Flashcards in Lesson B6 - Pharmacology Deck (44):
The psychoses are among the most severe psychiatric disorders. People with this disorder suffer
marked impairment of behaviour.
There are at least two subdivisions of psychosis
: (a) organic, and (b) functional (of unknown cause)
Organic psychoses are associated with
causes that are understood and definable e.g. toxic,
metabolic or neuropathological changes. T
Functional (of unknown cause) psychoses are characterized by
retention of orientation and
memory in the presence of severely disordered thought or reasoning, emotion and behaviour.
The functional psychoses include schizophrenia
Affective disorders are characterized primarily by a
change in emotion or mood
Affective disorders consist mainly of a single
disorder of mood - either mania or
Mania is characterized by elation,
hyperactivity, and uncontrollable thought and speech. An individual suffering from
has feelings of intense sadness and self-disapproval, and physical and mental slowing.
An individual suffering from manic-depressive disorder exhibits
alternating periods of mania
In contrast to the psychoses, individuals suffering from neuroses retain the ability to
Neuroses - . The symptoms may involve mood
changes such as anxiety, panic or restlessness, and a feeling of being ill at ease. Individuals may
abnormalities of thought such as obsessions or irrational fears or of behaviour
such as rituals or compulsions.
schizophrenia are classified as
positive and negative.
The positive symptoms include delusions
and hallucinations, bizarre behaviour, lack of logic and incoherence while
withdrawal and loss of motivation are among the symptoms referred to as negative symptoms.
The theory of schizophrenia – the dopamine hypothesis is the most fully developed theory of
schizophrenia, but recent evidence indicates
that other neurotransmitters such as serotonin,
gamma-aminobutyric acid, and glutamic acid may be involved in schizophrenia.
excessive dopaminergic activity
Two other transmitters have also been postulated to play a role in schizophrenia
serotonin and glutamate.
Most of the “typical” antipsychotic drugs are
potent blockers of postsynaptic dopamine
receptors in the CNS
Drugs that increase dopaminergic activity such as levodopa (a precursor of dopamine),
amphetamines (releasers of dopamine), or apomorphine (a direct dopamine receptor
aggravate schizophrenia or induce it in some individuals.
Using a technique known as positron emission tomography (PET), dopamine receptor
density has been shown to be
higher in schizophrenic than in non-schizophrenic persons.
Antipsychotic action can be explained by antagonism of dopamine receptors in the
mesolimbic and mesofrontal systems of the brain (meso = middle)
Extrapyramidal movement disorders: Antagonism of dopamine receptors in the
Extrapyramidal movement disorders: Endocrine effects: Dopamine in the hypothalamus exerts a tonic inhibitory effect on prolactin
m the pituitary gland
Blockade of histamine receptors:
Sedation, drowsiness, and weight gain
Blockade of α-adrenoceptors:
Postural hypotension (hypotension when assuming an erect position),
dizziness, reflex tachycardia
Clozapine is a very useful addition to our therapeutic armamentarium of antipsychotic drugs
because it relieves both the positive and negative symptoms of schizophrenia. Since patients
extrapyramidal side effects when taking clozapine, compliance is better with
clozapine than with older antipsychotics
Clozapine can cause
granulocytopenia (a decrease in
the number of white blood cells)
Lithium carbonate is a mood-stabilizing agent which is used to prevent mood swings in patients
manic-depressive disorder. It is also used to treat mania.
The mechanism of action of lithium has not been resolved. Three possibilities are under
1. Effect on electrolytes and ion transport.
2. Effects on neurotransmitters and the release of neurotransmitters.
3. Effect on second messengers that mediate transmitter action.
Lithium is the drug of choice for long-term maintenance to prevent
both manic and depressive
episodes in patients with manic-depressive disorder
The safety and efficacy of lithium is enhanced by
monitoring serum lithium concentration
Antidepressant Agents-There are several
types of depression and depressions are classified as follows:
Reactive (secondary) depression. This is the most common type and accounts for over
60% of all depressions.
Major depression (endogenous). In major depression there are characteristic disturbances
of major body rhythms of sleep, hunger and appetite
Depression associated with manic-depressive disorder.
The major theory which has been proposed to explain major depression is known as the amine
Animal studies showed that reserpine inhibited reuptake and storage of serotonin and norepinephrine in the vesicles of presynaptic nerve endings. As a result, there was
a depletion of amine stores in these vesicles and amine-dependent neurotransmission would be
diminished. Since reserpine induced depression and depleted stores of amine neurotransmitters,
it was reasoned that depression might be associated with decreased functional amine dependent
The amine hypothesis does not explain all the effects of antidepressants in depression. The
neurotrophic hypothesis suggests that depression is associated with
(growth and inter-connectivity of neurons) support and that antidepressants stimulate
neurogenesis and synaptic connectivity in cortical areas.
Tricyclic antidepressants: Imipramine is a member of this class of antidepressants which share a
Second-generation (atypical) antidepressants: Bupropion and amoxapine, introduced after
1980, are structurally unrelated to the tricyclic antidepressants and were introduced in an attempt
have available antidepressants with less adverse effects.
Selective serotonin reuptake inhibitors (SSRI’s):
The tricyclic antidepressants have anticholinergic
(muscarinic), antiadrenergic (alpha), and antihistaminic actions which do not contribute to their efficacy but do contribute to their toxicity. The SSRI’s, in contrast, have much less effect on the
autonomic nervous system and therefore have less toxicity.
Drugs that block Serotonin and norepinephrine uptake: Drugs such as venlafaxine block
transporters for both serotonin and norepinephrine and have an
advantage over the tricyclic
antidepressants due to their better safety profiles. (Less adverse effects).
Monoamine oxide (MAO) inhibitors: There are two monoamine oxidase (MAO) enzymes,
designated MAO-A and MAO-B. MAO-A is the enzyme primarily responsible for metabolism
norepinephrine, serotonin and tyramine.
MAO-B is more selective for dopamine metabolism.
Selective blockade of MAO-A is therefore
considered more selective for therapy of depression
Phenelzine and tranylcypromine are non-selective inhibitors of MAO-A and MAO-B. They
combine irreversibly with the enzymes and therefore have a
prolonged duration of action.
is a new
short-acting reversible inhibitor of MAO-A and 90% of the drug appears in urine within
12 hours of administration.
In the past, a tricyclic antidepressant such as imipramine has been considered as the drug of first
choice for treatment of
In recent years, an SSRI such as fluoxetine (Prozac) is often
used instead, especially for patients with
major depressive disorder anxiety disorder
SSRI’s: The SSRI’s cause nausea, headache, nervousness, and insomnia more commonly than