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Learn about neurodegenerative disorders, like multiple sclerosis (MS), and Parkinson's disease, their symptoms, available treatments, and care strategies. Discover the impact on daily life and ways to support sufferers effectively.
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Nervous System CSHALDERS/GOIT/2008
Neurodegenerative Disorders • Can cause morbidity and mortality • Most of these disorders produce a progressive deterioration in neuronal function and tend to be irreversible CSHALDERS/GOIT/2008
Multiple Sclerosis • Etiology unknown • The disease affects the white matter of the spinal cord and the brain, where autoimmune activity causes lesions CSHALDERS/GOIT/2008
Multiple Sclerosis • Wide variation in clinical manifestations and prognosis • Progressive form – which continually worsens with no remission • Relapsing – remitting from- characterised by a serious of attacks followed by partial remission CSHALDERS/GOIT/2008
Multiple Sclerosis (MS) • Autoimmune disorder causing destruction of myelin sheaths in CNS • appears between ages 20 and 40 • females twice as often as males • Symptoms include muscular weakness, stiffness. Parathesias, pain and muscle spasm are observed. • Emotions, memory vision motor coordination also affected CSHALDERS/GOIT/2008
Multiple Sclerosis • Survival time from diagnosis can be well over 20 years so important to offer sufferers • Every aid to improve their quality of life • Because the disease is autoimmune best causative treatment involves use of immunosuppressive drugs CSHALDERS/GOIT/2008
Multiple Sclerosis • Two specific immunosuppressive drugs used in MS are glatiramer and interferon • Both these drugs can reduce the number of relapses • Are given by subcutaneous injection CSHALDERS/GOIT/2008
Multiple Sclerosis • Glatiramer • Modify the immune process • 20 mg s/c daily • Adverse effects • Injection site reactions, vasodilation, taccycardia, palpitations, chest pain • Prec: Should not be given IV or IM • Rotate injection sites CSHALDERS/GOIT/2008
Multiple Sclerosis • Interferon β 16 • Requires monitoring complete blood count and liver function at baseline at three months at six months • Adverse effects • Flu like symptoms, lethargy weakness and fatigue. CSHALDERS/GOIT/2008
Multiple Sclerosis Dantrolene • Works as a muscle relaxant, interferes with release of calcium ions from skeletal muscle • Prec – hepatic disease, pre, BF photosensitivity • AR – drowsiness, dizziness, malaise GI • Inter – OC, alcohol verapamil, tranquilizers • Pres – 25mg 50 mg • Dose – Adult 25mg daily ^ to 50 mg – 100mg 3-4 * daily CSHALDERS/GOIT/2008
Multiple Sclerosis • Baclofen • Used for spasms • Antispasticity agent that acts on the spinal end of the upper motor neuron • Adverse effects • Nausea, vomiting, dry mouth, constipation • Considerations: take with food do not stop abruptly CSHALDERS/GOIT/2008
Multiple Sclerosis • Amantadine • For fatigue • Thought to stimulate the release of dopamine in the brain • Adverse effects- palpitations, hypotension, peripheral oedema • Considerations: Watch for postural hypotension CSHALDERS/GOIT/2008
Multiple Sclerosis • Corticosteroids such as prednisolone or methylprednisolone can be effective in acute phases • Aggressive antibiotic therapy used for infections • Tricyclic antidepressants used for depression • Propantheline for urinary urgency CSHALDERS/GOIT/2008
Parkinsons Disease • Named after a Doctor who discovered the disease • Cause is unknown research has shown a reduction in the dopamine in the brain which prevents correct brain cell function • Characterized by tremors and progressive muscle rigidity CSHALDERS/GOIT/2008
Parkinsons • Seen to affect more men than women • Middle age or later • Genetic factors ?viruses and environmental toxins • The reduction in dopamine leaves an excess of acetylcholine that causes over excitation • Dopamine receptors degenerate, causing excessive muscarinic activity CSHALDERS/GOIT/2008
Parkinsons • The seesaw remains unbalanced, as the dopaminergic activity is never sufficient to keep the seesaw in balance • This is the essence of parkinsons disease pathophysiology CSHALDERS/GOIT/2008
Parkinsons • To treat is to rebalance the seesaw • Two methods • Decrease the muscarinic activity and or increasing the dopaminergic activity CSHALDERS/GOIT/2008
Parkinsons • Aim of most drugs is to increase the amount of dopamine produced and available to the cerebral tissues • Levodopa is the precursor to dopamine • Can cross the blood brain barrier where it is converted into dopamine • The enzyme that converts levodopa to dopamine is decarboxylase CSHALDERS/GOIT/2008
Parkinsons • By giving large doses of levodopa the dopamine produced triggers severe peripheral adverse effects • To combat this carbidopa and benserazide unable to cross the blood brain barrier • We add one of these compounds to levodopa the peripheral conversion of levodopa to dopamine is inhibited, allowing more levodopa to cross the blood brain barrier CSHALDERS/GOIT/2008
Parkinsons • Ergot derivatives medications are also used in parkinsons disease to stimulate central dopamine receptors • Helps reduce muscle rigidity, but is less effective than levodopa CSHALDERS/GOIT/2008
Parkinsons • Carbidopa/Levodopa (Sinemet) • Used for treatment of parkinsons disease • Contra:Maoi’s glaucoma, melanoma • Pre: Ph psychotic episodes, convulsion, peptic ulcers,antihypertensives, arrythmias,asthma, preg, severe cardiac, renal pulmonary. • AR: muscle twitching depression • Inter: MAOI’s, tricyclics, iron, phenytoin,intal CSHALDERS/GOIT/2008
Parkinsons • Side effects of levodopa include nausea, depression, agitation and confusion as well as involuntary movements of the head lips and tongue. • Some of these effects can be avoided by using slow release preparations, which maintain more constant blood levels CSHALDERS/GOIT/2008
Parkinsons • The effect of levodopa tends to decrease with time until no effect is produced at all • Therefore the drug is given more frequently • This is probably due to progressive degeneration of the dopaminergic neurones CSHALDERS/GOIT/2008
Parkinsons • Levodopa should be taken at the same time each day and always with food to ensure uniform blood concentrations of levodopa Long term levodopa therapy can cause • On –off phenomenon where marked symptoms develop, for a period of time before normality returns. CSHALDERS/GOIT/2008
Parkinsons • Benzhexol (Artane) • Anticholernergic agent, relaxing effect on smooth muscle • Prec: cardiac dys, renal dys, hepatic dys, abrupt withdrawel, fever • AR: anticholernergic effects, psychiatric disturbances, taccycardia • Inter: CNS depressants, alcohol,anticonvulsants, coffee • Pres:2mg 5mg CSHALDERS/GOIT/2008
Parkinsons • Benztropine mesylate (Cogentin) • Anticholernergic effects Prec: taccycardia,preg, glaucoma • AR: antichol effects, confusion, tacycardia • Inter: phenothiazines, haleperidol, tricyclic antidepressants CSHALDERS/GOIT/2008
Parkinsons • Benserazide/Levodopa (Madopar) • Adverse reactions • Nausea vomiting drowsiness • Prec: Ph psychosis, depression,. Arrythmias, diabetes, abrupt withdrawel, preg • Inter: opiods • Dose: Madopar 62.5 caps=L50mg/B12.5 CSHALDERS/GOIT/2008
Parkinsons • Bromocriptine • Dopamine agonist • Stimulates dopaminergic receptors • Prec:arrythmias, psychosisa,BF • AR: GI, CNS dist • Inter: phenithiazines, haloperidol, metoclopramides CSHALDERS/GOIT/2008
Parkinsons • Bromocriptine is best used in conjunction with levodopa • Classified as a dopamine agonist • May cause nausea in initial stages CSHALDERS/GOIT/2008
Parkinsons • It is normal for combined therpy to be used in Parkinsons disease, however we need to be mindful of polypharmacy in this group CSHALDERS/GOIT/2008
Alzheimers Disease • Primarily a form of dementia, characterised by brain shrinkage, enlarged ventricles • Progressive deterioration of intellectual and cognitive functioning. • First signs forgetful, then confused, and later demented CSHALDERS/GOIT/2008
Alzheimers Disease • Reduction in levels of acetycholine and acetylcholinesterase occurs early in the disease • Evidence also suggests glutamate in the neurodegeneration underlying Alzheimers • Glutamate levels have been found to be raised CSHALDERS/GOIT/2008
Alzheimers disease • The acetylcholinesterase inhibitors rivastigmine,galatamine, donepezil usedin the treatment of mild to moderate alzheimers • Rationale for therapy by blocking the degenerative enzyme for acetylcholine more transmitter will be available and its action prolonged CSHALDERS/GOIT/2008
Alzheimers disease • Donepezil and riastigmine produce a number of adverse effects • Nausea, vomiting elevated liver enzymes, diarrhoea dizziness anorexia • Common adverse effects may be severe enough to stop drug therapy CSHALDERS/GOIT/2008
Alzheimers disease • Donepezil • Requires once day administration • Half life approx 70 hours • Generally well tolerated CSHALDERS/GOIT/2008
Alzheimers disease • Galantamine can cause Gi upset, weight loss anorexia, CNS disturbance, urinary tract infection and fatigue CSHALDERS/GOIT/2008
Alzheimers disease • Memantine • Management of moderate disease • Is an N- Methyl D asparate receptor antagonist that selectively restores the ungated receptors to the gated state and inhibits prolonged calcium ion influx without affecting normal glutamate neurotransmission CSHALDERS/GOIT/2008
Alzheimers disease • Memantine • Is excreted unchanged in the urine contraindicated in people with renal failure • Can make clients feel agitated insomnia drowsiness dizziness headache GIT disturbances CSHALDERS/GOIT/2008
Alzheimers disease • These drugs do not effect the underlying pathophysiological process but when effective do halt the disease for up to two years CSHALDERS/GOIT/2008
Huntingtons Disease • Huntingtons chorea genetic disease characterized by involuntary muscle movements and dementia • Autosomal dominant condition • Uncontrollable muscle movements, lack of coordination clumsiness and short term memory loss • Loss of speech and swallowing and death CSHALDERS/GOIT/2008
Huntingtons Disease • The synthesis of the brain protein called huntington is abnormal • The abnormal huntington accumulates leading to cell death CSHALDERS/GOIT/2008
Huntingtons Disease • Tetrabenazine • Acts by inhibiting the storage of dopamine thus decreasing dopamine activity • Adverse effects • Drowsiness, depression impaired alertness CSHALDERS/GOIT/2008
Huntingtons Disease • Clinical considerations • Do not take with alcohol • Stop if dysphagia occurs • Depression occurs reduce dose CSHALDERS/GOIT/2008
Motor Neuron Disease • Symptoms include muscle fasciculation, hypotonia, muscle wasting • Treatment is to relieve symptoms • No cure and death follows CSHALDERS/GOIT/2008
Motor Neuron Disease • Riluzole • Inhibits the release of glutamate into the neurones, leading to a slowing down of the paralysis • A/E nausea and decreased lung function CSHALDERS/GOIT/2008
Motor Neuron Disease • Supportive Therapy • Tryciclic antidepressants • Oxygen therapy • Antimuscarinics to reduce dribbling • Baclofen and diazepam for spasticity CSHALDERS/GOIT/2008
Nervous system • Sedatives and hypnotics are drugs which depress the CNS by inhibiting transmission of nerve impulses • Classified based on the degree of CNS depression they produce • Sedatives are agents which produces a diminished responsiveness to stimuli without producing sleep • Hypnotics have a more intense depressant effect and usually produce sleep CSHALDERS/GOIT/2008
Benzodiazepines • Most have the suffix azepam • Are thought to have there effects of the neurotransmitter GABA • Long acting are used as anticonvulsants • Medium acting and short acting are used for sleep • Very short are used for anesthesia CSHALDERS/GOIT/2008
Benzodiazepines • Used widely in the treatment of anxiety • Also used as anaesthetics, sedatives and hypnotics and anti anxiety agents. • Whether they are used as hypnotics or sedatives depends on the duration of their action in the body. CSHALDERS/GOIT/2008
Benzodiazepines • BZ1 receptors are found mainly in the cerebellum and are related to anxiety and sedation • BZ2 receptors are found mainly in the basal ganglia and hippocampus and are assoc with muscle relaxation, as well as memory and learning. CSHALDERS/GOIT/2008