Pharmacology

• Parkinsonism


  Chronic neurologic disorder that affects the extrapyramidal motor tract, causing issues with posture, balance, and locomotion
• Anticholinergics

  • Benztropine mesylate (Cogentin)
  • Trihexyphenidyl (Artane)
  • Ethopropazine (Parsidol)
  • Orphenadrine (Norflex)
• Anticholinergic

  Used to decrease acetylcholine levels, helps with rigidity, sweating, drooling, tremor, and depression
• Parkinsonism

  • Bradykinesia (slow movement & tremors)
  • Rigidity (abnormal increase of muscle tone)
  • No facial expression
  • Involuntary tremors of head & neck
  • Pill rolling movement of hands (involuntary)
• Carbidopa/levodopa (Sinemet)


  Replaces deficient dopamine in the brain, reestablishing the dopamine/acetylcholine balance
• Usual onset of Parkinsonism between 50 & 70 yrs
• Drug response will diminish as Parkinsonism disease progresses
• Pathophysiology of Parkinsonism


  • Imbalance of neurotransmitters dopamine & acetylcholine
  • Degeneration of neurons originating in substantia nigra of midbrain & terminating at basal ganglia
  • Cause is unknown
• Dopamine (DA)


  Inhibitory neurotransmitter from dopaminergic neurons
• Acetylcholine (ACh)


  Excitatory neurotransmitter from cholinergic neurons
• Dopamine normally controls acetylcholine & inhibits excitatory response
• Selegiline (Eldepryl)


  MAO-B inhibitor, may selectively inhibit MAO-B and extend the action of dopamine
• 80% of dopamine depleted by the time Parkinsonism symptoms appear
• Parkinson's medications


  • Anticholinergics
  • Dopaminergics
• Parkinson's medications treat symptoms of the disease, but do not cure it
• Myasthenia Gravis (MG)


  Autoimmune disease with antibody response against the acetylcholine (ACh) receptor at the skeletal muscle site, leading to lack of ACh reaching cholinergic receptors, causing weakness and fatigue of skeletal muscle and weak respiratory muscles
• Drugs for controlling MG

  • Acetylcholinesterase inhibitors (parasympathomimetics)
  • Anticholinesterase inhibitors
• Blood Brain Barrier (BBB)


  Impedes entry of drugs into the brain due to the tight cells composing the walls of the capillaries surrounding the brain
• Medications used to control MG

  • Neostigmine (Prostigmin)
  • Pyridostigmine bromide (Mestinon)
  • Ambenorium (Nlytelase)
• Cholinergic crisis can result from overdosing on MG medications, requiring atropine sulfate to counteract
• Edrophonium Chloride (Tensilon)


  Used in diagnosing MG to distinguish it from cholinergic crisis
• CNS has the ability to alter effects of drugs when taken chronically, leading to tolerance and physical dependence
• CNS Stimulants

  • Amphetamines & caffeine stimulate the cerebral cortex
  • Analeptics & caffeine act on brain stem & medulla to stimulate respiration
  • Anorexiants act on cerebral cortex & hypothalamus to suppress appetite
• Uses of CNS Stimulants

  • Narcolepsy
  • Attention Deficit Disorder (ADD)
  • Appetite suppressants
  • Stimulate respiration
  • Migraine headaches
• Tolerance - decrease response with prolonged use (parkinson's)
• Dependence - abrupt withdrawal = withdrawal syndrom (illegals)
• bradykinesia - slow movement and tremors
• rigidity - abnormal increase of muscle tone
• dopamine - inhibitory from dopaminergic neurons
• acetylcholine - excitatory from cholinergic neurons
• gamma amino butyric acid - released when acetylcholine takes over, and excitation and stimulation of neurons takes place
• GABA - movement disorders of Parkinson's
• Anticholinergic - block cholinergic receptors
• dopaminergic - stimulate dopamine receptors
• Benztropine mesylate - cogentin
• trihexyphenidyl - artane
• ethopropazine - parsidol
• Orphenadrine - norflex
• Levodopa - converted to dopamine in the brain by the enzyme dopa decarboxylase
• carbidopa - inhibits the enzyme dopa decarboxylase, so more levodopa available to be converted to dopamine in the brain