3.
1: INTRODUCTION TO PSYCHOTROPIC DRUGS
Lecturer: Sir Mark Angelo Cristino || 24 March 2022
Among the drugs taken to “fix things” are drugs that:
 treat delusions and hallucinations
(antipsychotics)
 slow down runaway thinking (mood
stabilizers or antimanic agents)
 improve mood (antidepressants)
 calm nerves (antianxiety drugs)
 improve thinking (drugs for Alzheimer
disease)
There are also drugs to correct problems caused by
some of the drugs just listed (e.g., antiparkinsonian
drugs)
Hippocrates (460-370 BC)
1. Drugs are not always warranted.
2. Drugs are not always effective.
3. Effective optimal outcomes typically occur
when other interventions are co-administered.
4. Psychotropic agents can be used to avoid the
hard work of getting better.
5. Many psychotropic drugs have significant or
even life- threatening side effects, drug
interactions, or both.
6. Finding the right regimen is often a trial-and
error exercise
SIGNIFICANT POINTS IN THE EVOLUTION OF
PSYCHOTROPIC DRUGS
 1949- Lithium “discovered” in Australia
 1951- Chlorpromazine, the first antipsychotic,
is “discovered” in France.
 1954- Lehman publishes the first article in the
United States on Chlorpromazine in the
Archives of Neurology and Psychiatry.
 1958- Kuhn publishes the first article on
tricyclic antidepressants in American Journal of
Psychiatry.
 1960- Harris presents Effectiveness of
Benzodiazepines in the Journal of the American
Medical Association.
 1980- A new class of antidepressants, selective
serotonin reuptake inhibitors (SSRI’s) is
developed. Prozac (first SSRI)
 1990- Clozapine (Clozaril) - the first truly new
antipsychotic agent in 40 years, is released in
the United States. Risperdal, Zyprexa,
Seroquel, Geodon, and ability follow over the
next 10 years or so.
 1990- Other SSRIs are developed (Zoloft, Paxil,
Celexa, Lexapro). A report linking Prozac to
suicidal behaviour is published in 1990.
 1990- Drugs used to treat patients with
Alzheimer’s disease are made available.
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NCM 117
 2004- concerns arise about the linkage of SSRIs
to violent and suicidal behaviour
 2010- new agents and new concerns about
psychotic agents continue to emerge
PHARMACOKINETICS:
WHAT THE BODY DOES TO THE DRUG
1. Absorption – getting the drug into the
bloodstream.
2. Distribution – getting the drug from the
bloodstream to the tissues and organs.
3. Metabolism— breaking the drug down into an
inactive and typically water-soluble form.
(Monoamine Oxidase System, Cytochrome P-
450 Enzyme System & Half-life).
4. Excretion – getting the drug out of the body.
ABSORPTION
Molecules pass through cell membranes (composed
of a phospholipid bilayer) in the following three ways:
1. Small molecules can fit through the pores or
channels in the membrane.
2. Some drug molecules have special transport
systems to ferry them though the membrane.
3. Lipid-soluble drugs (most drugs are lipophilic)
can pass through the phospholipid membrane
BIOAVAILABILITY- percentage of an oral drug that
reaches the systemic circulation. (It is only a fraction of
the dose for many drugs given orally because of
incomplete absorption and first-pass metabolism)
First-pass Metabolism- enzymatic breakdown of drugs
before they reach systemic circulation. (This occurs
during passage through the gut wall and in a
presystemic hepatic exposure)
Clinical relevance: Only absorbed drugs can have an
effect. Drugs with a high first-pass metabolism must
be significantly reduced in dose level if given
intramuscularly or intravenously.
DISTRIBUTION
If a psychotropic drug cannot leave the bloodstream, it
cannot have a therapeutic effect. Protein binding is
important because molecules that are bound to proteins
cannot leave the circulation – that is, protein is simply too
large to pass through the gaps in the capillary wall.
Protein-bound drugs do not have a pharmacologic effect,
cannot be metabolized and cannot be excreted.
Clinical relevance: Both desired and undesired effects
of highly protein-bound drugs result from the activity
of the relatively few free drug molecules in circulation.
Drug combinations that compete for protein binding
sites have the potential of causing significant increases
in levels of the free or active drug.
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 3.1: INTRODUCTION TO PSYCHOTROPIC DRUGS NCM 117

Lecturer: Sir Mark Angelo Cristino || 24 March 2022

METABOLISM
Cytochrome P-450 Enzyme System
Metabolism is the process whereby the body breaks
down a drug molecule. Most drugs are metabolized to  Point at which most drug interactions occur
inactive and water-soluble states in preparation for  CYTO stands for microsomal vesicles
excretion from the body in the urine.  P stands for pigmentation (enzymes contain
red-pigmented heme)
It is important to note that not all drugs are broken
 450 refers to the wavelength (in nanometers)
down into inactive forms, not all drugs are converted
at which light absorption occurs
into water-soluble particles, and not all drugs are
eliminated via the renal system.

Two Enzyme systems are of particular importance to

nurses who administer psychotropic drugs: (1) the
monoamine oxidase (MAO) system and (2) the
cytochrome P-450 (CYP-450) system.

The MAO System metabolizes monoamines (e.g.,

dopamine, norepinephrine, and serotonin) that are
already in the body. The other system, CYP-450, breaks
down most psychotropic drugs or chemicals brought
into the body.

Monoamine Oxidase System

 is the enzyme that rapidly inactivates

monoamines (e.g., serotonin, dopamine,
norepinephrine) and slowly metabolizes
noncatecholamines.
 Located in the liver, intestinal wall and central
nervous system in the terminals and synapses
of neurons containing serotonin,
norepinephrine, or dopamine. Clinical relevance: Most drugs must be metabolized
to an inactive and water-soluble form to be excreted
from the system. Certain conditions (e.g., liver
disease, kidney disease) or drug combinations that
inhibit metabolism can lead to significant or even
deadly results.

Half- Life of Drugs

 is the amount of time required for 50% of the

drug to disappear from the body.
 If drug X has a half-life of 4 hours, then 50% of
the drug will be out of the system in 4 hours. In
another 4 hours, only 25% of the original dose
will remain.
 Linear Kinetics- the amount of drug in the body
would decrease by 50% every 4 hours,
regardless of how many mg a patient takes.
 Washout period- when discontinuing drug,
four half-lives are required to eliminate 96% of
the drug. (It is basically the time frame allotted
for an administered drug to be eliminated from
the body or for a previously administered
intervention to become ineffective)

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 3.1: INTRODUCTION TO PSYCHOTROPIC DRUGS NCM 117

Lecturer: Sir Mark Angelo Cristino || 24 March 2022

EXCRETION
PHARMACODYNAMIC TOLERANCE
The kidney excretes most drugs in the urine. Pharmacodynamic tolerance describes a reduction in
receptor sensitivity (or desensitization). A good
Other Routes Of Factors That Can Affect
Excretion Excretion example is a chronic drinker of alcohol. When the
 Breast milk  Kidney Disease newspaper reports a person driving a car with a blood
 Bile  Age alcohol level (BAL) of 0.35, the story is likely about a
 Feces  Drug Competition case of pharmacodynamic tolerance. This person’s
 Saliva for active tubular receptors are no longer responding to the ethanol in
 Sweat transport the way a normal person’s receptors would respond.
 Lungs
Tolerance to a BAL that could cause deadly respiratory
depression does not occur. A person who is functioning
Clinical relevance: Drugs that are not adequately at an elevated BAL might drink only a little more
excreted (e.g., because of kidney disease), particularly alcohol and wind up dead.
drugs excreted unchanged (a few drugs are not
metabolized [e.g. lithium, amphetamine]) have a more Clinical relevance: Knowledge of downregulatory
pronounced effect compared with drugs that are functions helps the nurse explain the lag time between
excreted. initiating drug therapy and clinical improvement.

Clinical relevance: Knowledge of pharmacodynamic

PHARMACODYNAMICS: tolerance aids in teaching patients and families about
WHAT THE DRUG DOES TO THE BODY drug tolerance to some drug effects but little, if any,
tolerance to some lethal effects (e.g., respiratory
The two global responses to drugs are the desired depression) at just slightly higher doses.
effects and the side effects.

Agonists- drugs that activate receptors THE BLOOD-BRAIN BARRIER

Antagonists- drugs that block receptors
DOWNREGULATION
DOWNREGULATION of receptors is an important
concept, primarily because chronic exposure to certain
psychotropic drugs causes receptors to change.
Example: Consistent use of antidepressants causes
postsynaptic receptors to decrease in number. Because
this downregulation occurs at about the same time
that the antidepressant effect develops (approximately
2 to 4 weeks), it is thought by some that reduction in
postsynaptic receptors might provide a better
explanation for mood elevation than increases in
neurotransmitters.
The blood-brain barrier is also an important concept
for understanding psychotropic drug activity. The
brain, more than other organs of the body, requires a
constant internal milieu.
The brain is protected from fluctuations by the blood-
brain barrier. The barrier regulates the amount and
speed of substances in the blood entering the brain
The blood-brain barrier has three dimensions:
1. Anatomic dimension- structure of capillaries
that supply blood to the brain and prevent
many molecules from slipping through
2. Physiologic dimension- chemical and
transport system that recognizes and allows
certain molecules into the brain.
3. Metabolic dimension- prevents molecules
from entering the brain by enzymatic action
within the endothelial lining of the brain
capillaries.

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 3.1: INTRODUCTION TO PSYCHOTROPIC DRUGS
Lecturer: Sir Mark Angelo Cristino || 24 March 2022
NEURONS AND NEUROTRANSMITTERS
Nerve cells or neurons, are the basic units of the
Nervous system.
 Nerve cells- designed to receive and give
information.
 Dendrites- projections from the neuron;
receive information and transmit it to the cell
body
 Axons- send information from the nerve cell to
the dendrites, axons or cell bodies of other
neurons.
 Synapse- microscopic space that separate
axons of one cell from dendrites, axons, or cell
body of another cell.
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NCM 117
RECEPTORS
Receptors are proteins on cell surfaces that respond to
endogenous ligands or to drug molecules. A ligand is a
transmitter substance or molecule that fits and evokes
a response from a receptor. Examples of ligands
include drugs, neurotransmitters, hormones,
prostaglandins, and leukotrienes.
Receptors are configured so that only precisely shaped
molecules can fit and subsequently cause or prevent a
response. For example, the neurotransmitter serotonin
fits serotonin receptors, but acetylcholine molecules
do not fit serotonin receptors.
2 MOST COMMONLY ADDRESSED RECEPTOR
PROCESSES
1. Ligand- gated ion channel (first-messenger)
- When the ligand gated receptor is
activated, an ion channel such as the
sodium, calcium, chloride channel opens
and the respective ion flows through into
the cell. Depending on the ion, this action
causes cell depolarization (the cell fires) or
hyperpolarization (cell firing slows down or
cell does not fire). The process is extremely
rapid, occurring at a millisecond.
2. G-protein coupled process (second-
messenger)
- A more complex process. A biologic cascade
of an intracellular reaction develops and is
slower compared with the first-messenger.
- Norepinephrine, serotonin, dopamine,
acetylcholine (muscarinic receptors only),
peptides.
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 3.1: INTRODUCTION TO PSYCHOTROPIC DRUGS NCM 117

Lecturer: Sir Mark Angelo Cristino || 24 March 2022

Increased defecation Constipation

Sweating Decreased Sweating
NEUROTRANSMITTER AND
Enhancement of Cognitive Slowing
RELATED MENTAL DISORDERS
cognitive processes

NEUROTRANSMITTERS MENTAL DISORDERS

Increase in Dopamine
Decrease in
Norepinephrine
Decrease in Serotonin
Decrease In Acetylcholine
Decrease in GABA
Increase in Glutamate
Schizophrenia
RESULTS OF ACTIVATING AND ANTAGONIZING
NOREPINEPHRINE RECEPTORS
Depression
NOREPINEPHRINE NOREPINEPHRINE
Depression ACTIVATION ANTAGONIST
Antidepressant effect Depressive effect
Alzheimer’s disease Vasoconstriction (alpha- Vasodilation (alpha-1
1) antagonism)
Anxiety Increased heart rate Decreased heart rate
(beta-1) (beta blocker)
Excitotoxicity leading to Bronchial dilation Sexual dysfunction
neuronal death Other physical effects Other physical effects

Decrease in Glutamate Psychotic thinking

PSYCHOTROPIC DRUGS CAN AFFECT
NEUROTRANSMITTER IN SEVERAL WAYS
1. Prevent metabolism
2. Prevent reuptake
RESULTS OF ACTIVATING AND ANTAGONIZING 3. Block postsynaptic receptors
SEROTONIN RECEPTORS 4. Activate or block autoreceptors
5. Block calcium channels
SEROTONIN ACTIVATION SEROTONIN ANTAGONIST
Antidepressant effect Depression
Anxiety Dysthymia
Migraine headaches Suicidality
Nausea Aggresiveness
Vomiting Obsessive thinking
Other GI disturbances Sleep-wake cycle
Sexual dysfunction disruption
Decrease in penile Pain
erection capability Compulsive behaviour
Reduced appetite and Anxiety
weight loss Migraine headaches
Insomnia Panic
Movement disorders
RECEPTOR ANTAGONISM- is the process in
Temperature
dysregulation which receptor function is compromised
Psychotic thinking related to blocking of that receptor by a
psychotropic drug. Antagonist prevents the
endogenous ligand from activating the
RESULTS OF ACTIVATING AND ANTAGONIZING receptor.
ACETYLCHOLINE RECEPTORS RECEPTOR AGONIST- a drug that fits and
activates the receptor in the same manner as a
ACETYLCHOLINE ACETYLCHOLINE naturally occurring ligand.
ACTIVATION ANTAGONIST AUTORECEPTOR- a feedback mechanism that
Pupil contraction Dilated pupils neurons use to increase or decrease the
Decreased heart rate Increased heart rate release of a neurotransmitter. They are
Constriction of bronchi Dilation of bronchi typically but not always found on presynaptic
Increased respiratory Decreased respiratory neurons. Autoreceptor agonists tell the neuron
secretions secretions that enough of the neurotransmitter is
Increased voiding Decreased voiding present, hence a decrease in the release of the
Salivation Dry mouth neurotransmitter occurs. Autoreceptor
Increased gastric Decreased gastric antagonists ell the receptor to release more of
secretions secretions the neurotransmitters

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 3.1: INTRODUCTION TO PSYCHOTROPIC DRUGS NCM 117

Lecturer: Sir Mark Angelo Cristino || 24 March 2022

RECEPTOR AFFINITY- it is the strength of COMMON REASONS FOR NONCOMPLIANCE TO

attraction between the neurotransmitters and THERAPEUTIC REGIMEN/MEDICATIONS
receptors.
RECEPTOR LIFE CYCLE- the receptors are
continually being formed and continually being 1. FINANCIAL CONSTRAINTS
broken down. The life cycle of the average 2. SEXUAL DYSFUNCTION (SIDE EFFECT OF
receptor is short. DRUG)
RECEPTOR MODULATION- Some 3. SPECIFIC SIDE EFFECTS (insomnia, dry mouth,
neurotransmitters do not have a direct effect sleepiness)
but modulate the effect of another 4. EMOTIONAL DULLING
neurotransmitter. 5. COGNITIVE SLOWING
6. DENIAL OF THE NEED OF MEDICATION
7. FEAR OF BECOMING ADDICTED TO
MEDICATION / MEDICATION DEPENDENT
8. RELIGIOUS REASONS
9. INTERFERENCE WITH WORK
10. INABILITY TO USE ALCOHOL OR OTHER
RECREATIONAL DRUGS
11. PREGNANCY
12. ILLNESS (suspicion, delusion of conspiracy)

PATIENT EDUCATION

1. Discussion of side effect

2. Discussion of safety issues

 Does the patient take the drugs as
prescribed?
 Does the patient and the family know
which side effects should be reported to
the nurse or physician?
 Thoughts of self-harm must be discussed
 Does the drug have potential for abuse
or dependence?
 Patient should know that drugs must be
tapered when planning to discontinue

3. Attitudes of patient and nurse about

medications

4. Drug interactions

5. Instructions for older adult patients or

children of older adult patients

6. Instructions for pregnant or breast-feeding

patients

7. Awareness of metabolic differences in diverse

races and ethnicities
 Gene expression and mutation of certain
enzymes like CYP2D6 where it had been
shown to alter the rate in which the
medication are metabolized.
GOOOODLUCK! 

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