PSYCHOPHARMACOLOGY I The Brain, Body, and Drug Relationship.

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Presentation transcript:

PSYCHOPHARMACOLOGY I The Brain, Body, and Drug Relationship

2 DEFINITIONS Psychoactive drugs: those drugs that alter cognition, behavior, and emotions by changing the functioning of the brain. Psychopharmacology: the study of the use, mechanisms, and effects of drugs that act on the brain and subsequently alter behavior.

3 PHARMACOKINETICS Is the study of how drugs move through the body. –Absorption –Distribution –Metabolism –Elimination

4 DRUG ABSORPTION Oral Rectal Injection Inhalation Skin Mucous Membranes

5 DRUG DISTRIBUTION Factors that influence distribution: –Solubility –Reversible binding to plasma proteins –Body Membranes

6 Solubility Water-soluble molecules do not readily cross cell membranes Lipid-soluble molecules do cross cell membranes MOST PSYCHOACTIVE DRUGS ARE LIPID-SOLUBLE MOLECULES

7 Cellular Membranes Typical Cell Membranes Walls of Capillary Vessels Blood-brain Barrier Placental Barrier

8 DRUG METABOLISM Hepatic Cytochrome P450 enzyme system Drugs are enzymatically biotransformed into metabolites that are less fat soluble and therefore less capable of being reabsorbed from renal distal tubules.

9 ELIMINATION OF DRUG Kidneys Lungs Bile Skin Saliva Breast milk

DRUG HALF-LIFE Drug half-life: the time required for the drug concentration in blood to fall by one-half; determines the length of time necessary to reach a steady state concentration.

11 DOSE-RESPONSE RELATIONSHIP There is a relationship between drug level in the blood and the level of drug at the “receptor” site. Steady state: amount of drug entering blood stream is equal to the amount of drug being eliminated from blood.

12 Half-Life Calculations Drug with a 4 hour half-life: –12:00 take 100 mg –04:00 50 mg left; take 100 mg –08:00 25 mg left; 50 mg left; take 100 mg –12: mg; 25 mg; 50 mg; take 100 mg After 6 half-lives, drug concentration is at steady state: about 98.4%.

13 DRUG TOLERANCE A state of progressively decreasing responsiveness to a drug. Metabolic tolerance Cellular-adaptive tolerance

PHARMACODYNAMICS The study of the biochemical and physiological effects of drugs and their mechanism of action

15 DRUG-RECEPTOR INTERACTIONS Receptors are located on surface of cell membrane Attachment of transmitter to receptor activates the receptor, allowing for a signal to be transmitted to inside of cell Intensity of signal is determined either by percentage of receptors occupied or by rate of reversible transmitter binding

16 Drug-Receptor Interactions A drug can either enhance or diminish the signal by binding to the receptor site Note: a drug cannot import new functions to a cell Note: a drug does not create effects but merely modulates ongoing functions

17 Definitions AGONIST: A drug that is capable of mimicking the action of a neurotransmitter. ANTAGONIST: A drug that is capable of blocking the action of a neurotransmitter

18 DOSE-RESPONSE RELATIONSHIPS Potency: the absolute amount of drug needed to produce a defined effect. Efficacy: the maximum effect obtainable by a given drug.

19 Drug Responsiveness ED50: Effective dose for 50% of the subjects LD50: Lethal dose for 50% of the subjects Therapeutic Index: LD50/ED50 The higher the therapeutic index, the safer the drug!

20 The Nervous System Central Nervous System –Brain –Spinal Cord Peripheral Nervous System –Somatic nervous system –Autonomic nervous system Parasympathetic nervous system Sympathetic nervous system

21 The Brain Brain Stem –Medulla: decussation of motor cortex; vomit reflex –Pons: reticular activating system; locus coeruleus, raphe nucleus –Midbrain: auditory information, muscle movement; eye movement. Cerebellum: coordinating and smoothing out motor movements.

22 Diencephalon Subthalamus: functions with basil ganglia to from the extrapyramidal system Hypothalamus: involved with autonomic nervous system; eating, drinking, sleeping, body temperature, sexual behavior, emotion; controls hormone output of the pituitary gland.

23 Limbic System Amygdala: fear and aggression Hippocampus: consolidation of memory Exerts primitive types of behavioral control; integrates emotion, reward, and behavior with motor & autonomic function. Includes septum, nucleus accumbens, and cingulate gyrus.

24 The Brain Thalamus: sensory input, projections to the sensory area of the cortex Basil ganglia: motor functioning; extrapyramidal motor system. Includes the putamen, globus pallidus, and caudate nucleus Cerebrum: occipital, temporal, frontal, and parietal lobes of cortex

25 THE NEURON Structure –Dendrites, cell body, axon Function –Receptor/dendrite: electrical current: cell body, action potential: axon/synapse: neurotransmitter, receptor/dendrite

26 Action Potential Resting membrane potential Threshold; all or none response Influx of Na+ ions or Cl- ions Depolarization of cell membrane, or Hyperpolarization of cell membrane Return to the resting potential

27 Transmission of Information Transmitter released from presynaptic vesicles Diffusion across the cleft Receptor interaction on postsynaptic membrane Transmitter removed from the cleft –Metabolic inactivation, or –Active reuptake by a transporter protein/storage

28 Receptors Neurotransmitter must have an affinity for all three different receptors: –Postsynaptic receptor –Presynaptic receptor –Storage granule receptor

29 Receptor Affinity Presynaptic receptor: Cocaine binds to and blocks (dopamine/norepinephrine site) Storage granule transporter receptor: reserpine binds to and blocks (norepinephrine site) Postsynaptic receptor: Haldol binds to and blocks (Dopamine site)

30 Drug Interactions Additive effect: when = 4 Synergistic effect: when = 6 Antagonistic effect: when = 1 or 0

31 Classes of Receptors Fast receptors: linked directly to an ion channel (GABA (a) receptors) G-protein-coupled receptors: linked to modulary receptors that are linked to intracellular second messengers Transporter protein receptors: presynaptic receptors that function in uptake

32 NEUROTRANSMITTERS Acetylcholine –CNS: 2 separate areas: (1) septal nuclei and the nucleus basalis; (2) midbrain nuclei –PNS: neuromuscular junctions and within the autonomic nervous system, especially the parasympathetic system

33 Acetycholine Synthesis: Acetyl coenzyme A + Choline yields Acetycholine (Ach) Action: Binds reversibly to postsynaptic receptors. Terminated by acetylcholine esterase (AChE), degraded into acetate and choline that are taken back into the presynaptic axon terminal

34 Acetylcholine Function: Ach plays a role in learning and memory. May also be involved in circuits that modulate pain, sensory reception, arousal, attention, mood, and REM sleep. Destruction of Ach neurons within the septal nuclei/nucleus basalis gives rise to Alzheimer’s disease.

35 CATECHOLAMINES Dopamine and Norepinephrine Location: –Dopamine: Three major dopamine systems Local circuits in hypothalamus Substantia nigra to the basal ganglia Ventral tegmentum to the medial forebrain bundle

36 Catecholamines Location: –Norepinephrine CNS: cell bodies in the locus ceruleus and project to the limbic system, hypothalamus, and cortex PNS: adrenergic neurons play a major role in the sympathetic nervous system

37 Catecholamines Synthesis: –Tyrosine, an amino acid, is converted to dopa, then into dopamine, and then into norepinephrine, and then into epinephrine within the adrenal glands

Catecholamines Mechanism of action: Postsynaptic binding of DA or NE trigger a sequence of chemical events within the postsynaptic cell membrane affecting ion channels and intracelluar metabolic activity. Termination of transmitter action by presynapse reuptake mechanism and MAO enzyme degradation within axon terminal.

39 Catcholamines Function –Dopamine: regulation of certain body hormones, regulation of movement, and a major player in “reward center.” –Norepinephrine: produces alerting, focusing, positive feelings of reward, and analgesia. Also involved in hunger, thirst, emotion, & sex behavior modulation

40 Serotonin Location: CNS –Projections stemming from raphe nuclei (pons and medulla) and terminating in cerebral cortex, hippocampus, hypothalamus, and limbic system. Network parallels those of NE but not as widespread

41 Serotonin Synthesis: Manufactured in neurons from tryptophan, an essential amino acid, and then stored in vesicles within the axon terminal. Action: 5-HT activates postsynaptic cell membrane receptors. Action terminated by reuptake mechanisms.

42 Serotonin Function: –Seems to have the opposite effect of NE and is generally inhibitory in action. Plays a role in regulation of anger, mood, & sleep. Regulates release of hormonal factors from the hypothalamus.

43 Gamma-Amino-Butyric Acid Found in high concentrations in the brain and spinal cord. GABA(a): bind benzodiazepines;anxiety effects;found in cortex, hippocampus; ion channel receptor type. GABA9b): found in amygdala;G- protein-coupled receptor type

44 Opioid Peptides Greatest concentration of receptors in the amygdala, effects emotional behavior Four types of receptors: mu, kappa, sigma, and delta. Transmitter types include: met-enkephalin, and leu-enkephalin (endorphins) A role in stress response, mental illness, drug craving, & pain perception