Exam 1 - Psychopharmacology Flashcards
The use of psychotropic medications in the treatment of psychiatric disorders.
Psychopharmacology
Study of what the body does to drugs (i.e. absorption, distribution, metabolism and excretion)
Pharmacokinetics
Process by which the drug is metabolized by the cytochrome P450 enzymes (CYP 450) in the intestines and liver prior to going into the systemic circulation.
First pass metabolism:
Increase serum levels of other drugs that are substrates of that enzyme= cause toxic levels(SLOW METABOLISM)
e.g. Bupropion, Clomipramine, SSRIs, Ketoconazole, Grapefruit juice, Clarithromycin
Enzyme Inhibitors:
Decrease serum levels of other drugs that are substrates of that enzyme= can cause subtherapeutic drug levels (FAST METABOLISM).
e.g. Carbamazepine, St. John’s Wort, Tobacco, Phenobarbital, Phenytoin
Enzyme Inducers:
Study of what the drugs do to the body (i.e. target sites for drugs- receptors, ion channels, enzymes(MAOIs) and carrier proteins/reuptake pumps)
Pharmacodynamics:
Drug binds to receptors and activates a biological response
Agonist effect:
Drug causes the opposite effect of agonist
Inverse agonist effect:
Drug does not fully activate the receptors
Partial agonist effect:
Drug binds to the receptor but does not activate a biological response.
Antagonist effect:
Excitatory response:
Depolarization= The opening of Na+ and Ca+ channels so these ions go into the cell
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Inhibitory response: Repolarization= The opening of Cl- channels so that Cl- goes into the cell, K+ leaves or both
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-Nonmedicinal substances
-High abuse potential
-Not legally available by prescription
e.g. Heroin, Marijuana
Schedule 1
Medicinal drugs
High potential for abuse and dependency
Written prescription only
No telephone orders
No refills
e.g. Morphine sulfate, Methadone, Fentanyl, Oxycodone, Dilaudid
Schedule 2
-Medicinal drugs
Abuse potential
Refills limited to 5
e.g. testosterone, suboxone, appetite suppressants
Scheule 3
Medicinal drugs
Lesser abuse potential
e.g. Xanax, Librium, Klonopin, Ativan, Restoril,
Schedule 4
-Medicinal drugs
-Lowest abuse potential
-Handles like noncontrolled drugs
e.g. Lomotil
Schedule 5
___: Controlled studies show no risk
___: No evidence of risk in humans
___: Risk cannot be rule out
___: Positive evidence of risk
___: Absolutely contraindicated in pregnancy
A, B, C, D, X
A: Controlled studies show no risk
B: No evidence of risk in humans
C: Risk cannot be rule out
D: Positive evidence of risk
X: Absolutely contraindicated in pregnancy
Teratogenic risks common with psychiatric medications:
Benzodiazepines: Floppy baby syndrome, cleft palate
Carbamazepine (Tegretol): Neural tube defects
Lithium(Eskalith): Epstein anomaly
Divalproex sodium (Depakote): Neural tube deficits- specifically spina bifida, atrial septal defects, cleft palate and possible long-term developmental deficits
Locus Cerelus: Key center of NE production
Ralphe Nuclei: Key center for 5HT production
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Key center of NE production
Locus Cerelus:
Key center for 5HT production
Ralphe Nuclei:
Essential for maintaining homeostasis; controls basic needs (eating, drinking, temperature regulation, sleep-wake cycles
Impairment:
Disturbed sleep, eating, changes in body temperature, emotional instability.
Hypothalamus
Relay station for sensory information,
Impairment:
Sensory processing issues
Thalamus
Memory, converting STM to LTM, learning
Impairment:
Impaired memory and attention
Hippocampus
Regulates powerful emotions (fear, rage, sexual desires”
Impairment:
Irritability, anger, aggression
Amygdala
Serotonin (5HT) “Calming NT)
Derived from Tryptophan
Made in the Ralphe Nuclei
Precursor of melatonin
Affects sleep, mood and behavior
7- 5HT receptor families w/ 15+ subfamilies
NOTE: 90% of serotonin in found in the GI tract
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Norepinephrine (NE)
Made in the Locus Cerulus
Key player in mediating the sympathetic nervous system (i.e. Fight or Flight)
Implicated in mood disorders, GAD, ADHD, PTSD etc.
Noradrenergic pathways
- NE neurons innervates the amygdala and prefrontal cortex = areas important for anxiety and worry
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Dopamine (DA)
Produced in the Ventra Tegmental Area(Reward Pathway)
Associated with reward and pleasure
Involves 4 major pathways:
Mesolimbic Pathway
- Associated with positive symptoms of schizophrenia (i.e. hallucinations, delusions etc)
Mesocortical Pathway
- Associated with the negative symptoms of Schizophrenia (i.e. cognition, affect, apathy, behavior etc.)
Tuberoinfundibular Pathway
- Note: Dopamine inhibits prolactin
Therefore ↓DA= ↑ Prolactin
- Note: Dopamine inhibits prolactin
Nigrostriatal Pathway
- Low levels of DA in this pathway produces increased motor movements
e.g. EPS (Pseudo parkinsonism, Akathisia, dystonia & TD)
- Low levels of DA in this pathway produces increased motor movements
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Gamma-aminobutytric Acid (GABA) = “off”
Inhibitory at the postsynaptic neuron
Induces calmness and relaxation
Plays a role in anxiety disorders
e.g. Benzodiazepines & Barbiturates
GABA-a and GABA-b
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Glutamate = “on”
Excitatory at the
post-synaptic neuron
Pre-cursory of GABA
Involved in learning, memory, thought processing, sensory inputs.
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Acetylcholine (ACh)
Neurotransmitter of the parasympathetic autonomic nervous system and the sympathetic ganglia
Acts at the neuromuscular junctions
Involved in learning and memory (brain’s cholinergic neurons play a critical role in dementias)
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Antidepressants
Mood stabilizers
Antipsychotics
Anxiolytics
Psychostimulants
Benzodiazepines and Z-meds
Cognitive enhancers
Medications for
Substance-related and addictive disorders
Medication Classe
- Patient symptoms
- Previous treatment responses by the patient or a family member to a particular med
- Side effect profile
- Comorbid(medical and psychiatric) conditions
- Risk of suicide via overdose on the medication
- Cost (newer meds may be prohibitively expensive)
Determinants of choice of medications
Movement of drug from site of administration to the blood
Absorption
Movement of drug from blood to rest of body
Distribution
Breakdown of drug
Metabolism
Removal of drug’s metabolic waste products from the body
Elimination
Before the blood goes to the rest of the body from the GI tract, it passes through the liver
The liver is the major organ that breaks down drugs
Therefore, a certain amount of the drug will be inactivated or metabolized as it goes through the liver
Other routes may not be subject to this “first pass” effect (IV, IM, inhalation, subq)
First-Pass Metabolism
CYP450
Inducer: leads to increased level of that enzyme
Inhibitor: leads to decreased level of that enzyme
Substrate: the enzyme works on the substrate to make the “product”
- E.g. Venlafaxine is a substrate of CYP450 2D6 which converts it to desvenlafaxine
- E.g. 1A2 can be induced by smoking: this means increased levels of 1A2, therefore any substrate of 1A2 will decrease in level
- Major types affecting psych drugs: 1A2, 2D6, 3A4,
- Many “newer” medications circumvent CYP450 issues
- Genetic testing is often comprised largely of understanding the metabolism of this pathway for the individual
CYP450
reduces the enzyme activity due to direct interaction with a drug=decreased metabolism of meds= increased Med levels
Inhibition
increases the enzyme activity due to direct interaction with a drug =increased metabolism of meds= decreased Med level
Induction
Major Inducers of CYP450
“COPS”
Carbamazepine (aut0inducer)
Oxcarbazepine
Phenytoin/phenobarbital
Smoking/St. John’s Wort
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Major Inhibitors of CYP450 Enzymes
“G-PACMAN”
Grapefruit
Protease Inhibitors
Antifungals
Cyclosporine/Cimetidine
Macrolides
Amiodarone (and dronederone)
Non-DHP CCBs (diltiazem & verapamil)
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What the drug does to the body
Drug-receptor interactions
Dose-response relationships
Potency and efficacy
Effects:
Side effects/Adverse effects
Pharmacodynamics
Polypharmacy
- Combining medications to improve therapeutic outcome
- Also called “targeted drug combinations”
Drug Interactions
Principles regarding drug interactions
Pharmacodynamic interactions: two drugs have the same or overlapping mechanism of action
Pharmacokinetic interactions: one drug affects the other’s absorption, distribution, metabolism, or excretion
Inadequate dosing: doses are too low because of side effects
Clinical evaluation and oversight: should be ongoing
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What is the Therapeutic Index?
Find and fill in data.
