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63 Cards in this Set

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Why are most mechanisms of action of neuropharmacologic drugs approximations?
Approximations are made from information regarding effects of drugs in an isolated system. Extrapolation from biochemical events to behavior is difficult.
What is meant by the CNS being a "black box"?
You put the drugs in and the output is the behavior. You dont know how to explain the process of how it works.
What is specific mechanism of action?
A specific drug action affects a recognized protein target, i.e. receptor, ion channel, enzyme or transporter
Describe the various events in synaptic transmission which might be altered by drugs.
1. Action potential in presynaptic fiber
2. Synthesis
3. Storage
4. Metabolism
5. Release
6. Reuptake
7. Degradation
8. Receptor for the transmitter
9. Receptor-induced increase or decrease in ionic conductance
10. Synaptic transmission can be depressed by blockade of transmitter synthesis or storage
What are the 2 consequences of drug-induced alterations of membrane potential?
Excitatory and inhibitory
What is EPSP?
Excitatory
Partially depolarize --> closer to threshold
more likely to get the fire
How can you increase the size of the depolarization?
Increase the stimulus strength --> threshold for spike generation is reached
How can drugs make affect the nerves?
It makes the nerves more ready to fire by changing the resting membrane potential.
What is IPSP?
Inhibitory --> more electronegative and less likely to fire
What does the inhibitory pathway do?
It prevents the excitatory potential from reaching threshold.
What is a neurotransmitter?
Substance that is released (by nerves) locally and causes change in post-synaptic potential. IPSP or EPSP
What is a neuromodulator?
A substance which acts to modify the response of the synapse to a neurotransmitter --> increases or decreases intensity of action
What are the substances that have been proposed to act as CNS NT?
Acetylcholine
Amino acids
Biogenic amines
Peptides
Purines (ATP, adenosine)
Nitric oxide
What areionotropic receptors?
Associted with ion channels, and change ionic conductance; fast synaptic transmission
What are metabotrophic receptors?
Coupled with enzymes via G-proteins and other intermediates; calcium and potassium channels work this way
What is the BBB?
A diffusional barrier retarding the passage of substances from the central circulation to nerve cells
What characteristics regulate diffusion through capillaries?
Molecular weight
Lipid solubility
Ionization
What are the anatomical differences in CNS capillaries that are barriers?
Less permeable
tight junctions
few pinocytotic sites
surrounded by pericytes and astroglial processes
carrier mediated transport
What is the function of cognitive processing?
Interpretation of sensory information
What is a disorder of cogntive function?
Delirium-interpret the information wrong
What is the function of memory?
Results in motor activity, reasoning, forethought; ability to recall events
What is a disorder of memory?
Dementia and amnesia
What is the function of emotional processing?
COnscious perception of neuronal activity
What is a disorder of emotional processing?
Anxiety, mood disorders and schizophrenia
What is the function of sensory processing?
Bringing information in-vision, hearing, olfaction, touch, and pain
What is a disorder of sensory processing?
Sleep disorders, chronic pain (leads to changes in processing)
What is the function of motor processing?
Control of motion and posture
What is a disorder of motor processing?
Parkinson's Disease, degenerating and demylinization diseases
What does ACh bind to?
Muscarinic and nicotinic receptors
What happens when M1, 3, 5 binds with ACh?
Increase in IP3 and DAG
What happens with M2 and M4 bind to ACh?
Decrease in cAMP and increase in K
What happens when ACh binds to nicotinic receptors?
Inrease in Ca, K, and Na
How does Prozac work?
Inhibits reuptake of serotonin --> increases amt of serotonin in synapse
Is GABA inhibitory or excitatory?
Inhibitory
Is glycine inhibitory or excitatory?
Inhibitory
Is Glutamate and asparatate inhibitory or excitatory?
Excitatory
What is signal transduction?
Process by which signals are channeled from the outside of cell to inside
What may happen if ionotropic receptors are activated?
Inrease chloride, Na, K, or Ca conductance and cause excitatory or inhibitory membrane potentials
What can activation of metabotropic receptors lead to?
Synthesis of cAMP, IP3, and DAG which can altera variety of intracellular pathways
If the drug is lipid soluble, will it pass the BBB?
Yes
Will ionized drugs cross the BBB?
No, ionized drugs are not lipid soluble
Will an unionized drug cross the BBB?
Yes, and it alter the CNS activity
What pathway does NE follow in the CNS?
Noradrenergic pathway --> mainly in medial forebrain bundle and descending spinal tracts, terminate diffusely in cortex, hippocampus, hypothalamus, cerebellum, and spinal cord
What actions does noradrenaline have?
Maily inhibitory (Beta-adrenoceptors) but some are excitatory (alpha or beta adrenoceptors)
What is NE transmission believed to be important in?
Arousal system-controlling wakefulness and alertness
Blood pressure regulation
Control of mood (functional deficiency contributing to depression)
What are the three main Dopamine pathways in the CNS?
Nigrostriatal
Mesolimbic/mesocortical
Tuberohypophyseal
What does the Nigrostriatal pathway control?
Important in motor control
What is the Mesolimbic/mesocortical pathways responsible for?
Involved in emotion and drug-induced reward systems
What is the Tuberohypophyseal pathway?
Regulate secretions from pituitary gland
What do the Dopamine receptors D1 and D5 do?
Stimulate adenylate cyclase
What does D2, D3, and D4 receptors do?
Inhibit adenylate cyclase
What receptors may be implicated in schizophrenia?
D2 family
What receptor shows marked polymorphism in humans?
D4
What is Parkinson's associated with?
Deficiency of nigrostriatal dopaminergic neurons
What is 5-Hydroxytryptamine or 5-HT in the CNS?
Serotonin
Where is serotonin (5-HT) located?
Concentrated in midline raphe nuclei in pons and medulla, projecting diffusely to cortex, limbic system, hypothalamus, and spinal cord
What are the funtions associated with 5-HT?
Feeding behavior
Control of mood and emotion
Various behavior responses
Control of sleep-wakefullness
Control of sensory pathways
Vomiting
Is NMDA inhibitory or excitatory?
Excitotory
What are the two types of GABA receptors?
GABAa
GABAb
What does GABAa do?
Mainly postsynaptically --> directly coupled to chloride channels, opening of which reduces membrane excitability
What drugs interact with GABAa receptors and channels?
Benzodiazpine
Convulsants
Neurosteriods
What does GABAb do?
Are G-protein coupled --> linked to inhibition of cAMP formation --> pre and post synaptic inhibition by inhibiting calcium channel opening and increasing K conductance
What drug will interact with GABAb receptor?
Baclofen--a GABAb receptor agonist used to treat spasticity