Module 3- Drugs that Influence the CNS Flashcards
Excessive CNS excitation can lead to…
Deleterious effects including
- anxiety
- insomnia
- seizures
Neurochemistry of brain is dependent on
The balance between excitatory and inhibitory signals
What is the primary excitatory neurotransmitter in the brain?
Glutamate
What is the primary inhibitory neurotransmitter in the brain?
Gamma-aminobutyric acid (GABA)
Treatment for anxiety and insomnia?
Appropriate treatment can include
- behavioural changes (i.e. stress reduction and physical exercise)
- Prescription medication (i.e. sedative hypnotic agents)
Sedative Hypnotic agent examples
- anti-anxiety effect- used to treat anxiety disorders (OCD)
- sedation: relieve anxiety, decrease activity, moderate excitement and calm individual
- hypnosis: produce drowsiness and aid in the onset and maintenance of sleep
- general anesthesia: state of unconsciousness with absence of pain sensation
Examples of anxiety disorders sedative hypnotics treat
- generalized anxiety
- obsessive compulsive disorder
- panic disorder
- post traumatic stress disorder
- phobias
How doe sedative hypnotics treat anxiety?
Reduces the amount of glutamate-induced neural excitation by increasing the GABA inhibitory signalling in the brain
The Chloride ion channel
- GABA binds to chloride channel on the membrane of neuron in the brain and spinal cord
- binding causes channels to open and allows negatively charged ions to flow into the cell, resulting in an inhibitory effect
- SHAs also bind here, on a different site on the chloride channel -> resulting in an increase in synaptic inhibition and dampening neuronal responses
Drugs that bind to the chloride channel
- benzodiazepines
- Barbiturates
- The “Z” drugs
Where do benzodiazepines bind
bind to the chloride channel at the benzodiazepine receptor, and increases the frequency of GABA receptor mediated opening of the chloride channel
How are benzodiazepines classified?
Allosteric activator
Benzos bind to and activate a separate receptor on the chloride channel than the neurotransmitter GABA, which makes it an allosteric activator
Pharmacokinetics of benzodiazepines
absorption: usually taken as a capsule, or tablet
metabolism: have different durations of action, determined by the rate of liver metabolism and formation of, or lack of formation of pharmacologically active metabolites
Pharmacological properties of Benzodiazepines
- possess very high therapeutic index
- relieve anxiety
- produce sedation and amnesia
- decreased aggression
- some are effective hypnotics
- minimal suppression of REM type sleep
- skeletal muscle relaxation
- anticonvulsant action
Short term use of benzodiazepines
Produces: relaxation, calmness, and relieve from anxiety of tension
Adverse effects: drowsiness, lethargy, impairment of thinking/memory, nausea, and constipation
Moderate doses can impair motor coordination and driving, so patients should refrain
Long term use of benzodiazepines
Varies between individuals
- some take large amounts for long periods of time without major evidence of intoxication
- others demonstrate symptoms of chronic-sedative hypnotic intoxication (i.e. impaired thinking, poor memory/judgement, disorientation and incoordination)
Elderly and benzodiazepines
can produce cognitive dysfunction, because benzos metabolize more slowly than young adults, often leading to over-sedation, falls and injury
Pregnant/breastfeeding women and benzodiazepines
benzos freely cross the placenta and distribute int the fetus
- risk of fetal abnormalities
lethality and benzodiazepines
Death from overdose is rare, but does occur following ingestion of enormous doses
Flumazenil
Benzodiazepine receptor antagonist that blocks the effect of benzodiazepines
- Antidote for benzo overdosing
Benzodiazepines misuse potential
Low- as they are weaker reinforcing properties than barbiturates, opioids, and stimulants
Benzodiazepine use disorder
Low misuse, but high degree of cross tolerance among benzos and other sedative-hypnotic drugs
Barbiturates
Potent CNS depressants
Classes of barbiturate
Long acting (1-2 days)- phenobarbital
Short acting (3-8 hours)- secobarbital
ultrashort acting (20 mins)- thiopental