WHMC311. Session 17. Nervous System Disease Part IV. Naturopathic Medicine Department. Endeavour College of Natural Health endeavour.edu.

Transcription

1 WHMC311 Session 17 Nervous System Disease Part IV Naturopathic Medicine Department Endeavour College of Natural Health endeavour.edu.au 1

2 Topic Overview o Management of complex and multi-system conditions through the use of specific herbal medicines and their specific biochemical and physiological applications in the management of dementia, Alzheimer s disease and Parkinson s disease drawing upon relevant literature. o Discussion of relevant drug interactions and potentiations through an understanding of mechanisms of action of interactions. Endeavour College of Natural Health endeavour.edu.au 2

3 Dementia Endeavour College of Natural Health endeavour.edu.au 3

4 Dementia o Chronic deterioration of intellectual function/cognitive skills. o Common in elderly (affecting approx. 15% of persons >65 yrs old and 40% of persons >80 yrs old). o Signs & symptoms include; Poor memory and disorientation Cognitive impairment (aphasia, apraxia, agnosia, or a loss of executive functioning). o The appearance of clinical features suggest there is a substantial progression of the disease process. (Kumar & Clark, 2009) Endeavour College of Natural Health endeavour.edu.au 4

5 Dementia Varied causes of dementia include: o Cerebral atrophy - Alzheimer's disease accounts for over 65%, Parkinson s disease, Huntington s disease etc. o Diffuse vascular disease o Metabolic insufficiencies uraemia, liver failure o Nutritional deficiencies - vitamins B1, B3, B6 & / or B12 o Toxic damage alcohol, solvents, heavy metals o Head trauma & lesions o Infections HIV, neurosyphilis o Hypothyroidism, hypoparathyroidism (Kumar & Clark, 2009) Endeavour College of Natural Health endeavour.edu.au 5

6 Pharmaceutical Management Acetyl-cholinesterase Inhibitors Donepezil, Rivastigmine, Galantamine Mode of Action o Inhibit acetyl-cholinesterase thereby reducing Ach breakdown at nicotinic & muscarinic receptor sites. Delays cognitive decline in the initial stages, the disease will progress. Side Effects o Increased muscle activity in the eyes (pupil constriction), bradycardia, diarrhoea, muscle twitching, bronchoconstriction. o Also hypotension, increased lacrimation & sweating (Auchus, 2007; Bryant & Knights, 2011; Bullock et.al. 2007; Romi et.al, 2005) Endeavour College of Natural Health endeavour.edu.au 6

7 Pharmaceutical Management NMDA (N-methyl-d-aspartate) Antagonist Memantine Mode of Action o Selectively blocks glutamate receptors (N-methyl-daspartate receptor) to reduce overstimulation (characteristic of Alzheimer's). Slows the progression of the disease. Side Effects o Headache, dizziness, agitation. o Drowsiness, insomnia. o GIT disturbance o Coughing (Auchus, 2007; Bullock et.al. 2007) Endeavour College of Natural Health endeavour.edu.au 7

8 Information Gathering o Determine causative factors for cognitive decline Cardiovascular risk factors, metabolic syndrome, stress, nutritional deficiencies, trauma, infections, concomitant diseases o Naturopathic assessment Systems: digestive, immune, nervous,, cardiovascular Endeavour College of Natural Health endeavour.edu.au 8

9 Treatment Considerations o Improve executive function through improving cerebral blood flow and neuronal activity Ginkgo biloba Bacopa monnieri Panax ginseng Centella asiatica Endeavour College of Natural Health endeavour.edu.au 9

10 Treatment Considerations o Support anti-oxidant status Antioxidant herbs: Rosmarinus officinalis Minimise external/environmental toxins o Reduce inflammation Curcuma longa Salvia officinalis Endeavour College of Natural Health endeavour.edu.au 10

11 Treatment Considerations o Consider GIT support Bitters Liver detoxification/heavy metal chelation Chologogues Choloretics Hepatics Hepatoprotectives Antioxidants Fiber: Slippery elm, psyllium Endeavour College of Natural Health endeavour.edu.au 11

12 Alzheimer s Disease Endeavour College of Natural Health endeavour.edu.au 12

13 Alzheimer s Disease o Common, progressive form of dementia (50% - 70% of all cases), usually occurs in later life. o Cause unknown, difficult to diagnose. o Autopsy shows excessive number of senile plaques in the cerebral cortex and subcortical grey matter, which also contains b-amyloid and neurofibrillary tangles. o Signs & Symptoms Memory loss Impaired decision making (incl. financial) and language skills Behaviour and personality changes (depression, anxiety, aggression etc.) (Bryant & Knights, 2011; Kumar & Clark, 2009) Endeavour College of Natural Health endeavour.edu.au 13

14 Risk Factors o Age o Positive family history o Presence of APO-E4 gene significant o Trauma to the head o Cardiovascular risk factors, circulation disorders (hypertension, hypercholesterolemia, MI) o Hyper-inflammatory states o Heavy metal toxicity o Oxidative damage to brain tissue poor antioxidant status (Kumar & Clark, 2009) Endeavour College of Natural Health endeavour.edu.au 14

15 Pathogenesis o Various proposed pathogenesis mechanisms Amyloid plaque formation Neurofibrillary tangles Exaggerated pro-inflammatory responses increasing neuronal death and neurodegeneration Poor vascular function Heavy metal such as Zn, Cu and Fe Endeavour College of Natural Health endeavour.edu.au 15

16 Pharmaceutical Management The same drug regime is utilised for Alzheimer s disease as is used for dementia. o Acetyl-cholinesterase Inhibitors sustain levels of ACh at brain receptor sites, thereby reducing the decline at the initial stages of the disease. This slows inevitable progression. (Auchus, 2007; Bryant & Knights, 2011; Bullock et.al. 2007; Romi et.al, 2005) o NMDA (N-methyl-d-aspartate) Antagonists block glutamate receptors to minimise overstimulation, slowing the progression of the disease. (Auchus, 2007; Bullock et.al. 2007) Endeavour College of Natural Health endeavour.edu.au 16

17 Treatment Aims o Treat presenting complaints using holistic treatment protocol o Prevent further cognitive decline - support cognition, neurotransmitter synthesis, address inflammation o Improve cardiovascular status (vascular elasticity, antioxidant status) o Address comorbidities (mood, anxiety, sleep disorders) Endeavour College of Natural Health endeavour.edu.au 17

18 Cognition Support Cerebral Circulatory Stimulants o Gingko biloba o Vinca minor o Centella asciatica Cognitive Enhancers o Panax ginseng o Ginkgo biloba o Bacopa monnieri o Rosmarinus officinalis (Hechtman 2011, p.145) Endeavour College of Natural Health endeavour.edu.au 18

19 Heavy Metals o Levels of zinc, copper and iron are significantly altered in AD brain tissue o Curcumin anti-inflammatory may be due, in part, to metal chelating effects; also able to bind heavy metals (Cu and Fe) o Bacopa monnieri Endeavour College of Natural Health endeavour.edu.au 19

20 Bacopa monnieri o Traditionally used through Ayurvedic medicine for memory decline o Modulate cholinergic system o Anti oxidant o Remove beta-amyloid deposits o Metal chelator o Anxiolytic o Antidepressant o Adaptogen (Sarris & Wardle, 2010, p ) Endeavour College of Natural Health endeavour.edu.au 20

21 Ginkgo biloba o Walesuik et al. (2005) found that Ginkgo biloba was useful in ischemic conditions, senile dementia (including Alzheimer s disease), cerebral and retinal impairment (p. 186) o Ginkgo may also be useful in stress-induced cognitive disorders. Endeavour College of Natural Health endeavour.edu.au 21

22 Curcuma longa o The incidence of Alzheimer disease has been found to be lower in India and areas with a high traditional consumption of turmeric. o Evidence shows that levels of β-amyloid and tau are lower in people who consume large amounts of curcumin and that curcumin protects against β-amyloid toxicity, and decreases β-amyloid in Tg2576 transgenic mice. (Potter, 2010) Endeavour College of Natural Health endeavour.edu.au 22

23 Parkinson s Disease Endeavour College of Natural Health endeavour.edu.au 23

24 Parkinson s Disease o Parkinson s disease is a chronic degenerative neurological disorder, characterised by specific motor dysfunctions that include tremor, muscular rigidity, slowness of movement (bradykinesia) and characteristic disorders of gait and posture. o There are many other disorders with similar signs and symptoms to Parkinson s disease and the term parkinsonism is applied to any syndrome that exhibits signs that are typical of Parkinson s disease. Endeavour College of Natural Health endeavour.edu.au 24

25 Pharmaceutical Management o Restore the balance between dopaminergic and cholinergic function o This can be accomplished in different ways, such as: Increasing dopamine levels Augmenting dopamine levels with drugs that mimic dopamine activity Suppression of cholinergic activity (reduced acetylcholine levels). Endeavour College of Natural Health endeavour.edu.au 25

26 Pharmaceutical Management Levodopa (L-dopa) Mode of Action o L-dopa is the immediate pre-cursor of dopamine and can cross the blood-brain-barrier (unlike activated dopamine) where it is subsequently converted to dopamine. This raises dopamine levels in the brain reducing symptoms of Parkinson s disease. o Levodopa conversion is catalysed by the enzyme dopa decarboxylase which is present in peripheral tissue thereby only 1% of levodopa reaches the brain. o Pyridoxine is a co-factor for the peripheral conversion of levodopa; thus concomitant administration will reduce the amount of levodopa that is available to cross the blood-brainbarrier. (Bryant & Knights, 2011) Endeavour College of Natural Health endeavour.edu.au 26

27 Pharmaceutical Management Levodopa Side Effects o The peripheral conversion of levodopa is responsible for most of the adverse effects associated with the drug, such as nausea, vomiting, cardiac arrhythmias and postural hypotension. (Bryant & Knights, 2011) Endeavour College of Natural Health endeavour.edu.au 27

28 Pharmaceutical Management Carbidopa Mode of Action o Used combined with levodopa, carbidopa prevents the peripheral conversion of levodopa, making more levodopa available for transport to the brain where it is converted to dopamine allowing for lower doses of levodopa and reduced incidence of adverse effects. o In the presence of carbidopa, supplementation with pyridoxine (50-100mg/day) does not increase extracerebral conversion, thus drug efficacy is maintained Side Effects o The same as for Levodopa. (Bryant & Knights, 2011) Endeavour College of Natural Health endeavour.edu.au 28

29 Pharmaceutical Management Selegiline Mode of Action o Used in combination with levodopa in the late stages of the disease, selegiline inhibits the activity of the enzyme monoamine oxidase B (MAO-B), thereby delaying the breakdown of naturally occurring dopamine and dopamine derived from levodopa. Side Effects o Nausea, vomiting, stomach pain o Insomnia, dizziness, mood alteration, dyskinesia. (Bryant & Knights, 2011) Endeavour College of Natural Health endeavour.edu.au 29

30 Pharmaceutical Management Dopamine Agonists - Bromocriptine, Pergolide, Cabergoline Mode of Action o Directly stimulate the CNS dopamine (D 2 ) receptors providing symptomatic relief. o Used as adjuncts to levodopa therapy to prolong effectiveness, stabilize responses of and increase tolerance to levodopa. Side Effects o Similar to those for Levodopa. (Bryant & Knights, 2011) Endeavour College of Natural Health endeavour.edu.au 30

31 Pharmaceutical Management Anti-cholinergics - Biperiden, Benztropine Mode of Action o Block the action of acetylcholine, thereby helping to restore the balance between cholinergic and dopaminergic activity. Used in the early stages of the disease. Side Effects o Nausea, vomiting, constipation o Dry skin, dry mouth o Drowsiness o Irritability (Bullock et.al. 2007; Bryant & Knights, 2011) Endeavour College of Natural Health endeavour.edu.au 31

32 Treatment Aims o Support the liver and heavy metal chelation sulphate conjugation implicated in pathogenesis o Support neurotransmitter (dopamine) synthesis Withania somnifera may improve catecholamines and physiological abnormalities (RajaSankar et al, 2009) Hypericum perforatum neuroprotective, antioxidant and anti-depressant (Gómez del Rio et al, 2013) Camellia sinensis contains theanine (elevates dopamine) Endeavour College of Natural Health endeavour.edu.au 32

33 Treatment Aims o Support neurotransmitter (dopamine) synthesis Mucuna pruriens (velvet beans) and fava beans high in natural levodopa (100g serving = 250mg levodopa) (Pizzorno & Murray 2006) Vinca minor (periwinkle) Endeavour College of Natural Health endeavour.edu.au 33

34 Drug Herb Interactions Levodopa Piper methysticum (Kava) o Kava may potentially induce Parkinson-like reactions. Concurrent usage is theoretically contra-indicated. (Stargrove et al. 2008) Endeavour College of Natural Health endeavour.edu.au 34

35 Drug Herb Interactions o Natural therapies may be supportive in Parkinson s disease, but are not indicated as stand-alone therapies, given the nature of the disease o Currently, the only reported integrative interactions relate to levodopa, however care should be taken when prescribing any natural therapies in Parkinson s disease. o All natural therapies that act on catecholamines, especially dopamine or acetylcholine pathways, may theoretically lead to an interaction with the anti- Parkinson s drug therapies Endeavour College of Natural Health endeavour.edu.au 35

36 Pre-reading for next semester o Reading 1: Akhondzadeh, S Noroozian, M Mohammadi, M Ohadinia, S Jamshidi, A & Khani, M 2003, Melissa officinalis extract in the treatment of patients with mild to moderate Alzheimer's disease: a double blind, randomised, placebo controlled trial Journal Neurology Neurosurgery Psychiatry, vol. 74, no. 7, pp o med o Reading 2: Dos Santos-Neto, LL De Vilhena Toledo, MA Medeiros- Souza, P & de Souza, GA 2006, The Use of Herbal Medicine in Alzheimer's Disease A Systematic Review Evidence-Based Complimentary and Alternative Medicine, vol. 3, no.4, pp Endeavour College of Natural Health endeavour.edu.au 36

37 References Auchus, A. 2007, Dementia. Merk manual online for healthcare professionals. Viewed: 13/01/11 Avery s Drug Treatment 4 th Edition Adis International Braun L, Cohen M Herbs and Natural Supplements, An Evidence-based Guide 2 nd Edition. Churchill Livingstone Elsevier British Herbal Medicine Association, 1983, British Herbal Pharmacopoeia, British Herbal Medicine Association, Bournemouth, UK Bryant B, Knights K Pharmacology for Health Professionals 2 nd Edition. Mosby Elsevier Bullock, S., Manias, E. & Galbraith, A Fundamentals of pharmacology. 5 th ed. Pearson, NSW. Cuellar, A. C., Johnson, S. L. & Winters, R. (2005) Distinctions between bipolar and unipolar depression. Clinical Psychology Review. 25(3) pp Di Piro JT et al Pharmacotherapy, A Pathophysiological Approach (3rd Edition). Appelton Lange USA emims medical database. MIMS Desk Reference April/May 2006 Gómez del Rio M, Sánchez-Reus M, Iglesias I, Pozo M, García-Arencibia M, Fernández-Ruiz J, García-García L, Delgado M, Benedí J, 2013, Neuroprotective Properties of Standardized Extracts of Hypericum perforatum on Rotenone Model of Parkinson's Disease, CNS Neurol Disord Drug Targets, Aug, Vol 12, Iss 5, pp Leach MJ, Pincombe J, Foster G Using horsechestnut seed extract in the treatment of venous leg ulcers: a cost-benefit analysis,ostomy/wound Management. Apr;52(4):68-70, 72-4, Endeavour College of Natural Health endeavour.edu.au 37

38 References Lininger SW et al A-Z Guide to Drug-Herb-Vitamin Interactions. Healthnotes. Three Rivers Press. New York Micromedix Health Care Series (Database) Mills S, & Bone K, 2000, Principles and Practice of Phytotherapy: Modern Herbal Medicine, Churchill Livingstone, Edinburgh Mills S, Bone K The Essential Guide to Herbal Safety. Elsevier Churchill Livingstone. National Health and Medical Research Council, 2009, Cardiovascular Disease, viewed Medline Plus, 2010, Varicose veins, viewed , National Heart, Lung and Blood Institute, 2009, Disease and Conditions Index: What Is Atherosclerosis? Viewed National Collaborating Centre for Primary Care. The diagnosis and management of the epilepies in adults and children in primary and secondary care. London (UK): Royal College of General Practitioners; 2004 Oct. P525 (located at www. guideline.gov) Osiecki H The Physician s Handbook of Clinical Nutrition. Bioconcepts Publishing. Australia Pizzorno JE, Murray MT Textbook of Natural Medicine 3 rd Edition. Vol 2. Churchill Livingstone Quick Reference Guide: The Epilepsies: diagnosis and management of the epilepsies in adults in primary and secondary care National Institute for Clinical Excellence. Clinical Guideline 20. found at Endeavour College of Natural Health endeavour.edu.au 38

39 References RajaSankar S, Manivasagam T, Sankar V, Prakash S, Muthusamy R, Krishnamurti A, Surendran S, 2009, Withania somnifera root extract improves catecholamines and physiological abnormalities seen in a Parkinson's disease model mouse, J Ethnopharmacol. Sep 25, vol 125, iss 3, pp Walesiuk, A Trofimiuk, E & Braszko, JJ 2005, Ginkgo biloba extract diminishes stress-induced memory deficits in rats. Pharmacological reports, Vol. 57, pp Van Rossum, I., Tenback, D. & van Os, J (2009) Bipolar disorder and dopamine dysfunction: an indirect apporach focussing on tardive movement sydrome in a naturalistic setting Medscape viewed 02/09/2010: Yatham, L., Kennedy, S., Schaffer, A, Parikh, S. A., Beaulieu, S., O Donovan, C., MacQueen, R., McIntyre, R. S., Sharma, V., Ravindran, L., Young, T., Young, A. H., Alda, M., Milev, R., Vieta, E., Clabrese, J. R., Berk, M., Ha, K., & Kapczinski, F. (2009) Canadian network fro mood and anxiety treatments (CANMAT) and the International society for bipolar disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update Bipolar disorders vol 11 issue 3 pp Yurgelun-Todd, D. A., Gruber, S.A., Kanayama, G., Killgore, W.D., Baird, A.A., Young, A.D. (2000) fmri during affect discrimination in bipolar affective disorder. Bipolar Disorders. Vol 3 pp Endeavour College of Natural Health endeavour.edu.au 39