Neurobiology of Mental Illness (Weely 2) Flashcards
Cerebrum
Amygdala
hippocampus
midbrain
Involved in vision and hearing. Along with the hindbrain controls sleep, alertness and pain.
Manufactures serotonin, norepinephrine and dopamine.
cerebellum
thalamus
Relay station, transmits nerve impulses throughout brain.
hypothalamus
regulates bodily drives and bodily conditions
Pons
medulla oblongota
Forebrain
Structures:
Function: controls higher mental functions such as learning, speech, thought, memory.
Limbic System
Structures:
Involves experiencing and expressing emotions and motivation.
Hindbrain
Structures:
Controls motor movements, heart rate, sleep and respiration. Manufactures norepinephrine and serotonin.
Receptor
Configured so that precisely shaped molecules fit and cause or prevent a response
Ligand
Transmitter substance that fits and evokes a response from a receptor
Synapse
Structure that permits a neuron to pass an electrical or chemical signal to another neuron
Neurotransmission
Communication between neurons
Neurotransmitters
Electrochemical messengers that send signals from neuron to neuron. either excite or stimulate an action in the cells (excitatory) or inhibit or stop an action (inhibitory).
Absorption
Getting the drug into the bloodstream.
Drug must pass through the stomach or small intestine into blood vessels(when taken orally). Molecules pass through cell membranes.
distribution
Getting the drug from the bloodstream to the tissues and organs.
Factors affecting distribution: size of organ, blood flow, solubility, plasma protein binding, anatomic barriers.
Metabolism
breaking the drug down into the inactive and typically water-soluble form.
Excretion via urine or feces. Occurs in liver, kidney, lungs, GI tract, plasma.
Excretion
Getting the drug out of the body
Bioavailability
The fraction of the dose that reaches the systemic circulation
Protein binding:
Drugs bind to plasma proteins and cannot leave circulation, they are too large to pass through gaps in capillary wall.
-Several psychotropics are protein binding.
-The more protein binding the less drug activity.
Lipid solubility
Lipid solubility is necessary for drugs passing through blood-brain barrier. Then can also pass through placenta.
MAO system:
Metabolizes Monoamines including dopamine, norepinephrine, serotonin
Cytochrome P450 system
most drug interactions occur.
CYP2D6: Affects 90% of all drugs and 25% of all psychotropics. Found primarily in the liver. Also in intestine, lungs, brain, kidney.
Substrate
Enzyme surfaces that receive inducers or inhibitor enzymes
Inducers
Increases the drug metabolism to decrease serum drug concentration. Takes several days to weeks to develop.
Inhibitors
decreases the drug metabolism to increase serum drug concentrations. Happens almost immediately.
Effect of smoking on CYP 450
-Cigarette smoking causes induction of CYP-450 1A2, causes more enzyme to be synthesized.
-Leads to 40-50% reduction in serum level of target drug.
-Same effects from secondhand smoke.
-Maximum enzyme induction occurs with 7-12 cigarettes per day for some meds such as clozapine and olanzapine.
-1/2 ppd or more, higher dose of meds is needed.
Normal metabolizers:
Persons with one or 2 functioning copies of CYP2D6 or CYP C19.
Ultra-rapid Metabolizers
-Multiple copies of CYP2D6 or CYPC19.
-High risk for poor efficacy
-About 10-29% of people who are of East african or Middle eastern Descent are Ultra-Rapid metabolizers of CYP2D6 drugs.
Poor Metabolizers
Patients with 2 inactivated copies of either CYP2D6 or CYPC19. High risk for toxicity.
-5-10 % of caucasians have higher likelihood to have lower CYP2D6 activity making them poor metabolizers of CYP2D6 drugs.
-20% of Asian descent have reduced activity of CYP2C19 and require lower dose of certain psychotropics.
Half-Life
Amount of time required for 50% of drug to disappear from body.
Washout Period
To discontinue a drug, five half lives are required to eliminate approximately 97% of the drug.
Clearance:
Total amount of blood, serum, or plasma from which a drug is completely removed per unit time.
Lithium is one of the few psych drugs eliminated by kidneys.
Steady State
-Drug elimination equals drug availability.
-Reach steady state in about 5 times the elimination half life. rate of accumulation determined by half-life.
Pharmacodynamics
Effect the drug has on body: desired effects, side effects, adverse effects
Agonists
Substance activates receptors
Antagonists
Substance blocks receptors
Partial agonist
Cannot produce full response
Inverse agonists
Produces an effect other than agonist
Indirect agonist
Produces an effect without having the specific effect on a receptor
Down-regulation
Chronic exposure to certain drugs causes receptors to change. Pharmacodynamic tolerance causes reduction in receptor sensitivity.
Glutamate
Amino acid neurotransmitter
-Principle excitatory neurotransmitter
-Biosynthesized as byproduct of cell metabolism
-removed by reuptake
-Acts on NMDA, AMPA, Kainate receptors.
-at high levels can have major neurotoxic effects.
-implicated in the brain damage caused by stroke, hypoglycemia, sustained hypoxia or ischemia and some degenerative diseases.
Aspartate
Amino acid neurotransmitter
GABA
Amino acid neurotransmitter
-Principle inhibitory neurotransmitter
-GABA agonists: benzodiazepenes, barbiturates, alcohol.
-Biosynthesis: Glutamate acted on glutamic acid decarboxylase (GAD) and B6 to form GABA.
-Found in the brain, modulates other neurotransmitter systems rather that provide a direct stimulus.
-prevents brain from overstimulation.
-Reduction in GABA results in epilepsy.
Principle GABA Binding Sites
Benzodiazepine/alcohol (Agonist)
Barbiturate(indirect agonist)
Steroid(indirect agonist
Picrotoxin(inverse agonist)
Glycine
Amino acid neurotransmitter
Biogenic amines
medium concentration in brain.
Can be excitatory or inhibitory as a function of the receptor.
Slow acting and long duration.
Examples: acetylcholine, epinephrine, norepinephrine, dopamine, serotonin.
Histamine
Role of histamine in mental illness is under investigation.
Involved in peripheral allergic responses, control of gastric secretions, cardiac stimulation, and alertness.
Some psychotropic drugs block histamine. This results in weight gain, sedation and hypotension.
Acetylcholine
Has mostly excitatory effects
-Synthesized from dietary choline found in red meat and vegetables.
-Has 2 receptor types (nicotinic and muscarinic)
Epinephrine
norepinephrine
-Norepinephrine (noradrenalin), the most prevalent neurotransmitter in the nervous system.
-Precursor to Epinephrine (adrenaline) has limited distribution in the brain but controls the fight-or-flight response in the peripheral nervous system
-Involved in pulse, blood pressure, changes in attention, learning and memory, sleep and wakefulness, and mood regulation.
-Excess norepinephrine: several anxiety disorders
Deficits: memory loss, social withdrawal, and depression
Dopamine
-Involved in reward and motivation.
-located mostly in the brainstem
-involved in complex movements, motivation, cognition and regulation of emotional responses.
-generally excitatory, synthesized from tyrosine.
-implicated in schizophrenia, movement disorders, psychoses.
Serotonin
Major acetylcholine pathways
Dorsolateral Pons–>mid/hindbraine(REM sleep)
Basal Forebrain->Cortex (perceptual learning and attention
medial Septum->memory in the hippocampus
-Involved in Alzheimer’s (decreased acetylcholine secreting neurons) and myasthenia gravis (reduced acetylcholine receptors.
Dopamine pathways (D1-D4)
D1=Nigrostriatal (Substantia Nigra Striatum) [Motor movement]
D2=Mesolimbic (VTA limbic system) [Reinforcement and Addiction]
D3=Mesocortical (VTA prefrontal cortex) [Working memory and planning]
D4=Tuberoinfundibular tract (hypothalamus pituitary) [neuroendocrine regulation]
Norepinephrine pathway
locus ceruleus: acts throughout brain (vigilance and attentiveness.
5 HT Roles
Mood regulation
Eating disorders
Sleep and dreaming
Arousal
Sexual behavior
Pain
Aggression
Major 5HT Pathways
-Produced in the brain and intestines
-Serotonin contributes to the delusions, hallucinations, and withdrawn behavior seen in schizophrenia.
-Some antidepressants block serotonin reuptake causing longer availability of
-5-HT in the synapse= improved mood.
Dorsal Raphe Nuclei –>cortex, striatum
Medial Raphe Nuclei –> cortex, hippocampus
