Drug Dependence - Test 1

What are the big three drugs in adolescence?

Alcohol, Nicotine, Marijuana

How does early use affect substance abuse disorders?

Early use increases the risk of addiction

Why do people take drugs?

out of curiosity, peer pressure, to do better, to feel good, thrill seeking behavior, and to experience new things

what is a hazardous substance?

quantitative levels of consumption that increase an individual’s risk for adverse health consequences

What is Substance use disorder (SUD)?

the DSM-5 diagnosis category that encompasses significant impairment or distress resulting from specific categories of psychoactive drug use.

What is a drug addiction?

A state in which an individual exhibits an inability to self-regulate consumption of a substance

What is the criteria for Substance use disorders?

Impaired control , social impairment, risky use of substance, and pharmacological criteria

What is the triangle of dependence composed of?

Physiological Dependence, tolerance, and withdrawal

What is Drug Tolerance?

after repeated use, the same amount of drug is insufficient to cause the desired effect and thus more drug is used. This is a compensatory response: adaptation.

What are the three causes of Drug Tolerance?

Pharmacokinetic or metabolic, pharmacodynamic or functional, learned or behavioral

What is metabolic tolerance?

arises from an increase in the rate at which the body is able to metabolize and get rid of a drug. Repeated drug may increase the action of an enzyme the body uses to destroy the drug.

What is pharmacodynamic tolerance?

arises from an adaptation in receptor function, number or messengers

What is behavioral tolerance?

arises when an animal, through experience with a drug, learns to decrease the effect that the drug is having. This learning can involve both instrumental and learning and conditioning processes

What is cross tolerance?

When an individual has become tolerant to a drug and requires higher than normal doses of a second drug to have its effects. usually between drugs of the same class , but not between drugs in different classes.

What is physical dependence and withdrawals?

predictable group of signs and symptoms resulting from abrupt removal of a drug. They can be physical , affective, or cognitive. The signs are usually the opposite to the original effects of the drug.

What do physical withdrawal symptoms serve as?

these symptoms serve as negative reinforcement

What is physiological dependence?

dependence on a psychoactive substance for the reinforcement it provides. Motivational component : great subjective need, compulsion, drive to get the drug.

What is drug-self administration?

drugs as reinforcers in animals. high correlation with human dependence liability.

Why do some people become addicted to drugs while others do not?

Vulnerability : Genetic factors , drugs, Environment

What genetic factors contribute to vulnerability of drugs?

substance use disorders are highly polygenic and a large number of genetic variants that an individual contribute to their heritable risk of developing SUD influence the pleasurable effects of drugs, impulsivity , restraint, smell , taste, etc.

What are protective factors against SUD?

Individual characteristics such as high intelligence, resilient temperament, and competencies are protective factors against SUD. Prosocial opportunities, bonding, and healthy beliefs are also protective factors. Good self control, positive relationships, school anti-drug policies

What are risk factors for SUD?

aggressive behavior in childhood, poor social skills, availability of drugs at school, lack of parental supervision

What are the main types of abused drugs?

opiates- morphine, CNS stimulants- cocaine, amphetamines, CNS depressants - barbiturates , alcohol, Hallucinogens - LSD, mescaline Misc.-marijuana, nicotine, caffeine

What is the most intense route of administration of Cocaine?

IV, smoking, intranasal, oral

What is co-administration of drugs?

Many drugs are used in combination with other drugs from one or more categories

What do all abused substances enhance?

All abused substances enhance dopamine (neurotransmitter) activity related to pleasure, motor, and cognitive function

What is the mesolimbic dopaminergic reward pathway?

dopaminergic projections from the VTA to nucleus accumbens to the prefrontal cortex and is involved in reward processing behavior.

How do drugs of abuse affect dopamine?

When drugs of abuse are taken, dopamine increases are exaggerated, and communication is altered

How does prolonged drug use affect the brain?

prolonged drug use changes the brain in structural and functional ways

Where do drugs come from?

natural products, rational drug design , biotechnology

What are drug abuse receptors?

composed proteins that interact with drugs of abuse

What is a dose effect relationship?

the magnitude of a pharmacological effect is proportional to the drug’s concentration at the tissue of action. Tissue concentrations are usually proportional to the plasma drug concentration

What is efficacy

ability of a drug to produce a (maximum) response as a result of the receptor or receptors being occupied.

What is the potency of a drug?

the dose required to produce the desired biologic response

What is loss of effect- desensitization ?

the rapid decrease in drug effect

What determines the efficacy of a drug?

The properties of the drug and its receptor-effector system.

What is a dose-response curve?

graphical representation of the pharmacological effects of a drug at varying concentrations or doses

What is an agonist?

drugs that bind to receptor and mimic the effect of the endogenous ligand

What is a competitive antagonist?

Drugs that bind to the same receptor site as the agonist, but does not activate it. Thus, blocks the agonist’s action

What is a non competitive antagonist?

Drugs that bind to an allosteric site on the receptor to prevent activation on the receptor

What are receptor binding properties?

Binding drugs to receptors can involve all types of chemical bonds: ionic, hydrogen, covalent

What is structure-activity relationship?

the chemical structure of the drug determines its affinity for the receptor of interest

What is the allosterism theory?

Modulate the receptor protein by a non-competitive mechanism and also modulates the response of an endogenous ligand without having an effect on their own

What is allosterism advantage?

The natural state of receptor can be maintained and the overdose aspect of orthosteric ligands can be reduced.

What is the function of positive allosteric modulators?

modulate the receptor protein by a non-competitive mechanism. increase the response of an endogenous ligand without having an effect on their own

What determined affinity and efficacy?

chemical structure

What is a plasma concentration time curve?

curve that shows absorption, distribution, and elimination phases in a drug time course. Shows peak plasma concentration (Cmax) and time of peak plasma concentration (tmax)

What is the therapeutic range?

the dosage range or blood plasma concentration usually expected to achieve the desired therapeutic effect

What is the half life of a drug?

time required for plasma concentration of the drug to be reduced by 50%

What is distribution?

amount of drug found in various tissues , especially the intended ones

What factors affect distribution?

size of organ, blood flow, solubility, plasma protein, anatomic barriers

What is metabolism

the process by which the drug is altered and broken down into smaller substances that are usually inactive . lipid-soluble drugs become more water soluble, so they may be more readily excreted. carried out in the liver

What is cytochrome P450

the largest class of enzymes catalyzing oxidation of organic substances in all living things. Involved in metabolism of most psychiatric medications and chemicals may increase or decrease the activity.

What is drug elimination

the total amount of blood, serum, or plasma from which a drug is completely removed per unit time. Most drugs excreted via the liver.

What is the central nervous system (CNS) composed of ?

The brain and spinal cord

what is white matter?

Tissue compromised mostly of myelinated axons.

What is grey matter?

tissue compromised mostly of neuronal cell bodies.

What is white matter in the CNS and PNS

CNS- tract , PNS- nerve

What is grey matter in the CNS and PNS?

grey matter in the CNS is in the nucleus (nucleus accumbens) and cortex (cerebral cortex). grey matter in the PNS is in the ganglion (dorsal root ganglion).

What is the afferent direction?

coming into a neuron/region

what is the efferent direction?

leaving a neruron/region

What is the dorsal location?

superior; above

What is the ventral location?

inferior; below

What is the rostral location?

anterior

What is the caudal location?

Posterior

What are the cells in the CNS?

Neurons, the functional unit of the nervous system specialized for intracellular communication

What is the function of the cell body?

macromolecule synthesis

What is the function of the dendrites?

reception

What is the function of the axon and terminals in a neuron?

Action potential propagation, synthesis

How do neurons communicate?

Neurons communicate via synapses.

What is a presynaptic element?

The axon terminal. contains synaptic vesicles, enzymes to synthesize and degrade neurotransmitters, mitochondria

What is the synaptic cleft?

the space between the axon of one neuron and the dendrites of another

What is the post synaptic cleft?

the dendrite. contains cell body or axon of a second neuron, effector organ. The neurotransmitters and receptors at a synapse provide drug targets.

What are dendritic spines?

small projections from the surface of dendrites that are highly dynamic, the shape can change due to synaptic activity. They receive excitatory synaptic input (generally glutamate)

How do drugs affect the dendritic spine?

Plasticity can occur in response to stimuli. The spine structure and/or density may be affected by drugs exposure. Psychostimulants, nicotine, PCP, and MDMA increase dendritic spine desnity in nucleus accumbens and prefrontal cortex.

What are glial cells?

Three types : astrocytes, microglia, and oligodendrocytes that continue to divide in the adult and can form adult cancers.

What are astrocytes?

type of glial cells that provide physical support, metabolic and ionic homeostasis, and role in development and blood brain barrier

What are Microglia cells?

type of glial cells that provide phagocytosis and immune surveillance

What are oligodendrocytes?

type of glial cells that myelinate axons to improve conduction

What are the steps for astrocytes in the Tripartite synapse?

they buffer K⁺ released by neurons, efficiently uptake glutamate ( which has neurotoxic effects) and release gliotransmitter

What is the blood brain barrier?

the barrier to the entry of blood-borne substances into the brain. maintains a stable environment for neurons

What is the function of astrocytes in the blood brain barrier?

the end feet surround the outside of capillary endothelial cells. They regulate blood flow and water homeostasis in the CNS

What is the function of endothelial cells in the blood brain barrier?

tight junctions and lack of pores limit diffusion across vessel walls

What is the function of the basement membrane in the blood brain barrier?

Anchors signaling proteins and provides an additional barrier

What is the metabolic blood brain barrier?

enzymes metabolize substances to prevent them from entering the brain. ex. monoamine oxidase, peptidases, and several P450 enzymes limit substances for entry

What are types of mechanisms for substances to enter the brain ?

Diffusion, lipid solubility, transport mechanisms

How does diffusion help substances enter the brain?

Using a concentration gradient, small molecules cross more easily than large molecules

what is carrier mediated transport?

a transport mechanism for glucose, amino acids, and peptides to enter the brain

What is receptor mediated transcytosis

a transport mechanism for transferrin and insulin to enter the brain

What is transcytosis?

a transport mechanism for membrane bound carriers to selectively transport materials across the cell

What is the role of lipid solubility in drug uptake?

Lipophilic substances are readily transported into the brain

What is the ventricular system composed of?

Contains cerebrospinal fluid : clear , colorless liquid; ultrafiltrate of plasma

What is the function of the ventricular system?

Supports and cushions the CNS against trauma, carries waste products to the venous system, distributes hormones/releasing factors. supplies buoyancy to the brain.

Where is the ventricular system located?

located in the ventricles and subarachnoid space. produced by the choroid plexus

What is a way to administer drugs while avoiding the blood brain barrier?

Drugs can directly administered directly into the CNS via the intracerebroventricular or intrathecal cannula to avoid the blood brain barrier

What are Circumventricular organs?

regions that lack the blood brain barrier, making permeable capillaries that allow communication between blood and brain

How does circumventricular organs affect the hypothalamus?

the third ventricle allows the hypothalamus to sample physiological status to maintain homeostasis

what is the function of the cerebral cortex?

receives and integrates sensory information, initiation of voluntary movement, language production and understanding, higher order executive functions

What is the structure of the gyrus, sulcus , and fissure in the cerebral cortex?

Gyrus- upfold, sulcus- downfold, fissure- deep sulcus

What is the corpus callosum?

white matter tract in the cerebral cortex that connects hemispheres