Lecture 6: Psychopharmacology Flashcards
non-medicinal drug
can be defined as something, often an illegal substance, that causes addiction
medicinal drugs
substances that can be recognized by an official pharmacopeia
- intended for the treatment of diseases
psychoactive drugs
chemical substances that pass through the blood-brain barrier and reach the central nervous system to change something there
pharmaceutical drugs
substances used to diagnose/treat/prevent diseases or affect the structure/function of the body
psychopharmacology
the study that deals with the effect of drugs
class A
these drugs are considered the most harmful
- includes heroin, methadone, crack, ecstasy, magic mushrooms, and crystal meth
class B
these drugs are considered less harmful than class A drugs
- include amphetamines, barbiturates, and dihydrocodeine
- some class B are reclassified to class A when prepared for injection (amphetamines, dihydrocodeine, and codeine)
class C
these drugs are considered the least harmful of the controlled drugs
- bezodiazepines and steroids
pharmacokinetics
deals with the factors that influence a drug
- what the body does with the drug
- route of administration, rate of absorption, termination of drug action, and elimination of the drug are important
pharmacodynamics
what the drug does to the body
oral (PO) route of administration
through the mouth
- the drug must be lipid-soluble
- rate of absorption influenced by the contents of the stomach
rectal (PR) route of administration
administered into the rectum
- route is irregular, unpredictable, and incomplete
aerosol route of administration
inhaled through the lungs
- allow for rapid delivery of the drug molecules to the brain
transdermal (TD) route of administration
through the skin
transmucosal (TM) route of administration
administration through the mucous membranes
- intranasally (nose)
- sublingually (under tongue)
parenteral route of administration
does not go through the gastrointestinal system
intravenous route of administration
when a drug is delivered directly to the bloodstream and therefore reaches the brain very quickly
subcutaneous (SC) route of administration
when the drug is delivered just under the skin
- slow and depends on the blood supply to the area of injection
intreperitoneal (IP) route of administration
the drug is delivered through the abdominal wall into the abdominal cavity (peritoneal cavity)
intramuscular (IM) route of administration
the drug is administered into the muscle
intrathecal route of administration
the drug is injected into the subarachnoid space in the spinal canal, reaching the cerebrospinal fluid
intracerebroventricular (ICV) route of administration
the drug is delivered to the ventricles of the brain
- performed in animals
epidural route of administration
the drug is delivered to the epidural space
distribution of ingested drugs
the stomach and intestines must actively absorb it
- first passes through the blood vessels to the liver
- there is a separate blood vessel system that first passes through the liver and only then to the rest of the body
- the liver can transform the drug and therefore a smaller percentage can be measured in the blood than was initially taken
cell membrane
the drug must pass through the phospholipid cell membrane to enter the cell
- fat-soluble drugs can easily pass through the cell membrane, but many drugs are not fat-soluble
walls of the capillaries
to enter the cell, the drug must leave the capillaries
- thin and formed by a single layer of cells
- between the cells are small holes that allow the exchange of small molecules
blood-brain barrier
has 2 major components, capillaries and glial cells
- in the brain, capillaries are tightly packed together and covered by a glial sheath made by astrocytes
- all psychoactive drugs can cross the blood-brain barrier
placental barrier
the placenta connects the mother to the fetus
- the point where drugs that the mother has taken can be passed on to the unborn child
- drugs crossing this barrier can have devastating effects on the development of the fetus
exit routes of drugs
- kidneys (most common)
- lungs
- bile
- skin
two phases of biotransformation (hepatic metabolism)
phase 1: involves the oxidation of the drug
- the liver converts it into a compound that is less fat-soluble and also less active
phase 2: involves the combination (conjugation) of the drug and a small molecule by the liver
- small molecules, such as glucuronide that are important in inactivating the drug, produce a metabolite that is highly ionized (slow/passive)
the renal system
processes hydrophilic drugs and those that have undergone hepatic biotransformation
half-life of drugs
the time it takes for the drug concentration to drop by 50% and then by 50% again
- first half-life, then second half-life
shape and charge of binding protein
determine which ligands will bind
ligand
is a molecule that binds to a receptor
high-affinity binding site
the ligand binds to this site more easily because the protein has both the right shape and charge
intermediate-affinity binding site
the ligand matches the receptor in shape, but not in charge (e.g. both negatively charged)
low-affinity binding site
the ligand cannot bind to the receptor because they do not match in shape and charge
saturation
occurs at the time when 2 receptors can bind to the same ligand
non-competitive drug
does not bind to the same site as the neurotransmitter, so they can both bind
competitive drug
wants to bind to the same site as the neurotransmitter, so there is competition
efficacy
the property of a ligand that changes the target cell after binding
- subject to interpretation by cells and it is the interaction of drug and cell that result in the observed drug/receptor activity
agonists
full agonists facilitate action at the synapse
- produces the full maximal response capacity of the cell
antagonists (blockers)
inhibit the activity of a neurotransmitter at the synapse
- can block receptors by binding to the same site as the endogenous agonist (orthosteric), or by binding to a separate site and changing the conformation of the receptor (allosteric)
orthosteric antagonism
where the drug completely blocks the agonist effect without any degree of the antagonism (all or nothing)
- competitive
allosteric antagonist
can modulate drug effects without resorting to all or nothing principles
- non-competitive
partial agonists
function somewehere between full agonist and a full antagonist
- binds to the receptor, preventing other ligands from binding, but only has reduced efficacy at the receptor to produce a functional and biochemical change
- cause agonism at low doses when no other agonist is present
- cause antagonism when a full agonist is present
inverse agonists
produce a response opposite to that of an agonist
- antagonists inhibit a response (produce no response)
- inverse agonists produce an opposite (negative) effect
precursur-preloading drugs
these drugs improve the synthesis and increase the turnover of a neurotransmitter by acting as a precursor in the synthesis of the neurotransmitter
- provide some of the ingredients for a neurotransmitter, such as a percursor to dopamine
- one of the main therapies used in patients with Parkinson’s disease
synthesis inhibition
drugs can interrupt and inhibit synthesis, preventing a neurotransmitter from being made
storage prevention
once synthesized, drugs can prevent the neurotransmitter from being stored in the vesicle
enhance neurotransmitter release
drugs can enhance the release of neurotransmitters from presynaptic terminals
postsynaptic stimulation
drugs can act on the postsynaptic receptor and mimic endogenous neurotransmitters
postsynaptic antagonism
a drug can act on the postsynaptic receptor to block the action of endogenous neurotransmitters (an antagonist)
stimulation and antagonism of the autoreceptor
drugs can act at the autoreceptor to provide false feedback on synaptic activity
drugs that block reuptake
the level of neurotransmitters can be increased by drugs, which act at the reuptake transporter
- prevents the neurotransmitter from being removed from the synapse (blocking the metabolic escape route)
inhibition of metabolism
drugs can prevent the neurotransmitter from being metabolized
multiple sites of drug action
drugs often act in multiple locations, which may lead to increased therapeutic efficacy, but may also contribute to neurotoxicity and adverse effects
stimulants
- psychostimulants
include cocaine, amphetamines, nicotine, and caffeine
cocaine
a dopamine transporter (DAT) agonist and requires an action potential to release dopamine before it can be effective
- blocks the DAT, preventing the reuptake of dopamine into the synapse
- if it cannot be reabsorbed, it remains in the synapse and remains available to stimulate receptors
amphetamine
currently used in the treatment of narcolepsy and ADHD, but is also used by the military to keep personnel awake and alert
- works by increasing dopamine release from the presynaptic neuron
nicotine
acts on ACh receptors called nicotine receptors
- the activation of these receptors underlie the addictive nature of smoking
- stimulation of nicotinic receptors at the ventral temental area means that nicotine facilitates the release of dopamine in a similar manner to that of amphetamine
caffeine
has multiple effects, including the blockage of benzodiazepines at GABA-A receptors, the stimulation of calcium release, and the blockade of adenosine receptors
depressants
opioids, alcohol, anxiolytics
opioids
drugs that interact with endogenous neuropeptides (pain-relieving)
- opiates are CNS depressants and produce postsynaptic, axoaxonic and presynaptic inhibition
- heroin (diacetylmorphine) crosses the blood-brain barrier quickly (makes more morphine in the brain)
alcohol
a complex molecule with a broad spectrum of action, but the net effect is CNS depression
- the effects of alcohol are also dose-dependent with disinhibition and euphoria as characteristics at low doses
- deterioration of numerous cognitive and motor functions is characteristics at higher doses
anxiolytics
drugs used to treat anxiety include CNS depressants
- the action of these drugs targets the GABA receptor
- it is the GABA-A receptor that mediates the anxiolytic effects of the drugs
- Diazepam (Valium): a benzodiazepine agonist
mind-altering drugs
hallucinogens, cannabinoids
hallucinogens
mind-altering drugs that cause perceptual and cognitive changes
- LSD: symptoms include dizziness, restlessness, optical distortions, dreamlike state, feelings similar to intoxcation, a kaleidoscope of colors, and exaggerated imagination (higher doses cause dissociation and hallucinations)
- mescaline: has serotonergic effects
- psilocybin (magic mushrooms): has serotonergic effects
- ketamine and phencyclidine (PCP): psychedelic drugs that target glutamate as their site of action
cannabinoids
main active component of cannabis is the cannabinoid delta9-tetrahydrocannabinol (THC)
- THC is the common denominator in male forms of cannabis and its behavioral effects are well documented
- we have a endocannabinoid system: a widespread distribution of cannabis receptors with cortical and subcortical regions
tricyclic antidepressants (TCA)
a type of structure-based antidepressant
- affects more substances than just serotonin
monoamine oxidase inhibitors (MAOIs)
an antidepressant that blocks the enzymatic breakdown of catecholamines and indoleamine by monoamine oxidase
selective serotonin reuptake inhibitors (SSRIs)
a medication that blocks the reuptake of released 5-HT
- used as an inhibitor of an antidepressant
selective noradrenergic reuptake inhibitors (SNRIs)
a medication that blocks the reuptake of released norepinephrine
- used as an inhibitor and antidepressant
reuptake inhibitors
inhibit the reuptake of monoamines into the synaptic cleft
- are antagonists
antipsychotics
are used to treat schizophrenia and have been essential in developing a better understanding of the disorder
- the prevailing view is that all of these drugs cause a blockade of dopamine receptors
Nuremberg Code
focuses on the human rights of research subjects
declaration of Helsinki
adopted the original point of the Nuremberg Code as a guide to medical ethics
- focuses on the obligations of physician-investigators for research subjects
phases of clinical trials
phase I: takes place in a small number of human volunteers
- small amounts of the new drug given
- compared to placebos
phase II: studies involving administering the new drug to a small number of the target population
- highly controlled
phase III: includes many patients randomly assigned to treatment groups
- within the context of how the drug is marketed in terms of efficacy and safety
phase IV: takes place after a product has been licensed and marketed
- information obtained from such large studies allows for a clearer picture of a drug or intervention
randomized controlled trial (RCT)
applied to avoid contamination of experimentation effects of allocation supply
single-blind experiment
the individual participants do not know which group they are in
double-blind experiment
neither the experimenter nor the participant knows which group they are in
meta-analysis
can be usesd to convert a large amount of research work into one sensible account
