Download How Drugs Work in the Body and on the Mind

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.
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Routes of Administration
Oral
•
•
•
•
•
•
•
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
Routes of Administration
Injection
• 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
Routes of Administration
Inhalation *(into lungs... not the same as trans-mucousal!)
•
•
•
•
Non-invasive (does not penetrate skin)
very fast
recreational use often introduces toxins
therapeutic use limited to respiratory
system, anesthetics
Routes of Administration
Absorption
• 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
iClicker Question
What is the best route of drug administration?
A.
B.
C.
D.
Intravenous
Oral
Inhalation (into lungs, not intranasal)
It depends on the drug, and the
intended effect
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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
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
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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)
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Figure 3.1
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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.
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Figure 3.2
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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).
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Figure 3.3
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Understanding the Brain
Within the brain are three
major divisions: the hindbrain,
midbrain, and forebrain.
•
Hindbrain
-medulla, pons, cerebellum
•
Midbrain
-tegmentum, tectum
•
Forebrain
-Diencephalon
hypothalamus, thalamus
-Telencephalon
limbic system, basal ganglia,
cerebral cortex
Figure 3.4 in textbook
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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.
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iClicker Question
Structures commonly thought to regulate
motivational and emotional behaviors are
located in which major brain region?
A.
B.
C.
D.
The forebrain
The midbrain
The hindbrain
The spinal cord
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Figure 3.5
/ Axon terminal
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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 “allor-nothing” response.
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How do neurons
communicate?
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.
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Figure 3.7
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
**
OR by a cascade of
“second messengers” that
indirectly effect other
activities / functions of the
cell.
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Flow of information through
neurons
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.
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Figure 3.6
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The “Big Seven”
Acetylcholine
Dopamine
Catecholamines
Norepinephrine
Serotonin
Gamma aminobutyric acid (GABA)
Glutamate
Opiates
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 2nd messenger cascades
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Table 3.1
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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.
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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.
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Figure 3.8
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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.
B.
C.
D.
the sugar effect
the placebo effect
investigator bias
reporting error
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