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 onset oxidationactive met diazepam flurazepam oxazepam lorazepam temazepam triazolam

17. Comparison of Benzodiazepines Drugt 1/2 onset oxidationactive 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 (1 st line if mild-moderate); combined has better efficacy

23. Depression – comparison of agents  SSRI (fluoxetine, fluvoxamine, paroxetine, sertraline)  Nefazodone  Venlafaxine  Bupropion  TCAs: 1 st generation: amitriptyline  2 nd 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