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

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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

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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