1. PSYCHOPHARMACOLOGY Dr.Sujit Kumar Kar, MD Lecturer
Department of Psychiatry
King George’s Medical University
Lucknow, U.P

3. 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)

4. 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

5. Drug Effectiveness
Dose-response (DR) curve: Depicts the relation between drug dose and magnitude of drug effect
Drugs can have more than one effect
Drugs vary in effectiveness
Different sites of action
Different affinities for receptors
The effectiveness of a drug is considered relative to its safety (therapeutic index)

8. 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

9. 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

10. Synaptic Transmission
Transmitter 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

11. Drug Action on Synaptic Transmission
Agonist
Antagonists

12. Presynaptic Drug Actions
Presynaptic autoreceptors regulate the amount of NT released from the axon terminal
Drugs that activate presynaptic autoreceptors reduce the amount of NT released, an antagonistic action
Drugs that inactivate presynaptic autoreceptors increase the amount of NT released, an agonistic action
Presynaptic heteroreceptors are sensitive to NT released by another neuron, can be inhibitory or facilitatory

13. Neuromodulators
Neurotransmitter binding to receptors produces either EPSPs or IPSPs
Glutamate produces EPSPs
GABA produces IPSPs
Neuromodulators alter the action of systems of neurons that transmit information using either glutamate or GABA

14. Objectives Classification of psychotropic medications.
Mechanism of action of psychotropic medications.
Choose a psychotropic medication rationally.
Know common & dangerous adverse effects.
Manage failure of response to a therapeutic trial.

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

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

18. Psychopharmacologic Drugs Work over A Spectrum
Antipsychotics
Mood stabilizing agents
Others
Anxiolytics/sedatives
Antidepressants

19. General principles about adverse effects
Psychopharmacological agents affect the whole body.
Remember the common and dangerous side effects.
They indicate the drug is working.

20. Antipsychotics

22. 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

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

30. 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 ( mg/d)
Imipramine( mg/d)

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

36. Potential Adverse Effects of Antidepressant Therapy
Slide 16
Central Nervous System
Dizziness, cognitive impairment,
sedation, light-headedness,
somnolence, nervousness,
insomnia, headache, tremor, changes in satiety and appetite
Cardiac
Orthostasis
hypertension
heart block, tachycardia
Gastrointestinal
Nausea, constipation,
vomiting, dyspepsia,
diarrhea
Urogenital
Erectile dysfunction,
ejaculation disorder,
anorgasmia, priapism
Autonomic Nervous System
Dry mouth, urinary retention,
blurred vision, sweating
4/17/2017

37. 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

39. 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.

40. Common Mood Stabilizers
Carbamazepine
Valproic Acid
Lithium
Therapeutic Level
4-12 mg/ml
mg/ml
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)

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

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

43. 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).

44. Prescribing a Psychotropic Agent After Diagnostic Assessment
Choose a medication based on FDA approval
Family or personal hx of response
Adverse effects vs. key symptoms
Starting dose
Monitor side effects & clinical response
Adjust dose if needed

45. 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?

46. Thank you