CNS Flashcards
CNS drugs can act on ___ and ___ receptors to produce an affect, causing one of what five actions?
pre and post synaptic receptors
- production
- storage
- release
- termination of action
- activate or block receptors
CNS is very similar to ANS in terms of the actions that occur at the synaptic clefts… what 3 things make it different?
- CNS= more complex and many more synapses
- CNS= strong inhibitory neuron network constantly modulating transmission
- CNS= More neurotransmitters
some drugs acting on the CNS do so by manipulating what two ion channel types?
- voltage-gated (response to changes in membrane potential- channel types: Na, K, Ca)
- ligand -gated: NTs bind receptors
ligand- gated ion channels: what are 3 types of receptor-channel coupling?
- receptor acts directly on channel
- Receptor is coupled to ion channel which is regulated by NTs and their receptors
- Receptor is coupled to G protein that activates 2nd messenger…
- Cyclic adenosine monophosphate (cAMP)
- Inositol triphosphate (IP3)
- Diacylglycerol (DAG)
Neurotransmitter bind to postsynaptic neuron receptor, elicits response and trigger what two things?
EPSP and IPSP
excitatory post-synaptic potential and inhibitory post-synaptic potentials
what are our two excitatory NTs?
Ach, glutamate
what are our two inhibitory NTs?
GABA and glycine
EPSP is generated by…
Binding to receptor= small depolarization to stimulate EPSP
–> increased permeability of Na+
–>increase intensity and more presynaptic fibers activated
When enough excitatory fibers activated get complete depolarization of postsynaptic neuron
IPSP is generated by…
Stimulation if inhibitory neuron =release of inhibitory NTs to bind to postsynaptic neuron
–> increased permeability of K+ and Cl- channels
–> hyperpolarization (which stops that transmission from going on)
This diminishes action potential and neuron firing
3 characteristics of NTs found in CNS
- Found in high concentrations in synaptic area
- Release via calcium-dependent mechanism
- Produce postsynaptic response resulting in physiologic activity
what are our 4 main types of NTs found in the CNS?
- Ach
- Amino acids
- Monoamines
- peptides
what are the amino acids in the CNS?
glycine, glutatame, GABA
what are the monoamines in the CNS?
Serotonin, histamine
Catecholamines:
Dopamine, Epinephrine, Norepinephrine
what are the peptides in the CNS?
endorphin, opioid peptides, substance P
binding of excitatory NT Ach causes ____ while binding of inhibitory NT GABA causes _____
depolarization (Na + enters cell)
hyperpolarization (Cl- enters cell)
what three receptor types does Ach bind to? excitatory or inhibitory?
Binds to M1 receptors: excitatory (like agonist)
Binds to M2 receptors: inhibitory (like antagonist)
Binds to Nicotinic receptors: excitatory (like agonist)
what does serotonin bind to and cause?
Bind to serotonin GPCR – 14 different receptors to date
Depending on receptor subtype can cause excitation or inhibition
what does histamine bind to and cause?
Bind to histamine GPCR – 4 (H1-H4)
Affect arousal, body temp, vascular dynamics, gastric acid secretion
what does dopamine bind to and cause?
Binds primarily to D2 receptor
Exerts slow inhibitory actions postsynaptically
Inhibits calcium channels presynaptically
-more in CNS than periphery
what does norepi bind to and cause?
Excitatory effects produced when activate α1 & β1
Inhibitory effects produced when activated α2 presynaptically
tell me about what we know about Epi?
Small amount in CNS
Physiologic properties not clearly defined
what does glutamate bind to and cause?
Excitatory
Bind to ionotropic (NMDA, AMPA, KA) and metabotropic (8– mGluRs) receptors
Excess attributes to damage and cell death
what does GABA bind to and cause? where is it located?
CNS-slow things down
Primary IPSP in the brain – inhibitory
Bind to GABAA or GABAB receptors
what does glycine bind to and cause? where is it located?
Primary IPSP in the spinal cord – Inhibitory
Bind to ionotropic glycine receptors
selectivity of a drug is based on what? more selective = ?
based on the fact that neurons with different functions have different neurotransmitters
more selectivity = less side effects
what are the downsides to the lipid solubility of CNS drugs?
lipid soluble to get into CNS…but that means they also readily cross the placenta and enter fetal circulation
almost all require hepatic metabolism to become polar (water soluble) for elimination/excretion
CYP450 enzymes and drug interactions needs consideration
This can impact clearance of CNS drugs, affect intensity and/or duration of their effect
lots of anti-epileptic have interactions
NT may inc Cl- conductance to cause?
inhibition
NT may inc K+ conductance to cause?
inhibition
NT may inc Na+ conductance to cause?
excitation
NT may inc Ca+ conductance to cause?
excitation
how is the scheduling of controlled substances set up?
Schedule I greatest potential for abuse–>
Schedule V least potential for abuse
schedule 1
high potential for abuse
NO currently accepted medical use
lack of accepted safety for use under medical supervision
Can only get with special paper work, no prescriptions can be written
Heroin, LSD, PCP (general examples)
schedule 2
high potential for abuse accepted medical use. Abuse: severe psychological or physical dependence May not be refilled Examples: opiods, amphetamines
what are 4 opiod/amphetamine schedule 2 drugs?
Fentanyl
Methadone
Cocaine (vasoconstrictive- severe nose bleeds)
Methylphenidate (ritalin)
schedule 3
potential for abuse less than schedules I and II
accepted medical use.
Abuse: moderate or low physical dependence or high psychological dependence
Examples:
Testosterone
Buprenorphine
Dronabinol
schedule 4
low potential for abuse relative to schedule III drugs accepted medical use. Abuse: limited physical dependence or psychological dependence relative to the drugs in schedule III Examples: Tramadol (pain) Alprazolam (benzodiadepam) Phenobarbital (seizure meds) Zolpidem (ambien-sleep aid)
schedule 5
low potential for abuse relative to a schedule IV drug
accepted medical use
Abuse:limited physical dependence or psychological dependence relative to schedule IV
Examples:
Pregabalin
Codeine (mg limit)
Diphenoxylate/atropine (Lomotil)- used for diarrhea
Cannabidiol (Epidiolex)- new seizure med
