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Nervous System

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Title: Nervous System


1
Nervous System
2
Neurodegenerative Disorders
  • Can cause morbidity and mortality
  • Most of these disorders produce a progressive
    deterioration in neuronal function and tend to be
    irreversible

3
Multiple Sclerosis
  • Etiology unknown
  • The disease affects the white matter of the
    spinal cord and the brain, where autoimmune
    activity causes lesions

4
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

5
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

6
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

7
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

8
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

9
Multiple Sclerosis
  • Interferon ß 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.

10
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

11
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

12
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

13
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

14
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

15
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

16
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

17
Parkinsons
  • To treat is to rebalance the seesaw
  • Two methods
  • Decrease the muscarinic activity and or
    increasing the dopaminergic activity

18
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

19
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

20
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

21
Parkinsons
  • Carbidopa/Levodopa (Sinemet)
  • Used for treatment of parkinsons disease
  • ContraMaois glaucoma, melanoma
  • Pre Ph psychotic episodes, convulsion, peptic
    ulcers,antihypertensives, arrythmias,asthma,
    preg, severe cardiac, renal pulmonary.
  • AR muscle twitching depression
  • Inter MAOIs, tricyclics, iron, phenytoin,intal

22
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

23
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

24
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.

25
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
  • Pres2mg 5mg

26
Parkinsons
  • Benztropine mesylate (Cogentin)
  • Anticholernergic effects
  • Prec taccycardia,preg, glaucoma
  • AR antichol effects, confusion, tacycardia
  • Inter phenothiazines, haleperidol, tricyclic
    antidepressants

27
Parkinsons
  • Benserazide/Levodopa (Madopar)
  • Adverse reactions
  • Nausea vomiting drowsiness
  • Prec Ph psychosis, depression,. Arrythmias,
    diabetes, abrupt withdrawel, preg
  • Inter opiods
  • Dose Madopar 62.5 capsL50mg/B12.5

28
Parkinsons
  • Bromocriptine
  • Dopamine agonist
  • Stimulates dopaminergic receptors
  • Precarrythmias, psychosisa,BF
  • AR GI, CNS dist
  • Inter phenithiazines, haloperidol,
    metoclopramides

29
Parkinsons
  • Bromocriptine is best used in conjunction with
    levodopa
  • Classified as a dopamine agonist
  • May cause nausea in initial stages

30
Parkinsons
  • It is normal for combined therpy to be used in
    Parkinsons disease, however we need to be mindful
    of polypharmacy in this group

31
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

32
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

33
Alzheimers disease
  • The acetylcholinesterase inhibitors
    rivastigmine,galatamine, donepezil used in 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

34
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

35
Alzheimers disease
  • Donepezil
  • Requires once day administration
  • Half life approx 70 hours
  • Generally well tolerated

36
Alzheimers disease
  • Galantamine can cause Gi upset, weight loss
    anorexia, CNS disturbance, urinary tract
    infection and fatigue

37
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

38
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

39
Alzheimers disease
  • These drugs do not effect the underlying
    pathophysiological process but when effective do
    halt the disease for up to two years

40
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

41
Huntingtons Disease
  • The synthesis of the brain protein called
    huntington is abnormal
  • The abnormal huntington accumulates leading to
    cell death

42
Huntingtons Disease
  • Tetrabenazine
  • Acts by inhibiting the storage of dopamine thus
    decreasing dopamine activity
  • Adverse effects
  • Drowsiness, depression impaired alertness

43
Huntingtons Disease
  • Clinical considerations
  • Do not take with alcohol
  • Stop if dysphagia occurs
  • Depression occurs reduce dose

44
Motor Neuron Disease
  • Symptoms include muscle fasciculation, hypotonia,
    muscle wasting
  • Treatment is to relieve symptoms
  • No cure and death follows

45
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

46
Motor Neuron Disease
  • Supportive Therapy
  • Tryciclic antidepressants
  • Oxygen therapy
  • Antimuscarinics to reduce dribbling
  • Baclofen and diazepam for spasticity

47
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

48
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

49
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.

50
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.

51
Benzodiazepines
  • Midazolam strongly acts on BZ2 receptors thus
    causing amnesia
  • Other receptors are assoc with seizure activity

52
Benzodiazepines
  • Duration of action is dependant on liver
    metabolism
  • Rate of oxidation in the liver decreases with age
    so their effect tends to be longer in the elderly
  • Over dosage may result in CNS depression
  • Antidote is flumazenil (anexate) receptor
    antagonist

53
Benzodiazepines
  • Lorazepam has a short duration of action because
    it is quickly metabolized by the liver into
    inactive products
  • Those with a longer action are more likely used
    to treat anxiety

54
Benzodiazepines
  • Their use does not appear to cause toxicity so
    they are safe for patients who need longer
    therapy, however they are addictive
  • Adverse effect include
  • vertigo, dizziness, depression, blurred vision,
    oversedation, confusion and excitement,
    particularly in elderly patients

55
Benzodiazepines
  • Some benzodiazepines like clonazepam and diazepam
    are effective muscle relaxants.
  • This makes them useful as antiseizure drugs in
    epilepsy and muscle spasticity
  • Short half life benzodiazepines are useful in
    initiation of sleep
  • Temazepam has a longer half life 8 hours ideal as
    sleeper

56
Benzodiazepines
  • More than 2-4 weeks of use can cause dependence
    and tolerance
  • Should be considered for short term treatment
  • A sudden decrease in dose may lead to withdrawal
    symptoms
  • Little evidence to suggest they are effective in
    treating depression
  • Short term treatment of severe anxiety and
    agitation

57
Benzodiazepines
  • Divide into groups and research
  • Diazepam
  • Lorazepam
  • Alprazolam
  • Nitrazepam
  • Temazepam
  • Midazolam

58
Benzodiazepines
  • Diazepam
  • Regularly given parenterally
  • Available in suppository and orally
  • Useful as a premed, treatment status epilepticus

59
Benzodiazepines
  • Clonazepam
  • Most potent
  • Strong muscle relaxant properties
  • Useful for epilepsy or restless leg syndrome
  • Drowsiness and potential for addiction are major
    problems

60
Benzodiazepines
  • Lorazepam
  • One of the most addictive
  • Half life 12-24 hours
  • Treatment of anxiety and insomnia and as a pre
    med

61
Benzodiazepines
  • Alprazolam
  • Unique as possesses antidepressant activity can
    be useful in treatment of depression associated
    with anxiety
  • Takes up to two weeks for anti depressant action
    to appear

62
Barbiturates
  • Work by exerting a depressant effect on the CNS
    ranging from mild sedation to deep anaesthesia
  • Thought to work by impairing the chemical
    transmission of impulses across synaptic
    junctions in the brainstem

63
Barbiturates
  • Some barbiturates e.g phenobarbitone and
    methylphenobarbitone also exert a selective
    action on the motor cortex and produce an
    anticonvulsant effect
  • These drugs reduce REM sleep in the first few
    days Therefore diminished capacity to deal with
    normal stress levels

64
Barbiturates
  • Can also cause excitement characterised by
    restlessness, confusion, disorientation,
    nightmares and delirium
  • Can interfere with warfarin as it increases
    hepatic enzyme activity, and hence increases its
    metabolism

65
References
  • Bullock S. Manias E. Galbraith A. Fundamentals of
    Pharmocology. 5th Edition. Pearson Education
    Australia 2007
  • Ref Bryant, Knights, Salerno 2nd Edition Toronto
    2005
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