© Copyright 2011, Pearson Education, Inc. All rights reserved. Chapter 3 How Drugs Work in the Body and on the Mind

© Copyright 2011, Pearson Education, Inc. All rights reserved. How Drugs Enter the Body There are four basic ways to administer drugs into the body: –oral administration –injection –inhalation –absorption through the skin or membranes. Each of these imposes constraints on which kinds of drugs will be effectively delivered into the bloodstream.

Oral Routes of Administration easy—no skill required non-invasive (does not penetrate skin barrier) may interact with food may cause nausea must be readily absorbable (not suitable for all drugs) generally inefficient precise dosing can be difficult

Injection Routes of Administration Intravenous (i.v.) o fast-acting, dosing precise, efficient, short-lived Intramuscular (i.m.) o slower-acting, longer lived than i.v., small volume Subcutaneous (s.c.) o slow acting, longer lived than i.v., small volumes

Inhalation *(into lungs... not the same as trans-mucousal!) Routes of Administration Non-invasive (does not penetrate skin) very fast recreational use often introduces toxins therapeutic use limited to respiratory system, anesthetics

Absorption Routes of Administration trans-dermal o very slow, long lasting trans-mucosal (e.g. intranasal, intra-oral) antihistamines, drugs of abuse

Routes of Administration This figure was taken from Dr. Lori Knackstedt’s lecture: Psychopharmacology and Neural Communication

© Copyright 2011, Pearson Education, Inc. All rights reserved. iClicker Question What is the best route of drug administration? A.Intravenous B.Oral C.Inhalation (into lungs, not intranasal) D.It depends on the drug, and the intended effect

What happens to drugs once in the body? 1. Metabolized by liver enyzmes metabolites excreted in urine (also sweat, breath and feces to lesser extent) 2. Excreted as administered 3. Metabolized by target to active form e.g. l-DOPA  dopamine, heroine  morphine 4. Metabolized by target to inactive form, excreted in urine

© Copyright 2011, Pearson Education, Inc. All rights reserved. How Drugs Exit the Body Most drugs are eliminated from the body through urinary excretion. Drugs are broken down for elimination by the action of enzymes in the liver (and in the brain). An index of how long this process takes is the elimination half-life: how long it takes for the current amount of drug to lose ½ of it’s pharmacokinetic activity

© Copyright 2011, Pearson Education, Inc. All rights reserved. Factors Determining the Behavioral Impact of Drugs The factors that can make the physiological effect of a drug vary include the time elapsed since its administration, drug interactions when it is administered with other drugs at about the same time, and the personal characteristics of the individual consuming the drug. –Examples: weight, gender, and ethnic background (predisposition to certain biological traits)

© Copyright 2011, Pearson Education, Inc. All rights reserved. Figure 3.1

© Copyright 2011, Pearson Education, Inc. All rights reserved. Introducing the Nervous System Understanding the organization of the nervous system helps us to understand where and how psychoactive drugs are working in our bodies.

© Copyright 2011, Pearson Education, Inc. All rights reserved. Figure 3.2

© Copyright 2011, Pearson Education, Inc. All rights reserved. Introducing the Nervous System The nervous system consists of the peripheral nervous system and the central nervous system, with the latter divided into the brain and the spinal cord. Autonomic nerves control our cardiac and smooth muscles to respond either to stress (sympathetic activation) or to demands for nurturance and renewal (parasympathetic activation).

© Copyright 2011, Pearson Education, Inc. All rights reserved. Figure 3.3

© Copyright 2011, Pearson Education, Inc. All rights reserved. Understanding the Brain Hindbrain -medulla, pons, cerebellum Midbrain -tegmentum, tectum Forebrain -Diencephalon hypothalamus, thalamus -Telencephalon limbic system, basal ganglia, cerebral cortex Within the brain are three major divisions: the hindbrain, midbrain, and forebrain. Figure 3.4 in textbook

© Copyright 2011, Pearson Education, Inc. All rights reserved. Understanding the Biochemistry of Psychoactive Drugs Understanding the functioning of neurons and their interaction through synaptic communication helps us to understand how psychoactive drugs work in our bodies.

© Copyright 2011, Pearson Education, Inc. All rights reserved. iClicker Question Structures commonly thought to regulate motivational and emotional behaviors are located in which major brain region? A.The forebrain B.The midbrain C.The hindbrain D.The spinal cord

© Copyright 2011, Pearson Education, Inc. All rights reserved. Figure 3.5 / Axon terminal

How do neurons communicate? 1.The dendrites and cell body of a neuron receive information from other neurons in the form of chemical signals (neurotransmitters). 2.These chemical signals cause changes in the receiving neuron from its “resting state” (an electrochemical equilibrium of about -70 mv) these changes can cause the equilibrium to change to a more positive voltage (depolarization) or more negative voltage(hyperpolarization) 3.If the receiving neuron is depolarized to its threshold (about -65 mv), an “action potential” will occur down the length of its axon, causing it to release neurotransmitters from the axon terminal **Note: once threshold is reached, an action potential will always occur – it is an “all- or-nothing” response. © Copyright 2011, Pearson Education, Inc. All rights reserved.

How do neurons communicate? © Copyright 2011, Pearson Education, Inc. All rights reserved. This figure illustrates an action potential. You DO NOT need to memorize the specific order of ion channel opening / closing in an action potential for this course.

© Copyright 2011, Pearson Education, Inc. All rights reserved. Figure 3.7 ** OR by a cascade of “second messengers” that indirectly effect other activities / functions of the cell. Neurotransmitters are packaged into vesicles primarily near the cell body, not at the axon terminal, as illustrated in the book. Change in voltage caused by action potential results in vesicle docking / transmitter release

Flow of information through neurons

© Copyright 2011, Pearson Education, Inc. All rights reserved. Understanding the Biochemistry of Psychoactive Drugs In general, psychoactive drugs work by altering neurotransmitter release, receptor binding, or reuptake at the synapse. Agonists enhance neurotransmitter action Antagonists reduce neurotransmitter action –NOTE: antagonists do bind to the receptor, but do not exert the an effect like the neurotransmitter would.

© Copyright 2011, Pearson Education, Inc. All rights reserved. Figure 3.6

The “Big Seven” Acetylcholine Dopamine Norepinephrine Serotonin Gamma aminobutyric acid (GABA) Glutamate Opiates Catecholamines Monoamines

Receptor Subtypes Each Neurotransmitter has multiple types of receptors it can bind to. Each receptor causes a slightly different effect on the neuron. –Example: D1 dopamine receptors = excitatory* D2 dopamine receptors = inhibitory* * these channels cause their effects INDIRECTLY through 2 nd messenger cascades © Copyright 2011, Pearson Education, Inc. All rights reserved.

Table 3.1

© Copyright 2011, Pearson Education, Inc. All rights reserved. Physiological Aspects of Drug-Taking Behavior Three important issues need to be understood in looking at the physiological effect of drugs: –the extent to which drugs pass from the bloodstream to the brain –the extent to which tolerance effects occur –the extent to which a drug influences activity in the nucleus accumbens in the forebrain This area is highly involved with reward and motivation, so it is also technically involved in “psychological” factors.

© Copyright 2011, Pearson Education, Inc. All rights reserved. Psychological Factors in Drug-Taking Behavior Although the physiological actions of psychoactive drugs are becoming increasingly well understood, great variability in the effect of these drugs remains, largely because of psychological factors.

© Copyright 2011, Pearson Education, Inc. All rights reserved. Figure 3.8

© Copyright 2011, Pearson Education, Inc. All rights reserved. Psychological Factors in Drug-Taking Behavior The most prominent psychological factor is the influence of personal expectations on the part of the individual consuming the drug. The impact of expectations on one’s reaction to a drug, a phenomenon called the placebo effect, is an important consideration in drug evaluation and research.

© Copyright 2011, Pearson Education, Inc. All rights reserved. iClicker Question In clinical studies on drugs, one group is often given a sugar pill instead of the drug. Patients in this control group often report some improvement in symptoms, similar to the group actually receiving the drug. This is due to ____________. A.the sugar effect B.the placebo effect C.investigator bias D.reporting error