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Pharmacology > CNS Pharmacology > Flashcards

CNS Pharmacology Flashcards

1
Q

Blood Brain Barrier

A

Isolates the CNS
Modified endothelial cells so there are tight junctions instead of fenestrations
Highly lipophilic
Astroglial processes and pericytes surround the endothelial cells

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2
Q

Up-regulation (sensitization)

A

You have a drug that is blocking the receptor or something, so the postsynaptic cell is making more receptors to try to get any of the NT. When you remove the drug you can have an amplified response because you have way more receptors now

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3
Q

Down-regulation (desensitization)

A

Also called tolerance
Drug stops working after a while because there is a max response of receptors for a long time so the postsynaptic receptors are internalized and degraded which means less of a response is generated

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4
Q

Membrane delimited metabotropic ion channel

A

Ligand binds to receptor (7 TM one), activates G protein, and then the G protein subunits go and directly activated an ion channel (usually K)

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5
Q

Diffusible second messenger metabotropic ion channel

A

GPCR activated by ligand, binds G protein, creates second messengers, then they can go activate and open ion channels

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6
Q

Steps of an action potential

A
  1. Excitatory impulse reaches the cell
  2. Na channels open and Na enters the cell (cell membrane depolarizes
  3. K channels open, K begins to leave the cell (slowing of depolarization)
  4. Na channels close when cell gets too positive
  5. K leaves cell (repolarization)
  6. K channels close (afterhyperpolarization)
  7. Excess K outside diffuses away
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7
Q

Cellular Organization

  1. Long tract
  2. Local circuit
  3. Divergent
A
  1. Messages over long distances, motor control
  2. Short, modulating, shape recognition in the optic tract
  3. Widely projecting neurons, global functioning, sleep-wake cycles
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8
Q

4 Criteria for a NT

A
  1. To be present at higher [ ] in the synapse than in other areas (localized)
  2. To be released by electrical or chemical stimulation via a Ca dependent mechanism
  3. Produce a postsynaptic response similar to nerve stimulation (synaptic mimicry)
  4. Mechanism for termination of transmitter action
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9
Q

Amino acid NTs

A

High concentration in the SNS
Potent modifiers of excitability
Excitatory: Glutamate
Inhibitory: GABA and glycine

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10
Q

GABA synthesis

A

Glutamine –(glutaminase)–> glutamate –(glutamate decarboxylase)–> GABA

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11
Q

Glutamate

where, types, termination

A

Major excitatory NT in CNS
Ionotropic subtypes: NMDA receptor, AMPA receptor and KA receptor
Also mGluR 1 (postsynaptic Gq) and 2/3 (presynaptic, Gi)
Termination: Glia Uptake

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12
Q

GABA

Function, receptors

A

Inhibitory
Ionotropic (GABAa, Cl-) and metabotropic (GABAb; Gq)
Widely expressed
GABAb can be presynaptic
Ligand gated ion channels (it is the orthosteric ligand, barbituates are the allosteric ligand)

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13
Q

Glycine

Function, receptors, location

A

Inhibitory
Ionotropic (Cl-)
Limited expression (interneurons in spinal chord and brainstem)

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14
Q

Acetylcholine

Receptors, function, disease target

A

Has ionotropic (nicotinic receptor) and metabotropic (muscarinic receptor)
Excitatory/Inhibitory
Widely expressed
Cognitive functions (sleep, wakefulness)
Target in treatment of Alzheimer’s disease

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15
Q

Ionotropic

A

Ion channels - not GPCRs

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16
Q

Metabotropic

A

GPCRs - use G proteins and their receptors to cause downstream signalling

17
Q

Acetylcholine synthesis

A

Acetyl CoA + choline –(choline acetyltransferases) –> Acetylcholine (stored in vesicles and then transported)

18
Q

Acetylcholine receptors

A

Found in the basal ganglia and cortex.
Excitatory: M1, M3, M5 (all are Gq - cause increase in IP3, DAG and then Ca) or nicotinic (ion channel - increases Ca, K, and Na conductance)
Inhibitory: M2, M4 (both are Gi - cause decrease in cAMP and gK)

19
Q

Monoamines

Examples, functions

A 
Also called catecholamines
Dopamine, NOR, and serotonin
Derived from amino acids
Small amounts
Complex functions (alertness, conciousness, cognition, reward)
20
Q

Dopamine

Receptors, Function, disease

A 
D1 and D2 receptor families
Metabotropic
Inhibitory
Diffuse
Target in treatment of Parkinson's disease
21
Q

Dopamine Synthesis

A

L-tyrosine –(Tyrosine hydroxylase)–> DOPA –(L-amino acid decarboxylase)–> Dopamine

TOH is rate limiting

22
Q

Dopamine Receptors

A

D1 and D5: Gs (increase cAMP) and Gq (increase IP3/DAG/Ca)

D2, D3, and D4: inhibitory - Gi/o (decrease cAMP, increase K currents, decrease VDCC)

23
Q

3 Dopaminergic Pathways in the CNS

A
  1. Nigrostriatal tract: responsible for movement - Parkinson’s
  2. Mesolimbic system: reward system - if drugs dont target the mesolimbic system they wont cause addiction
  3. Mesocortical system: important in cognition and motivation
24
Q

Norepinephrine

Receptors, function

A

Adrenergic receptors (alpha and beta - metabotropic)
Excitatory
Diffuse
Attention, arousal
Function in midbrain: anxiety, learning, memory, mood, sensory processing, sleep

25
Q

NOR synthesis

A

Dopamine –(Dopamine beta hydroxylase)–> NOR

26
Q

NOR receptors

A

Alpha 1: Gq (increase IP3/DAG/Ca
Alpha 2: Gi (decrease cAMP)
Beta 1 and 2: Gs (increase cAMP)

27
Q

Serotonin

Receptors, function

A

15 Receptors, all metabotropic except 5-HT3
Tend to be inhibitory (some excitatory)
Diffuse
Sleep, temperature, appetite, and neuroendocrine control
Target in treatment of depression

28
Q

Serotonin Synthesis

A

Tryptophan –(tryptophan hydroxylase)–> 5-hydroxytryptophan –(L-amino acid decarboxylase)–> 5-hydroxytryptamine (5HT)

29
Q

Serotonin Receptors

A

Excitatory (5-HT2,3,4) or inhibitory (5-HT4)

See slides for more info

30
Q

Neuropeptides

types, receptors

A

Many of them: Opioids - pain sensation - target of analgesics - drugs of abuse
Metabotropic
Can be released with other NTs

31
Q

How are neuropeptides different from non-peptide transmitters?

A
  1. They are synthesized in the cell body before transport to nerve ending
  2. No reuptake or enzyme degradation identified for termination of action
32
Q

Endocannabinoids

A

Rapidly synthesized (not stored)
Act at presynaptic receptors (retrograde messengers)
Cannabinoid receptor 1 is one of the most abundant in your brain - metabotropic
Memory, cognition, pain perception

33
Q

Nitric Oxide

A

Gas formed from arginine by NO synthase in CNS neurons

May participate in retrograde neurotransmission and LTP

34
Q

Leptin and Orexin

A

Hormone neuromodulators formed in hypothalamus

Important in regulating appetite

35
Q

Purines

A

Adenosine and ATP
Activate specific receptors
Evidence that ATP is a co-transmitter

Pharmacology (18 decks)

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