Psychopharmacology Test 1
What are the six classical neurotransmitters and their major receptor types?
acetylcholine: the neurotransmitter substance that is released at the synapses of parasympathetic nerves and at neuromuscular junctions between the vagus nerve and cardiac muscle fibers. It also serves as a neurotransimitter at synapses in the ganglia of the visceral motor system and at a variety of sites within the CNS. The actions of this within the CNS are not well understood dopamine: A monoamine neurotransmitter involved in reward, motivation, and motor control. Found majorly in the corpus striatum. Too little = parkinsons. MAO and COMT are the two major enzymes that are involved in it's catabolism. norepinephrine: helps control alertness and arousal; neurotransmitter(undersupply can depress mood). Used in the locus coeruleus. Synthesis requires dopamine beta-hydroxylase (can be made from dopamine serotonin: a neurotransmitter that affects hunger,sleep,arousal,and mood. appears in lower than normal levels in depressed persons. Found in the raphe region of the pons and upper brainstem. Synthesized from tryptophan by tryptophan 5 hydroxylase GABA: major inhibitory neurotransmitter; small molecule neurotransmitter. Degradation of this can result in the production of gamma-hydroxybutyrate the "date rape" drug. It is degraded by ------ Transaminase and succinic semialdehyde dehydrogenase. glutamate: a major excitatory neurotransmitter involved in information transmission throughout the brain; small molecule neurotransmitter and during brain trauma, there is an excessive release of this.
Define half-life. How does half-life apply to steady state? if a drug has an elimination half-life of 6 hours, how long does it take for the drug to be essentially eliminated from the body after administration of a single dose.
Half life is the amount of time it takes for literally half of the drug to be eliminated. With a steady state a continual amount of the drug has to be administered at specific time intervals in order to extend the life of the drug. -12 hours
What are the major divisions of the central nervous system?
Hindbrain, midbrain, and forebrain
What is a neuron?
The neuron is the basic functional unit
What is meant by the term pharmacokinetics?
"The way the body interacts with the drugs." The root kinetics implies movement and time. Knowledge of movement and time offers significant insight into the action of a drug. At the very least, it helps distinguish a particular drug from other related drugs. For example, the main difference between the two benzodiazepines lorazepam and triazolam is their pharmacokinetics. Both drugs depress the functioning of the brain. causing sedative and anti anxiety effects. Lorazepam however persists for at least 24 hours in the body which triazolam persists only for about 6-8 hours. Three ranges in blood plasma because of kinetic differences. (Toxic range, therapeutic range, and ineffective range)
Main parts of the neuron (2)
Organelles perform vital functions, for example, mitochondria produce energy from nutrients, while golgi bodies package substances (such as neurotransmitters) into vesicles for storage.
Distinguish between the terms pharmacodynamics and pharmacokinetics.
Pharmacokinetics is the study of what the body does to a drug (distribution and elimination). Pharmacodynamics is the study of what the drug does to the body (the pharmacological and clinical effect). The interaction of the drug with the specific molecules and chemicals found in the body.
Agonists
drugs that increase the action of a neurotransmitter
Allosteric
while an allosteric ligand binds to another separate site (or sites) on the receptor. Allosteric ligands possess several advantages over orthosteric compounds.
What is meant by the terms therapeutic drug monitoring and therapeutic window?
-TDM is the measurement of drug concentration at receptor site -Therapeutic window is well defined range of blood levels associated with primal clinical response -The TDM (therapeutic drug monitoring system) shows a blood plasma threshold for a drug to remain active as a therapeutic agent. Anything below that threshold will not have an effect. Anything over that threshold pushes in to toxic
Describe the basic characteristics of the cerebral spinal fluid system in the brain
-The CSF (Cerebral Spinal Fluid) provides nutrients and chemical substances filtered from the blood, removes waste products from the brain, and transports hormones to various brain structures. -The brain floats in CSF and provides cushion against physical impacts
Summarize the processes involved in synaptic transmission.
1)Neurons in a resting state on the inside of the cell are negatively charged. 2)Stimulus activates neuron making it positively charged for a split second. 3)Action potential occurs creating an electric impulse that travels down axon to end of neuron. 4) Action potential arrives at terminal button of axon and has to cross the synapse between the presynaptic neuron and postsynaptic, the synapse gap. 5) Axons have sacs at the end called synaptic vesicles. They contain neurotransmitters that diffuse across the synapse to the next neuron. 6)When action potential reaches synaptic vesicles they release neurotransmitters across the synaptic gap and bind to specialised receptors on the surface of the cell that are activated by that particular neurotransmitter. 7)when a neurotransmitter crosses synapse the postsynaptic receptor site (Dendrites) convert the chemical message back into an electrical impulse. 8)Process terminated by reuptake where the neurotransmitter is taken up again by presynaptic neuron. stored and made available for later release.
How is the synaptic transmitter terminated? Give examples.
1. Diffusion of the transmitters 2. Degradation by enzyme 3. Reuptake by transporter 4. Desensitization
Define the placebo response and discuss the history and the major factors that influence it.
1. any medical procedure that produces an effect in a patient because of its therapeutic effect, not because of its specific nature
What is the difference between a competitive and noncompetitive/irreversible antagonist?
A competitive antagonist binds to the same site as the agonist but does not activate it, thus blocks the agonist's action. A non-competitive antagonist binds to an allosteric (non-agonist) site on the receptor to prevent activation of the receptor.
What is a drug receptor? What are the major types and how do they differ?
A drug receptor is a substance in the body that produces an effect when a drug interacts with it. These drug receptors are usually located on the top of neurons in the brain. Ion channel receptors G-Protein-Coupled Receptors Transporter Proteins Enzymes
Which factors influence drug safety and toxicity and how is drug safety measured?
Administration (Route), Pharmacokinetics (Drug Absorption, Drug Distribution, Drug Metabolism, and Drug Excretion), and Pharmacodynamics (Impact of Drugs on the Body)
Discuss the advantages and disadvantages of the various methods of administrating drugs
Administration by inhalation: -lung tissues have a very large surface area which large amounts of blood flow, allowing for rapid absorption from lung into the blood (often within seconds) -may have even faster onset of effect than intravenously (injection into the vein) -the rapid onset of effect can be intense and may promote compulsive use. Administration through the skin: -allows for slow, continuous absorption of the drug over hours or even days, potentially minimizing side effects associated with rapid rises and lows in plasma concentration. Administration by injection: -can be intravenous (directly into vein), intramuscular (into the muscle, subcutaneous (just under the skin) or spinally (epidural or intrathecal, directly on spinal cord) -rapid response than oral administration -permits more accurate dose because of the unpredictable processes of absorption through the stomach and intestine. Oral Administration: -Easy to take, moderately fast absorption. -possible damage to the stomach lining, difficult to gauge the amount of drug the body is taking in because of stomach acid and enzyme activity. Rectal Administration: -Good for when someone can't swallow or is throwing up. -Not pleasant, and some drugs are irritating to the tissues.
What are the major structures of the limbic system?
Amygdala (emotion) and the Hippocampus (memory)
Antagonist
An antagonist is a molecule that binds to a target and prevents other molecules (e.g., agonists) from binding.
inverse agonist
An inverse agonist is a compound that binds to and prevents constitutive receptor activity in the absence of an agonist.
Orthosteric
An orthosteric ligand interacts with the same binding site as the natural endogenous agonist (neurotransmitter or hormone)
Describe the role of the liver and the hepatic enzyme system in drug metabolism
Any drug that isn't able to be passed through the way of the kidneys, gets reabsorbed by hepatocytes and transformed into less soluble molecules (less likely to be reabsorbed again). Whatever is not reabsorbed is passed through urine.
What is drug tolerance? & Why does it occur?
Drug tolerance is when someone become decreasingly responsive to a drug. In this case that person must have higher dosages of the same drug to have the same response as behavior. 1) Once the body has been exposed to a drug for a long period of time, the brain compensates and takes away some of the receptors for the drug or overall become less sensitive. In the same scope the body can also increase the amount of enzymes for that particular drug molecule.
Why must a psychoactive drug be altered metabolically in the body before it can be excreted?
In order for drugs to be passed through elimination by some means (lungs, liver, kidneys) it must be lipid-soluble. If the drugs did not get metabolized in different areas they would continue to work because they wouldn't ever be passed.
What are the major functions of the basal ganglia?
Integration of movement
Discuss the blood-brain barrier as a limitation to drug transport.
The BBB (Blood Brain Barrier) does not have pores that drug molecules can flow through. The BBB also has a glial sheath which is a fatty barrier. In order for drugs to pass through the BBB they have to be small and lipid soluble. If they are big or not lipid soluble, there is only one other way in. With help of transcytosis, a substance will attach to a receptor on the cell wall membrane and then from there create a vesicle to cross over and fuse with the other side.
What are the major structures of the basal ganglia?
The Caudate nucleus and the Putamen (together are called the striatum). The Globus pallidus- consists of the lateral (external) and medial (internal) parts. These three structures are sometimes called the Corpus Striatum Two additional structures are the Subthalamic nucleus and the Substantia nigra
What are the major subdivisions of the central nervous system?
The central nervous system (defined as the brain and spinal cord) is usually considered to have seven basic parts: the spinal cord, the medulla, the pons, the cerebellum, the midbrain, the diencephalon, and the cerebral hemispheres. The medulla, pons, and midbrain are collectively called the brainstem. the diencephalon and cerebral hemispheres are collectively called the forebrain.
What are the major functions of the limbic system?
The limbic system and the hypothalamus interact to regulate emotion and emotional expression. The site of action for many psychoactive drugs that alters mood, affect, emotion, or responses to emotional experiences.
Summarize the major structures of the limbic system and respective functions
The limbic system- is considered our primitive brain and plays a key role in our survival. The limbic system is largely involved in emotions (e.g., fear, anger, pleasure), basic drives (e.g., sex, hunger), learning, olfaction, and memory. The limbic system also influences our autonomic nervous system and endocrine system.
Summarize the major structures of the basal ganglia and respective functions
The main nuclei of the basal ganglia include 1- caudate nucleus, 2- putamen, 3- substantia nigra, 4- globus pallidus, 5- subthalamic nucleus The basal ganglia play a vital role in the regulation and coordination of movement and with establishing posture. The main nuclei of the basal ganglia include the caudate nucleus, putamen, substantia nigra, globus pallidus, and subthalamic nucleus. The basal ganglia are inhibitory. They generally function to put the brakes on movement, allowing us to be still and maintain posture. In order to move voluntarily, the brakes must then be released.
What are the major components of a dose-response function and what do they represent?
The relationship between the size on an administered dose and the intensity of the response produced. This response determines the minimum amount of drug we can use. Directly Proportional relationship. Dose response curves reveal two characteristic properties of drugs: maximal efficacy and relative potency.
Discuss the receptor phenomena of upregulation and downregulation.
Up regulation occurs when a cell produces more receptors, the cell decreases its degradation of receptors or by activating already present recpetors. ... Down regulation is when a cell decreases its sensitivity to a hormone by decreasing the amount of available receptors.
main parts of a neuron (3)
extending from the soma in one direction are many short fibers called dendrites, which receive input from other neurons through receptors located on the dendritic membrane. when a signal arrives from another cell a message is generate and travels down the dendrite to the soma. extending in another direction from the soma is a single process called an axon, which can vary in length from a few millimeters up to a meter which transmits the signal through a electrochemical process (the action potential) -axons are usually covered by myelin sheath.
Main parts of the neuron
glia provide support and protection. The main types of glial cells in the CNS are oligodendrocytes, astrocytes, ependymal, and microglial cells. -A typical neuron has soma (cell body) which contains the nucleus (including genetic material of the cell) and several other structures. -Oligodendrocytes: form the myelin sheath around axons. -Astrocytes: provide neurons with nutrients and structural support. They maintain the extracellular environment of neurons by regulation their ionic surroundings, modulating the rate of signal transmission reuptake of neurotransmitters.
What is "irrational polypharmacy" and how can it be avoided?
inappropriate use by using multiple drugs, possibly not prescribed or that are contraindicative ............................ no apparent reason for the drug-duplicate drugs (multiple drugs prescribed for the same effect)-contraindicated drugs-drug interactions-inappropriate dose-using drugs to treat an ADR-improvement when drug is discontinued
Which diseases and drugs of abuse are associated with each of the major neurotransmitters?
norepinephrine: ADHD, depression, Amphetamine, for example, is a stimulant that increases release of norepinephrine. dopamine: alterations in hormone are commonly in people with schizophrenia who are taking various antipsychotics, which block dopamine receptors. parkinsonism side effects produced by antipsychotic drugs (which block these receptors) all involve this pathway. serotonin: LSD-induced hallucinations might be caused by alterations in the functioning serotonin neurons and be involved in abnormal behavioral functioning. serotonin plays a role in depression, anxiety, OCD, panic, phobias, sleep, sex, cardiovascular function, and regulation of body temp. use of a sari to treat depression can be associated with side effects such as insomnia, anxiety, and loss of libido.
Which major brain structures are associated with the neural pathways that release norepinephrine, dopamine, and serotonin?
norepinephrine: neurons are located in the brain stem, mainly in a structure in the pons called the locus coeruleus. From there, axons project widely throughout the brain to nerve terminals in the cerebral cortex, the limbic system, the hypothalamus, and the cerebellum. Anoxal projections also travel down the spinal cord, where they exert an analgesic action. (The release of norepinephrine produces an alerting, focusing, orienting response, positive feelings of reward, and analgesia) dopamine: originate in the brain stem, sending axons both forward (rostral) to the brain and backward (caudal) to the spinal cord. 1. Goes to the hypothalamus. 2. Substantia nigra to striatum. 3. Cerebral cortex and the limbic system. serotonin: Many originating spots. Goes: 1. To the cerebral cortex, hippocampus, thalamus, hypothalamus, and basal ganlgia. 2. To the spinal cord and cerebellum.
Define the terms full, partial, and inversive agonist; allosteric drug; and antagonist.
partial: Bind to receptor but do not evoke responseHave affinityLack full efficacy because they don't completely activate the receptor
