Rao_Psychopharmacology_24 Nov 2023 14-16hr.ppt

NEUROPSYCHOPHARMACOLOGY

1. Dental Implications in
PsychoPharmacology
Dr.R.Rao Prethendhira Singh
BDS.,Msc.(Med.Pharmacology).,PGDCR
Dept.of Pharmacology,
Sri Ramakrishna Dental College & Hospital,
Coimbatore, Tamilnadu

2. Neurosciences
•Neuroscience is the scientific study of the
nervous system (the brain, spinal cord, and
peripheral nervous system), its functions and
disorders. –Multidisciplinary Anat, Physio,
psych,medicine, stat, biology, CS etc.
•Neuropsychopharmacology – Studies/ science
that examines how neurons (nerve cells) in the
brain interact with the mind and drugs.
•Psychopharmacology- studies the effects of
drugs on the mind without the same emphasis
on neurons. Instead, the latter may investigate
other chemicals like neurotransmitters.

3. Psychopharmacological agents or Psychotropic
drugs are those having primary effects on psyche
(mental processes) and are used for treatment of
psychiatric disorders.

4. Classification of Mental Disorder/Psychiatric
Nosology/ Psychiatric Taxonomy
•Neuroses –Less serious ,
ability to comprehend
and reality is not lost
1.Anxiety
2.Phobia
3.Obsessive
compulsive disorder
(OCD)
4.Reactive
depression
5.Post traumatic
stress disorder
6.Hysteria
•Psychoses –Distorion of thought,
Behaviour, capacity to recognize reality and
perception
1.Acute - Delirium& Chronic - Dementia
Organic brain syndrome (Cognitive
disorders) – Korsakoff Syndrome –
Confusion defective memory
2.Functional Disorders
1.Schizophrenia (Split Mind) – Split
personality / hallucination
2.Paranoid states (Delusion/False
belief)
3.Mood (Affective disorders) –
Mania , Depression –Uni/Bipolar

5. ICD 10 Class. Of all Physical and mental disease by WHO
•F0 - F9: Organic, including symptomatic, mental disorders
•F10 - F-19: Mental and behavioural disorders due to use of psychoactive
substances
•F20 - F25: Schizophrenia, schizotypal and delusional disorders
•F30 -F39: Mood [affective] disorders
•F40 - F49: Neurotic, stress-related and somatoform disorders
•F50 - F59: Behavioural syndromes associated with physiological
disturbances and physical factors
•F60 - F69: Disorders of personality and behaviour in adult persons
•F70 - F79: Mental retardation
•F80 - F89: Disorders of psychological development
•F90 - 98: Behavioural and emotional disorders with onset usually
occurring in childhood and adolescence
•In addition, a group of F99 "unspecified mental disorders"

7. What is Psychotropic Drugs?
•A psychotropic describes any drug that affects behavior, mood, thoughts, or
perception. It’s an umbrella term for a lot of different drugs, including
prescription drugs and commonly misused drugs.
1.Antipsychotic drugs (Neuroleptic, ataractic, Major tranquilizers)
usefull in all types of functional psychoses.
2.Antimanic Drugs/ Mood Stabilizers
3.Anti depressant drugs – Used in Minor and major depressive
disorders, OCD
4.Antianxiety drugs – Anxiolytic / Minor tranquilizers.
5.Psychotomimetic Drugs – (Psychedelic, Psychodysleptic,
Hallucinogens) – LSD & Cannabis
Note: Tranquillizer It is an old term meaning “a drug which reduces mental tension and
produces calmness without inducing sleep or depressing mental faculties.”

8. Psychosis – Variety of
disorder (Excessive
limbic dopaminergic
activity)
Schizophrenia – a
particular disorder with
marked thinking
disturbance
Atypical – 2
nd
Generation

9. •Anhedonia - inability to experience pleasure in normally pleasurable acts.
•Alogia is a symptom that causes you to speak less, say fewer words or
only speak in response to others
•Avolition - a total lack of motivation that makes it hard to get anything
done

10. Mech. Of Action / Hypothesis
•Serotonin Hypothesis –(5HT- Hystotryptamine) - 5HT2A
receptor blockade (Mostly 2
nd
generation) – Inverse
agonist. Modulates the release of Dop, Ach, Na,
Glutamate, GABA. 5HT2c leads to inhibition of cortical
and limbic dopamine.
•Dopamine Hypothesis - Blocks post synaptic D2
receptors –Diminished cortical /hippocampus
dopaminergic activity.
•Glutamate Hypothesis – inhibits NMDA receptor (n
methyl D aspartate.

11. Dopaminergic System
•1
st
– Mesolimbic –Mesocortical pathway
•2
nd
– Nigro striatal Pathway
•3
rd
– Tuberoinfundibular pathway
•4
th
– Medullary periventricular pathway
•5
th
– Incertohypothalamic pathway
Dopaminergic Receptors
•D1 like (D1, D5)
•D2 like (D2, D3, D4)
Gs coupled activation adenylyl cyclase (cAMP)

18. •Schizophrenia
•Mania
•Antiemetic
•Intractable
hiccups

20. AFFECTIVE DISORDERS-
(Mood Disorders)
Affective disorders can be
1.Depression (Minor,
Major)
1.Unipolar – Reactive
Depression ,
Endogenous
2.Bipolar – Manic
Depressive psychosis
(MDP)
2.Mania

21. Lithium (Mood Stabilizing drugs)
MOA:
•Reduces activity of DAG and IP3- blunts the
effects of muscarinic and  stimulation
blunted – relieves mania.
Kinetics:
•Orally, absorbed well.
•First enters ECF then ICF
•Excreted by breast milk, enters placenta
•Serum li level should be about 0.8-1.2 mEq/L

23. Actions of lithium
•CNS:
•Effect start after2 weeks.
•Prophylactic drug in MDP
•No Sedative or euphoriant or depressant
action in normal persons
•Kidney: It opposes the actions of ADH
•Have some insulin like action
•Increases leukocyte count
•Reduces thyroxine synthesis.

24. ADR
•Tremor, confusion, ataxia, Seizures.
•Pregnancy – Ebstein’s anomaly to the
foetus
•DI
•Goiter
•Nausea, vomiting
•Acute lithium poisoning - Osmotic diuretic
and bicarbonate, dialysis.

25. Drug – drug Interactions
1.Tetracyclines and ACE inhibitors- Li retention
2. Cautious with insulin and Sulfonyl urea
- hypoglycemic effect
3. Li accentuates the effects succinyl choline and
pancuronium
4. Diuretics tend to cause Li retention

26. Uses;
1.Acute manic episode : along with
neuroleptic
2. Prophylaxis of MDI
3.Cluster Headache
4. Chemotherapy induced leukopednia
5. SIADH

27. Carbamazepine
•Clinical uses
1. Treat acute episodes of mania
2. Prophylaxis against MDP
•Mechanism of action is unknown
•Dose Start with 200mg, BD
•It can be used as first line therapy against
mania or can be used in combination with
Li

28. Valproic acid
•Firstline drug
•750mg/day - increased up to 2000mg/day
Other drugs
1.Clonidine, Verapamil
2.Olanzapine
3.Lamotrigine, Gabapentin
4.Topiramate

29. Hallucinogens – Dissociative drugs
(Psychotomimetics, Psychedelics, Psychodysleptics, Psychotogens)
•having bright colours or
patterns or strange sounds
•psychedelic drugs that can
potentially change the way
people see, hear, taste,
smell or feel, and also
affect mood and thought.

30. •LSD (Lysergic acid Diethyl
amide)
•Mescaline
•Psilocybin
• PCP
•Cannabinoids
(Tetrahydocannabinol) –
Bang Doodh –Holy, Ganja, Charas,
Dronabinol, Nabinole
•Ecstasy
•Ketamine
• salvia

31. Antidepressants or thymolytics
1. Tricyclics and Polycylics
•Imipramine, Amitryptyline, *Nortriptyline,
•* Desipramine, Trimipramine, Maprotiline
•Doxepine, * Amoxapine, Clomipramine,
•Dothepin, * Protriptyline

32. 2. SSRI
•Fluoxetine, Paroxetine
•Fluvoxamine,
•Sertraline, Nefazodone
•Venlafaxine, Citalopram

33. 3. MAOI:
•Phenelezine, Isocarboxazid
•Tranylcypromine
•Moclobamide – MAO – A I
•Selegiline – MAO – B I

4. Atypical
•Trazodone, Bupropion,
•mianserin, Tianeptine

34. TCAs and Polycyclic antidepressants
•MOA:
•inhibit reuptake of two monoamines, viz,
NA and serotonin.
1. The clinical benefits after 2-4 weeks.
2. Excess NA in the synaptic gap in the local
region, leads to down regulation of 
adrenoceptors.

35. 3. increased sensitivity for the 5HT receptors,
particularly 5HT1A receptor
4. beneficial effects on neurotrophic factors
5. Block many receptors, viz, adrenergic ,
muscarinic and histamine receptors -side
effects (eg, dry mouth, postural hypotension
etc).
this also in some unknown way to
relieve depression

36. PHARMACOLOGICAL EFFECTS
1. CNS
•In depression the mood is elevated but not in normal
persons
•Some TCAs - sedative effects
2. ANS
• Dry mouth, Difficulty in urination, constipation and
blurring of vision- all due to antimuscarnic effects.
1 adrenergic blockade action and can produce
postural hypertension.
•Anti histamine side effects

37. 3. CVS:
•Cardiac arrhythmia ( Increased NA)
•Postural hypotension - due to  blockade.
Pharmacokinetics
•Orally, well absorbed.
•Highly lipophilic enter brain and have a
long t1/2 as well as their Vd is large.
•Exhibits therapeutic window phenomenon

38. Clinical uses
1.Major depression
2. Panic disorders
3. Imipramine- Nocturnal enuresis
4. Chronic pain
5. Imipramine - Attention deficit disorder

39. Adverse effects
1.Aantimuscarinic effect, dry mouth, increased
intraocular pressure (IOP), urinary hesitancy
(specially in BPH), constipation
2. Epileptic fits
3. Weight gain
4. Low therapeutic index

40. 5. Slowing of cardiac conductivity, heart
block (specially in elderly), cardiac
arrhythmia, T wave inversion in ECG,
postural hypotension, tachycardia can
develop.
6. Acute poisoning:
Bicarbonate infusion, Physostigmine
Propranolol, Diazepam

41. SSRI
characteristics which distinguish from the
TCAs:
•Inhibit only the reuptake of serotonin
•Do not have blockade action of muscarinic,
 adrenergic and H1 receptors.

42. MOA
•Inhibition of serotonin reuptake - increased
serotonin in the local region  this relieves
depression.

43. Pharmacological effects of SSRIs
•Increased 5HT – relieves depression
 adrenergic, muscarinic, H1 receptor
blocking actions are absent. Side effects
do not appear.
•do not inhibit they NA reuptake. Hence no
signs of NA over activity and cardio
toxicity

44. Pharmacokinetics
•Well absorbed
•T½ is usually long
Clinical use
•Endogenous depression
•Obsessive-compulsive disorders

45. Adverse effects
•Anorexia, sexual hypo function, loss of libido,
anxiety and tremor.
Drug interaction
•Fluoxetine reduces the hepatic degradation of
TCAs  TCA toxicity
•Combination of MAOI and SSRI can produce
excess 5 HT level – serotonin syndrome
(hyperthermia, muscle rigidity and mental
deterioration)

47. MAOI
•MAO-A is found in the gut, liver and ANS
•MAO-B is found in the neurons of brain.
Actions of MAOI
•Antidepressant action requires 2-3 weeks to
appear
•Euphoric effect in normal persons

48. No Longer very popular:
•Increased storage of NA - manic state and or
hypertensive crisis.
•Cheese reactions: Old cheese , animal liver,
wine, fava beans, meat and many others in
tyramine
•Drug-drug interaction.
•Safer drugs are now available.

49. MOA:
•MAOIs bind with MAO irreversibly - NA, 5 HT
and DA accumulate
•Non-specific, both within the brain and
periphery.
•On stoppage of MAOI activity depends on
fresh synthesis of MAO
•cause mood elevation -in normal persons

50. Clinical uses
•Where SSRIs or TCAs cannot be used in
depression, eg, intolerance to these drugs.
•Not responding satisfactorily to SSRI or TCA
•Atypical depression (characterized by over-
eating, over-sleeping, weight gain etc)
•In some phobic states MAOIs can be used.

51. Adverse effects
•Cheese and allied foods rich in tyramine
hypertensive Crisis.
•Drug-drug interactions :
MAOI and SSRI
Levodopa +MAOI
Ephedrine containing drugs + MAOI-
Hypertensive crisis

52. Some individual Antidepressants
1.Imipramine - Desipramine is its active
metabolite
2. Amoxapine - Plasma t1/2 (8hrs).
blocks D2 R- neuroleptic action
Seizure is a special adverse effect
3. Fluoxetine - Active metabolite norfluoxetine.
SIADH – elderly.
used in recurrent depression.

53. 4. Mianserin atypical antidepressant
Increase release of NA by blocking
presynaptic 2 R .Cause blood dyscrasias
5. Bupropion atypical depressant
6. Venlafaxine - Strong 5 HT reuptake and
noradrenaline (SNRI)
Sedative, or no antimuscarinic

54. 7. Trazodone: less arrhythmia-elderly
8. Nefazodone: Congener of Trazodone:
Inhibits uptake of 5HT
9. Tianeptine: Increase 5 HT uptake.
10. Mirtazepine: blocks 2 auto (NA) and
hetero (5HT) – increase release of NA and
5HT.