Chapter 6 Flashcards
Psychopharmacology
Study of the ways drugs affect the nervous system and behavior
Psychoactive Drug
Substance that acts to alter mood, thought, or behavior, used to manage neuropsychological illness
Often used recreationally
Drugs
Chemical compounds administered to produce a desired change
Improvement of physical/mental symptomatology
Routes of Drug administration
Orally → safest and most convenient: ingestion » absorption by stomach/small intestine » then enters bloodstream (water-soluble)
Inhaled → encounter few barriers enroute to the brain » absorbed into bloodstream almost immediately
Injected into bloodstream → fewest barriers to brain but must be HYDROPHILIC » dosage can be reduced by factor of 10
Injected into muscle → encounter more barriers than inhaled drugs
Injected into brain → acts quickly and in LOW doses
Absorbed through skin → adhesive patches into bloodstream » small-molecule drugs can penetrate
Weak acid drugs
Pass from stomach into bloodstream
Weak base drugs
Pass from intestines to bloodstream
Factor of 10 rule
1 milligram of amphetamine produces noticeable behavior change orally
If inhaled into lungs or injected into blood, a dose of 100 ug yields the same results
If amphetamine is injected into CSF, 10 ug is enough for identical outcome
1 ug if drug directly applied to target neurons
Blood-brain barrier
Cell membranes, capillary walls, and placenta → all barriers to internal movement of drugs
Blood-brain barrier prevents most substances from entering brain via the bloodstream
Protects brains ionic balance
Denies neurochemicals that can disrupt neural communication
Protects brain from circulating hormones and from toxins/infectious diseases
Endothelial cells → blood-brain barrier
Form a cell layer that lines blood vessels → regulates exchanges between bloodstream and surrounding tissues
Endothelial cells in capillaries throughout the body are not tightly joined: easy for substances to move in and out of the bloodstream
Endothelial cell walls in brain are fused to form fight junctions → most substances cannot squeeze between them
Barrier-free Brain sites
Pineal gland → entry of chemicals that affect day-night cycles
Pituitary gland → entry of chemicals that influence pituitary hormones
Area postrema → entry of toxic substances that induce vomiting
What helps access and support brain function?
Brain needs oxygen and glucose for fuel and amino acids to build proteins
Fuel molecules reach brain cells from blood, carbon dioxide + other waste products are excreted from brain cells and carried away by the blood
Molecules of these vital substances cross the blood-brain barrier in 2 ways:
↳small, uncharged molecules (ex. Oxygen and carbon dioxide) are fat soluble and can freely pass through the endothelial membranes
↳complex molecules of glucose, amino acids, and other food components are carried across the membrane by active transport systems or ion pumps
SOME psychoactive drugs (must be small or have correct chemical structure) DO gain access to the CNS
How body eliminates drugs
Drugs are catabolized in the kidneys, liver, and intestines → then excreted in urine, feces, sweat, breast milk, and exhaled air
Liver is active in catabolizing drugs: houses a family of enzymes involved in drug catabolism
The cytochrome P450 enzyme is involved in drug catabolism → some of which are also present in gastrointestinal tract microbiome
Liver is capable of turning drugs into other forms that are more easily excreted from body
Agonist vs. Antagonist drugs
Agonist → drugs that increase neurotransmission
Antagonist→ drugs that block; decrease neurotransmission
Drugs and Major steps in neurotransmission
Drugs can influence synthesis of NT, packaging and storage of NT, release of NT, receptor interaction with the NT, and reuptake/degradation of the NT
Tolerance to drugs → 3 types
Decreased response to a drug with repeated exposure → 3 types
Metabolic tolerance: increase in number of enzymes in liver, blood, or brain used to break down a substance → metabolized faster = blood levels decrease
Cellular tolerance: activities of brain cells adjust to minimize effects of substance → accounts for low signs of intoxication with high blood-alcohol levels
Learned tolerance: People learn to cope with being intoxicated so they may no longer appear intoxicated
Sensitization relative to drugs
Sensitization more likely to develop with periodic use → occasional drug taker may have an increased responsiveness to successive, equal doses
Related to dependence→ before a person becomes dependent they must be sensitized by numerous experiences with the drug
Life experiences (stress) can produce effects resembling sensitization that prime nervous system for addiction
Sensitization to SSRI’s causes them to work → must be taken for several weeks first
Psychoactive drugs
Psychoactive drugs can be grouped based on the primary neurotransmitter system that they are known to effect
Priming
Synapse first receives chemical then becomes more ready to fire after first dose
Main psychoactive drugs → 9 types
Adenosinergic antagonist → caffeine
Cholinergic agonist → nicotine or diazepam, alprazolam, clonazepam
Glutamatergic antagonists → ketamine/PCP or memantine
Dopaminergic antagonists → Thorazine, Haldol, clozaril
Dopaminergic agonists → cocaine, amphetamine, methamphetamine, or aderall, Ritalin etc.
Serotonergic agonists → DMT, ecstasy, LSD or Zoloft, Prozac, tofranil
Opiodergic agonists → opium, morphine, heroin, or codeine, oxycodone,fentanyl
Cannabinergic agonists → THC
Adenosinergic antagonist
Most widely consumed psychoactive drug: caffeine
Binds to adenosine receptors without activating them → suppresses endogenous adenosine which includes drowsiness → leads to alertness
Also inhibits enzyme that usually breaks down the second messenger; cyclic adenosine monophosphate (cAMP): resulting increase in cAMP leads to increased glucose production→ resulting in more available energy and higher rates of cellular activity
Promotes release of dopamine and acetylcholine
Repeated daily use: mild form of drug dependence → fade within a week of abstinence
Cholinergic agonist
Nicotine→ feelings of relaxation, sharpness, calmness, and alertness
Within a few seconds from inhalation, nicotine stimulates acetylcholine nicotinic receptors
Acetylcholine nicotinic receptors cause the release of acetylcholine, norepinephrine, epinephrine, serotonin, endorphins, and dopamine
At low doses can act as a stimulant→ very high doses: dampens neuronal activity
Dependence involves both psychological and physical aspects
Potentially lethal poison → smoking can be a risk factor for Alzheimer’s disease
GABAergic agonists
Alcohol
At low doses: reduce anxiety, medium doses: sedate, at high doses: they anesthetize or induce coma → death
GABAa receptor contains a binding site for GABA, one for alcohol, and one for benzodiazepines and a Cl-
Excitation of the GABAa receptor produces an influx of Cl- through its pore → influx of Cl- increases concentration of negative charges inside the cell membrane, hyperpolarizing it (less likely to propagate an AP) → widespread reduction of neuronal firing underlies the behavioral effects of drugs that affect GABAa synapse
Summation in GABAergic agonists
Sedative-hypnotic drugs (alcohol) increase GABA binding, thereby maximizing the time the pore is open
Antianxiety drugs (benzodiazepines) influence the frequency of pore opening
Because actions summate, they should not be taken together
Cross tolerance for benzos and alcohol→ act on NS in similar ways
GABAergic Receptors
Alcohol consumption has short-term psychological and physiological effects that depend on: alcohol volume, body mass, food intake, genetics, etc.
Small amounts improve mood, sociability, fine muscle coordination, etc.
Medium doses result in lethargy, sedation, lack of balance, etc.
Long-term and frequent consumption can lead to increased risk of alcoholism → results in damage to central and peripheral nervous systems, as well as nearly every other system and organ in the body