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New Medications Presentation

New Medications Presentation. Jayne S. Reuben, PhD jreuben@bcd.tamhsc.edu 2008 National Primary Oral Health Care Conference November 13, 2008. Objectives. After review of this material, the dental professional should be able to:

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New Medications Presentation

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  1. New Medications Presentation Jayne S. Reuben, PhD jreuben@bcd.tamhsc.edu 2008 National Primary Oral Health Care Conference November 13, 2008

  2. Objectives After review of this material, the dental professional should be able to: • Recognize the clinical indications of recent drugs approved by the FDA • Explain the mechanism of actions of the drugs discussed in this presentation • Identify their clinically relevant adverse reactions and drug interactions

  3. Outline • Diabetes • CNS • Cancer • Pulmonary/CVS • HIV-1 Infection • Misc

  4. New Medications-Diabetes DPP4 (Dipeptidyl Peptidase IV ) inhibitors sitagliptin phosphate* (JANUVIA) vildagliptin (not approved) sitagliptin and metformin*(JANUMET) Incretin mimetics exenatide* (BYETTA) Antihyperglycemic analogues pramlintide acetate* (SYMLIN)

  5. Incretin Hormones GLP-1:glucagon-like peptide-1 GIP: glucose-dependent insulinotropic polypeptide (aka gastic inhibitory peptide) Both promote -cell proliferation in pancreas, inhibit apoptosis GLP-1 also stimulates insulin secretion, inhibits gastric emptying, inhibits glucagon secretion, promotes satiety Release is stimulated by nutrient ingestion and degraded by dipeptidyl peptidase-4 (DPP-4).

  6. GLP-1 and GIP Cell Metabolism, Volume 3, Issue 3, 2007

  7. Effects of GLP-1 Cell Metabolism, Volume 3, Issue 3, 2007

  8. Effects of GLP-1 Cell Metabolism, Volume 3, Issue 3, Pages 153-165

  9. DPP4 (Dipeptidyl peptidase IV ) inhibitors Drugs: sitagliptin phosphate*(JANUVIA), po vildagliptin sitagliptin and metformin*(JANUMET) MOA: inhibiting the inactivation of incretin hormones- GLP-1 and GIP Indication: adjunct to treat type 2 diabetes Adverse : URI, headache runny nose, sore throat CI: type I diabetes, renal dz gastroparesis,hypersensitivity diabetic ketoacidosis, caution in pregnancy

  10. Incretin Mimetic exenatide* (BYETTA), sc pen Synthetic GLP-1 receptor agonist MOA: Binding results in  glucose- dependent insulin synthesis and secretion,  glucagon secretion,  gastric emptying and  food intake Used for type 2 diabetes alone or with other meds (not insulin) Adverse: N&V, diarrhea, hypoglycemia, antibodies CI: hypersensitivity, type 1 or diabetic ketoacidosis severe renal impairment

  11. Antihyperglycemic Analog pramlintide acetate* (SYMLIN), sc Synthetic analog of human amylin-secreted by  cells to control postprandial [glucose] MOA:  glucagon,  gastric emptying, satiety Indication: adjunct with insulin for type 1 and 2 (with sulfonylureas & metformin in type 2) Adverse: severe hypoglycemia, N&V, diarrhea CI: hypersensitivity, gastroparesis, hypoglycemic unawareness DI: anticholinergics, -glucosidase inhibitors, oral agents

  12. Dental Implications • DI: Propoxyphene, NSAIDs enhance hypoglycemia • Also, -blockers and ACE inhibitors • Morning appointments to minimize stress-related hypoglycemia • Keep glucose on hand -if hypoglycemia becomes severe, pt may become unconscious.

  13. CNS Parkinson’s: Rotigotine (NEUPRO)- RECALLED Rasagiline (AZILECT) ADHD: LisdexamfetamineDimesylate (VYVANSE) Epilepsy: Levetiracetam(KEPPRA) Oxcarbazepine (TRILEPTAL) Schizophrenia: Paliperidone(INVEGA)

  14. Replacing the synthesis of dopamine - L-Dopa Combination Pills: L-dopa + carbidopa (SINEMET) Inhibiting the catabolism of dopamine – selegiline (ELDERPRYL) rasagiline (AZILECT) entacapone (COMTAN) tolcapone (TASMAR) Parkinson’s Disease: Agents that Increase Dopamine functions SE: Orthostatic Hypotention

  15. Parkinson’s Disease: Agents that Increase Dopamine functions Stimulating the dopamine receptor sites directly – bromocriptine (PARLODEL) pramipexole (MIRAPEX) ropinrole (REQUIP, REQUIP XL rotigotine (NEUPRO)-RECALLED Blocks uptake and enhances dopamine release– amantadine (SYMMETREL) Stimulating the release of dopamine - amphetamine

  16. Rotigotine (NEUPRO) • Transdermal Patch system for early-stage parkinson’s • Common side effects: N&V, dizziness, allergy sleep, disturbances, headache • Serious Adverse effects: falling asleep, low BP, fainting, hallucinations, compulsive behavior RECALLED on May 1, 2008

  17. Agents that decrease Acetylcholine function Blocking Acetylcholine receptors: Atropine benztropine (COGENTIN) biperiden (AKINETON) procyclidine (KEMADRIN) Inhibit Acetylcholine production: trihexyphenidyl (formally ARTANE) Side effects from blocking Acetylcholine: Dry mouth, Urinary retention, Blurred vision, Constipation

  18. Lisdexamfetamine Dimesylate (VYVANSE) • 1st prodrug ADHD but not for long term use (>4 wk) • High potential for abuse • Some dry mouth • growth suppression, pyrexia sudden death, stroke, MI, • The effects of tricyclic antidepressants, meperidine, phenobarbital and phenytoin may be potentiated by amphetamines. • CI: hypertension, hyperthyroidism, glaucoma history of drug abuse, MAOIs w/in 14d

  19. Typical: block DA Haloperidol (HALDOL) Loxapine (LOXITANE) Molindone (MOBAN) Atypical- block DA & 5-HT clozapine (CLOZARIL, FASACLO ODT) olanzepine (ZYPREXA) quetiapine (SEROQUEL) aripirazole (ABILIFY) respiridone (RESPERDAL) paliperidone (INVEGA)* ziprasidone (GEODON) Antipychotics/Schizophrenia Newer Atypicals block DA and 5-HT receptors.

  20. Typical Extrapyramidal effects Hyperprolactinemia Sedation Orthostatic hypotension Neuroleptic Malignant syndrome Moderate Weight Gain Dry Mouth Atypical Extrapyramidal effects Diabetes Mellitus Hyperprolactinemia Orthostatic hypotension Hypercholesterolemia Sedation  Weight Gain Seizures Prolonged QT, Vent Arrhythmias Agranulocytosis Dry Mouth TYPICAL vs ATYPICAL

  21. Paliperidone(INVEGA) • New Atypical for Schizophrenia but NOT approved for dementia-related psychosis • Metabolite of resperidone • Hypersensitivity reactions, including anaphylactic reactions and angioedema, have been observed in patients treated with risperidone and paliperidone. • Minimal anti-cholinergic effects

  22. Mechanisms of AEDs Phenobarbital Benzodiazepine Valproic acid Gabapentin? Phenytoin Carbamazepine Valproic acid Ethosuximide Valproic acid

  23. The Players- AEDs Old School phenobarbital (1912) phenytoin (1938) carbamazepine (1952) ethosuximide (1958) valproic acid (1963) benzodiazepines (1965) Newbies felbamate (1993) gabapentin (1994) lamotrigine (1994) tiagabine (1997) topiramate (1998) levetiracetam (1999) zonisamide (2000) oxcarbazepine (2003) vigabitrin (not approved)

  24. levetiracetam (KEPPRA) Inhibits synchronous neuronal firing by an unknown mechanism T1/2 6-8, clinical effect longer  bid Approved add-on but increasingly 1st line for CPS, GTC Psychiatric (may be alleviated with B6), sedation, ataxia Renally cleared, no hepatic metabolism No known drug interactions

  25. oxcarbazepine (TRILEPTAL) Blocks Na channels T1/2 10, bid 1st line or add-on for CPS Fewer side-effects than CBZ since no epoxide metabolite Hyponatremia, rash, ataxia, sedation Induces UGT, CYP3A4. Inhibits 2C19. Some drug interactions, esp decr OCPs aprepitant, aripiprazole, barbiturates, bortezomib, bosentan, buprenorphine, BZDs, all, CCBs, dihydropyridines, contraceptives, oral, contraceptives, other, disopyramide, docetaxel, efavirenz, eplerenone, ethanol, gefitinib, itraconazole, ketoconazole, lamotrigine, paclitaxel, phenytoins, repaglinide, risperidone, sildenafil, sodium oxybate, tadalafil, tricyclic antidepressants, verapamil, voriconazole

  26. Cancer • Granisetron Transdermal System (SANCUSO) similar to Ondansetron (ZOFRAN) (5-HT3) receptor antagonist – N & V • Nilotinib HCl Monohydrate (TASIGNA): CML Bcr-Abl kinase inhibitor see also imatinib (GLEEVEC)

  27. Cancer Temsirolimus (TORISEL): adv renal cell sim sirolimus (RAPAMUNE) tacrolimus (PROGRAF)

  28. Metastatic/advanced breastCancer • Lapatinib Ditosylate (TYKERB):adv breast MOA: EGFR tyrosine kinase inhibitor SE:stomatitis Admin w/ capecitabine (XELODA) • Ixabepilone (IXEMPRA) MOA: microtubule inhibitor SE: sensory neuropathies, stomatitis, mucositis

  29. Cancer Biologics

  30. Pulmonary/CVS • Aliskiren (TEKTURNA)-hypertension MOA:renin inhibitor SE: • Nebivolol (BYSTOLIC) – hypertension MOA: 1-selective antagonist SE: • Ambrisentan (LETAIRIS)- PAH MOA: endothelin receptor antagonist SE:

  31. HIV-1 Infection • Maraviroc (SELZENTRY) MOA: CCR5 antagonist SE: Hepatoxicity, URI, Pyrexia CCR5-tropic HIV-1 detectable, drug- resistant • Raltegravir Potassium (ISENTRESS) MOA: HIV-1 integrase strand transfer inhibitor (HIV-1 INSTI)

  32. Miscellaneous • Doripenem (DORIBAX): Intra-ab and UTIs • Methoxypolyethylene glycol-epoetin eta (MIRCERA) • Patients w/ chronic renal failure

  33. Drug Classes which may cause Xerostomia http://www.pharmacytimes.com/issues/articles/2007-11_002.asp

  34. References • Pharmacy Times http://www.pharmacytimes.com • Drugs@FDA http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm • Mosby’s Dental Drug Reference 2008 • NIH Institute websites www.nih.gov

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