depression ,symptoms, mechanism of depression ,classification of antidepressants , tri cyclic anti depressants and its pharmacological actions ,acute poisoning and treatment
2. DEPRESSION
Depression is a Mood Altering Illness
Affecting
- Energy
- Sleep
- Appetite
- Libido
- Function Ability
The symptoms of depressions are intense
feeling of sadness, hopelessness, despair
and inability to experience pleasure in usual
activities.
3. SYMPTOMS
Persistently sad, anxious, or empty moods
Loss of pleasure in usual activities (Anhedonia)
Feelings of helplessness, guilt, or worthlessness
Crying, hopelessness, or persistent pessimism
Fatigue or decreased energy
Loss of memory, concentration, or decision-making
capability
Restlessness, irritability
Sleep disturbances
Change in appetite or weight
Physical symptoms that defy diagnosis and do not respond
to treatment (especially pain and gastrointestinal
complaints)
Thoughts of suicide or death, or suicide attempts
Poor self-image or self-esteem (as illustrated, for example,
by verbal self-reproach)
4. MECHANISM OF DEPRESSION
Depression is associated with changes in the level
of neurotransmitters in the brain that help nerve cells
to communicate.E.x Serotonin,Dopamine,Nor
epinephrine.
The level can be influenced by physical illness,
genetics, substance abuse, diet, hormonal changes,
brain injuries or social circumstances.
5. ANTIDEPRESSANTS
Drug which enhance alertness and may result in
an increased output of behaviour.
Potentiate directly or indirectly the action of
Dopamine
Serotonin
Nor adrenaline
The purpose of antidepressants is to increase
the neurotransmitters in the synapse.
9. TRICYCLIC ANTIDEPRESSANTS
They have been employed in drug therapy since the
late 1950s.
Largest group of drug agents used for the treatment
of depression.
Referred as “ tri cyclic ” compounds –three rings.
Properties of TCA
Characteristic three ring nucleus.
All are metabolized in liver .
High protein binding.
High lipid solubility.
N
N
R1
R2
A
B
C
1
2
37
5
6
8
9
10 11
11. PHARMACOLOGICAL ACTIONS
CNS:
In normal individuals: It induces a peculiar clumsy feeling,
tiredness, light-headedness, sleepiness, difficulty in
concentrating and thinking, unsteady gait. These effects
tend to provoke anxiety.
In depressed patients: Little acute effects are produced,
except sedation (in the case of drugs which have sedative
property). After 2–3 weeks of continuous treatment, the
mood is gradually elevated, patients become more
communicative and start taking interest in self and
surroundings.
12. PHARMACOLOGICAL ACTIONS CONTD…
ANS:
TCAs are potent anticholinergics cause dry mouth, blurring
of vision, constipation and urinary hesitancy as side effect.
CVS :
Effects on cardiovascular function are prominent, occur at
therapeutic concentrations and may be dangerous in
overdose.
Tachycardia: due to anticholinergic and NA potentiating
actions.
Postural hypotension: due to inhibition of cardiovascular
reflexes and α1 blockade.
ECG changes and cardiac arrhythmias: NA potentiating +
ACh blocking
13. SIDE EFFECTS
Muscarinic M1 receptor antagonism - Anticholinergic effects
including dry mouth, blurred vision, constipation, urinary retention
and impotence.
Histamine H1 receptor antagonism -Sedation and weight gain
Adrenergic α receptor antagonism - Postural hypotension
Direct membrane effects - reduced seizure threshold, arrhythmia
Serotonin 5-HT2 receptor antagonism - weight gain
Nonselectivity results in greater side effects
TCAs can also lead to cardiotoxicity
Slow cardiac conduction
High potency can lead to mania
Contraindicated with persons with bipolar disorder or manic
depression
14. ACUTE POISONING & TREATMENT
Excitement, delirium and other anticholinergic symptoms as
seen in atropine poisoning, followed by muscle spasms,
convulsions and coma.
Respiration is depressed, body temperature may fall, BP is
low, tachycardia is prominent. ECG changes and
ventricular arrhythmias are common.
Treatment is primarily supportive with gastric lavage,
respiratory support, fluid infusion, maintenance of BP and
body temperature.
Acidosis must be corrected by bicarbonate infusion.
Diazepam may be injected i.v. to control convulsions and
delirium.
Most important is the treatment of cardiac arrhythmias, for
which propranolol/lidocaine may be used;
15. DRUG INTERACTIONS
TCAs potentiate directly acting sympathomimetic amines (in
cold/asthma remedies).
1. Adrenaline containing local anaesthetic should be avoided.
However TCAs attenuate the actions of indirect
sympathomimetics (ephedrine, tyramine).
2. TCAs abolish the antihypertensive action of guanethidine
and clonidine by preventing their transport into adrenergic
neurones.
3. TCAs potentiate CNS depressants, including alcohol and
antihistaminics.
4. Phenytoin, phenylbutazone, aspirin and CPZ can displace
TCAs from protein binding sites and cause toxicity.
5. Phenobarbitone induces as well as competitively inhibits
imipramine metabolism.
16. DRUG INTERACTIONS CONTD…
6. SSRIs inhibit metabolism of several drugs including
TCAs—dangerous toxicity can occur if the two are given
concurrently.
7. By their anticholinergic property, TCAs delay gastric
emptying and retard their own as well as other drug’s
absorption. However, digoxin and tetracyclines may be
more completely absorbed. When used together, the
anticholinergic action of neuroleptics and TCAs may add
up.
8. MAO inhibitors—dangerous hypertensive crisis with
excitement and hallucinations has occurred when given
with TCAs.
Notas del editor
MUST HAVE one of the top two
AT LEAST five of the other symptoms
Nearly DAILY
For at least TWO WEEKS
