Medication Effects on Function

1. Medication Effects on Function Kathleen R. Bell, MD June 28, 2010

2. Outline General principles of medication use Medications that directly affect the CNS Medications that treat pain Medications that treat cardiovascular disease Medication potpourri Herbs and potions Human performance can be assisted with the use of medications such as steroids for strength and speed, various hormones for growth or enhanced oxygen utilization. In the same way, human performance can be detrimentally affected in an unintentional way through the use of medications used to treat medical conditions. For those of you familiar with the PDR or other drug references, you are award that the lists of adverse reactions are legion even for the simplest drug. And, of course, there are the drugs we don�t even acknowledge as suck, including caffeine and alcohol.Human performance can be assisted with the use of medications such as steroids for strength and speed, various hormones for growth or enhanced oxygen utilization. In the same way, human performance can be detrimentally affected in an unintentional way through the use of medications used to treat medical conditions. For those of you familiar with the PDR or other drug references, you are award that the lists of adverse reactions are legion even for the simplest drug. And, of course, there are the drugs we don�t even acknowledge as suck, including caffeine and alcohol.

3. Effects and �Side� Effect Every medication has desired effects, adverse effects and �other� effects Balance Effects Costs Expected results Unexpected results

4. Danger Points in Medication Prescription Starting and stopping new medications Individual response Pharmacogenetics Drug interaction Effective dose level

5. Pharmacogenetics For instance, neuroleptic medication that are used to treat psychosis Dopaminergic drugs Multiple dopamine receptors For D3 receptor Ser9 allele is associated with + response to typical antipsychotics Gly9 allele is associated with + response to atypical antipsychotics

6. Polypharmacy KISS (KEEP IT SIMPLE, STUPID) AVOID MEDICATIONS IF POSSIBLE DISCONTINUE UNNECESSARY DRUGS

8. Overall, 44 percent of all Americans, including children, were taking at least one prescription drug in 1999-2000, a statistically significant 5 percent increase since 1994. The proportion taking three or more prescription drugs increased from 12 to 17 percent during that same time� Washington Post December 3, 2004

9. Any given week, 81% adults take at least 1 drug; 27% take five Elderly: 12% of the population and 32% of prescriptions Average for >65: 2-6 prescription drugs and 1-3 OTC drugs

12. KISS and Medication prescription PICK THE LEAST OFFENSIVE DRUG SINGLE CASE STUDY (A-B-B�-A) REMEMBER THE GOAL OF STARTING THE DRUG IN THE FIRST PLACE

13. Case 1 A 42 year old woman with chronic neck and shoulder pain is referred for a physical therapy program. She has been given the diagnosis of fibromyalgia and is being treated for depression. Her medications include citalopram 40 mg daily and nortriptyline 50 mg at bedtime.

14. Antidepressants Used to treat depression, anxiety, sleep disorders, pain, emotional lability, nocturnal enuresis, hypersalivation, impaired cognition Why so many indications? Insurance coverage, direct marketing, new drug availability, clinical guidelines, aging population, we don�t really know how the CNS works

15. Tricyclic Antidepressants Gold standard for antidepressants Block the reuptake of serotonin or noradrenaline at the presynaptic neuron quick action �Down regulates� the receptors slow action

16. Tricyclic Antidepressants Wide range of dosing Slow onset of antidepressant actions Possibly faster onset of other actions Long half-life (amitriptyline � average of 15 hours)

17. Side effects Peripheral anticholinergic dry mouth constipation urinary hesitancy ocular changes (blurred vision and glaucoma) Central anticholinergic memory loss delirium (patients with brain damage or the elderly)

18. Side effects Histamine blockade results in drowsiness Cardiac arrhythmias Weight gain ?- adrenergic blockade results in orthostatic hypotension amitriptyline> imipramine= doxepin> nortriptyline =desipramine

19. Selective Serotonin Reuptake Inhibitors (SSRIs) Prozac (fluoxetine), Zoloft (sertraline), Paxil (paroxetine), Celexa (citalopram), Lexapro (escitalopram) Fluoxetine has longest half life (2-3 days) Thought to have fewer side effects of the TCAs and less lethal in overdose BUT...

20. SSRI Side Effects Headache, insomnia, drowsiness, anxiety, nervousness, tremor Nausea, diarrhea, anorexia, dyspepsia Rash Sexual dysfunction including impotence OD: agitation, restlessness, nausea, vomiting, seizures, hypomania Withdrawal symptoms Remember, that some of these �side effects� can be desired effects when used in the right situation. For instance, later we will meet up with Prozac (fluoxetine) again when we are discussing neurostimulants because it is not uncommonly used to activate those with motor retardation or slowed processing with depression or due to other CNS conditions.Remember, that some of these �side effects� can be desired effects when used in the right situation. For instance, later we will meet up with Prozac (fluoxetine) again when we are discussing neurostimulants because it is not uncommonly used to activate those with motor retardation or slowed processing with depression or due to other CNS conditions.

21. Other antidepressants SNRIs (Serotonin-Norepinephrine) Venlafaxine (Effexor) Cymbalta (duloxetine) � diabetic neuropathy Trazadone (Desyrel) - sleep Buproprion (Wellbutrin) � smoking cessation Mirtazapine (Remeron)

22. Case 2 A 23 year old man sustained a left frontotemporal contusion with hemorrhage in a MVA and has cognitive deficits, mild right hemiparesis and has a cranial defect. His medications include phenytoin 400 mg at night, trazadone 50 mg at night, and pain medications as needed

23. Antiepileptic drugs Used for prophylaxis against and treatment for seizures, pain, behavioral dyscontrol syndromes, psychosis, depression, mania, headache

24. Seizure lifetime prevalence between 2-5% Control of seizure disorders Prevention of seizures in TBI � first week after injury Longer for significant intracranial bleeding Brain tumor seizure prophylaxis

25. AED categories Phenytoin (Dilantin) cognitive dysfunction sedation ataxia gingival hyperplasia DRUG Interactions Drug levels Carbamazepine (Tegretol) dizziness lightheadedness diplopia ataxia nausea/vomiting SIADH (hyponatremia) SIADH (Syndrome of Innapropriate Antidiuretic Hormone) results in salt wasting and hyponatremia which can be manifest by confusion, imbalance, nausea/vomiting, seizureSIADH (Syndrome of Innapropriate Antidiuretic Hormone) results in salt wasting and hyponatremia which can be manifest by confusion, imbalance, nausea/vomiting, seizure

26. AED Categories Phenobarbital drowsiness/sedation memory impairment, perceptual motor deficits vertigo ataxia primidone (Mysoline) Benzodiazepines (Valium, Ativan, Clonazepam Acute treatment sedation/lethargy impaired coordination, dependence or abuse

27. AED Categories Valproate (Depakote) cognitive dysfunction, nausea, asthenia, somnolence, dyspepsia, dizziness Bipolar disorder or episodic dyscontrol syndromes in TBI Migraine

28. AED Categories GABA Derivatives Gabapentin (Neurontin) somnolence dizziness ataxia nystagmus headache tremor, fatigue PAIN Lamotrigine (Lamictal) Felbamate (Felbatol)** Topiramate (Topamax) Levetiracetam (Keppra) irritability Gabitril (tiagabine) Lyrica (pregabalin) Zonisamide Lamotrigine - life-threatening rashes in 1:1000 adults dizziness, headache, diplopia, ataia, nausea, amblyopia, somnolence, vomiting Felbamate � rash or aplastic anemiaLamotrigine - life-threatening rashes in 1:1000 adults dizziness, headache, diplopia, ataia, nausea, amblyopia, somnolence, vomiting Felbamate � rash or aplastic anemia

29. Case 3 A 52 year old who is perimenopausal is experiencing anxiety attacks during the day with tachycardia and tingling feelings. She has just started to take lorazepam 1 mg daily as needed.

30. Sedative/Hypnotics Decrease the level of consciousness barbiturates benzodiazepines chloral hydrate Antidepressants zolpidem (Ambien), eszopiclone (Lunesta), zaleplon (Sonata), ramelteon (Rozerem)

31. Anxiolytics Benzodiazepines (Ativan, Valium, Clonazepam) buspirone (Buspar) sertraline (Zoloft) Paroxetine (Paxil) beta blockers (propranolol) Propranolol - performance anxiety, long term use may result in depressionPropranolol - performance anxiety, long term use may result in depression

32. Neuroleptics Used to treat psychosis (schizophrenia, psychotic depression), severe agitation after brain trauma, sundowning in the elderly*, acute delirium delusions and hallucinations Black box label: increased risk of death although low for individual person

33. Phenothiazines -Chlorpromazine (Thorazine) Butyrophenones - Haloperidol (Haldol) Thiothanxenes - Thiothixene (Navane) Heterocyclic compounds - molindone (Moban), loxapine (Loxapac) Atypicals - clozapine (Clozaril), risperidone (Risperidol, olanzapine (Zyprexa), quetiapine (Seroquel)

34. Adverse Effects Extrapyramidal symptoms (stiffness and limb rigidity, loss of facial expression, slow movement) Sedation Tardive dyskinesia Neuroleptic malignant syndrome (muscle rigidity, fever, autonomic instability, delirium) Cognitive slowing Metabolic syndrome (hyperglycemia, hypertension, central obesity, lower HDLs, higher triglycerides)

35. Neurostimulants/Cognitive Agents The Road to El Dorado - the search for nootropics (drugs that improve conscious thought) Still searching

36. Neurostimulants Dextroamphetamine (Dexedrine, Adderall), methylphenidate (Ritalin, Concerta), pemoline (Cylert), phentermine Cocaine Modafinil (Provigil) Amantadine Caffeine (Prozac, Paxil, Serzone, Effexor) (zolpidem)

37. Neurostimulants - How and Why? ADHD Depression Narcolepsy Impaired attention TBI, stroke, other brain disorders Use very carefully - abuse potential, seizures, cardiac side effects

38. Cognitive Enhancers Tacrine Donepezil (Aricept) Piracetam Memantine (Namenda) Rivastigamine Very modest effects with improved short-term memory and spatial function

39. Antispasticity Drugs Generalized approach Non-pharmacological means Patient�s specific needs Reevaluate after one week and establish titration schedule Either achieve therapeutic goal, reach maximum dose or intolerable adverse events Check reality Add second agent Consider other methods

40. Baclofen (Lioresal) inhibiting both monosynaptic and polysynaptic reflexes at the spinal level Tizanidine (Zanaflex) � hypotension Supraspinal and spinal level action Benzodiazepines (Valium) Dantrolene (Dantrium) - liver toxicity Inhibits release of Ca from sarcoplasmic reticulum Sedation Others: clonidine, cannabis, neurontin

41. �Muscle Relaxants� Cyclobenzaprine (Flexeril) Carisprodol (Soma) Methocarbamol (Robaxin) Metaxalone (Skelaxin) Use acutely, sparingly, ONLY in conjunction with physical modalities and exercise

42. Intrathecal agents and Injections Why and how? Poor tolerance of oral medications Poor response to oral medications localized spasticity problem (injections) generalized spasticity problem (intrathecal) Intrathecal baclofen (opioids, bupivicaine) Intramuscular botulinum toxin Inhibits release of acetylcholine Perineural injections of phenol or alcohol

43. Multiple sclerosis agents Burgeoning field with multiple new agents within the last First - symptom management Second - disease modifying drugs Interferon (Betaseron, Avonex), Glatiramer acetate (Copaxone), Corticosteroids Third � Novantrone (mitoxantrone) Fourth � natalizumab (Tysabri) - 2009

44. Medication to treat pain Acute pain management Narcotic, non-narcotics Chronic pain management Non-narcotics usually Acetaminophen #1 drug used in U.S. Issues: level of pain, quality of pain, duration of pain, associated disorders, tolerance, addiction, rebound

45. Headache Occasional tension headache - acetaminophen, aspirin, ibuprofen Migraine headache - episodic treatment, prophylactic treatment Chronic headache - avoid narcotics and typical analgesics because of rebound - antidepressant , beta blockers, AEDs

46. Why not medicate forever? Narcotics - tolerance, (addiction), constipation (Exc: cancer) Abuse, drug diversion, death (see next slide) Acetaminophen - liver toxicity NSAIDs - GI bleeding, renal failure, CNS effects (indocin, aspirin), cardiovascular effects (Exception: RA)

48. Cardiovascular medications Antihypertensives always with lifestyle modifications (weight reduction, sodium restriction, moderate ETOH consumption, increased physical activity, smoking cessation) Consider: severity of HTN, target organ disease, risk factors, associated conditions

49. Diuretics - mild hypertension or adjunct (HCTZ, furosemide, spironolactone) affect glucose metabolism, potassium Beta blockers - protective against MI and death by MI (propranolol, met�) cardiac effects, glucose, lipids, bronchospasm, quality of life (depression, fatigue, impotence) Calcium channel blockers (nifedipine) ACE inhibitors (benazepril) A2RBs (angiotensin 2 receptor blockers)(losartan)

50. Exercise and antihypertensives Thiazide diuretics (HCTZ) - fatigue, post-exertional worsening of dehydration, muscle cramping Nonselective beta-blockers - ? COP, VO2 max, maximal heart rate, exercise duration

51. Immunosuppressants Azathioprine (Imuran) - myalgias Cyclosporine - tremor, leg cramps Tacrolimus (FK506) - neurotoxicity daclizumab (Zenapax) - dizziness

52. Herbs and Alternative Drugs Explore with patient the use of alternative therapies including medicinals IF the patient can identify the product, review it with the pharmacy or on the databases available

53. Ask the patient to bring in the bottle if they don�t know what they are taking Discuss with other prescribing professional Concerns: adverse effects of herbs, interactions with prescribed medication such as anticoagulants Encourage �scientific� approach to trying herbal medications

54. Most commonly used herbals Lutein Lycopene Glucosamine Garlic Chondroitin Gingko biloba Co-enzyme Q Saw palmetto Flaxseed oil Thea sinensis

55. Gingko biloba Bleeding St. John�s Wort Gastrointestinal disturbances, allergic reactions, fatigue, dizziness, confusion, dry mouth, photosensitivity Ephedra (ma huang) Hypertension, insomnia, arrhythmia, nervousness, tremor, headache, seizure, cerebrovascular event, myocardial infarction, kidney stones Kava Sedation, oral and lingual dyskinesia, torticollis, oculogyric crisis, exacerbation of Parkinson's disease, painful twisting movements of the trunk, rash

56. Ginkgo biloba Aspirin, warfarin (Coumadin), ticlopidine (Ticlid), clopidogrel (Plavix), dipyridamole (Persantine) St. John's wort Antidepressants Ephedra Caffeine, decongestants, stimulants Ginseng Warfarin Kava Sedatives, sleeping pills, antipsychotics, alcohol, antiepilepticdrugs