CNS

• Neurodegenerative Diseases

  • Parkinson's Disease
  • Alzheimer disease
• Anti-Parkinson's Drugs

  • Levodopa
  • Carbidopa
  • MAOIs (Selegline, Rosagline)
  • COMT inhibitors (Entacapone, Tolcapone)
  • Amantadine
  • Dopamine agonists (Bromocriptine, Pergolide, Pramipexole, Ropinirole)
• Anti-Alzheimer's Drugs

  • Acetylcholinesterase inhibitors (Donepezil, Tacrine, Rivastigmine, Galantamine)
  • NMDA receptor antagonist (Memantine)
• Neurotransmitters of the Central Nervous System (CNS)

  • Acetylcholine
  • Norepinephrine
  • Dopamine
  • Serotonin (5-HT)
  • GABA
  • Glycine
  • Glutamine
  • Substance P
  • Met-Enkephalin
• Excitatory post synaptic potential (EPSP)


  Depolarization caused by Na+ entry
• Inhibitory post synaptic potential (IPSP)


  Hyperpolarization caused by Cl- influx or K+ efflux

  
• Parkinson's Disease

  • Decreased activity of inhibitory dopaminergic neurons in Substantia Nigra & Corpus Striatum
  • Tremors & muscle rigidity
  • Bradykinesia (slowing of voluntary movements)
  • Postural & gait abnormalities
  • Masked face
• Levodopa

  Dopamine precursor that crosses the blood-brain barrier, converted to dopamine in the CNS
• Carbidopa

  Dopa decarboxylase inhibitor that doesn't cross the blood-brain barrier, increases availability of levodopa to the CNS and reduces peripheral side effects

  
• Levodopa effectiveness

  Decreases after 4-5 years due to receptor changes (wearing off effect)
• Levodopa Adverse Effects


  • Nausea & vomiting
  • Arrhythmia & Hypotension
  • Mydriasis
  • Blood dyscariasis
  • Diplopia
  • Visual & auditory hallucinations
  • Dyskinesia
  • Depression & Anxiety
• Levodopa Interactions

  • Vitamin B6 (increases peripheral breakdown)
  • MAO-Inhibitors (hypertensive crisis)
  • Antipsychotic drugs (exacerbate Parkinsonism)
  • Antihypertensives & TCAs (increased hypotension)
  • Glaucoma (increased intraocular pressure)
  • Malignant melanoma (activation)
• Indirect Acting Dopamine Agonists

  • MAO-Inhibitors (Selegline, Rosagline)
  • Amantadine
• Direct Dopamine Agonists


  • Ergot derivatives (Bromocriptine, Pergolide)
  • Non-Ergot derivatives (Pramipexole, Ropinirole, Apomorphine, Rotigotine)
• COMT inhibitors


  Inhibit the enzyme Catechol-O-Methyl Transferase, which metabolizes levodopa, increasing its availability in the CNS

  
• COMT Inhibitors


  • Tolcapone
  • Entacapone
• Alzheimer's Disease

  • Accumulation of senile plaques (beta-amyloid)
  • Loss of cholinergic neurons
  • Formation of neurofibrillary tangles
• Anxiolytics


  • Benzodiazepines (Flurazepam, Estazolam, Lorazepam, Oxazepam, Triazolam, Alprazolam, Chlordiazepoxide)
  • Other Anxiolytics (Buspiron, Hydroxyzine, Antidepressants)
• Hypnotics


  • Benzodiazepines (Flurazepam, Estazolam, Triazolam, Temazepam)
  • Other Hypnotics (Amobarbital, Thiopental, Phenobarbital, Secobarbital, Phentobarbital, Antihistamines, Ethanol, Chloral Hydrate, Eszopiclone, Zolpidem, Ramelteon)
• Benzodiazepines


  Bind to GABA-A receptors, increasing the frequency of chloride channel opening and enhancing the inhibitory effect of GABA

  
• Benzodiazepine Actions


  • Reduce anxiety
  • Cause muscle relaxation
  • Have sedative & hypnotic effects
  • Cause anterograde amnesia
  • Have anticonvulsant effects
• Benzodiazepine Uses


  • Treat anxiety disorders
  • Treat muscular disorders
  • Induce sleep
  • Cause amnesia for medical procedures
  • Treat convulsions
• Flumazenil is a benzodiazepine antagonist
• GABAA Receptors

  Receptors that benzodiazepines act on
• Anti-convulsant


  • One of the uses of benzodiazepines
• Uses of benzodiazepines


  • Anxiety disorders
  • Muscular disorders
  • Sedative
  • Amnesia
  • Anticonvulsants
• Clonazepam, Lorazepam & Diazepam (CLD)

  Used for long term treatment of anxiety disorders
• Alprazolam


  Drug of choice in panic disorders, but causes withdrawal symptoms
• Diazepam


  Used for muscle spasm
• Sedative benzodiazepines


  • Triazolam
  • Flurazepam
  • Temazepam (TFT)
• Esczopiclone, Zoleplone & Zolpidem


  Other hypnotics that don't affect sleep stages, preferred over benzodiazepines
• Midazolam


  Used for amnesia, IV only
• Diazepam & Lorazepam


  Used to treat grand mal and status epilepticus
• Chlordiazepoxide is used for the treatment of delirium tremors (shaking due to withdrawal from alcohol)
• Triazolam is used to induce sleep but is used intermittently due to withdrawal symptoms
• Flurazepam is used for both inducing sleep and awakening
• Temazepam is used to decrease awakening frequency only
• Duration of action of benzodiazepines


  • Long acting (1-3 days)
  • Intermediate acting (10-20 hrs)
  • Short acting (3-8 hrs)
• Physiological and physical dependence can develop with benzodiazepines
• Withdrawal symptoms are more common with short acting benzodiazepines (Triazolam & Oxazepam) than long acting (Flurazepam)