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Agents for Brain Injury

This PPT is part of a lecture given to second year pharmacy students in a pharmacology & toxicology class.

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Agents for Brain Injury

  1. 1. Agents for Traumatic Brain Injury Brian J. Piper, Ph.D., M.S. piperbj@husson.edu February 15, 2013
  2. 2. Objective• Pharmacy students should be familiar with different pharmacotherapies used with brain injury including their: – mechanisms of action – relative efficacy – adverse effects
  3. 3. falls motor-vehicle/assaults falls/motor-vehicleBurns & Hauser (2003) Epilepsia, 44(S10), 2-10.
  4. 4. Individual Differences following TBI apoE4+ (N=27) apoE4- (N=42) Unconscious for >1 week 77.8% 38.1%* Dysarthria 63.0% 33.3%* Overall Function: excellent 3.7% 31.0%* * p < .05Friedman et al. (1999). Neurology, 52(2), 244-250.
  5. 5. Secondary Injury• All brain damage does not occur at the moment of impact (primary injury) but evolves over the ensuing hours and days (secondary injury).• The injured brain is extremely vulnerable to hypotension, hypoxia, and increased intracranial pressure which are causes of secondary injury.
  6. 6. ↓ Blood Pressure: Tx-Dopamine• MOA: D1 > α1• Effects: ↑ systolic bp
  7. 7. Intra-Cranial Pressure• There is only one way out of the intracranial vault, the opening at the base of the skull: foramen magnum
  8. 8. ↑ Intracranial Pressure: Tx-Mannitol • History: sugar derivative of mannose-1961 • Frequency: majority of trauma centers • Effect: – immediate ↓ ICP; withdrawal ↑ ICP – renal failureGrande & Romner (2012). J Neurosurg, 24(4), 407-412.
  9. 9. Mannitol versus Hypertonic Saline ->Vialet et al. (2003). Critical Care Medicine, 36, 795-800.
  10. 10. Mannitol versus Hypertonic SalineVialet et al. (2003). Critical Care Medicine, 36, 795-800.
  11. 11. ↑ Intracranial Pressure: Tx- Barbiturates • Indications: – ↑ ICP refractory to other treatments • Frequency: minority of trauma centers • Rationale: – ↓ neuron activity ↓ metabolic demands – ↓ free radical formation • Effect: – immediate ↓ ICP; hypotension (25%)Roberts & Sydenham (2012). Cochrane Database of Systematic Reviews, 10.1002/14651858.CD000033.pub2.
  12. 12. Absence of evidence ≠ Evidence of absence • “There is insufficient reliable evidence to make recommendations on the use of mannitol in the management of patients with traumatic brain injury.” • “There is no evidence that barbiturates improve outcomes in people with acute brain injury.”Wakai et al. (2008). Cochrane Database of Systematic Reviews, 10.1002/14651858.CD001049.pub4.Roberts & Sydenham (2012). Cochrane Database of Systematic Reviews, 10.1002/14651858.CD000033.pub2.
  13. 13. Propofol Factoids
  14. 14. Propofol• Indication: hypnotic (not analgesic)• MOA: – GABAA agonist – NMDA antagonist – ↓ glutamate release – ↓ excitotoxicity/antioxidant• General: consistent, rapid loss (& recovery) of consciousness, amnesic, excellent safety margin• Other ingredients: egg phosphatate & edetate disodium (EDTA) Example 0:35 to 1:20: http://www.youtube.com/watch?v=kmMFLOXLD-Q Kotani et al. (2008). CNS Neuroscience & Therapeutics, 10.1111/j.1527-3458.2008.00043.x
  15. 15. Propofol Infusion Syndrome• Combination – critically ill children + long-term/high-dose propofol – catecholamines or steroids too• Symptoms: – rhabdomyolasis – renal/cardiac failureVasile et al. (2003). Intensive Care Medicine, 29, 1417-1425.
  16. 16. Memory• ------------------------|---------------------------- trauma• Anterograde Memory: propofol decreases memory of events that happen post-trauma• Retrograde Memory: propofol increases memory of events that occur pre-trauma
  17. 17. Passive Avoidance Day 1: Training Drug Day 3: TestHauer et al. (2011). Anesthesiology, 114(6), 1380 – 1388.

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