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Transcript
Psychopharmacology
Rebecca Sposato MS, RN
A busy brain
• Receive, process and analyze stimuli (touch,
sound, sights, smells, taste)
• Use data to construct thoughts and emotions
• Receive and produce communication
• Physiological regulation
• Move muscles
• Remember things
Brain Anatomy
• Brain Stem: Physiological
regulation, instincts, emotion
• Cerebellum: Motor coordination
and balance
• Cerebrum: thoughts, emotions,
memories, sensory data and
movement
▫ White matter: cell bodies at
surface; Gray matter: cell wires
interconnecting
▫ Lobes: sensory data and decisions
▫ Hippocampus/Amygdala:
emotions, memory
▫ Basal Ganglia: movement
Brain Diagnostics
• Structural Imaging
▫ Magnetic Resonance Imaging
(MRI) and Computed
Tomography (CT) Shows structures and shapes
of tissues, presence of solids,
liquids, gasses
• Functional Imaging:
▫ Functional-MRI
 Tagged blood for detecting
oxygenation levels
▫ Positron Emission
Tomography (PET)
 Shows uptake of glucose by
brain cells revealing where
the location of active brain
cells
Parts of a Neuron
•Switching the location of sodium and potassium ions sends an
electrically charged signal (the action potential) down the axon
•Normally, potassium is concentrated inside the cell and sodium
outside the cell until the neuron opens its channels on the cell wall and
the two trade places for a microsecond
•Signals only travel in one direction because the channels quickly close
Synapse
• The space where one neuron can
start a signal in the next neuron
• Each neuron manufactures only one
type of neurotransmitter and its
corresponding enzyme
• When the action potential reaches
the terminal button, the vesicles
migrate to the cell’s surface and drop
the neurotransmitters into the
synapse and triggers the next neuron
• Psychoactive drugs influence one
step of this process to increase or
decrease the firing of its neuron
Neuroconduction
• http://www.youtube.com/watch?v=90cj4NX87
Yk
• http://www.youtube.com/watch?v=ifD1YG07fB
8&NR=1
Pharmacology Terms
• PharmacoDYNAMICS – how the drug affects the body
▫ The drugs action on the targeted cells
▫ The other cells involved
• PharmacoKINETICS – how the body affects the drug
1. How the body absorbs, stores, moves, destroys
and eliminates the drug
 Most often the liver and kidney play a part
• Therapeutic Index – median effective/median
adverse or lethal
▫ The blood level between 50% of users feeling better
and 50% of users feeling worse
Pharmacology Terms
• Tolerance: lower effectiveness of medication at
current dose level
• Withdrawal: unpleasant psychological and physical
symptoms experienced when a chemical is abruptly
stopped
• Blood Brain Barrier: cerebral capillaries have very
few pores
▫ hinders most WATER soluble molecules from crossing
between blood and brain tissue
▫ LIPID soluble molecules can cross
▫ Some medications (sinemet) must saturate proteins in
the blood (albumin) to have enough molecules in the
plasma to enter brain
Anti-anxiety Medications
• Glutamate tells your neuron to thrill, gammaaminobutyric acid (GABA) tells your neuron to
chill (GABA can control Na+ or K+ channels)
• Benzodiazepines: ativan (lorazepam), valium
(diazepam), klonopin (clonazepam), and xanax
(alprazolam). Controlled substances
▫ indirect agonist (mimics) for GABAa, attaches to
the same binding site (without blocking it)
▫ Treats seizures, withdrawal symptoms, anxiety
Precautions for Benzodiazepines
• Impairs attention and motor coordination
(ataxia)
▫ Due to GABA receptors in the cerebellum
▫ More dramatically in the elderly – fall risk
• In higher doses can also mimic the effects of
GABA in the brain stem leading to sedation
▫ Increased affect when combined with alcohol,
opiates, and tricyclic anti-depressants
Insomnia Medications
• Sedative/Hypnotics: Zolpidem (Ambien),
temazepam (restoril), Zaleplon (Sonata), and
Eszopiclone (Lunesta)
• Act on a more specific sub-group of GABA
receptors, promotes sleep but do treat anxiety
• Not recommended for long term use
• Side effects: amnesia, ataxia, unusual sleeping
behaviors (walking, eating etc.)
Insomnia Medications - melatonin
• Melatonin – a hormone secreted when dark by
the pineal gland (b/t midbrain and cerebellum),
involved in seasonal and circadian rhythms by
acting upon the suprachiasmatic nucleus (SCN)
the brain’s clock
• Ramelton (Rozerem): melatonin receptor
agonist (mimics)
▫ Not a controlled substance and can be used long
term
The alternative anxiolytic
• Buspar (buspirone): approved to treat mild to
moderate anxiety as partial serotonin agonist
with a mild influence on dopamine-2
▫ Does NOT act upon GABA, less sedation
compared to benzodiazemines
Monoamine Oxidase Inhibitors (MAO-I)
• MAO – the presynaptic
enzyme that destroys recently
reabsorbed serotonin,
nor/epinephrine, dopamine
• Inhibitors stop the enzyme
from destroying the
neurotransmitters, increasing
their supply in the synapse
• MAO also works in the liver to
break down tyramine, a
chemical in food that tells your
blood vessels to SQUEEZE
• Not liked, rarely used
▫ Diet restrictions – cheese,
wine, smoked fish
▫ Interferes w/ other meds
Tricyclic Antidepressants (TCA)
• Block to reuptake of
norepinephrine or
norepinephrine and
serotonin
• Amitriptyline (elavil),
nortriptyline (pamelor)
• Narrow therapeutic range
• Side action block
muscarinic (named after
a mushroom) receptors
for acetylcholine
Anticholinergic
side effects: pupil
dilation, confusion,
urinary retention,
increase HR
Selective Serotonin
Reuptake Inhibitors (SSRI)
• Popular anti-depressant
• Prozac, Celexa, Luvox, Zoloft, Paxil
• http://www.youtube.com/watch?v=ocSptPUBb
uo
• Block re-absorption of serotonin by the PREsynaptic neuron, re-exciting the POST-synaptic
neuron
• Serotonin correlates with feeling content
Adverse Affects of SSRI
• Common: Weight gain, impaired sexual arousal
• Terotogenic: pulmonary HTN in newborn, heart
defects, etc.
• Bleeding risk: inhibits platelet coagulation
• Serotonin Syndrome: caused by combining
serotonin-acting medications
▫ Mild: restless, sweaty, tachy
▫ Moderate: HTN, hyperthermia, rigid, lethargic
▫ Severe: Seizures, shock and coma
• Serotonin discontinuation Syndromeabruptly stopping after long term use
▫ GI symptoms, malaise, moody etc.
Alternative Anti-depressants
• Wellbutrin (Bupronion)/Zyban: blocks reuptake
of dopamine and norepinephrine
▫ May treat smoking withdrawal: side action of
inhibiting nicotinic acetylcholine receptors
▫ Lowers the seizure threshold
Lithium
• The element is in the same column on the
periodic table of elements as Na+ and K+
• Makes neurons less excitable
▫ Influences the conduction of neurons though its
influence on Na+
▫ Reduce effect of glutamate
• Mood Stability in bipolar disorder
▫ Reduction in number and severity of manic
episodes, improves depression
Precautions with lithium
• Narrow therapeutic range, lithium toxicity
threatens all conductive activity in the body
• Long term use may damage thyroid
▫ Goiter, hypothyroid
• Low sodium enhances the toxicity of lithium
• Signs of toxicity: (>1.5)
▫ Tremor, confusion, N/V/D, arrhythmias, polyuria,
polydipsia, edema
Anti-Convulsants
• Work through their anti-conductive properties
on neurons to stabilize mood
• Carbamazine (tegretol): affects sodium channels
to reduce firing, prevent and treat mania
▫ Side effects: anticholinergic, ataxia, orthostatic
BP, rash,
• Valporate (depakote): increases GABA to treat
both manic and depression features of bipolar
disorder
▫ Side effects: tremor, weight gain, sedation
▫ Serious side effects: Fetal encephalopathy,
thrombocytopenia, pancreatitis, hepatic disease
• Check drug levels, CBC, liver panel
More anti-convulsants
• Lamotrigine (lamictal) blocks Na+ channel,
preventing the release of
glutamate and aspartate
▫ prevent mania (does
NOT treat acute
mania), improves
depression
▫ Rashes may progress to
Steven Johnson
syndrome
Classic antipsychotics
• Chlorpormazine (thorazine)and Haldol
(haloperidol): 1950s, 1st psych meds
▫ Very broad acting: blocks dopamine among other
neurotransmitters (histamine, nor/epinephrine
and acetylcholine) to treat positive symptoms of
schizophrenia and psychoses
▫ Anticholinergic side effects
▫ Stops dopamine’s role in the hormone prolactin’s
feedback loop, increase levels lead to feminization
▫ Extra-pyramidal side effects – abnormal,
involuntary and repetitive facial/neck movements
▫ AIMS score:
http://www.youtube.com/watch?v=FUr8ltXh1Pc
Atypical Antipsychotics
• Treats both negative and positive symptoms of
schizophrenia
• Action is more specific to dopamine yielding fewer
and EPS and anti-cholinergic side effects
• Many affect the pancreas leading to insulin
resistance
• Clozaril- block dopamine in the limbic system
▫ Convulsions, bone marrow suppression, low WBC
• Risperdone- some EPS and weight gain, orthostatic
BP, CVA risk in elderly
• Seroquel (quetiapine) - blocks dopamine,
histamines, epinephrine and serotonin
▫ sedation
More anti-psychotics
• Olanzapine (Zyprexa) – attaches to specific
serotonin and dopamine receptors
▫ Sedation and metabolic syndrome
• Apriprzole (Abilify) – creates more level
dopamine levels in the cerebrum
psychostimulants
• Ritalin (methylphenidate), Adderall
(dextroamphetamines): controlled substances
• Increase levels of dopamine and norepinephrine
by inhibiting their reuptake
▫ Increase alertness and attention
▫ Paradoxical in ADHD/ADD
• Stratterra (atomoxetine) – selective
norepinephrine reuptake inhibitor
▫ Non-stimulant option for ADHD/ADD
Anti-dementia
• Aricept (donezepil), galantamine (reminyl)
• Interfere with acetylcholinesterase (the enzyme
that breaks down Acetylcholine in the postsynaptic neuron ) increasing its concentration in
the synapse
• Mematine (Namenda) blocks the N-methyl-daspartate receptor, preventing glutamate from
opening the Ca+ channels and the resulting
corrosion
Herbals/Dietary Supplements
• NCCAM – NIH office for alternative medicine
• DSHEA – dietary supplement health and
education act (1994) – law states dietary
supplements and herbals do NOT need FDA
approval before being sold
▫ FDA may intervene if product causes harm to
consumer