3 - PHARMACO IN NEUROREHAB Flashcards
Requirements for definition of NT
- Synthesized by neuron
- Pre-synaptic vesicles
- Subsides regulatory mechanism
- Specific receptors
- When provided artificially
Transmission & re-uptake
- Synaptic cleft
- Post-synaptic receptors
- Pre-synaptic receptor
- Re-uptake & destruction
Categories of NT
Amines
- EPI
- His
- ACh
- NE
- SE
- DA
Amino-acids
- Glycine
- Asparate
- Glu
- GABA
DA => presynaptic receptors + transport
SE & NE => transport
Norepinephrine description
Norepinephrine (NE)
- Used by neurons located on locus coeruleus (brainstem nucleus)
- Action on sleep, wakefulness, feeding behavior & affecting attention and memory consolidation
- Leading CNS into state of high alert
- Receptors: NE alpha & NE beta
Serotonin description
- 5-hydroxitryptamine
- Produced by brainstem nuclei
- Pathways leading to hypothalamus & dorsal spinal cord Rexed Laminae
- Receptors: 1A, 1B, 1D, 2A, 2C, Ser3, Ser4, Ser5, Ser6, Ser7
- Behavioral effects: modulates mood, perception, memory, anger, aggression, fear, appetite & sexuality
- Plays role in stress responses & addiction
- Influences: indirect way plays role in motor control, cerebellar function, circadian rhythm,
vascular tone in CNS, respiratory drive & body temperature
Dopamine
- description
- DADR
Dopamine (DA)
- Mesocortical pathway: associated with direct behavior, attention & motivational responses
- Mesolimbic pathway: associated with goal directed behavior, pleasure & emotional processes
- Nigrostriatal pathway: associated with movement coordination, attention & adaptation
TABLE
Glutamate
Glutamate (Glu)
- Most common excitatory NT in CNS
- Involved variety of processes, from cognition, memory consolidation & learning
- Most studied receptors: NMDA & AMPA, post-synaptic receptors responsible for activation of post-synaptic neuron
GABA
- acronym
- description
Gamma-aminobutyric acid (GABA)
- Synthetized directly from Glu
- Most important & most common inhibitory NT found in CNS
- Involved in avoiding “over-excitation” of neurons, playing role in inhibitory control
- Receptors GABAa & GABAc
Why prescribed medication
Prescription
- Pain management
- Management of movement disorder
- Increase sleep
- Increase arousal
- Reduce anxiety, depression
Selection criteria:
- clinical
- technical
Selection criteria
Clinical
- DTC
- Clinical efficiency
- Recommendations
- Approved indications
- Scientific literature
- Legal status
Technical
- Packaging
- Convenience
- Label
- Expirations
- Storage
- Safety of utilization
- Storage
Substances supporting neuroplasticity
Substances supporting neuroplasticity
- As general rule: stimulants that mimic excitatory NT
- Not case in regulatory issues affecting systems modulated by these NTs
- Positive impact on CNS physiology, associated with BDNF and/or GNDF release, doesn’t consider systemic impact
- These substances highly likely to lead to withdrawal syndrome & addiction
Substances slowing down neuroplasticity
Substances slowing down neuroplasticity
Patients showed significantly worse functional outcomes, in comparison to controls
- Anti-convulsive
- Phenytoin
- Barbiturates
- Benzodiazepines
- Butyrophenones
- Clonidine
- Prazosin
Common substances prescribed in TBI & stroke
Common substances prescribed in TBI & stroke
Psychotropic medication in TBI common, with 4/10 being prescribed these substances. Lower GCS &
midline deviation independently associated with increased medication use, suggested to be directly
correlated to late mortality
- Diuretics
- Anticonvulsants
- Barbiturates
- Calcium channel blockers
- Stimulants
- Antipsychotics
- Pain relievers & relaxers
Diuretics:
- other name
- side effects
- adverse effects
Table
Anticonvulsants:
- side effects
- adverse effects
Table
Barbiturates:
- other name
- side effects
- adverse effects
- steps
Table
Calcium channel blockers:
- other name
- side effects
- adverse effects
- steps
Table
Stimulants:
- other name
- side effects
- adverse effects
Table
Antipsychotics:
- other name
- side effects
- adverse effects
- steps
Table
SSRIs:
- acronym
- description
Selective serotonin reuptake inhibitors
SSRIs
- Citalopram, Escitalopram, Fluoxetine, Paroxetine, Sertraline
- Clearer from circulation by liver
- Reaching CNS, impairs SE reuptake
- Decrease symptoms of depression & anxiety
- Causes increase in BDNF release (side effect)
- Treatment time between 3 to 8 weeks
Over activity => serotonin syndrome
SSRI discontinuation => withdrawal syndrome
Serotonin syndrome:
- neuromuscular symptoms
- cognitive effects
- autonomic effects
Neuromuscular symptoms
- Ocular myoclonia
- Tremor
- Hyperreflexia
Cognitive effects
- Agitation
- Inability to remain still
- Attention deficit
- Working memory
Autonomic effects
- Hypertension
- Tachycardia
- Sweating
- Dilated pupils
SSRI withdrawal syndromes:
- description of symptoms
- impact
SSRI withdrawal syndrome
- Dizziness
- Sleep disturbance
- Sweating
- Tremor
- Nausea
- Brain zaps
Impact:
- Participation in ADLs
- Communication & interpersonal relationships
- Learning & skill development
- Recovery from injury
- Balance & RoF
Dopaminergic agents in PDs & secondary Parkinsonism:
- aims & methods
- most used medication
Aims & methods
- Influence balance in DA pathway’s activity
- Most used medication:
o DA precursors (L-dopa, Duopa)
o DA agonists (Pramipexole, Ropinirole, Rotigotine, Apomorphin)
o MAO B inhibitors (Slegiline, Rasagiline, Safinamide)
o COMT (Entacapone)
o Anticholinergics (Bensotropine, Thrihexyphenidyl)
o Amandatine
DA precursor description
DA precursors
- Carbidopa allows levodopa to cross BBB to then be converted into DA
- Side effects include dyskinesia (higher doses)
- Adaptation responsible for necessity of re-adjusting dosage from time to time
- L-dopa most used, administered orally, Duopa can be administered continuously IV
DA agonists
DA agonists
- Not as effective as L-Dopa, but with longer half-life
- Often used as adjunct to L-dopa therapy
- Side effects often seen hallucinations, sleepiness & compulsive behavior
Amantadine
Amantadine
- Short-symptom relief
- Mostly used at later stages of DA diseases
- Adverse effects often observed include cardiovascular dysfunction & hallucinations
- Withdrawal & dependency might be issue
Anti-AChergic
Anti-AChergic
- Used as adjunct to L-Dopa therapy
- Can be helpful in regulating (persistent) dyskinetic symptoms
- Adverse effects include memory deficit, confusion, hallucinations, constipation &
impaired urination
COMT inhibitors
COMT inhibitors
- Inhibits another enzyme responsible for DA metabolism in brain
- Used to prolong effects of L-dopa
- Side effects: may increase intensity of dyskinetic behavior, diarrhea
- Tolcapone (common COMPT inhibitor) rarely prescribed due to increased risk of liver damage
MAO B inhibitors
MAO B inhibitors
- Prevent breakdown of DA in brain by inhibiting enzyme monoamine oxidase B
- Side effects: nausea & insomnia
- When administered with L-dopa, prevalence of hallucinations increased
- Life-threatening adverse effects have been observed when in association with antidepressants and/or narcotics
Benzodiazepines:
- definition
- name of each
- half life
GABAergic substances, that bind-activating, potentializing synapse
Half-life of benzodiazepines
Alprazolam: 6 to 12 hours
Chlordiazepoxide: 5 to 30 hours
Clonazepam: 18 to 50 hours
Diazepam: 20 to 100 hours
Lorazepam: 10 to 20 hours
Oxazepam: 4 to 15 hours
Temazepam: 8 to 22 hours
Triazolam: about 2 hours
Alprazolam:
- description
Alprazolam
- GABA-a agonist, binding activating, increasing duration of chloride channels opening
- Xanax®, Luvox®, Serzone®, Fycompa®, Briviact®, Krlym® and Incivek®
- Most frequently prescribed benzodiazepine
- Treatment of anxiety disorders and, in fewer cases, also depression & premenstrual syndrome
o Drowsiness
o Headache
o Irritability
o Memory & attention deficit
o Nausea
o Constipation
o Difficulty urinating
o Articular pain
Used only for short periods of time due to high addictive quality, some physicians still
recommend prolonged used in many cases
Alprazolam described by addiction specialists as possessing abuse liability which described
probability led to abuse & thereby, become addictive
Lorazepam:
- description
- side effects
- adverse effects
Lorazepam
- Often prescribed for schizophrenia, bipolar disorder & depression, as well as in irritability
associated with ASD & Tourette’s syndrome
- Ativan®, Luvo®, Equetro®, Lyrica®, Abilify®, Aripripazole®, Zyprexa®, Aristada®, Lunesta®, Meridia®
- Used to treat epilepsy, insomnia, nausea (caused by chemotherapy) & control agitation caused by alcohol withdrawal
- Main goals of treatment include:
o Rapid tranquilization in panic & phobia
o Treat effects of alcohol withdrawal syndrome
o Support sleep
o Reduce delirium
o Reduce chemotherapy associated nausea & vomiting
o Reduce psychogenic catatonia
TABLE
Clonazepam:
- description
Clonazepam
- GABAergic, same mechanism
- Klonopin & sabril
- Anti-epileptic (anti convulsant)
- Used to treat dyskinetic & myoclonic seizures, as well as in panic disorders
o Muscle weakness
o Loss of coordination
o Confusion / change in alertness
o Depression
o Suicidal thoughts / attempts
o Memory & attention deficit
o Swelling of face & tongue (allergic reaction)
Non-benzodiazepine:
- name one
- describe it
- its side effects
- its adverse effects
- mechanism of action
Zolpidem (ambien)
- Non benzodiazepine sedative
- Used in severe sleep disorders
- Ativan, Luvo, Equetro, Lyrica, Abilify, Aripripazole, Zyprexa, Aristada, Lunesta, Meridia
TABLE
Mechanism of action
- Mechanisms relaying partial recovery of speech, cognitive & motor function on TBI patients under influence of zolpidem not fully understood
- Studies proposed mechanistic model, based on altered EEG dynamics in patients on & off
medication
If no zolpidem, all subjects show strong/low frequency oscillatory peak 6-10 Hz (mostly frontal)
6-10 Hz activity proposed to arise from intrinsic membrane properties of pyramidal neurons
