Integrated Case

1. Integrated Case November 28, 2002

2. Drug-Related Problems for Mrs. Smith • Mrs. Smith is continuing to experience signs and Sx of Parkinson’s disease for which she may be receiving too low a dose of Sinemet and/or require additional therapy • Mrs. Smith is at risk of developing another episode of TIA and/or stroke for which she requires drug therapy • Mrs. Smith is experiencing Sx of short-term insomnia for which she may benefit from therapy • Depression?

3. Parkinson’s disease How does it present? • Four classical feature: • 1. Tremor • 2. Rigidity • 3. Bradykinesia • 4. Postural disturbances • Other Sx… Mrs. Smith’s disease progression: Mrs. Smith’s RFs:

4. Parkinson’s Disease Mrs. Smith’s disease progression: • started with unilateral hand tremor and progressed to both hands • decreased motor activity or bradykinesia seen as • difficulty initiating physical activities such as walking, • difficulty buttoning her clothes, and • picking up objects • likely has masked facies and a slow gait Mrs. Smith’s RFs: • age, rural area??

5. Parkinson’s disease Is Tx needed? Tx Options: Levodopa + Carbidopa/benserazide Selegiline (Deprenyl) Anticholinergic medications Amantadine (Symmetrel) Dopamine agonists COMT inhibitor -Tolcapone (Tasmar) ; Entacapone (Comtan)

6. Mrs. Smith’s management • She is presently on Sinemet 100/25 tid • Options for management:

7. At risk for TIA and/or stroke • What is TIA? • RIND: reversible ischemic neurological deficit • What is stroke? • Thrombus vs. embolus

8. TIA / Stroke General Risk Factors HTN, prior TIA/stroke, age, male, smoking, etc. (consider cardiac RF) Mrs. Smith’s RF Is Tx needed?

9. TIA / Stroke Tx options - Prophylaxis • ASA • Ticlopidine • Clopidogrel • Warfarin • Dipyridamole • Sulfinpyrazone • tPA – for acute ischemic stroke (within 3 hours)

10. TIA / Stroke - Aspirin efficacy and place in therapy: • Dutch TIA (30mg vs. 300mg ASA), UKTIA (300mg vs. 1200mg ASA): effective in secondary prophylaxis at lower doses • Decreases RR by 24% in secondary Px • Dose tried: 30mg daily – 600 mg bid • Side effects: GI upset, PUD • Convenience: daily • cost: cheap

11. TIA/Stroke • What would be an appropriate agent for Mrs. Smith and why?

12. Mrs. Smith’s sleep problem • What is insomnia? • Types of insomnia

13. Mrs. Smith’s sleep problem • Drug-induced causes: • Reason for Mrs. Smith’s insomnia • Is Tx needed?

14. Mrs. Smith’s sleep problem • Tx Options: • Non-pharmacological options • benzodiazepines • antihistamines • Zopiclone • zaleplon • chloral hydrate • barbiturates

15. Non-pharmacological Strategies • Good Sleep “Hygiene” • alcohol use, caffeine, cigarette smoking, fluids • chronic insomnia: counselling, behavioural & biofeedback, sleep deprivation, etc.

16. Comparison of Benzodiazepines Drugt 1/2 onsetoxidationactive met diazepam flurazepam oxazepam lorazepam temazepam triazolam

17. Comparison of Benzodiazepines Drugt 1/2 onsetoxidationactive met Diazepam 2-4ds quick yes yes Flurazepam 2-3ds inter-fast yes yes Oxazepam 5-15h slow no no Lorazepam 10-20h interm no no Temazepam 10-20h slow-inte no no Triazolam 2-5h quick-int yes no

18. Mrs. Smith’s sleep management

19. Depression • How is it diagnosed? • RF

20. Depression Typical Signs and Sx: emotional Sx: no interest in life, social w/d, worthlessness physical Sx: fatigue, insomnia/hypersomnia, loss of wt. & appetite or weight gain cognitive Sx: difficulty concentrating, poor memory, indecisiveness Does Mrs. Smith have depression?

21. Depression – Goals of Tx • Reduce Sx of acute episode and facilitate pt’s return to same level of functioning: remission • Acute phase: Tx 6-12 weeks (to relieve Sx) • To prevent relapse: Tx 4-9 mos (continuation phase) • To prevent recurrence: Tx > 1 year (mtce phase) • Consider risk of recurrence: after 1 episode: 50%

22. Depression – general approach to Tx • Antidepressants of equivalent efficacy in grps of pts. in comparable doses • Initial choice empirically done (consider pt’s Hx of response, family Hx, depression subtype, concurrent medical conditions, DI, ADR, cost) • 65-70% of pts will respond to first agent • Non-pharmacological Tx: psychotherapy (1st line if mild-moderate); combined has better efficacy

23. Depression – comparison of agents • SSRI (fluoxetine, fluvoxamine, paroxetine, sertraline) • Nefazodone • Venlafaxine • Bupropion • TCAs: 1st generation: amitriptyline • 2nd generation: desipramine • Moclobemide • MAOI: phenelzine, tranylcypromine

24. Depression – comparison of agents • Consider MOA • Efficacy equal • Onset of effect • Potential side effects • Potential drug interactions (see CANMAT guidelines from readings) • Switching between antidepressants (see guidelines)

25. Pharmacy Care Plan • Clinical Outcomes • To control Sx of PD and decrease further disease progression • To prevent future TIAs and/or stroke • To help Mrs. Smith fall asleep at night and to feel well rested • Pharmacotherapeutic Outcome • appropriate anti-Parkinosonian medication… • Appropriate anti-platelet agent… • Ensure that she receives counselling re: good sleep hygeine…

26. Pharmacy Care Plan • Pharmacotherapeutic Endpoints • Improvement in initiating walking, buttoning blouse, picking up objects, in 3 days to a week and optimal in one month • No TIAs/ stroke while on therapy (confusion, paresthesias, etc.) • Able to fall asleep within ½ hour in 3-4 days

27. Pharmacy Care Plan • Alternatives & Assessment Parkinson’s Disease: TIA/Stroke: insomnia:

28. Pharmacy Care Plan • Therapeutic Plan

29. Pharmacy Care Plan • Therapeutic Plan Endpoints Sinemet: nausea, vomiting, wearing off effect, on-off effect… ASA: nausea, no blood in stools (tarry stools), no PUD Selegiline: insomnia, jitteriness DA agonist: nausea, orthostatic hypotension, insomnia, dyskinesias…

30. Pharmacy Care Plan • Monitoring Plan Work closely with patient, family, caregivers and health care providers