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P. pharm > Chapters 1-3 > Flashcards

Chapters 1-3 Flashcards

1
Q

PHARMACOKINETICS

A

THE BODY’S ACTION ON THE DRUG
Absorption
Distribution
Excretion
Metabolism

Cytochrome (CYP)-450 - CYP enzymes are estimated to account for the biotransformation of about 60% of the most commonly prescribed drugs in America. These enzymes are primarily in the liver and are classified according to family (1, 2, or 3) and isoform. There are six important enzymes (pathways) in psychopharmacology expressed in this nomenclature:

CYP1A2
CYP2B6
CYP2C9
CYP2C19
CYP2D6
CYP3A4

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2
Q

PHARMACODYNAMICS

A

THE DRUG’S ACTION ON THE BODY
Four mechanisms for this action:
1. Enzyme activity
2. Nonspecific chemical or physical interactions
3. Acting as antimetabolites-
4. Binding to cell receptors- Receptors are proteins that bind to compounds generating cellular signals

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3
Q

Neurotransmission: anatomical/chemical/electrical

A

anatomical infrastructure but chemical operation

consists of neurons & synapses. Synapses can form on many parts of neuron & are asymmetric (communication in one direction) so presynaptic elements differ from postsynaptic elements
Neurons are cells of chemical communication in brain

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4
Q

structure of neuron

A

general structure but they are really unique depending upon where in the brain they are/function

soma= cell body, command center, contains nucleus
axon= sends information which forms presynaptic terminals as the axon passes by/ends
dendrites= receive information from other neurons through them (some through dendrite spines)

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5
Q

6 key neurotransmitters in brain (even though > 12)

A

serotonin, norepinephrine, dopamine, acetylcholine, glutamate, GABA (y-aminobutyric acid)

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6
Q

classic neurotransmission process step 1-3

A
  1. start w/ electrical process > neurons send electrical impulses from one part of cell to another part of same cell via axons. Needs chemical messenger (neurotransmitter) at receptors of second neuron usually at synaptic connections but not always
  2. electrical impulse in first neuron is converted to chemical signal at synapse between it and second neuron (excitation-secretion coupling) typically in one direction from presynaptic axon terminal to second postsynaptic neuron
  3. in second neuron, chemical info from first neuron gets converted back to electrical impulse or by the chemical info from first neuron more chemical messages are triggered within second neuron to change molecular & genetic functioning
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7
Q

is communication between neurons at synapses chemical or electrical?

A

chemical

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8
Q

retrograde neurotransmission & examples

A

postsynaptic neurons can “talk back” to presynaptic neurons

ex: endocannibinoids, neurotrophic factors like nerve growth factor, & nitric oxide

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9
Q

volume neurotransmission & example

A

aka nonsynaptic diffusion neurotransmission; part of chemically addressed nervous system
neurotransmission that does not need synapses

chemical messages spill over from neuron to neuron by diffusion (much like cell phone tower)

ex: dopamine in prefrontal cortex; not many dopamine receptors, so it is free to spill over & diffuse to neighboring dopamine receptors & stimulate them even though there is no synapse at these sites
ex: somatodendric autoreceptors

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10
Q

where’s somatodendric site of neuron

A

top of neurons

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11
Q

where’s anoxal end of neuron

A

bottom

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12
Q

in excitation-secretion coupling, electrical impulses open what ion channels

A

voltage-sensitive sodium channels (VSSC) and voltage-sensitive calcium channels (VSCC) by changing ionic charge across neuronal membranes

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13
Q

in short, what does excitation-secretion coupling do

A

The way the neuron transduces an electrical stimulus into a chemical event

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14
Q

signal transduction cascades

A

cascade of events after stimulation of postynaptic receptor. They can activate third messenger enzymes (kinases) which add phosphate groups to proteins to = phosphoproteins. Others activate phosphatases which remove phosphate from phosphoproteins. This balances determines degree of downstream chemical activity that gets translated into diverse bio responses like gene expression & synaptogenesis

figure 1-9 pg. 10

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15
Q

two major targets of signal transduction

A

phosphoproteins and genes

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16
Q

what are the two signal transduction cascades in brain triggered by neurotransmitters

A

G-protein-linked & ion-channel-linked

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17
Q

first messenger

A

extracellular

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18
Q

second messenger (G-protein cascade vs ion-channel)

A

intracellular
G-protein= the second messenger is a chemical
Ion-channel= the second messenger can be an ion like calcium

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19
Q

epigenome

A

genomes= words while epigenome= the story that arranges the words (p.23)

turn genes on/off by modifying chromatin in the cell nucleus

epigenetics= parallel to genetics; determines what genes are made into RNA & protein for expression & which are silenced

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20
Q

general action of methylation of genes

A

silences them

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21
Q

3 target sites of psychotropics

A
  1. one of the transporters for a neurotransmitter
  2. receptors coupled to G proteins
  3. enzymes
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22
Q

2 types of neurotransmitter transport

A

presynaptic reuptake & vesicular storage

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23
Q

2 major subclasses of plasma membrane transporters for neurotransmitters

A
  1. solute carrier SLC6 gene family (sodium/chloride coupled transporters). Includes transporters for monoamines serotonin, norepinephrine, dopamine & also GABA & the amino acid gylcine
  2. solute carrier SLC1 gene family (high-affinity glutamate transporters)
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24
Q

3 subclasses of intracellular synaptic vesicle transporters for neurotransmitters

A
  1. SLC18 gene family (vesicular monoamine transporters/VMATs for serotonin, norepinephrine, dopamine, & histamine) & VAChT
  2. SLC32 gene family (vesicular inhibitory amino acid transporters/VIAATs)
  3. SLC17 gene family (vesicular glutamate transporters)
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25
Q

how do monoamines get the energy for neurotransmitter transport

A

They require energy to concentrate monoamines into presynaptic neuron
Energy provided by transporters in SLC6 gene family= downhill transport of sodium & uphill transport of monoamine

sodium-dependent cotransporters (usually involves cotransport of chloride & sometimes countertransport of\ potassium)

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26
Q

how often to neurotransmitter transporters go in and out of the membrane

A

12

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27
Q

presynaptic transporters for histamine and neuropeptides

A

none known

28
Q

What vesicular transporters for monoamines (VMATs) in the SLC18 gene family of what neuron are mostly targeted by psychotropic drugs? Ex?

A

dopamine neurons in the SLC18 gene family. Ex:
amphetamine (target= monoamine transporters & VMATs)
methylphenidate (target= only monoamine transporters)

29
Q

what do agonists do to G-protein-linked receptors

A

produce conformational change in receptors that leads to full receptor activation and thus full signal transduction

30
Q

what’s unique about the structure of G-protein coupled receptors

A

they have span the transmembrane SEVEN times

31
Q

what mediates pharmacokinetic actions

A

hepatic and gut drug metabolizing system know as the cytochrome P450 (CYP450) enzyme system

32
Q

what are the most important ions that are regulated by ion channels in psychopharm

A

calcium, sodium, chloride, potassium

33
Q

two major classes of ion channels

A

ligand-gated aka ionotropic receptors aka ion-channel-linked receptors

&

voltage-gated aka voltage-sensitive ion channel

34
Q

ligand

A

literally means “tying”
a neurotransmitter, drug, or hormone that binds to a receptor

35
Q

ligand-gated ion channels

A

ion channels linked to receptors that regulate their opening and closing

36
Q

what do 1/5 of psychotropic drugs act on that cause immediate changes

A

inotropic receptors (BZO, sleep aides)
because inotropic receptors immediately change the flow of ions on the contrary to drugs that act on G-protein linked receptors which need to wait for cellular function changes through signal transduction cascade

37
Q

why are ligand-gated ion channels called pentameric

A

they are assembled from 5 protein subunits

38
Q

allosteric sites

A

“the other” sites that molecules other than neurotransmitters could bind to in ligand-gated ion channels

little to no activity on their own without a neurotransmitter present (which is why called allosteric modulators)

39
Q

two types of allosteric modulators

A

positive allosteric modulators (PAM)= boost what neurotransmitter does

negative allosteric modulators (NAM)= block what the neurotransmitter does

they do nothing unless neurotransmitter is also binding to its site

40
Q

in psychopharm what part of VSCCs are of most interest

A

subtypes that are presynaptic, that regulate neurotransmitter release, and that are targeted by certain psychotropic drugs

41
Q

the amygdala

A

.Part of the brain that regulates powerful emotions such as fear, rage,
sexual desires

42
Q

thalamus

A

The relay station for sensory information

43
Q

hypothalamus

A

Essential for maintaining homeostasis, controls basic needs such as sleep-
wake cycles

44
Q

frontal lobe

A

This lobe is involved in executive functioning, high order planning, speech
and motivation

45
Q

What is derived from tryptophan and made in the raphe nuclei?

A

Serotonergic System. The raphe nucleus is responsible for most of the serotonergic cortical and striatal innervation. Tryptophan, the precursor of serotonin, is first converted into 5-hydroxytryptophan, by the rate-limiting step catalyzed by tryptophan hydroxylase, and promptly transformed into serotonin by AAD

46
Q

Made in the Locus Ceruleus and involved in the noradrenergic pathways

A

norepinephrine

47
Q

90% of serotonin receptors are found in the

A

GI tract

48
Q

Produced in the VTA and involved in the four major pathways

A

?? dopamine

49
Q

Dopamine inhibits prolactin in this pathway =_________________________

A

Tuberoinfundibular

50
Q

Increase dopamine in this pathway is associated with positive symptoms

A

mesolimbic

51
Q

Decrease dopamine in this pathway is associated with negative symptoms

A

mesocortical

52
Q

Decrease dopamine in this pathway produces motor symptoms

A

Nigrostriatal Dopamine Pathways
(contains 80% DA in brain)

53
Q

Main inhibitory neurotransmitter that induces calmness and relaxation

A

Gamma-aminobutyric acid (GABA)

54
Q

Main excitatory neurotransmitter =________________________________

A

glutamate

55
Q

Major organ that breaks down drugs in the body =___________________

A

liver

56
Q

Electrolyte imbalance commonly associated with psychotropic medication
use =____________________________________

A

hyponatremia

57
Q

The time needed to clear 50% if drugs from the plasma =________________

A

half life

58
Q

The process of becoming desensitized and less responsive to a particular
medication dose overtime necessitating an increase =____________________

A

tolerance

59
Q

A ration describing toxic dose to effective dose = _____________________

A

therapeutic index

60
Q

A chemical that binds to a receptor to produce a biologic response
=________________________________

A

agonist

61
Q

A chemical that binds to a receptor but does not fully activate the
receptor =

A

partial agonist

62
Q

A chemical that binds to a receptor, blocking it to inhibit a biologic
response

A

antagonist

63
Q

An agent that binds to the same receptor as an agonist but induces an
opposite biological response =___

A

inverse agonist

64
Q

A usually undesired but foreseeable effect that occurs regardless of dose
and often resolves after continued therapy = _

A

side effects

65
Q

S/S opposite of what it was meant to treat =_

A

?

66
Q
A

P. pharm (8 decks)

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