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Neurotransmission in the CNS
IL - Block 4
43
Pharmacology
Professional
01/07/2012

Additional Pharmacology Flashcards

 


 

Cards

Term
general mechanism of action
Definition

all these drugs alter the transport of ions = altering the conentration of chemicals (neurotransmitters) at synapses

 

one exception: antiseizure drugs act by altering membrane potentials along axon

 

Term
mechanism of action of antiseizure drugs
Definition
alter membrane potentials along axons
Term
blood brain barrier
Definition

- restricts entery of drugs into the CNS

- due to tight junctions between endothelial cells in the capillaries in the brain

- no such thing in peripheral nervous system

Term
so how do you bypass the blood-brain barrier?
Definition

1) lipophilic drugs

2) transport into the CNS via transporters that are normally for nutrients

3) inflammation of the meninges or the brain

Term
what does P-glycoprotein do?
Definition
it is a nonspecific transporter that actively transports drugs out of the brain
Term
resting membrane potential
Definition

-70 mv

 

kept by the Na-K ATPase (Na pumped out, K in)

 

Cl also going out

Term
voltage gated ion channels
Definition

PROPIGATION OF THE ACTION POTENTIAL

 

Sodium rushes in through voltage-gated Na channels (these channels are present on nerve and muscle cells) - open in response to depolarization to further depolarize (or repolarize) the membrane

Term
repolarization
Definition
potassium floods out via K+ leak channels
Term
ligand-gated ion channel
Definition
channel opens in response to bidning of a neurotransmitter -- responsible for synaptic transmission
Term
what does reserpine do?
Definition
blocks neurotransmitter storage
Term
what does cocaine do?
Definition
blocks reuptake (MOA in synapse)
Term
what do cholinesterase inhibitors do?
Definition
block degradation
Term
how do opiods work?
Definition
they affect the receptors on the post-synaptic neuron
Term
what does amphetamine do?
Definition
Increases neurotransmitter release
Term
heirarchical neural systems
Definition

anatomically well defined systems, in particular the sensory and motor systems

 

generally utilize amino acids as neurotransmitters

Term
diffuse systems
Definition

anatomically less well-defined

 

tend to be implicated in global functions

 

utilize monoamines and peptides as neurotransmitters

Term
monoamine neurotransmitters in the CNS
Definition

1) Norepinephrine

2) Dopamine

3) Serotonin (5-HT neurons)

Term
norepinephrine
Definition

cell bodies found in:

1) Pons (locus ceruleus)

2) Midbrain

 

Project diffusely to virtually all regions of the crebral cortex and limbic system

 

regulates arousal and mood

Term
what determines specificy of NE-releasing neurons?
Definition
cellular targets are determined by the location and  pattern of postsynaptic receptors rather than the location of the release sites
Term
α11 receptors (NE system)
Definition
these are excitatory - decrease the rectifying K conductance
Term
α22 receptors (NE system)
Definition
inhibitory - increase the rectifying K conductance
Term
clinical considerations for NE
Definition
noradrenergic neurons in the limbic system are thought to be a major target for antidepressant medications (which increase the amount of NE in the synapse, so there is a downregulation of receptors on postsynaptic cell- especially β2)
Term
dopaminergic neurons
Definition

1) anatomically more limited than noradrenergic neurons

2) extrapyramidal motor control (site of action of antiparkinson drugs)

3) limibic system (site of action of antipsychotic drugs)

4) hypothalamic-pituitary axis

Term
how many dopamine receptor subtypes are there?
Definition

five receptor subtypes


fall into D1 or D2 family


D1 - Agonist = none in use

- Antagonist= phenothiazines


D2 - Agonist = bromocriptine

-Antagonist=phenothiazines

Term
the three important ascending dopaminergic pathways
Definition

1) Nigrostriatal - extrapyramidal motor control

- important for movement disorders (parkinson's, Frozen Man Syndrome)

 

2) Tuberoinfundibular (neuroendocrine regulation)

 

3) Mesolimbic (emotions, reward system)

Term
what does dopamine generally do, inhibit or excite?
Definition
generally inhibits neuronal activity
Term
dopamine clinical considerations
Definition

1) Nigrostriatal Pathway = Parkinson's (selective cell death), MPTP Frozen Man syndrome (toxin transported into neurons)

 

2) Substantia nigra to limbic system and widespread cortex = addiction and behavioral disorders


3) Arcuate nucleus of hypothalamus to anterior pituitary (via portal veins): inhibits prolactin secretion

Term
serotonin/5-HT - location of neurons
Definition

most cell bodies = in midline region of the pons;

 

project diffusely to most of the CNS (ascend to the cerebral cortex and limbic system from the midline tegmentum (raphe nucleus)

Term
what functions do serotonin neurons control?
Definition

-regulating emotions

- sleep-wake cycles

-temperature control

Term
clinical consideration for serotonin
Definition

Antipsychotics and antidepressants


1) mood disorders (SSRIs improve depression)


2) migrane pain


3) chemotherapy-induced emesis (ondasetron 5-HT3 antagonist)


4) LSD activates 5-HT1 and 2 receptors

Term
basic information about ACh
Definition

both long and short cholinergic pathways are present at all levels of the CNS, particularly cerebral cortex and limbic system

 

most CNS effects are mediated by a large family of muscarinic receptors (slow excitation)

 

implicated in cognitive function (esp. MEMORY)

 

action is terminated by cholinesterase

Term
what type of muscarinic receptors predominate in the CNS?
Definition

Answer: M1 type - they slowly open the rectifying potassium channel causing slow excitation

 

(Nicotinic and M2 receptors are present, but in much lower density)

Term
Clinical considerations for ACh
Definition

1) Motor neurons in spinal cord to the NMJ - acetylcholinesterases (nerve gases), insecticides; myasthenia gravis; botulism

 

2) basal forebrain to cortex - Alzheimer's disease (selective cell death/atrophy = cognitive defects --> tacrine, donepizil, galantamine, rivastigmine are CE inhibitors used for Alzheimer's tx);


autosomal dominant frontal lobe epilepsy (mutations in CNS ACh receptor)

 

3) Atrophy of neurons in extrappyramidal system is thought to contribute to the tremor in Parkinson's

Term
glycine
Definition

amino acid NT

 

cell bodies found primarily in the spinal cord

 

INHIBITS NEURAL ACTIVITY

 

Strychnine (poison) antagonizes glycine inhibition by blocking the glycine receptor --> convulsions

Term
GABA
Definition

mediates inhibitory actions of local interneurons

 

found in: - cerebellum

-cerebral cortex

-limbic system

 

two receptor subtypes: GABA-A, GABA-B

Term
Clinical consideration for GABA
Definition

1) Major inhibitory NT in brain: sedative - hypnotic drugs act by facilitating the action of GABA

 

barbituates in high does can directly activate the GABA receptor -- profound respiratory depression and CV collapse

 

2) Epilepsy - gabapentin and valproic acid increase GABA

Term
glutamate
Definition

widely distributed in the CNS,

 

generally excitatory


two major classes of receptors: NMDA and non-NMDA


NMDA: blocked by ketamine, PCP; activated by a new class of antipsychotics

Term
clinical considerations for glutamate
Definition

1) tranquilizing/anesthetic agents - ketamine and phencyclidine; act by blocking the NMDA receptor --> disordered thinking similar to schizophrenia

 

2) antiphyschotic drugs in develoment are NMDA agonists

Term
opioid peptides
Definition

these proteins are cleavage products of a larger peptide (pro-opiomelanocortin)

 

are part of endorphin/enkephalin families --> variety of receptors; generally inhibitory

 

endogenous ligands for the opioid receptors

Term
leptin
Definition

167 amino acid long - secreted only by adipose tissue (not strictly a NT)

 

its receptors are found in the CNS

 

obese individuals have INCREASED levels

 

binds to ventromedial hypothalamus to induce satiety and increase lipogenesis (obesity = leptin insensitivity)

 

 

Term
other peptide neurotransmitters
Definition

Present in gut and endocrine tissues and in CNS:

  • vasoactive intestinal peptide (VIP)
  • cholecystokinin (CCK)
  • thryotropin releasing hormone (TRH)
  • somatostatin

 

 

Substance P = transmission of pain

Term

endocannabinoids

Definition

Receptor = CB1 = is widely distributed in the CNS -- are primarily presynaptic


endogenous ligands are thought to be brain lipids (which is different from other NTs because these are NOT STORED. Instead, they are synthesized in response to stimuli and act in a retrograde fashion)


secreted from the postsynaptic neuron and bind on CB1 on presynaptic neuron --> inhibit neurotransmitter release


Activation of these receptors affects: memory, cognition, and pain perception

Term
fnx of inhibitory ligand-gated receptor?
Definition
ligand binding causes the receptor to hyperpolarize the membrane by increasing the chloride ion flux
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