antiparkinsonian agents l.
Download
Skip this Video
Loading SlideShow in 5 Seconds..
ANTIPARKINSONIAN AGENTS PowerPoint Presentation
Download Presentation
ANTIPARKINSONIAN AGENTS

Loading in 2 Seconds...

play fullscreen
1 / 57

ANTIPARKINSONIAN AGENTS - PowerPoint PPT Presentation


  • 186 Views
  • Uploaded on

ANTIPARKINSONIAN AGENTS. MA. LENY ALDA G. JUSAYAN, MD DEPARTMENT OF PHARMACOLOGY. PARKINSONISM. Tremors are present even at rest Rigidity & impairment of voluntary movements Postural tremor, intention tremors. The UK Parkinson's Disease Society Brain Bank Criteria For Clinical Diagnosis:.

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'ANTIPARKINSONIAN AGENTS' - jesse


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.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
antiparkinsonian agents

ANTIPARKINSONIAN AGENTS

MA. LENY ALDA G. JUSAYAN, MD

DEPARTMENT OF PHARMACOLOGY

parkinsonism
PARKINSONISM
  • Tremors are present even at rest
  • Rigidity & impairment of voluntary movements
  • Postural tremor, intention tremors
the uk parkinson s disease society brain bank criteria for clinical diagnosis
The UK Parkinson's Disease SocietyBrain Bank Criteria For Clinical Diagnosis:
  • Bradykinesia plus one of rigidity, tremor, or postural instability
  • At least three of rest tremor, progressive symptoms, unilateral onset, early response to levodopa, revodopa-induced dyskinesia
  • No identifiable cause for the parkinsonism.
motor symptoms
Motor Symptoms:
  • Tremor:
    • 70% of patients suffer resting tremor
    • pill rolling quality
    • can affect all of the limbs as well as the face, neck, head and jaw.
  • Rigidity:
    • increased tone or stiffness in the muscles
    • mask-like face and clog-like release of muscles.
  • Bradykinesia
    • difficulty initiating and continuing movement.
slide5

Postural Instability

    • Forward flexion of neck, hips, knees and elbows leads to poor balance.
  • Gait disorders
    • Shuffling, small steps described as festination, reduced arm swing and sudden freezing spells lead to problems walking
  • Swallowing (dysphagia) and Speech disorders (dysarthria)
  • Handwriting: Micrographia
nonmotor symptoms
Nonmotor Symptoms:
  • Depression:
    • 20-90% major depressive episode, reactive or endogenous
  • Dementia:
    • 20% of patients will become demented (have impairments of 3 of the following in the presence of clear consciousness: language, memory, visuospatial skills, emotionality, personality and cognition
slide7

Sleep disturbances:

    • Problems with sleep fragmentation, sleep initiation, early morning awakening, excessive daytime somnolence and parasomnias.
  • Sexual dysfunction
  • Ability to drive a car
  • Ability to gain employment
  • Constipation
chorea
CHOREA
  • Irregular, unpredictable involuntary jerks
  • Impaired voluntary activity
  • ballismus
athetosis
ATHETOSIS
  • Slow & writhing movements
  • Abnormal postures (dystonia)
slide11
TICS
  • Sudden coordinated abnormal movements
  • Repetitive sniffing
  • shoulder shrugging
  • face & head movement
pathogenesis
PATHOGENESIS:
  • Idiopathic
  • Exposure to unrecognized neurotoxins
  • Oxidation reaction with generation of free radicals
  • Reduced level of dopamine in the basal ganglia
slide14
Pyramidal System:

begins in the primary motor cortex

descends through the corticospinal and corticobulbar tracts

affects the lower motor neurones in the brain stem and spinal cord.

slide15

Extrapyramidal System:

    • basal ganglia and their cortical connection
    • basal ganglia are made up of the:
      • Caudate Nucleus
      • Putamen (Striatum)
      • Globus Pallidus interna (Gpi)
      • Globus Pallidus externa (Gpe)
      • Subthalamic Nucleus
      • Substantia Nigra
      • main outputs of this system are the Substantia Nigra and the Gpi, both of which feed to the ventrolateral thalamus.
slide16

The main Pathological feature of Parkinson’s disease is the loss of the dopaminergic nigrostriatal pathway

  • 80% of the Dopamine producing cells must be lost before symptoms begin to show
goals of treatment
GOALS OF TREATMENT:
  • Pharmacologic attempt to restore dopaminergic activity with levodopa and dopamine agonists
  • Restore normal balance of cholinergic & dopaminergic influences on the basal ganglia
pathophysiologic basis of treatment
PATHOPHYSIOLOGIC BASIS OF TREATMENT:
  • Dopaminergic neurons in the substantia nigra that normally inhibit the output of GABAergic cells in the corpus striatum are lost
levodopa
LEVODOPA
  • (-) -3-(3-4 dihydroxyphenyl) L- alanine
  • Immediate metabolic precursor of dopamine
  • Levorotatory stereoisomer of dopamine
pharmacokinetics
PHARMACOKINETICS:
  • Rapidly absorbed from the SI
  • Food delays absorption
  • Amino acids in food competes with drug
  • Peak plasma concentration: 1-2 hrs
  • Plasma t ½ : 1-3 hrs
  • HVA, DOPAC (dihydroxyphenylacetic acid) are main metabolites
clinical use
CLINICAL USE:
  • Responsiveness may be lost secondary to disappearance of dopaminergic nigostriatal nerve terminals
  • Early use lowers mortality rate
  • Combined with Carbidopa & Benseraside
  • Sinemet – dopa preparation containing levodopa in fixed proportion (1:10 or 1:4)
  • Sinemet 25/100 TID
  • 30 -60 minutes before meals
adverse effects
ADVERSE EFFECTS:
  • GIT effects
  • Cardiovascular
  • Dyskinesias
  • Behavioral effects
  • Fluctuations in response
  • Misc: mydriasis, blood dyscrasias, hot flushes, gout, brownish discoloration of the urine, abnormal smell
drug interactions
DRUG INTERACTIONS:
  • Vitamin B6 enhance extracerebral metabolism of levodopa
  • MAO – A inhibitors
contraindications
CONTRAINDICATIONS:
  • Psychoses
  • Angle closure glaucoma
  • Cardiac dysrhythmia
  • PUD
  • Melanoma or suspicious undiagnosed skin lesions
dopamine agonists
DOPAMINE AGONISTS
  • Do not require enzymatic conversion for an active metabolite
  • No potential toxic metabolites
  • Do not compete with other substances for an active transport
  • First line in parkinsonism
  • End of dose akinesia to levodopa
  • On & off phenomenon refractory to levodopa
ergot alkaloids
ERGOT ALKALOIDS:
  • BROMOCRIPTINE
    • D2 agonists
    • Endocrinologic disorders (hyperprolactinemia)
    • Absorbed variably in GIT
    • Peak plasma levels: 1-2 hrs
ergot alkaloid
ERGOT ALKALOID:
  • PERGOLIDE
    • Stimulates both D1 and D2
    • More effective than bromocriptine
clinical use37
CLINICAL USE:

BROMOCRIPTINE:

  • 7.5 mg & 30 mg
  • 1. 25 mg BID after meals X 2-3 months and increase 2.5 mg q 2 wks

PERGOLIDE:

- 3 mg daily

- 0.05 mg starter dose

adverse effects38
ADVERSE EFFECTS:
  • GIT
  • Cardiovascular
  • Dyskinesias
  • Mental disturbances
  • Misc: erythromelalgia
non ergot dopamine agonists
NON-ERGOT DOPAMINE AGONISTS:
  • PRAMIPEZOLE
    • Preferential affinity to D3
    • Monotherapy is effective
    • Neuroprotective (H scavenger)
    • Enhance neurotrophic activity
    • Rapidly absorbed
    • Peak plasma concentration: 2 hrs
    • 0.125 mg TID then doubled after 1 wk
    • Increments of 0.75 mg at weekly intervals
non ergot alkaloids
NON-ERGOT ALKALOIDS:
  • ROPINIROLE
    • Pure D2 receptor agonists
    • 0.25 mg TID then total daily dose is increased by 0.75 mg at weekly intervals until the 4th wk & increased by 1.5 mg thereafter
side effects
SIDE EFFECTS:
  • Postural hypotension
  • Fatigue
  • Somnolence
  • Peripheral edema
  • Nausea
  • Constipation
  • Dyskinesias
  • Confusion
monoamine oxidase inhibitors
MONOAMINE OXIDASE INHIBITORS
  • MAO – A: metabolizes NE & serotonin
  • MAO – B: metabolizes dopamine
selegiline deprenyl
SELEGILINE (Deprenyl)
  • Selective inhibitor of MAO-B
  • Retards breakdown of dopamine
  • Adjunct in fluctuating response to levodopa
  • 5 mg with breakfast & lunch
  • Cause insomnia when taken during the day
  • Not to be taken with meperidine, TCAs, SSRIs
  • Increase adverse effects of levodopa
rasagiline
RASAGILINE
  • MAO-B inhibitor
  • Potent than selegiline
  • CI with levodopa – HPN crisis
cathecol o methyltransferase inhibitors
CATHECOL-O-METHYLTRANSFERASE INHIBITORS:
  • TOLCAPONE- central & peripheral metabolism
  • ENTACAPONE
    • peripheral metabolism
    • Prolong the duration of levodopa by decreasing its peripheral metabolism
    • Helpful in patients receiving levodopa who have fluctuations
    • t ½ = 2 hrs
amantadine
AMANTADINE
  • Antiviral agent
  • Potentiates dopaminergic function by influencing the synthesis, release, reuptake of dopamine

PHARMACOKINETICS:

  • peak plasma concentration: 1-4 hrs after oral dose
  • Plasma t ½ = 2-4 hrs
clinical use49
CLINICAL USE:
  • Less potent than levodopa and benefits are short-lived
  • 100 mg BID-TID

ADVERSE REACTIONS:

  • Restlessness, depression, irritability, insomnia, agitation, excitement, hallucinations & confusion
  • Livedo reticularis
contraindications50
CONTRAINDICATIONS:
  • History of seizures
  • Heart failure
acetylcholine blocking agents
ACETYLCHOLINE BLOCKING AGENTS:
  • Improve tremor & rigidity of parkinsonism but have little effect in bradykinesia
  • Benztropine mesylate
  • Biperiden
  • Orphenadine
  • Procyclidine
  • Trihexyphenidyl
adverse effects52
ADVERSE EFFECTS:
  • CNS
  • Mydriasis, urinary retention, constipation, tachycardia, tachypnea, increase IOP, palpitations, cardiac arrythmias
  • Acute suppurative parotitis
contraindications53
CONTRAINDICATIONS:
  • Prostatic hyperplasia
  • Obstructive GI diseases
  • Angle closure glaucoma
slide54

The net result of all of these medications is the balancing out of the acetylcholine/dopamine balance and an improvement in movement

surgical procedures
SURGICAL PROCEDURES:
  • Thalamotomy – conspicous tremor
  • Posteroventral pallidotomy