1 / 33

Anti-Parkinson Drugs

Anti-Parkinson Drugs. Dr Gareth Noble. Aims. To review pathogenesis of Parkinson's To review clinical presentation To identify treatment drugs. Prevalence. 1.5 million in USA and 120,000 in the UK – accounts for about 10% of all acute hospital admissions

matthew-mendoza
Download Presentation

Anti-Parkinson Drugs

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Anti-Parkinson Drugs Dr Gareth Noble

  2. Aims • To review pathogenesis of Parkinson's • To review clinical presentation • To identify treatment drugs

  3. Prevalence • 1.5 million in USA and 120,000 in the UK – accounts for about 10% of all acute hospital admissions • Effects 2 in 1,000 people; aged 80+ incidence is 1 in 50. • Mainly affects adults in later life • Slightly more common in men, Afro-Caribbean's and people from the Indian subcontinent • Affects the quality of life of about 500,000 (family, carers etc)

  4. Causes • Unclear, but is a number of factors: • Environmental – toxins • Free Radicals – there is a increase in post-mortem brain sections • Aging – age related decline in dopamine production • Genetic – possible, no single gene identified

  5. Parkinson’s Disease • A degenerative and progressive disorder • Associated with neurological consequences of decreased dopamine levels produced by the basal ganglia (substantia nigra) • Dopamine is a neurotransmitter found in the neural synapses in the brain • Normally, neurones from the SN supply dopamine to the corpus striatum (controls unconscious muscle control) • Initiates movement, speech and self-expression

  6. Balance, posture, muscle tone and involuntary movement depends on the roles of dopamine (inhibitory) and acetylcholine (Ach: excitatory) • If dopamine missing, Ach produces more of an effect on muscles • Basis to exploit by drugs: • Restore dopamine function • Inhibit Ach within corpus striatum

  7. Consequences of dopamine reductions • Tremors – hands and head develop involuntary movements when at rest; pin-rolling sign (finger and thumb) • Muscle rigidity – arthritis-like stiffness, difficulty in bending or moving limbs; poker face • Brandykinesia – problems chewing, swallowing or speaking; difficulty in initiating movements and controlling fine movements; walking becomes difficult (shuffle feet) • Postural instability – humped over appearance, prone to falls

  8. Additional symptomology • Anxiety • Depression • Sleep disturbance • Dementia • Disturbance of ANS (difficulty in urinating)

  9. Altered body image (depression) Poor balance Bradykinesia (slow movement) Bradyphrenia (slowness of thought) Constipation Dribbling/drooling Dyskinesias (involuntary movements) Dysphagia (difficulty swallowing Dystonia (pain spasms) Excessive sweating (impaired thermoregulation) Festinating gait Hullucinations (visual) Postural hypotension Restless leg syndrome (leg aches, tingle, or burn) Rigidity Sleep disturbance Slurring/slowing of speech Tremor Clinical Presentation Ref: Noble C (2000) Parkinson’s Disease – the challenge. Nursing Standard, 15 (12), 43-51

  10. Videos GO TO MEMORY STICK

  11. Treatment (early stage) • Clinical judgements based upon level of disability, age, cognitive status, concurrent medial problems • Initial pharmacological therapies are titrated to determine optimal dose per person • Agent used: Levodopa • Social support and health education vital • Referrals to other professional groups (SLT, PT, OT etc)

  12. Treatment (maintenance stage) • Speech therapist is prophylactic and deals with swallowing problems (recommend exercises etc) • Impaired thermoregulation – use beta-blockers • Disturbance in sleep – can be side effects of medication; change time of intake or use a controlled release drug delivery system • Continued health education and liaison with other professionals

  13. Treatment (complex stage) • Function has deteriorates to such a level a combination of drugs are prescribed • Dyskinesias and Dystonia – can be associated with long-term Levodopa use and it can be difficult to manage these effects – co-agent is co-beneldopa • Restless-leg – dopamine agonists • Anxiety – relaxation, distraction, CBT • Depression – alterations in dose of anti-parkinson’s drugs

  14. Cognitive problems – referral to clinical psychologist and prescription of anti-dementia agents • Hallucinations - ?anti-psychotics Essentially, a multidimensional approach to pharmacological treatment combined with a multidisciplinary approach

  15. Medication Rational • Replace depleted levels of dopamine • Stimulate the nerve receptors enabling neurotransmission • Increase the effect of dopamine on nerve receptors (agonist) • Counteract the imbalance of Ach and Dopamine

  16. The Drugs: • Dopaminergic drugs (improving dopamine functioning) • Levodopa • Dopamine receptor agonists • Amantadine • Selective monoamine oxidase B inhibitors • Catechol-O-methyltransferase inhibitors • Antimuscarinic drugs (Ach inhibitors)

  17. Levodopa (Madopar & Sinemet) • Can not administer dopamine directly, as it does not cross the blood brain barrier • A natural amino acid that the brain converts into dopamine (replacement therapy) used since the 1960’s • To make it slow release, combined with benserazide (an enzyme inhibitor) to create co-beneldopa or co-careldopa (Sinemet) • Dose = 50, 100 or 200mg (12.5, 25 or 50mg)

  18. Source: Adams et al (2006). Pharmacology for Nurses – A Pathophysiologic Approach. Prentice Hall Publishers

  19. Pharmacokinetics: • Absorbed by the small intestine by an active transport system • Decarboxylation occurs in peripheral tissues (gut wall, liver and kidney • decrease amount available for distribution – 1% of an oral dose • Extracerebral dopamine amounts causing unwanted effects (benserazide) • Short half-life

  20. Adverse effects: • As a result of the amount of peripheral dopamine levels • Nausea, vomiting • Postural hypotension • As a result of the amount of CNS dopamine levels • Dyskinetic involuntary movements (face & neck) • Hallucinations and confusion

  21. Dopamine receptor agonists • Apopmorphine (APO-go): • SC administration • Rescue therapy – rapid onset with a short duration of action (~50mins) • Bromocriptine (Parlodel); Pergolide (Celance); Ropinirole (Requip) • Direct agonists of dopamine receptors in the brain • ?longer lasting therapeutic effects that Levodopa

  22. Start a pt on this alone, then combine with levodopa to ‘smooth out’ control when PD is getting progressive (especially young) • Pharmacokinetics: • Incompletely abosrbed need extensive first-pass metabolism (biotransformed in liver) • Pergolide & Ropinirole have higher bioavailability (distribution) • Short to medium half life (Potency)

  23. Adverse effects: • Use gradual dose titration • N + V (particularly Apomorphine) • Dyskinesia • Hallucinations and confusion • Peripheral vasospasm (Raynaunds) • Respiratory depression (Apomorphine

  24. Amantadine (Symmetrel) • Originally an antiviral drug, now used as conjucntive therapy for dyskinesis effects produced by Levodopa • MoA: • stimulates/promotes the release of dopamine stored in the synaptic terminals • Reduces reuptake of released dopamine by pre-synaptic neuron • Pharmacokinetics: • Well absorbed, long half-life, excreted unchanged by the kidney • Adverse effects: • Not many • Ankle oedema, postural hypotension, nervousness, insomnia, hallucinations (high dose)

  25. Other Disease Modifying Drugs • Selective monoamine oxidase B inhibitors (selegiline – Trade name Eldepryl/Zelapar): • MoA: prolongs the effects of levodopa as MAO-B degrades dopamine • Pharmacokinetics: completely absorption, short half-life • Adverse effects: N, V, Dia, Constipation; dry mouth, sore throat; transient dizziness; insomnia, confusion and hallucinations • Early stage – prescribed on it is own to delay need for levodopa and there is good evidence for its slowing down of PD progression

  26. Catechol-O-methltransferase inhibitors - COMT (entacapone, Trade name Comtess) • MoA: inhibits the breakdown of levodopa • Pharmacokinetics: variability of absorption, extensive first-pass metabolism, short half-life • Adverse effects: dyskinesias, hallucinations; N, V, Dia and abdominal pain • New combination – Levodopa/carbidopa/entacapone (Stalevo) as 1 tablet (50, 100, 150mg)

  27. Antimuscarinic/Anticholinergic Drugs: • Trihexyphenidyl (Broflex, Artane, Agitane); Benztropine (Cogentin); Orphanadrine (Disipal); Procycline (Kemadrin, Arpicolin) • Less common drugs but they affect Ach based interactions • MoA: blocking cholingeric (Ach) receptors to restore balance • Pharmacokinetics: fairly well absorbed, extensive hepatic metabolism, intermediate to long half-lifes • Adverse effects: dry mouth and confusion

  28. Disease Modifying Drugs Overview

  29. Symptom Management Drugs • PD is multidimensional, therefore there are a number of clinical presentations that require supplementary agents • Drug-Drug reactions is the problem • Major area is depression

  30. Antidepressants • Amitriptyline (Tryptizol), imipramine (Tofranil), Nortriptyline (Allegron), Iofepramine (Gamanil) • MoA: block re-uptake of noradrenaline and serotonin => Sedative actions, can help with drooling and loss of appetite • Adverse effects: sleepiness, dry mouth, increased hunger, cardiac arrhythmias and changes in BP • Can interfere with the effects of levodopa!

  31. Other Drugs to Avoid

  32. Video Sites • HealingWell.com • Birmingham Teaching Tutorials (hopefully) • The Neuron Connection • www.bio.davidson.edu/projects/neuron/video.asp • Useful Websites: • Parkinson’s Disease Society • http://www.parkinsons.org.uk/ • Nursing Standard (CPD) • http://www.nursing-standard.co.uk/

  33. Textbook References • Karch AM (2006) Focus on Nursing Pharmacology, 3rd Edition. Lippincott Williams & Wilkins • Rang et al (2003) Pharmacology, 5th Edition. Churchill Livingstone. • Lilley et al (2005) Pharmacology and the Nursing Process, 4th Edition. Mosby • Page et al (2002) Integrated Pharmacology, 2nd Edition. Mosby. • Martini (2005) Principles of Anatomy and Physiology, Pearson Education Publishers

More Related