Principles of Pharmacokinetics Pharmacokinetics of IV Administration, 1-Compartment
CHAPTER 2 Anatomy/ Pharmacokinetics/Addiction. Pharmacokinetics.
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Transcript of CHAPTER 2 Anatomy/ Pharmacokinetics/Addiction. Pharmacokinetics.
CHAPTER 2 Anatomy/ Pharmacokinetics/Addiction
Pharmacokinetics
How Drugs Get to the Brain
Distribution
Metabolism/Elimination
Half Life – Steady State
PharmacodynamicsReceptor model
ReceptorAction
Dose-Response
Introduction to the Nervous SystemsAll nervous systems consist of specialized
nerve cells called neurons.Neurons are responsible for conducting the
homeostatic functions of the brain and other nervous systems by receiving and sending information
Sending and receiving information is an electrochemical process
CNS Organization
Old Brain/New BrainOld Brain
Brain StemCerebellumMidbrain (includes Limbic System)
Regulates PhysiologyBasic Emotions-cravingsSurvival memoriesMost frequently involved in addiction
Old Brain/New BrainNew Brain
Cerebrum/Cerebral cortexProcessing centerData from old brain
CNS - Spinal CordSpinal CordOrganizing and modulating motor impulsesCarrying sensory input (e.g. pain)Autonomic control of vital functionsCarrying sensory information
CNS - Brain StemBrain StemResponsible for conduction of all impulse
between spinal cord and brain (both directions)MedullaPonsMidbrain
CNS - Brain StemBrain StemRegulation of vital functions (breathing, heart
rate, BP, GI, sleep, wakefulness)Behavior alteringAttentionArousal
CNS - CerebellumCerebellumMovementPosture
CNS - MidbrainHypothalamus – integration of the
autonomic system, pituitary, emotion, hormonal systems
Subthalamus – motor controlLimbic system – Reward/Reinforcement
PathwayIntegrate emotion, reward behavior with motor
and autonomic functions Amygdala Hippocampus
CNS - MidbrainHypothalamus and Limbic SystemInteract to regulate
EmotionEmotional expression
Important Site for Psychoactive DrugsDopamine-rich reward centers
Ventral tegmental area Median forebrain bundle Nucleus accumbens
CNS - Cerebrum
CNS - CerebrumVisionHearingSpeechSensory PerceptionEmotion
NeuronSoma – Cell bodyDendrites – receptorsAxon - transmitter
Neurons
Transfer of Messages by NeuronsThe receiving region of the neuron is
affected by a chemical message that either excites or inhibits
If the message is excitatory, an impulse moves from the receiving region of the neuron down the axon to the sending region, the terminal, and chemical messengers, neurotransmitters, are released
Transfer of Messages by NeuronsThe neurotransmitters travel and attach to
receiving proteins called receptors on the target cells.
Activation of receptors by neurotransmitters causes a change in the activity of the target cell; the target cells can be other neurons or cell that make up organs, muscles, or glands
Sending Messages by Neurons
Sending Messages by Neurons
Neurons
Neurons are highly versatile and can send discrete excitatory or inhibitory messages to their target cells
Neurons are distinguished by the type of neurotransmitter they release
Neurotransmitters represent a wide variety of chemical substancesExample: dopamine and pleasure center
Drug ReceptorsThe chemical messengers from glands and
neurons exert their effects by interacting with special protein regions in membranes called receptors.
Receptors only interact with molecules that have specific configurations
Drug Receptors
Drug ReceptorsAgonists are substances or drugs that
stimulate receptorsAntagonists are substances or drugs that
attach to receptors and prevent them from being activated
Drug Receptors
NeuronPresynaptic
Synaptic vesicles Store neurotransmitters Release – mediated by Calcium ions
Synaptic Cleft – space between axon and dendrite (or target cell)
NeuronPostsynaptic
Protein receptorsNeurotransmitters from axon activate cell
NeuronTermination of Synaptic Transmission
Enzymes in synaptic cleft destroy free neurotransmitters
Neurotransmitters re-absorbed by receptors on presynaptic cell for re-use
Common Neurotransmitters
Drug ActionPsychoactive Drugs
mimic neurotransmitters – or –Stimulate release of neurotransmitter(s) – or-Inhibit release/action of neurotransmitters
Drug ActionDrugs must leave the circulatory system to
get to the site of actionBlood-Brain BarrierPlacental Barrier
Blood-Brain BarrierCapillaries of the brain are difficult to
penetrateSurvival response to prevent poisons from
having easy access to the brainLipid sheathLipid solubility major factor in crossing the
blood-brain barrier
Placental BarrierEasy to penetrateDesigned to allow small molecules to cross
into fetus, prevent large molecules (e.g. proteins) from crossing
What mother takes, fetus takesFetal metabolism may not be developed
NeurotransmittersAcetylcholine
Memory/learningSensory processingNeuromuscular/neurotransmissionBehavioral arousalAttentionEnergy conservationMoodREM Sleep
NeurotransmittersCatecholamines
DopamineNorepinephrineEpinephrine – peripheral nervous systemCNS Sensory processingCerebellar functionSleep, mood, learning, memory, anxietyReuptake from cleftBound inactivated by MAO enzymes
NeurotransmittersCatecholamines
Norepinephirne Brain Stem - Alerting, focusing, orienting response,
positive reward, analgesiaDopamine
Hypothalamus - Hormone regulation Brain Stem - Movement (Parkinsonism) Midbrain, Cerebral Cortex, Limbic System – central
reward pathway. Linked to continued use of most drugs of abuse
NeurotransmittersSerotonin
Emotional processingMoodAppetite, sleepPain processingHallucinationsReflex regulationBrain Stem – Pons, medulla, cerebral cortex,
hypothalamus, limbic systemEffect opposite DopamineSSRI
NeurotransmittersAmino Acids
GlutamateAspartateMemoryMain excitatory and inhibitory functions in
CNS and PNS
NeurotransmittersGABA – gamma aminobutyric acid
Major inhibitory transmitter for CNSCerebral cortex, cerebellum Neurotransmitters
PeptidesOpioid peptides
Endorphins – 16-30 amino acids Enkephalins – 5 amino acids Mu receptor – analgesic, reinforcement
Pain perception Reward Emotional stability, energetic “highs” Acupuncture
Substance P Pain transmission – peripheral to spinal cord/brain
PhysiologyTolerance
Metabolic Systems adapt to drug, requiring increasing amounts to be used for effect
Desensitization of neuronsLearned behaviorCross Tolerance – similar drugs
Physiological DependenceCells change to require the presence of
substance
Psychological DependenceReward/Reinforcement – Limbic System
Turn on the “More”Turn off the “StopCraving – can have physical manifestations
Social PressuresHabituation – associated activities
AddictionContinued use in spite of known negative
consequencesCompulsion to useWithdrawal
FORMS OF ACCEPTABLE DRUG USE IN AMERICATHERAPEUTIC DRUG USE
DIAGNOSISRELIEF OF SYMPTOMSCURE DISEASEDRUG EFFECT EXPECTED TO BE DIRECT,
RELIABLE AND PREDICTABLESTRICT AND EXPLICIT DIRECTIONS FOR
USETHERAPEUTIC FAILURE OR TOXICITY -
FAILURE TO COMPLY WITH RULES
FORMS OF ACCEPTABLE DRUG USE IN AMERICARELIGIOUS DRUG USE
RELIGIOUS RITUAL PROTECTED BY TABOONO INTENT TO CONSUME INTOXICATING
AMOUNTFOCUS ON HIGH MORAL STANDARDS AND
CONSIDERATION OF NATURE AND ONE’S FELLOW MAN
FORMS OF ACCEPTABLE DRUG USE IN AMERICACULTURAL DRUG USE
NORMAL, COMMONPLACE BEHAVIORPERSPECTIVE OF PSYCHOACTIVE DRUG
EXPOSURECULTURAL LIMIT ON DOSE AND PATTERN
OF USECOFFEE, TEA
FORMS OF ACCEPTABLE DRUG USE IN AMERICASOCIAL DRUG USE
LOW-DOSE ALCOHOLLEGAL AGEIN COMPANY OF OTHERSEXPECT MILD PSYCHOACTIVE EFFECTEXPECTATION THAT INDIVIDUALS WILL ACT
RESPECTABLY AND SENSIBLY
ACCEPTABLE SOCIAL DRUG USESOCIAL MORES AND CUSTOMS DEFINE
ACCEPTABLE PATTERNSUSE OF SOCIALLY-SANCTIONED DRUGS BY
THOSE OF LEGAL AGEACCOUNTABILITY FOR ACTIONSEXPECT INCREASED SOCIAL
INTERACTIONS“SOCIALIZATION” NOT “ADDICTION”
ACCEPTABLE SOCIAL DRUG USESOCIAL MORES AND CUSTOMS DEFINE
ACCEPTABLE PATTERNSUSE OF SOCIALLY-SANCTIONED DRUGS BY
THOSE OF LEGAL AGEACCOUNTABILITY FOR ACTIONSEXPECT INCREASED SOCIAL
INTERACTIONS“SOCIALIZATION” NOT “ADDICTION”
STAGES OF DRUG USESTARTING POINTREWARD VS. CONSEQUENCES OF USECONTINUED AND INCREASED USEPSYCHOLOGICAL DEPENDENCE
CRAVINGPREOCCUPATION WITH USECHANGING LIFESTYLES
STAGES OF DRUG USETOLERANCE INCREASESNEGATIVE CONSEQUENCES INCREASEPHYSICAL DEPENDENCERELAPSE
VARIABLES CONTRIBUTING TO DRUG RESPONSE
ROUTE OF DOSEADMINISTRATION
SETTING
DRUG EFFECTSET
OTHER DRUGS IN BIOCHEMICAL COMBINATION AVAILABILITY
Theories of AddictionDisease Model
Chronic, progressive, relapsing, incurable and potentially fatal condition Hereditary predisposition Environment Triggered by substance
Theories of AddictionBehavioral/Environmental
Significant stresses can cause a person to seek relief via drug(s) Abuse Anger Peer pressure PTSD-like
Theories of AddictionAcademic
Adaptation to substance at physiologic and cellular level
Exemplified by: Tolerance Physiological dependence Withdrawal Psychological dependence
Theories of AddictionDiathesis-Stress
Combination of the above
Factors in AddictionHeredity
Predisposition to addictionTwin studiesAddiction associated genes
EnvironmentIncreased stressors increase likelihood of
abuse/addictionShapes normative behavior
Factors in AddictionPsychoactive Drugs
Change brain chemistryInterfere with normal neurotransmitter
functionIncreased frequency of use increases riskCan cause permanent damage (e.g.
amphetamines, alcohol)
Factors in AddictionOther Behaviors
“Compulsive Behaviors” can act similarly to drugs to trigger addiction Gambling Eating Sex Shopping Video games Internet
SummaryAddiction is complex, but can be thought of,
in simple terms, as compulsive behavior in spite of negative consequences
Once a person becomes an addict, change is difficult and not totally under the person’s control