local & general anesthetic

• Topical formulation


  Usually combined with benzocaine
• Lidocaine


  • Most widely used local anesthetic
  • EMLA (Lidocaine + Prilocaine) - Eutectic Mixture of Local Anesthetic
  • Used for pediatric procedures during venipuncture, circumcisions, IV Cannulation
  • Lidoderm, transdermal medication used for postherpetic neuralgia
• Etidocaine


  • Similar with Lidocaine but with longer duration of action

  
• Bupivacaine


  • Most widely used local anesthetic for obstetric anesthesia but causes cardiac depression more frequently than do other Local anesthetic
  • Used for child delivery
• Ropivacaine


  • Newer drug that may cause fewer cases of cardiac toxicity
• Levobupivacaine


  • Used in epidural anesthesia for labor and delivery
• Prilocaine


  • Congener of Lidocaine
  • Converted to O-toluidine (toxic metabolite) that can cause methemoglobinemia wherein the hemoglobin cannot deliver enough oxygen
  • EMLA Component

  
• Dibucaine


  • Formulated in an ointment used to relieve the pain and itching of hemorrhoids and other problems in rectal area
• Adverse effects (if systemically absorbed)

  • CNS Stimulation followed by inhibition (drowsiness, sedation, euphoria, tremor)
  • Headache, Paresthesia (abnormal sensation of skin), Nausea
  • Higher concentration: Seizures followed by coma
  • Respiratory failure
  • Hypotension and cardiac depression
  • Tachyarrhythmias characterized by a wide QRS complex at toxic levels
  • Blockade of autonomic ganglia and neuromuscular transmission (loss of visceral and skeletal muscle tone)
  • Hypersensitivity reaction (PABA)

  
• Ester Type of Local Anesthetics are almost obsolete. So frequently used is the AMIDE FORM
• They can potentiate the effect of neuromuscular blocking agent (intensified muscle weakness). Use it with great caution to patients with Myasthenia Gravis because it can intensify muscle weakness.

  
• Alzheimer's, Huntington's, Parkinson's, and Multiple Sclerosis Disease have great importance when talking about Neurodegenerative Diseases

  
• Alzheimer's Disease (AD)


  • Most common type of dementia
  • Severe, chronic, progressive, irreversible neurodegenerative and incurable disorder (memory loss, cognition impairment, behavior abnormalities, personality changes)

  
• Manifestations of Alzheimer's Disease


  • Memory Loss
  • Cognition Impairment
  • Behavior Abnormalities
  • Personality Changes

  
• Alzheimer's Disease


  • Neuronal death which results to shrinking of cerebral cortex
  • Loss of density
  • Shrinkage of volume in the brain

  
• Alzheimer's Disease is diagnosed through different CT scan or MRI

  
• Neuropathological hallmarks of Alzheimer's Disease


  • Severe, chronic, progressive, irreversible neurodegenerative and incurable disorder (memory loss, cognition impairment, behavior abnormalities, personality changes)
  • Neuronal death

  
• Alzheimer's Symptoms


  • Confusion with time & location
  • Difficulty completing familiar tasks
  • Misplacing items
  • Difficulty solving problems
  • Memory loss
  • Withdrawal social activities
  • Poor judgment
  • Trouble with images and spaces
  • Unfounded emotions
  • Difficulty with words

  
• Global Deterioration Scale for Assessment of Primary Degenerative Dementia

  • No cognitive decline
  • Very mild cognitive decline (Age Associated Memory Impairment)
  • Mild cognitive decline (Mild Cognitive Impairment)
  • Moderate cognitive decline (Mild Dementia)
  • Moderately severe cognitive decline (Moderate Dementia)
  • Severe cognitive decline (Moderately Severe Dementia)
  • Very severe cognitive decline (Severe Dementia)

  
• Neuropathological hallmarks of Alzheimer's Disease


  • Reduction of acetylcholine
  • Increased glutamate neurotransmission
  • Deposition of amyloid plaques or neuritic plaques
  • Aggregation of neurofibrillary tangles (hyperphosphorylated tau proteins)

  
• Centrally-acting acetylcholine inhibitors (reversible)


  Donepezil, Rivastigmine, Galantamine

  
• Donepezil


  • A reversible cholinesterase inhibitor
  • Selectively inhibits degradation of acetylcholine, increasing acetylcholine level in the cerebral cortex
  • Well absorbed after oral administration, crosses the blood-brain barrier
  • Long half-life of about 70 hours, administered once daily

  
• Rivastigmine


  • Delays global cognitive impairment associated with Alzheimer's Disease
  • Taken in divided doses
  • Transdermal formulation (Exelon Patch) to increase patient compliance

  
• Galantamine


  • Delays global cognitive impairment associated with Alzheimer's Disease

  
• Tacrine, the prototype of centrally acting acetylcholine inhibitors, was already withdrawn because it caused liver toxicity

  
• Memantine


  • Non-competitive antagonist at NMDA receptors
  • Inhibits the activation or opening of NMDA receptor, inhibiting the binding of glutamate
  • Does not delay Alzheimer's Disease progression, but may help initiate the excitotoxic effect of glutamate that may underlie the pathophysiologic process of neuronal loss

  
• No currently approved drugs are known to target the deposition of amyloid plaques or the aggregation of neurofibrillary tangles, which are other neuropathological hallmarks of Alzheimer's Disease

  
• Drugs for Alzheimer's Disease


  • Donepezil (Anticholinesterase, all stages)
  • Galantamine (Anticholinesterase, mild to moderate)
  • Rivastigmine (Anticholinesterase, mild to moderate)
  • Memantine (NMDA-receptor antagonist, moderate to severe)
  • Combination of Donepezil & Memantine (moderate to severe)

  
• Huntington's Disease, also known as Huntington chorea, is an autosomal dominant hereditary neurodegenerative disease

  
• Tau aggregation


  1. Tau binds to microtubules

  2. Tau causes neurofibrillary tangles

  
• MAPT (Microtubule Associated Protein Tau)


  Aggregation results in accumulation of neurofibrillary tangles (NFT)

  
• Tau


  Plays a role in the stabilization of microtubules

  
• Tau hyperphosphorylation


  1. Leads to creation of insoluble helical structures

  2. Aggregates to form NFT

  
• Tau aggregation inhibitor


  Targeted mechanism for Alzheimer's disease hallmark
• Alzheimer's disease drugs


  • Donepezil (Anticholinesterase, All stages)
  • Galantamine (Anticholinesterase, Mild to moderate)
  • Rivastigmine (Anticholinesterase, Mild to moderate)
  • Memantine (N-methyl-D-aspartate (NMDA)-receptor antagonist, Moderate to severe)
  • Combination of Donepezil & Memantine (Moderate to severe)

  
• Huntington's Disease


  • Autosomal dominant hereditary disorder
  • Caused by degeneration of GABA in the striatum
  • Glutamate-induced toxicity
  • Loss of GABA neurons leads to disinhibition of thalamic nuclei and uncontrolled movement

  
• Multiple Sclerosis


  • Chronic disease characterized by demyelination of neurons in the CNS
  • Disruption of nerve transmission
  • Inflammatory response and formation of plaques in brain and spinal cord

  
• Amyotrophic Lateral Sclerosis


  • Progressive disease of the motor neuron
  • Cause unknown, but evidence suggests defect with superoxide dismutase

  
• Spasmolytic agent


  Also known as antispasmodic agent, used to treat skeletal muscle spasm, act centrally
• Muscle relaxants


  • Spasmolytics
  • Neuromuscular blockers (curare, succinylcholine - act peripherally)