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138
Textbook of Pharmacotherapeutics
11
Psychiatric Disorders
11.1 DEPRESSION
Mental depression is a mood disorder prevalent in a large percentage of the
population and has a strong familial predisposition. It can disrupt normal social life
and may have suicidal tendencies.
Aetiology
It is likely that genetic, hormonal, biochemical, environmental, and social factors all
have some role in determining an individual’s susceptibility to developing the
disorder, with major life events sometimes acting as precipitants for a particular
episode.
Pathophysiology
Although the pathophysiology of depression is complex, it may have a biochemical
basis that is related to decreased synthesis of 5-HT, noradrenaline, and dopamine as
well as an increased accumulation of acetylcholine. The endocrine system, particularly
the hypothalamic-pituitary-adrenal axis and the hypothalamic-pituitary-thyroid axis,
also seems to be involved in its genesis. Some endocrine disorders, like hypothyroidism
and Cushing’s syndrome, have been associated with mood changes.
Clinical Manifestations
A low mood accompanied by a loss of interest in normally enjoyable activities is the
main clinical feature of depression. In severe cases, the patients might experience
delusions and hallucinations and can become suicidal. Symptoms like anxiety,
agitation, sleep disturbances, weight loss, and loss of appetite are also present.
Depressed people also complain of gastric problems and non-specific aches. Sexual
drive is reduced and, in some cases, there is excessive eating and sleeping.
Non-pharmacological Treatment
Psychotherapy: Interpersonal therapy, cognitive-behavioural therapy, marital
therapy, etc. are some of the types of psychotherapies used in the treatment of mild to
moderate depression. It can be used alone or with antidepressant medication. The
therapist works with the patient alone or in groups to replace the negative thoughts
and feelings of guilt with more positive thoughts. The therapist also tries to search for
the possible external factors contributing to the depressive illness and tries to reduce
their impact by modifying the environment.
138
Psychiatric Disorders
139
Electroconvulsive therapy (ECT): It is the most effective treatment available for
psychotic depression and treatment-resistant depression. A series of 2 to 3 ECT
treatments per week for 2 to 3 weeks is usually effective.
Pharmacological Management
Tricyclic antidepressants: All the tricyclic antidepressants block the reuptake of
noradrenaline and 5-HT. Imipramine, amitriptyline, nortriptyline, and doxepin are
some of the examples of tricyclic antidepressants in current clinical use. To begin with,
imipramine is generally administered at a dose of 25 mg twice a day and then
increased to 50 mg 2–3 times a day during the second and third weeks, depending on
the response.
Monoamine oxidase inhibitors (MAOIs): MAOIs inhibit the enzymes responsible
for the oxidation of noradrenaline, 5-HT, and other biogenic amines. Tyramine-rich
foods like cheese, meat, yeast extract, and broad bean pods must be avoided as these
can result in hypertension crises. Phenelzine and tranylcypromine are effective
antidepressants.
Selective serotonin reuptake inhibitors (SSRI): These are widely used now as they
are well tolerated by most patients, less toxic in overdose, and have relatively fewer
cardiovascular and cholinergic effects. Some of the commonly used SSRIs are
fluvoxamine, fluoxetine, paroxetine, sertraline, citalopram, and escitalopram. The
initial doses of fluvoxamine and sertraline are 50 mg at bedtime and increased to
100 to 150 mg daily. The initial dose of fluoxetine is 10 mg once daily in the morning.
Paroxetine can be initiated at 10 to 20 mg at bedtime, with most patients requiring
doses of 20 to 40 mg. Citalopram can be started at a dose of 20 mg. All SSRIs can be
given once daily. Common adverse effects include insomnia, gastrointestinal distress,
and sexual dysfunction.
Other Drugs
Venlafaxine and duloxetine: These drugs belong to the class of serotonin-noradrenaline
reuptake inhibitors (SNRIs).
Reboxetine: It is a specific noradrenergic reuptake inhibitor that is used in patients
who experience serotonergic-related side effects.
Trazodone and nefazodone: Both are effective antidepressants used for severe
depression but have sedation and orthostatic hypotension as side effects.
Mirtazapine: The postsynaptic blockade of 5-HT
and 5-HT3 receptors minimises
2
gastrointestinal distress and sexual dysfunction effects, which are commonly seen
with SSRIs.
KEY POINTS
• Mental depression is a mood disorder which can disrupt normal social life.
• Symptoms include anxiety, agitation, sleep disturbances, weight loss, and loss of appetite.
• Selective serotonin reuptake inhibitors (SSRIs) are widely used now as they are well tolerated by
most patients.
• Electroconvulsive therapy (ECT) is most effective treatment available for psychotic depression.
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Textbook of Pharmacotherapeutics
11.2 ANXIETY
Anxiety is a normal protective, psychological response to an unpleasant or threatening
situation that can improve performance if it is mild to moderate anxiety. However,
excessive or prolonged symptoms cause severe distress and impairment in social
functioning. Anxiety disorders include generalized anxiety disorder (GAD), panic
disorder (PD), obsessive-compulsive disorder (OCD), post-traumatic stress disorder
(PTSD), and social phobia (SP).
Pathophysiology
Anxiety occurs where there is a disturbance of the arousal systems: The general arousal
system, the emotional arousal system, and the endocrine/autonomic arousal system.
These arousal systems activate responses such as increased muscle tone, increased
sympathetic activity, and increased output of anterior and posterior pituitary
hormones. An increase in autonomic activity is often associated with anxiety.
Several neurotransmitters like acetylcholine and gamma-aminobutyric acid (GABA)
are also involved in anxiety. Acetylcholine is the main transmitter maintaining general
arousal, but increased emotional arousal is associated with noradrenergic and
serotonergic activity. Central stimulant drugs (caffeine, amphetamine), withdrawal
from chronic use of CNS depressant drugs (hypnotics, alcohol), and metabolic
disturbances (hyperventilation, hypoglycaemia, thyrotoxicosis) can also cause
anxiety. Anxiety disorders also have a genetic aetiology.
Clinical Manifestations
Apart from the psychological symptoms of apprehension and fear, individuals
complain of somatic symptoms like headaches, palpitations, shortness of breath,
dysphagia, gastrointestinal disturbances, and tremors.
Generalized anxiety disorder (GAD): The main feature is excessive and unrealistic
worry about several life situations that have been present for 6 months or longer. This
fear is accompanied by symptoms like restlessness, fatigue, difficulty concentrating,
irritability, muscle tension, and disturbed sleep. Many patients also experience the
somatic symptoms discussed above.
Panic disorder (PD): In this condition, the patient has recurrent, unexpected
attacks of overwhelming anxiety accompanied by severe physical symptoms like
hyperventilation and sympathetic nervous system activity. Many patients with PD
also develop symptoms of agoraphobia (fear of having a panic attack where help may
be unavailable), for example, being in places away from home, being in crowds, being
on bridges, and travelling in a bus, train, or car.
Obsessive-compulsive disorder (OCD): It is a condition characterized by recurrent
obsessions and compulsions that cause significant distress and interfere with normal
social occupational functioning. Obsessions are persistent ideas, thoughts, or images
that are distressing and senseless. Examples of obsessions are recurrent thoughts of
harming a loved one, or recurrent thoughts of contamination. Compulsions are
repetitive, intentional behaviours performed in response to an obsession. Examples of
compulsions are repetitive hand washing, counting, checking, etc.
Post-traumatic stress disorder (PTSD): PTSD may develop in response to a
stressful event or situation of an exceptionally threatening nature. Causes include
Psychiatric Disorders
141
natural or human disasters, war, serious accidents, witnessing the violent deaths of
others, being the victim of sexual abuse, rape, torture, terror, or being kidnapped. Such
individuals experience flashbacks, insomnia, avoidance of activities that remind them
of the incident, and intense anxiety.
Social phobia: It is characterised by a persistent fear of social or performance
situations in which embarrassment may occur. Such individuals, when exposed to
social or performance situations, experience an immediate anxiety response
(palpitations, tremors, sweating, gastrointestinal discomfort, diarrhoea, muscle
tension, blushing, and confusion).
Some other phobias include claustrophobia (fear of enclosed spaces), and
arachnophobia (fear of spiders). Children are phobic about the dark and ghosts.
Non-pharmacological Management
• Relaxation techniques can be effective for mild to moderate anxiety. This can be
achieved through meditation and yoga.
• Behavioural therapy (graded exposure) is the treatment of choice for a phobia. In
this, the patient practises exposure to the stimulus until no fear is felt.
• Cognitive behaviour therapy (CBT) is the treatment of choice for panic disorder
and generalised anxiety disorder, where the therapist identifies the mental cues
that exacerbate the anxiety of panic attacks and works with the patient to reduce
those anxieties.
Pharmacological Management
Commonly used anti-anxiety medications include benzodiazepines, tricyclic
antidepressants, selective serotonin reuptake inhibitors, monoamine oxidase
inhibitors, buspirone, and beta-blockers.
Benzodiazepines: These drugs are commonly prescribed to provide immediate
relief from the symptoms of severe anxiety. All benzodiazepines have sedative/
hypnotic, anxiolytic, muscle relaxant, and anticonvulsant actions, with minor
differences in the relative potency of these effects.
Most of the effects of benzodiazepines result from their interaction with postsynaptic
GABA receptors (GABA is the most important inhibitory neurotransmitter in
the central nervous system). The anti-anxiety agents under the category of
benzodiazepines include alprazolam, chlordiazepoxide, clonazepam, clorazepate,
diazepam, lorazepam, and oxazepam. Adverse effects include drowsiness, lightheadedness, confusion, ataxia, and amnesia. Chronic use of benzodiazepines can lead
to the development of drug dependence.
Tricyclic antidepressants (TCAs): Certain TCAs such as clomipramine, imipramine,
and amitriptyline are found to be effective in some anxiety disorders but are
associated with adverse actions such as anticholinergic effects, hypotension, and
weight gain.
Selective serotonin reuptake inhibitors (SSRIs): These agents are considered first-
line drugs for most anxiety disorders. The currently available SSRIs are fluoxetine,
sertraline, paroxetine, fluvoxamine, and citalopram. SSRIs are free of anticholinergic,
orthostatic, and sedative effects. Sexual dysfunction, nausea, headache, nervousness,
and insomnia are the common side effects.
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Textbook of Pharmacotherapeutics
Monoamine oxidase inhibitors (MAOs): These agents are rarely used in practice
because of their interaction with other medicines and tyramine in the diet. Phenelzine
and moclobemide are occasionally used for social phobia.
Buspirone: It is used for short-term relief of anxiety symptoms. It causes less
sedation and fewer psychomotor difficulties than benzodiazepines. It does not cause
drug dependence like benzodiazepines.
Beta-adrenergic blockers: Propranolol may be considered useful in selected
patients with GAD who have prominent cardiovascular symptoms of anxiety, like
tachycardia, palpitations, and tremors.
KEY POINTS
• Anxiety is a normal protective, psychological response to an unpleasant or threatening situation.
• Anxiety disorders include panic disorder (PD), obsessive-compulsive disorder (OCD) and posttraumatic stress disorder (PTSD).
• Benzodiazepines are commonly prescribed to provide immediate relief from the symptoms of
severe anxiety.
• Selective serotonin reuptake inhibitors (SSRIs) are considered first-line drugs for most anxiety
disorders.
11.3 PSYCHOSIS
The term “psychosis” is broader and includes infectious, metabolic, endocrine, and
drug-induced causes of psychotic symptoms like delusions and hallucinations. Many
psychiatric and neurologic disorders, like mania, major depression, and dementia, also
cause psychotic symptoms.
Schizophrenia is a chronic thought illness in which characteristic psychotic
symptoms are seen during the acute phase of the illness, with either partial or full
resolution of symptoms between psychotic episodes. There is a persistent disturbance
in the perception of reality, leading to characteristic changes in perception, thought,
affective responses, and behaviour.
Aetiology
The aetiology of schizophrenia is unknown, although several precipitating factors are
recognised along with a genetic predisposition. The neurodevelopmental delay has
been implicated and it has been proposed that the disease is triggered by some life
events in individuals predisposed by an abnormal (biochemical/anatomical)
mesolimbic system. The concept of an underlying neurochemical abnormality is
advanced by the dopamine theory of schizophrenia. The majority of antipsychotics
block dopamine receptors in the forebrain. 5-Hydroxytryptamine, glutamine
hypoactivity, GABA hypoactivity, and -adrenergic hyperactivity are also potential
neurochemical targets.
Pathophysiology
Positive symptoms such as hallucinations, delusions, and thought disorders are
believed to be due to the overactivity of mesolimbic and mesocortical dopaminergic
pathways to the temporolimbic region and frontal cortex, whereas the relative lack of
Psychiatric Disorders
143
dopaminergic function in the prefrontal cortex has been suggested to explain the
negative symptoms of schizophrenia-like apathy and social withdrawal.
Clinical Manifestations
The clinical features include unexpected changes in behaviour, mood abnormalities
like anxiety, depression, irritability or euphoria, auditory hallucinations (voices),
which command the patients or comment on their actions, delusions relating to
the control of thoughts, and a lack of insight into illness. The mental function
is impaired enough to interfere with the capacity to meet the ordinary demands
of life.
Pharmacological Management
Antipsychotic (neuroleptic) drugs: These are used mainly for major psychoses like
schizophrenia and manic-depressive illness. These drugs block both D
and D
1
dopamine receptors and reduce the delusions and hallucinations associated with
schizophrenia.
The older antipsychotics have side effects such as hypotension, extrapyramidal
symptoms, and anticholinergic effects, which limit their use in maintenance
therapy.
Phenothiazines are a group of neuroleptics widely used. Chlorpromazine (100–
1000 mg daily) is the drug of choice when a more sedating drug is required.
Trifluoperazine is used when sedation is undesirable. The adverse effects of
phenothiazines are extrapyramidal reactions (EPR) like tremors, muscular rigidity,
excessive salivation, akinesia, and dystonia; behavioural reactions like drowsiness,
restlessness, excitement, and confusion; and orthostatic hypotension.
Butyrophenones (haloperidol 2–30 mg daily) are also used in the treatment of acute
schizophrenia and mania. They cause dystonia and/or extrapyramidal effects but are
less sedating than phenothiazines.
Atypical antipsychotics: These are called atypical as they block D
than D
and thus cause fewer extrapyramidal side effects.
1
receptors less
2
Clozapine: It is used in patients who have failed to respond to at least two
conventional antipsychotic drugs. It is expensive and causes severe agranulocytosis,
so it is prescribed very carefully with monitoring or blood counts weekly. The starting
dose is 25 mg per day, with a maintenance dose of 150–300 mg daily.
Risperidone: It has both D
receptor and 5-HT receptor blocking properties. Dosage
2
ranges from 6–10 mg daily. It has fewer sedative and extrapyramidal effects as
compared to conventional antipsychotics.
Olanzapine: It has an affinity for 5-HT
, D1, D2, and muscarinic receptors.
2
Dosage ranges from 5–10 mg daily and has a low incidence of extrapyramidal side
effects.
Psychological treatment: This includes reassurance, support, and a good
doctor–patient relationship. Cognitive behaviour therapy reduces the intensity of
delusions.
Social treatment: This involves paying attention to the patient’s environment and
social functioning. Family education can help to provide emotional and social
stimulation for the patient.
2
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Textbook of Pharmacotherapeutics
KEY POINTS
• Schizophrenia is a chronic thought illness in which there is a persistent disturbance in the
perception of reality, leading to characteristic changes in perception, thought, affective responses,
and behaviour.
• The mental function is impaired enough to interfere with the capacity to meet the ordinary
demands of life.
• Phenothiazines are a group of neuroleptics widely used, e.g. chlorpromazine
• The adverse effects of phenothiazines are extrapyramidal reactions (EPR) like tremors, muscular
rigidity, excessive salivation, akinesia, and dystonia.
Ophthalmology
145
12
Ophthalmology
12.1 CONJUNCTIVITIS (BACTERIAL AND VIRAL)
Conjunctivitis is the inflammation of the conjunctiva, i.e. the transparent membrane
which lines the eyelid and eyeball, due to a bacterial or viral infection. It is a very
commonly treated ophthalmic disorder. It is characterised by redness of eye, irritation
and discharge. Pain is minimal but vision may be affected due to excessive tearing and
irritation.
Bacterial Conjunctivitis
Common causative bacteriae are S. aureus, S. epidermidis, Streptococcus pneumoniae and
H. influenzae.
Manifestations are acute onset of redness, foreign body sensation, mucopurulent
discharge and excessive eyelid crusting upon waking. Normally both the eyes are
involved but onset of symptoms start with one eye preceding another by a day. Simple
bacterial infection is self-limiting. It may get resolved by itself within 10 to 14 days.
But for a patient’s comfort, treatment can be given for 5 to 7 days with topical
antibiotics such as sulphacetamide 10% or trimethoprim and polymyxin or ciprofloxacin
four times daily with combination of erythromycin or bacitracin antibiotic ointment
at bedtime. A conjunctivitis swab must be taken for routine culture and sensitivity
testing before treatment begins. For intracellular Gram-negative diplococci,
ceftriaxone 1 g in a single intramuscular dose should be given. If peripheral corneal
ulcer formation is seen, hospitalization is required for administration of intravenous
antibiotics (ceftriaxone 1 g in every 12 to 24 hours) and close observation. Frequent
irrigation of the eye with sterile saline is required to clear the discharge and topical
erythromycin and bacitracin can be applied four times a day. For concomitant
chlamydia infection, 250 to 500 mg oral tetracycline four times daily or doxycycline
100 mg twice daily for 2 to 3 weeks can be given. To avoid spread of the disease
patients should be advised to wash their hands frequently, not to touch their eyes and
to avoid direct contact with others.
Viral Conjunctivitis
Adenovirus is a common causative agent for viral conjunctivitis. Watery mucus
discharge, conjunctival hyperaemia, and lid oedema are common symptoms. It is a
self-limiting condition with spontaneous resolution in 2 to 3 weeks. Discomfort
can be treated with artificial tears every 2 to 3 hours along with cool compresses at
15 mins intervals four times daily. It will help to reduce lid swelling and itching.
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Textbook of Pharmacotherapeutics
Patients should be educated for frequent hand washing and not sharing the towels
and linen.
In herpes simplex conjunctivitis, corneal involvement should be determined to
prevent the loss of vision. Topical antivirals such as 1% trifluorothymidine can be
given 5 times a day for 7 to 10 days. Cool compresses and artificial tears will also help
to get symptomatic relief.
Allergic Conjunctivitis
Allergic conjunctivitis or hay fever is a very common condition. Itching, oeyelid
oedema and epiphora (excessive watering of eyes) are common symptoms. Use of
contact lenses or any chronic foreign body can initiate the symptoms. These symptoms
can be subsided by cold compresses, topical vasoconstrictors, antihistamines and mast
cell stabilizers such as cromolyn sodium. A topical antihistamine such as levocabastine
can be used in combination with mast cell stabilizers to provide immediate relief of
symptoms like itching and burning. Olopatadine (Patanol) is a recently available
combination of topical mast cell stabilizers and antihistamine. The antihistamine
component provides immediate relief of symptoms and mast cell stabilizers provide
long term protection.
KEY POINTS
• Conjunctivitis is a widely observed eye infection.
• Common symptoms are redness of eyes, pruritus and discharge
• Mucopurulent discharge and eyelid crusting upon waking are characteristic of bacterial conjunctivitis
while watery mucus discharge and palpebral follicular response are common in viral conjunctivitis
• For allergic conjunctivitis, combination of antihistamine and mast cell stabilizers is effective
12.2 GLAUCOMA
Glaucoma is defined as a disease condition in which the ganglion cells and optic nerve
is damaged. It may cause various degrees of loss of vision and blindness.
Glaucoma can be classified as:
• Open angle glaucoma
• Angle-closure or closed angle glaucoma.
Classification is based on the mechanism of obstruction of outflow of aqueous
humor and ophthalmologists can decide treatment strategies based on it. Open angle
glaucoma is more common (80 to 90% cases) than closed angle glaucoma. Glaucoma
can also be congenital or secondary. Congenital glaucoma normally results from
developmental ocular abnormalities and is observed in less than 2% patients.
Secondary glaucoma is associated with other ocular disorders, systemic disorders, eye
injury, side effects of medication or intraocular surgery.
Aetiopathogenesis
Following are the risk factors associated with glaucoma. They are either IOP
(intraocular pressure) dependent or IOP-independent.
• Family history
• Elevated intraocular pressure
Ophthalmology
147
• Diabetes
• Myopia
• Long term steroid consumption
• Eye injury
• Elevated blood pressure
Pathophysiology of the glaucoma relies on aqueous humor dynamics, IOP, and
optic nerve anatomy and physiology.
Increased IOP is clearly associated with damage and eventual death of optic nerves.
IOP maintains the curvature of the cornea which is required for refractive properties
of the eye. Normal range of IOP is 10 to 21 mm of Hg, and if it goes beyond 21, it is
considered as elevated IOP.
Aqueous humor is optically neutral fluid which provides oxygen and
nourishment to the lens and cornea. It is secreted by the ciliary body in the posterior
chamber and flows towards the trabecular meshwork through the pupil, where it
outflows into Schlemm canal and episcleral venous system. IOP depends on the
balance between production of aqueous humor and its outflow from the anterior
segment.
Open angle glaucoma: In open angle glaucoma, the flow of aqueous humor
is obstructed between the trabecular sheets and episcleral veins which will
retard the elimination of aqueous humour. This will lead to elevate the IOP up
to 25 to 35 mm of Hg and causes visual defects. Pressure independent causes of
optic neuropathy are oxidative stress, inflammation and abnormal ocular
perfusion.
Angle-closure glaucoma: Pupillary block and iris plateau are the responsible
mechanisms for angle closure glaucoma. Pupil dilates to a degree where the iris comes
in greater contact with lens, and the flow of aqueous humor from posterior to the
anterior chamber is hampered. Since aqueous humor is continually secreted, pressure
increases behind the iris in the posterior chamber. It forces the iris to bow forward and
cause complete blockage.
Fig. 12.1: Production and flow of aqueous humour in the eye