Integrated Case November 28, 2002 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? 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: 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?? 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) Mrs. Smith’s management • She is presently on Sinemet 100/25 tid • Options for management: At risk for TIA and/or stroke • What is TIA? • RIND: reversible ischemic neurological deficit • What is stroke? • Thrombus vs. embolus TIA / Stroke General Risk Factors HTN, prior TIA/stroke, age, male, smoking, etc. (consider cardiac RF) Mrs. Smith’s RF Is Tx needed? TIA / Stroke Tx options - Prophylaxis • ASA • Ticlopidine • Clopidogrel • Warfarin • Dipyridamole • Sulfinpyrazone • tPA – for acute ischemic stroke (within 3 hours) 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 TIA/Stroke • What would be an appropriate agent for Mrs. Smith and why? Mrs. Smith’s sleep problem • What is insomnia? • Types of insomnia Mrs. Smith’s sleep problem • Drug-induced causes: • Reason for Mrs. Smith’s insomnia • Is Tx needed? Mrs. Smith’s sleep problem • Tx Options: – – – – – – – Non-pharmacological options benzodiazepines antihistamines Zopiclone zaleplon chloral hydrate barbiturates Non-pharmacological Strategies • Good Sleep “Hygiene” • alcohol use, caffeine, cigarette smoking, fluids • chronic insomnia: counselling, behavioural & biofeedback, sleep deprivation, etc. Comparison of Benzodiazepines Drug t 1/2 diazepam flurazepam oxazepam lorazepam temazepam triazolam onset oxidation active met Comparison of Benzodiazepines Drug t 1/2 onset oxidation active met Diazepam 2-4ds quick yes Flurazepam 2-3ds inter-fast yes Oxazepam 5-15h slow no Lorazepam 10-20h interm no Temazepam 10-20h slow-inte no Triazolam 2-5h quick-int yes yes yes no no no no Mrs. Smith’s sleep management Depression • How is it diagnosed? • RF 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? 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% 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 Depression – comparison of agents SSRI (fluoxetine, fluvoxamine, paroxetine, sertraline) Nefazodone Venlafaxine Bupropion TCAs: 1st generation: amitriptyline 2nd generation: desipramine Moclobemide MAOI: phenelzine, tranylcypromine 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) 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… 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 Pharmacy Care Plan • Alternatives & Assessment Parkinson’s Disease: TIA/Stroke: insomnia: Pharmacy Care Plan • Therapeutic Plan 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… Pharmacy Care Plan • Monitoring Plan Work closely with patient, family, caregivers and health care providers