Psychophramacology

1. Dr Kamal Narayan Kalita

2. Psychopharmacology
Psychopharmacology is the study of the effects of
drugs on affect, cognition, and behavior
The term drug has many meanings:
 Medication to treat a disease
 A chemical that is likely to be abused
 An “exogenous” chemical that significantly alters the
function of certain bodily cells when taken in relatively low
doses (chemical is not required for normal cellular
functioning)

3.  The term "psychopharmaceutical" first appeared
in 1548 in the title to a collection of prayers of
consolation, and prayers for the dead, called:
"psychopharmakon, hoc est: medicina animae."
 The term here related to spiritual medicine, which
was to be used in miserable and hopeless
situations in life.
 The word "pharmakos" originally meant
scapegoat; a pharmakos was a person who was
sacrificed as a remedy for whatever maladies
another person might have been experiencing.
Around 600 BC the term came to refer to
medicine, drug or poison

4.  Naturally occurring psychoactive agents are
fundamental to most cultures and the routine use of
stimulants and depressants is so pervasive in most
societies that most of us don't even consider such
substances to be drugs, but rather an actual nutrient.
Indeed, the border between drug and nutrient is
blurring.
 How many people can get through the day without the
assistance of the “natural drugs” coffee, tea, tobacco,
alcohol, cocoa, or their illegal cousins marijuana,
cocaine, or heroin?

6. Our ancestors were very aware of these properties and
sought them out for remedies for a variety of illnesses.
The use of plant and synthetic products as medicine is but
one in a long line of revolutions that occurred to alter
culture and the way we view drugs.

7. The first revolution:
-- treatment of communicable diseases.
Pasteur and Koch (19th century) developed vaccines
against measles and other disorders.
This introduced us to drug taking on a large scale.

8. The second pharmacological revolution resulted
from the evolution of sulpha drugs: penicillin, and the
broad spectrum antibiotic agents.
The third pharmacological revolution was the
advent of tranquilizers for the treatment of the
mentally ill (1950's).
First time that compounds were widely used for their
effect on the mind and not on the body.

9. The fourth pharmacological revolution is still in progress.
Development of oral contraceptives. Their impact cannot yet
be predicted.
The most important point - for the first time, potent chemicals
are being widely used by healthy people because of their social
convenience.
The evolution of our view of drugs that affect the brain
continues with the introduction of cognitive enhancing drugs
and neuroprotectants.

10. 4 basic principles
First: drugs per se are not "good" or "bad". When drug abuse
is talked about, it is the behavior, the way the drug is being
used, that is being referred to as bad. Drugs are simply
chemicals!
Second: every drug has multiple effects, they act in many
different areas of the brain and may have different effects than
intended.
Third: the effects of a drug depend on the amount taken.
Varying doses can change the magnitude and the character
of the drug effect. This is called a dose-response effect.
Fourth: (possibly the most difficult to document) the
effects depend in part on the individual's history and
expectations of the drug taking experience.

11. Principles of Drug Action

12. Pharmacokinetics
Drug molecules interact with target sites to effect
the nervous system
The drug must be absorbed into the bloodstream and
then carried to the target site(s)
Pharmacokinetics is the study of drug absorption,
distribution within body, and drug elimination
 Absorption depends on the route of administration
 Drug distribution depends on how soluble the drug
molecule is in fat (to pass through membranes) and on
the extent to which the drug binds to blood proteins
(albumin)
 Drug elimination is accomplished by excretion into
urine and/or by inactivation by enzymes in the liver

13. Routes of Drug
Administration
Routes of drug administration into the body
 Intravenous (IV): into a vein (rapid absorption)
 Intraperitoneal (IP): into the gut (used in lab animals)
 Subcutaneous (SC): under the skin
 Intramuscular (IM): into a muscle
 Inhalation of the drug into the lungs
 Topical: absorbed through the skin
 Oral (PO): via the mouth

16. Tolerance and Sensitization
Repeated administration of a drug can alter its
subsequent effectiveness
Tolerance: Repeated drug administration results in
diminished drug effect (or requires increased dosage to
maintain constant effect)
 Withdrawal effects are often the opposite of the drug effect
and often accompanies tolerance
 Tolerance can reflect decreased drug-receptor binding or
reduced postsynaptic action of the drug
Sensitization: Repeated drug administration results in
heightened drug effectiveness

17. Pharmacodynamics
Synaptic TransmissionTransmitter substances are
Synthesized, stored, released, and terminated
Susceptible to drug manipulation
Definitions:
Direct agonist: a drug that binds to and activates a
receptor
Antagonist: a drug that binds to but does not activate a
receptor
Indirect antagonists are drugs that interfere with the normal
action of a neurotransmitter without binding to its receptor
site

18. Drug Action on Synaptic
Transmission
 Agonist
 Antagon
ists

19. Why Medications ?
Dopaminergic theory of Schizophrenia
Monoaminergic theory of Mood Disorders

20. 1. Synthesis
2. Storage
3. Enzymatic destruction if not stored
4. Exocytosis
5. Termination of release via binding with autorecptors
6. Binding to receptors
7. Inactivated
Drugs are developed that address these actions as an
AGONIST (mimic the NT ) or ANTAGONIST (block
the NT)
Neurotransmitters Go
through 7 steps

22. Psychopharmacologic Drugs
Work over A Spectrum
Antipsychotics
Mood stabilizing agents
OthersAnxiolytics/sedatives
Antidepressants

23. General principles about adverse effects
 Psychopharmacological agents affect the whole body.
 Remember the common and dangerous side effects.

26. Antipsychotics Treat psychotic symptoms.
 Divided into:
Typical/1st generation = D2 receptor antagonist
Effective against +ve > -ve
Atypicals/2nd generation = Serotonin-dopamine antagonists
Effective against both +ve & -ve sx
 Requires ~ one month for significant antipsychotic effect

28. Antipsychotics
Average Daily Doses in mg
Typicals
Haloperidol (5-15)
Thioridazine(100-300)
Chlorpormazine (50-400)
Atypicals
Risperidone (4-8)
Olanzapine (10-20)
Quetiapine (600-1200)
Clozapine (100-600)
Lower numbers indicate higher potency

34. Antidepressants
 Used in many psychiatric disorders other than Depression.
 Full clinical response in 6-8 weeks in major depression, up
to 6/12 in obsessive compulsive disorder.
Examples:
Fluoxetine & Paroxetine (20-60 mg/d)
Fluovoxamine & Sertraline (50-200 mg/d)
Imipramine(200-300 mg/d)

36. THREE PHASES OF TREATMENT
Time
Normal
Acute
Phase (3 months+)
Continuation
Phase (6-12 months)
Maintenance
Phase (years)
Response
Remission
Relapse
Relapse Recurrence
> 50%
STOP
Rx
65 to 70%
STOP
Rx
Recovery

40. Potential Adverse Effects of
Antidepressant Therapy
2/5/2016 40
Cardiac
Orthostasis
hypertension
heart block,
tachycardia
Urogenital
Erectile dysfunction,
ejaculation disorder,
anorgasmia,
priapism
Central Nervous System
Dizziness, cognitive impairment,
sedation, light-headedness,
somnolence, nervousness,
insomnia, headache, tremor,
changes in satiety and appetite
Gastrointestinal
Nausea, constipation,
vomiting, dyspepsia,
diarrhea
Autonomic Nervous System
Dry mouth, urinary retention,
blurred vision, sweating

41. Antidepressants and the Cytochrome P450
System
 Antidepressants and mood stabilizers may be
inhibitors, inducers or substrates of one or more
cytochrome P450 isoenzymes
 Knowledge of their P450 profile is useful in
predicting drug-drug interactions
 When some isoenzymes are absent of inhibited,
others may offer a secondary metabolic pathway
 P450 1A2, 2C (subfamily), 2D6 and 3A4 are
especially important to antidepressant metabolism
and drug-drug interactions

43. Mood Stabilizers
 Lithium, Valproic acid, Carbamazepine, Lamotrigine,
Gabapentine, Topiramate.
 Used in the treatment of Bipolar affective disorder and
similar conditions associated with impulsivity.
 Drug level measurements are available for many of them.
 Mechanism of action is not clearly understod.

44. Common Mood Stabilizers
Carbamazepine Valproic Acid Lithium
Therapeutic Level
4-12 mg/ml
40-100 mg/ml 0.5-1.2 mEq/L
Common S/E
Dizziness, sedation,
ataxia, leukopenia,
rash,
nausea, diarrhea,
ataxia, dysarthria,
weight gain, slight
elevation of hepatic
transaminases
nausea,
hypothyroidism,
tremors, dysarthria,
ataxia
Dangerous S/E
Agranulocytosis,
teratogenicity (neural
tube defect), induction
of hepatic metabolism
teratogenic (neural
tube defects)
sinus node
dysfunction, T-wave
changes,
teratogenic (cardiac
anomalies)

45. Anxiolytics/sedatives
 Benzodiazepines, Trazodone, Zolpidem and others
 Alprazolam, clonazepam, lorazepam, diazepam.
 Risk of dependence & withdrawal.

46. Other pharmacological agents
Cholinesterase inhibitors:
Donepezil, Rivastigmine, Galantamine, (Tacrine has been
withdrawn)
Sympathomimetics:
Methylphenidate, Dextroamphetamine.
Anticholinergic agents:
Procyclidine, Benztropine

47. Dangerous Side Effects
Hypertensive crisis
Associated with MAOIs.
Neuroleptic malignant syndrome
Autonomic instability, severe EPS, delirium, ↑CK, ARF, myoglobulinuria
Serotonin syndrome
Restlessness, myoclonus, ↑reflexes, tremors, confusion.
Due to combination of serotenergic agents
Agranulocytosis
( Clozapine, carbamazepine).

48. Prescribing a Psychotropic Agent
After Diagnostic Assessment
• Choose a relatively safer medication as per EBM
• Family or personal hx of response
• Adverse effects vs. key symptoms
• Starting dose
• Monitor side effects & clinical response
• Adjust dose if needed

49. Failure of Response
What to do?
 Check Compliance & availability
 Review the diagnosis
 Is the dose appropriate?
 Is the duration of treatment long enough?
 Any ongoing substance abuse?
 Other drugs/preparation causing drug-drug Interaction?
 Individual Variation?

50. Thank you