Chapter 4: Psychopharmacology Flashcards
Psychopharmacology
Study of effects of drugs on nervous system and behavior
Drugs
Exogenous chemical not necessary for normal cellular functioning that significantly alters functions of certain cells of body when taken in relative low doses
Drug Effects
Observable changes in individual’s physiology and/ or behavior
Sites of Action
Location where drug molecules interact with molecules on or in cells to affect biochemical processes
Absorption
Drug is administered and absorbed through tissue
Distribution
Drug is distributed throughout blood and body
- Rate at which drug reaches sites of action is based on lipid solubility
Lipid Solubility
Ability of fat-based molecules to pass through cell membranes
Ex. Heroin is more lipid- soluble than morphine
Metabolism
Drug is changed to inactive form by enzymes (usually in liver)
Excretion
Drug is excreted in urine by kidneys
Intravenous (IV) Injection
Injection of substance directly into brain
Intraperitoneal (IP) Injection
Injection of substance into peritoneal cavity
Intramuscular (IM) Injection
Injection of substance into muscle
Subcutaneous (SC) Injection
Injection of substance into space beneath skin
Oral Administration
Administration of substance into mouth so that it is swallowed
Sublingual Administration
Administration of substance by placing in beneath tongue
Inhalation
Administration of vaporous substance into lungs
Topical Administration
Administration of substance directly onto skin or mucous membrane
Insufflation
Administration of substance by sniffing or snorting
- drug is absorbed through mucous membranes of nose
Dose Response Curve
Graph of magnitude of effect of drug as function of amount of drug administered
Therapeutic Index
Ratio between dose that produces desired effects in 50% of animals and dose that produces toxic effects in 50% of animals
Drugs vary in effectiveness because of:
- site of action
- affinity of drug with site of action
Drug Affinity
Readiness with which two molecules join together
- most desirable drug has high affinity for sites of action producing therapeutic effects and low affinity for sites of action producing toxic side effects
Opiates have more than one effect
- Analgesia
- Depress heart rate and respiration
Tolerance
Decrease in effectiveness of drug that is administered repeatedly
Sensitization
Increase in effectiveness of drug that is administered repeatedly
Withdrawal Symptom
Appearance of symptoms opposite to those produced by drugs when drug is administered repeatedly and then suddenly no longer taken
Physical Dependence
Compensatory changes following repeated use of drug that results in withdrawal symptoms when drug is no longer taken
Compensatory mechanisms that come with repeated drug use:
Decrease in effectiveness of binding
- Receptors become less sensitive - Receptor downregulation
Coupling process between receptors to ion channels or production of 2nd messengers is less effective
Receptor Downregulation
Decreased number of receptors
Placebo Effects
An inert substance that is given to organism instead of psychologically active drug
- used experimentally to control for effects of mere administration of drug
Antagonist
Drug that opposes/ inhibits effects of particular NT on postsynaptic cell
- drug inactivates enzymes used to synthesize NTs
Agonist
Drug that facilitates effects of particular NT on postsynaptic cell
- rate of synthesis and release of NT increases when precursor is administered
Antagonist Effects on Storage and Release of NTs
- Transporter molecules that fill synaptic vesicles are capable of being blocked by drugs
- Prevent release of NTs from termonal buttons
- Deactivate proteins that cause synaptic vesicles to fuse with presynaptic membrane
Direct Agonist
Drug that binds with and activates a receptor
Direct Antagonist
- Receptor blocker
- Drug that binds with receptor but doesn’t activate it
- Prevents natural ligand from binding with receptor
Noncompetitve Binding
Binding of drug to site on receptor
- Doesn’t interfere with binding site for principle ligand
Indirect Antagonist
Drug that attaches to binding site on receptor and interferes with action of receptor
- Doesn’t interfere with binding site for principal ligand
Indirect Agonist
Drug that attaches to binding site on receptor and facilitates action of receptor
- Doesn’t interfere with binding site for principal ligand
Agonist Effects on Reuptake or Destruction of NTs
- Molecules of drug attach to transporter molecules that are responsible for reuptake and inactivate them
- Molecules of drug bind with enzymes that normally deactivate NT and prevents enzymes from working
Glutamate
Most important excitatory NT in brain
- found in all neurons except pain neurons (produce substance P)
Vesicle Glutamate Transporter
Protein in vesicle membrane that pump Glu into vesicle
NMDA Receptor
Specialized ionotropic Glu-R that controls Ca2+ channel that is normally blocked by Mg2+ ions
- has several other binding sites (Glu and Gly co-agonists)
AMPA Receptor
Ionotropic Glu-R that controls Na+ channel
- stimulated by AMPA
Kainate Receptor
Ionotropic Glu-R that controls Na+ channel
- stimulated by kainic acid
Metabotropic Glutamate Receptor
Category of metabotropic receptors that are sensitive to Glu
PCP
Drug that binds with PCP binding site of NMDA receptor and serves as indirect antagonist
Ketamine
Drug that binds with noncompetitive binding site of NMDA-R and serves as an indirect antagonist
Excitatory Amino Acid Transporter
Proteins that remove Glu from synapse
Glutamine Synthase
Enzyme that breaks Glu—>Gln
Glutamate Excitotoxicity
Toxic overstimulation of postsynaptic cell by excess Glu
GABA
Most important inhibitory NT in brain
Vesicle GABA Transporter
Proteins in vesicle membrane that pump GABA into vesicle
GABAa Receptors
- Ionotropic
- Control Cl- channels
- Contain 5 binding sites
- Antagonist: picrotoxin
- Can be excitatory if [Cl-] is higher in cell than out
GABA Transporter
Proteins that remove GABA from synapse
Acetylcholine
Primary NT secreted by axons of PNS that terminate at muscle cells to control muscle contraction
- CNDS= Facilitates learning, Memory, and Sleep
3 ACh pathways in CNS
- Dorsolateral pons- REM sleep
- Basal forebrain- activate cerebral cortex and facilitate learning (especially perceptual learning)
- Medial septum- control electrical rhythms of hippocampus and modulate functions
Choline acetyltransferase (ChAT)
Transfers acetate ion from acetyl CoA to choline
Vesicle ACh Transporter
Proteins in vesicle membrane that pump ACh into vesicle
Botulinum Toxin
ACh antagonist
- Prevents release by terminal buttons
2 types of ACh receptors
- Nicotinic- ionotropic and agonist is nicotine
2. Muscarinic- metabotropic and agonist is muscarine
ACh deactivated by […]
ACh deactivated by acetylcholinesterase (AChE)
- Neostigmine
- AChE inhibitors used to treat myasthenia gravis
Neostigmine
Inhibits activity of AChE
Monoamines
Indolamine- serotonin
Catecholamine- dopamine, norepinephrine, and epinephrine
Dopamine Functions
Movement, attention, learning, reinforcing drug effects, planning, problem solving
Dopamine pathways
- Nigrostriatal System
- Mesolimbic System
- Mesocortical System
Nigrostriatal System
System of neurons originating in substantia nigra and terminatingin neostriatum (caudate nucleus and putamen)
- degeneration causes Parkinson’s disease
Mesolimbic System
System of DAergic neurons originating in VTA and terminating in NAcc, amygdala, and hippocampus
Mesocortical System
System of DAergic neurons in VTA and terminating in PFC
Parkinson’s disease
Neurological disease characterized by tremors, rigidity of limbs, poor balance, and difficulty in initiating movements)
Vesicle Monoamine Transporter
Proteins in vesicle membrane that pump monoamine NTs into vesicle
Dopamine Receptors
Most common: D1-type (D1, D4, D5)
Autoreceptor: D2- type (D2, D3)
Apomorphine
Drug that blocks DA-AR at low doses
- At high doses, blocks postsynaptic receptors as well
DA Transporter
Proteins that remove DA from synapse
Amphetamine
Antagonist at DA and NE transporters that cause them to run in reverse, releasing NTs into synapse
Methamphetamine
Antagonist at DA and NE transporters that cause them to run in reverse, releasing NTs into synapse
Cocaine
Drug that inhibits reuptake of DA
Methylphenidate
Drug that inhibits reuptake of DA
Monoamine Oxidase (MAO)
Class of enzynmes that destroy monoamines
Norepinephrine
NT found in brain and sympathetic division of ANS
- CNS= vigilance - cell bodies in pons. medulla, one region of thalamus
Epinephrine
Hormone secreted by adrenal medulla
-CNS= vigilance
Most important noradrenergic system begin in […]
Most important noradrenergic system begin in locus coeruleus
Locus coeruleus
Dark-colored group of noradrenergic cell bodies located in pons near rostral end of flood of fourth ventricles
Most neurons that release NE don’t go through terminal buttons on ends of axonal branches
Release through axonal varicosity
Axonal Varicosity
Enlarged region along length of axon that contains synaptic vesicles and releases a NT or neuromodulator
Norepinephrine Receptors
GPCRs: a1-, a2, B1, B2- adrenergic receptors
- found in neurons in CNS and various organs of body
Norepinephrine Transporter
Proteins that remove NE from synapse
- Excess NE in the terminal buttons is deactivated by MAOA
5-HT Receptors
- 9 types
- Autoreceptor: 5-HT1A
- All are metabotropic except 5-HT3 (ionotropic; Cl- channel)
Serotonin Transporter
Proteins that remove 5-HT from synapse
Fluoxetine
Drug that inhibits reuptake of 5-HT
MDMA
Drug that serves as NA and 5-HT agonist
- aka ecstasy - excitatory and hallucinogenic effects
Histamine
- Found in tuberomammillary nucleus
- Plays important role in stimulating wakefulness in CNS
- PNS: immune response
- Receptors: H1, H2, H3, H4
- Diphenhydramine
Diphenhydramine
Antihistamine drug
- antagonist at histamine receptors
Peptides
- Produced in soma
- Terminal buttons release peptides in conjunction with classical NT
- Regulated sensitivity of presynaptic and postsynaptic receptors
- Released from all parts of terminal buttons
- Deactivated by enzymes
ex. Endogenous opioid
Endogenous Opioids
Class of peptides secreted by brain that acts as opiates
- opium, morphine, heroin, oxycodone, enkephalin
Opioid Receptors
Mu, delta, kappa
Methadone
Agonist for opiate receptor
Naloxone
Drug that blocks opiate receptors
Endocannabinoids
Endogenous ligand for cannabinoid- R, binds THC
- Synchronized on demand
CNS: Appetite regulation
PNS: immune response
THC
Active ingredient in MJ
- activates CB1-R—> analgesic effects
Endocannabinoid Receptors
CB1 and CB2
- both metabotropic
Anadamide is deactivated by […]
Anadamide is deactivated by FAAH (fatty acid amide hydrolase)
Pharmacokinetics
the process by which drugs are absorbed, distributed within the body, metabolized, and excreted
Agonist Effects on Storage and Release of NTs
bind with proteins and trigger release of NTs
Serotonin
CNS= mood regulation, eating, sleep, dreaming, arousal, impulse control PNS= involved in enteric nervous system
- located in raphe nulcei of midbrain, pons, and medull
- Released from varicosities
Opioid Function
CNS: reinforcement, pain modulation
PNS: pain modulation
Glycine
inhibitory NT in spinal cord and lower brain stem
Enkephalin
one type of endogenous opioids
