1. Agents for Traumatic Brain
Injury
Brian J. Piper, Ph.D., M.S.
piperbj@husson.edu
February 15, 2013
2. Objective
• Pharmacy students should be familiar with
different pharmacotherapies used with brain
injury including their:
– mechanisms of action
– relative efficacy
– adverse effects
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 < .05
Friedman et al. (1999). Neurology, 52(2), 244-250.
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.
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.
17. Passive Avoidance
Day 1: Training
Drug
Day 3: Test
Hauer et al. (2011). Anesthesiology, 114(6), 1380 – 1388.
Notes de l'éditeur
Post-mortem CT of bullet through brain (note bone fragments, white, and gas build-up, black).
T2 MRI showing micro-hemorage (black).
Age distribution is tri-modal with peaks in infancy, adolescence/young-adulthood, and elderly. TBIs are most likely to be fatal among the elderly.
APOE is an attractive target because it is thought to play an important role in synaptic repair, remodeling,and neuron protection.After a follow-up period of 6 to 8 months, a functional assessment regarding mobility and independence in activities of daily living was performed. Residual communicative disorders, either dysphasia or dysarthria (difficulty with articulation), were determined by speech pathologists. Note that this finding has not been consistently replicated.
Dopamine has less prominent effects on adrenergic receptors. Higher doses can elevate diastolic and heart rate.
Manitol is a sugar alcohol. The root of both "mannose" and "mannitol" is manna, which the Bible records as the food supplied to the Israelites during their journey in the region of Sinai. There are case reports of renal failure.
Failure was defined as the persistence of intracranial hypertension despite two successive infusions of the same osmotic agent.
Dr. Conrad Murray was convicted of involuntary manslaughter in 2011 and sentenced to 4 years. 3/5 of people receiving Propofol will report pain upon initial administration and 1/5 will report severe pain. A common solution is to co-administer with lidocaine.
This agent has a moderate effect on somatodendritic GABAB receptors too. Due to white color, this agent is also know as “milk of amnesia”. This agents can put people to sleep in 30 seconds. Edetate disodium is used to inhibit bacteria & fungal growth but likely contributes to the antioxidant effect.
Rhabdomyloysis:An acute, sudden, potentially fatal disease that destroys skeletalmuscle and is often accompanied by the excretion of myoglobin in the urine.