprtective effect by increasing bicarbnate and mucus prductin, stimulating gastric mucsal bld flw and strengthening the mucsal barrier against H + diffusin. At higher dses misprstl has an antisecretry effect and acts by blcking histamine, pentagastrin and meal-stimulated gastric acid utput. Endeavur Cllege f Natural Health c885995ba47d4cd68cac1908b0b8e7dc Last updated n 12-Jul-17 Page 8 f 11

9 Adverse Effects Prstaglandin analgues Misprstl is assciated with a incidence f adverse effects cmpared t the ther antiulcer drugs Diarrhea, cnstipatin, abdminal pain, nausea, fatigue, dyspepsia, headache Abrtifactant with a stimulant effect n uterine tne and can cause uterine bleeding and miscarriage in pregnant wmen, therefre its use is restricted in wmen f childbearing age. Teratgenic in large dses Warnings & Cntraindicatins Prstaglandin - analgues Can cause hyptensin in peple with cerebrvascular and crnary artery disease Cytprtecitve agents Sucralfate (sucrse with sulphur and Al(OH) 3 Example Sucralfate (Carafate ) Indicatins Shrt-term (up t 8 weeks) peptic ulcer treatment and fr the preventin f stress-induced ulcers Mechanism f Actin In the presence f acid, frms a gel that frms a prtective, acid resistant barrier in the ulcer which hastens healing Stimulates prductin f mucus and prtective prstaglandins Adverse Effects Cnstipatin, nausea, vmiting, dry muth, dizziness, back pain, rash Drug Interactins Antacids (reduce effectiveness), sme antibitics digxin, thephylline, phenytin (decreased absrptin and biavailability f these drugs take 2 hurs befre sucralfate Drugs used t treat nausea Antispasmdic - antimuscarinics Example: Hyscine (Buscpan, Kwells ) Indicatins Travel sickness, gastr-intestinal spasm Mechanism f Actin Antichlinergic spasmlytic (cmpetitive antagnist f actins f acetylchline) at muscarinic receptrs Adverse effects (antichlinergic) Dry muth, thirst, blurred visin, cnstipatin, urinary retentin, tachycardia, restlessness and irritability Dpamine receptr D2 antagnist Prchlrperazine Indicatins Endeavur Cllege f Natural Health c885995ba47d4cd68cac1908b0b8e7dc Last updated n 12-Jul-17 Page 9 f 11

10 Fr nausea and vmiting due t causes such as migraine, vertig and Meniere s disease. Nt indicated fr nausea assciated with travel sickness, nr chemtherapy Mechanism f Actin Phenthiazine derivative that has an inhibitry actin n the chemreceptive Trigger Zne, CTZ and vmiting centre Act as D2-receptr antagnists Adverse effects Cnstipatin, dry muth, sleepiness, dizziness, blurred visin, extrapyramidal effects (Parkinsn s in the elderly and dystnia in yunger peple) Dystnia is a neurlgical mvement disrder, in which sustained muscle cntractins cause twisting and repetitive mvements r abnrmal pstures. The disrder may be hereditary r caused by ther factrs such as birth-related r ther physical trauma, infectin, pisning (e.g., lead pisning) r reactin t pharmaceutical drugs, particularly neurleptics (antipsychtics). Treatment is difficult and has been limited t minimizing the symptms f the disrder, since there is n cure available. Drug causes phtsensitivity reactins Warnings & Cntraindicatins CNS depressin D 2 antagnist als prkinetic - Metclpramide Indicatins Gastr-esphageal reflux disease (GORD) Diabetic gastrparesis (stmach paralysis) Preventin f nausea and vmiting secndary t cancer drug therapy Mechanism f actin Central and peripheral actins in preventing r relieving nausea and vmiting Centrally, blcks dpamine (D2) receptrs in the chemreceptr trigger zne (CTZ) Peripherally, increases gastric emptying time, reduces reflux frm dudenum and stmach int the esphagus, enhances mtility f upper GIT Drug Interactins Additive CNS depressant effect with ther CNS depressant drugs (avid cmbinatin) Adverse Effects Drwsiness / sedatin / fatigue,dizziness, headache, extrapyramidal symptms (e.g. acute dystnia, tardive dyskinesia), hyptensin, tachycardia Warnings & Cntraindicatins Avid use in peple with phaechrmcytma Use with cautin in peple with Parkinsn s, depressin Use with cautin severe renal impairment Endeavur Cllege f Natural Health c885995ba47d4cd68cac1908b0b8e7dc Last updated n 12-Jul-17 Page 10 f 11

11 Sertnin antagnists at 5-HT3 receptr the setrns Example Indicatins Ondansetrn Preventin f nausea and vmiting assciated with the use f cyttxic agents and raditherapy Mechanism f Actin Sertnin antagnists selective fr 5-HT3 receptrs fund n afferent fibres f vagus nerve in GIT tract and brainstem 5-HT released in respnse t administratin f antineplastic agents cannt bind t the receptrs Adverse effects Transient headache, diarrhea, cnstipatin Warnings & Cntraindicatins Used with cautin in patients with impaired liver functin References Brayfield A (ed), Martindale: The cmplete drug reference. [nline] Pharmaceutical Press, Lndn < (accessed in LibGuides) Veitch, N., Smith, M., Barnes, J., Andersn, L. and Phillipsn, D. 2014, Herbal medicines, [nline] 4 th editin, Pharmaceutical Press, accessed 22 Octber Additinal Resurces If yu find ther educatinally-useful vides, add them t the Lp / Frums Visit re hyperchlesterlaemia and treatment. myvirtualmedicalcentre, 2014, Crnary heart disease, My Virtual Medical Centre viewed 7 th July 2016, myvirtualmedicalcentre, 2010, Acid reflux: gastr-esphageal reflux disease, GORD, My Virtual Medical Centre, viewed 7 th July 2016, myvirtualmedicalcentre, 2006, Diarrhea, My Virtual Medical Centre, viewed 7 th July 2016, Better Health Channel, 2013, Diarrhea, Victrian Gvernment, viewed 7 th July 2016, myvirtualmedicalcentre, 2010, Peptic ulcer disease, My Virtual Medical Centre, viewed 7 th July 2016, Endeavur Cllege f Natural Health c885995ba47d4cd68cac1908b0b8e7dc Last updated n 12-Jul-17 Page 11 f 11