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THE BRAIN
Functions: Mental disturbances can affect any of these functions of the brain:
PARIETAL LOBE
Sensory & Motor
Abstract Thought
Proprioception
Reading/Math
Right/Left Orientation
OCCIPTAL LOBE
Vision
Visual Association
Visual Memory
Language Formation
TEMPORAL LOBE
Auditory Processes
Language
Memory
Connects with Limbic
CEREBELLUM
FRONTAL LOBE Balance & Coordination
Thought Processes Maintains Equilibrium
Intelligence Coordinates Skeletal Muscle
Social Judgment Contraction
MIDBRAIN
Voluntary Motor Ability
Pupilary reflexes
Eye movement
PONS
Auditory Pathway MEDULLA OBLONGATA
Reflex Centers
Balance
Heart rate
Respirations
Cough, swallow, sneeze
Page 1 of 12 Blood pressure
Vomiting
NERVOUS SYSTEM
Neurotransmitter (NT): Definition: A chemical that modifies or results in the transmission of nerve
impulses between two synapses. (Mosby’s Dictionary, 7th ed., 2006)
NT Release: Neurotransmitters are made in the cell body of the neuron and then transported
down the axon to the axon terminal. Molecules of neurotransmitters are stored in
small "packages" called vesicles. Neurotransmitters are released from the axon
terminal when their vesicles "fuse" with the membrane of the axon terminal,
spilling the neurotransmitter into the synaptic cleft. (Chudler, University of Washington)
Reception of NT: The NT will only bind to post-synaptic cell receptors that recognize them. If these
receptors are altered or blocked, then the NT will not bind and the NT action will
be prevented.
MONOAMINES
Dopamine (DA) D1, D2 • Fine muscle movement • Parkinson’s • Schizophreni
(Synthesized from • Integration of emotions and thoughts • Depression a
Deactivated
Tyrosine) by • Mania
• Involved with decision-making
(Catecholamine) Monoamine
Oxidase • Stimulates hypothalamus to release hormones (sex, thyroid, adrenals)
Norepinephrine α1, α2 • Level in brain affects mood • Depression • Mania
(NE)
β1, β2 • Plays a part in sleep/wake cycle • Anxiety
(Synthesized from
Dopamine) Deactivated • Stimulates sympathetic branch of ANS for “fight or flight” • Schizophreni
by a
(Catecholamine)
Monoamine
Oxidase
Serotonin 5-HT • Actual name is “5-hydroxytryptamine” • Depression • Anxiety
(5-HT) Deactivated • Most of 5-HT’s function is vasoconstriction in cardiovascular, respiratory and GI systems.
(Synthesized from by
Tryptophan) Monoamine • Plays a role in sleep regulation, dreaming, hunger, mood, pain perception, aggression and
Oxidase sexual behavior
• Is found in platelets and plays a role in platelet aggregation
AMINO ACIDS
Glutamate NMDA • Most prevalent neurotransmitter in the Central Nervous System. Used by more that 50% of • Depression
(Derived from α- mGluR1,2 neurons • Suicide
ketoglutarate) • Glutamate is the most important excitatory (EPSP) neurotransmitter, exciting about 90% of
Deactivated • Multiple
by Glial Cells the postsynaptic terminals to which it contacts
sclerosis
in CNS
(Astrocytes)
• As an excitatory neutrotransmitter, it binds to ionotropic receptors, causing depolarization by
opening Na+ ion channels
• At metabotropic receptors, it is modulatory; Plays a major role in cellular metabolism
• Principle excitatory amino acid in CNS
Gamma- GABAA • The most important inhibitory (IPSP) neurotransmitter • Anxiety • Reduces
aminobutyric Acid GABAB Anxiety
• Present in high concentrations in the CNS, preventing the brain from becoming overexcited • Schizophrenia
(GABA)
•
(Synthesized directly • As an inhibitory neutrotransmitter, it binds to both ionotropic and metabotropic receptors,
Huntington’s
Chorea
from glutamate) causing hyperpolarization by opening Cl- ion channels
• Used by inhibitory interneurons in the spinal cord
• Plays a role in inhibition; reduces aggression, excitation and anxiety
• May play a role in pain perception
• Has anticonvulsant and muscle-relaxing properties
Neurotransmitter Receptor Action Decreased Elevated
NEUROPEPTIDES
CRH Acts on • Plays a role in mental activity • Depression • Stress
Corticotropin Pituitary to
•
Releasing Hormone release • Initiates the CRH-ACTH-Cortisol reaction in stress
Anxiety
ACTH
Endorphins Opiate o Substance P and enkephalins: Active during inflammation and pain transmission in the PNS
receptors
o Endorphins: Endogenous opiates which cause euphoria, suppress pain, or regulate responses
(Derived from to stress
secretory proteins
formed in the cell • Are either excitatory or inhibitory, and can also act as neuromodulators, affecting the
body) amount of neurotransmitter released
• Some form part of the neuroendocrine system by functioning both as hormones and
neurotransmitters
• Plays a part in physiological processes including euphoric feelings, appetite modulation, and
the release of sex hormones.
CHOLINERGICS
Acetylcholine Nicotinic • The only small molecule NT that is not an amino acid or derived from one • Alzheimer’s • Depression
(ACh) (N1, N2) • Precursor choline cannot be synthesized by the body and must be obtained from external • Huntington’s
food sources Chorea
(Synthesized from Muscarinic • Used by motor neurons as an excitatory neurotransmitter in the spinal cord • Parkinson’s
Choline)
(M1, M2) • Used at neuromuscular junctions as an excitatory neurotransmitter to influence muscle
activation
Deactivated • Used by the Autonomic Nervous System, such as smooth muscles of the heart, as an
by inhibitory neurotransmitter in preganglionic neurons and postganglionic parasympathetic
Cholinestera neurons
se • Used everywhere in the brain. For example, memory systems of the CNS (may be related to
Alzheimer's Disease).
“Dopaminergic” Known as D1 or D2. (D2 is implicated in addiction.) They bind specifically with dopamine and are active in
many areas of the CNS:
Basal ganglia: MOVEMENT
Limbic: MOOD, EMOTIONS
Pituitary: INHIBITION OF PROLACTIN
Medulla Oblongata: VOMITING
Hypothalamus: ERECTION
“Adrenergic” Think “ADRENALIN”. They bind with the catecholamines (dopamine, norepinephrine, epinephrine) and are
active in the sympathetic response.
Alpha1: VASOCONSTRICTION; located on blood vessels in the skin, vas deferens and GI tract…
the effect is reduced blood flow to these areas.
Beta1: INCREASED HEART RATE; located in the heart where stimulation results in enhanced
myocardial contractility.
Beta2: BRONCHIAL DILATION; located in the lungs
“Serotonergic” Bind with serotonin. Serotonin affects mood, anxiety, arousal, aggression, impulse control, and thinking
abilities; but also contributes to physiological effects such as vasoconstriction, GI motility and smooth
muscle contractions.
5-HT1: CNS inhibitor affecting sleep, appetite, thermoregulation, anxiety, pulmonary vasoconstriction.
5-HT2: CNS excitation affecting behavior, learning and smooth muscle contraction (including stomach
contraction)
5-HT3: Affects anxiety and vomiting mechanism in the intestines
5-HT4 Increases GI motility
“Cholinergic” Bind with acetylcholine. The effects of cholinergic receptor stimulation include: vasodilation of blood
vessels; slower heart rate; constriction of bronchioles and reduced secretion of mucus in the respiratory
tract; intestinal cramps; secretion of salvia; sweat and tears; and constriction of eye pupils.
Muscarinic: Located throughout the CNS and PNS and affect smooth muscles.
“Histaminergic” Bind with histamine. Histamine is a chemical involved in local immune responses as well as regulating
physiological function in the gut and acting as a neurotransmitter. New evidence also indicates that
histamine plays a role in chemotaxis of white blood cells. It also maintains ALERTNESS.
H1: Found on smooth muscle, endothelium, and central nervous system tissue; causes vasodilation,
bronchoconstriction, smooth muscle activation, and separation of endothelial cells (responsible for
hives), and pain and itching due to insect stings; the primary receptors involved in allergic rhinitis
symptoms and motion sickness. In stomach, it stimulates secretion of gastric acid.
H2: Located on parietal cells, which primarily regulate gastric acid secretion
Pharmacokinetics
“Agonists”: Drugs that enhance or potentiate the effects of a neurotransmitter or hormone. May be
accomplished by mimicking the effects, activating the receptors, increasing the amount of NT in the
synapse, or inhibiting the deactivation of the NT.
“Antagonists: Drugs that decrease or limit the effects of a neurotransmitter or hormone. May be accomplished by
blocking the receptors, preventing the NT from binding with the receptors (changing its shape, for
example), preventing the NT’s release, or increasing the rate of the NT’s deactivation.
It is thought that some of the symptoms of psychosis are the result of too much or not enough neurotransmitter.
Therefore, drugs try to counter the effects of this imbalance by “correcting” or modulating the action. However,
because the nervous system is complex in its interconnectedness, changing the action at one transmission/receptor
site has effects in other areas. This is why psychotropic drugs have such debilitating side effects.
Modulation of NTs
In schizophrenia, the victim suffers from excess Dopamine. Blocking the dopamine
receptors prevents the NT from binding with its receptors and thereby reduces the effects
of the NT with the goal of reducing the effects of the schizophrenia.
However…dopamine not only effects mood and thought processes, it also controls the
modulation and fine-tuning of motor activity and inhibits the release of prolactin in the
pituitary.
Again, in depression, the goal of antidepressants is to elevate the level of NTs. Besides
blocking the reuptake, another strategy is to prevent the destruction of the NT once it has
been re-absorbed by the neuron that released it.
However…MAOs are also located in the liver and are responsible for breaking
down all monoamines, including food substances and drugs. Tyramine, for
example (found in aged cheese, pickled and smoked herring, and wine) is a
monoamine that must be broken down by MAOs. If not broken down, tyramine
can cause life-threatening hypertension.
However…the molecules that bind to the pre-synaptic receptors, also tend to bind with the
muscarinic receptors for acetylcholine, the alpha-1 receptors for norepinephrine and the
H-receptors for histamine.
This results in the anticholinergic effects of dry mouth, blurred vision, constipation
and urinary retention; the orthostatic hypotension and erectile dysfunction
associated with norepinephrine blockage; and sedation and weight gain
associated with histamine blockage.
To counter the side effects of general reuptake inhibition, some drugs preferentially block
the uptake of certain NTs. SSRIs target only serotonin pre-synaptic receptors and
therefore do not bind with the muscarinic, adrenergic or histaminergic receptors, and
thereby reduce the anticholinergic and antihistamine side effects.
Example: Buspirone
Another way to elevate levels of NT at the synapse is to deactivate the mechanism for
shutting off its release. Pre-synaptic cells contain an autoreceptor that binds with the NT.
When the autoreceptor is bound, the release of the NT is stopped. Autoreceptor blockers
prevent the NT from binding with the autoreceptors, and as a result, the NT continues to
be released into the synapse.
DRUG CLASSES
ANTIPSYCHOTICS
Atypical: Block serotonin and dopamine receptors. Have fewer side effects than traditional.
• Clozapine (Clozaril)
• Blocks dopamine in the limbic system only (no motor dysfunction)
• Side Effects: Bone marrow suppression (agranulocytosis); convulsions;
myocarditis; sedation, hypersalivation, tachycardia, dizziness.
• Not a first choice drug because of side effects.
• Risperidone (Risperdal)
• Treats both positive and negative symptoms of schizophrenia.
• No motor dysfunction at normal doses.
• Elderly at increased risk of CVA with dementia and agitation
• Side Effects: weight gain, sexual dysfunction
• Quetiapine (Seroquel)
• Binds with broad range of receptors (dopamine, serotonin, histamine,
norepinephrine, acetylcholine)
• Best with Lewy Body Dementia
• Not for use with Alzheimer’s or vascular dementia
• Side effects: weight gain, sedation
• Olanzapine (Zyprexa)
• A derivative of clozapine
• Antagonist of serotonin, dopamine, histamine, norepinephrine and muscarinic
receptors.
• Side effects: anticholinergic effects, sedation, hyperglycemia and Type II
diabetes mellitus
• Ziprasidone (Geodon)
• Affects serotonin and norepinephrine
• Acts as both a reuptake inhibitor and binds serotonin, dopamine, norepinephrine
and histamine receptors
• Side effects: anticholinergic effects, sedation and can prolong the QT interval
(may be fatal with a history of arrhythmia).
• Aripiprazole (Abilify)
• Partial agonist at dopamine receptor site (stabilizes dopamine system)
• Can decrease dopamine if too much is released, or it can stimulate receptors to
increase dopamine levels if not enough.
• Side effects: sedation, hypotension, anticholinergic effects
ANTIDEPRESSANTS
SSRIs Fluoxetine (Prozac); sertraline (Zoloft); paroxetine (Paxil); citalopram (Celexa); escitalopram
(Lexapro)
• Block the reuptake and destruction of serotonin only
• Has a decreased ability to block the muscarinic and histamine receptors than the TCAs,
therefore fewer anticholinergic/sedative effects MAOIs
ATTENTION DEFICIT
ALZHEIMER’S DISEASE