psychopharmacology

1. GENERAL PRINCIPLES OF
PSYCHOPHARMACOLOGY
Dr Salman Kareem
1st yr Resident
Department of Psychiatry

2. PSYCHOPHARMACOLOGY
 Psychopharmacology:
 The study of the effects of drugs on the nervous system and
on behavior.
 Drug effects:
 The changes a drug produces in patient‟s physiological
processes and behavior.
 Sites of Action:
 The locations at which molecules of drugs interact with
molecules located on or in cells of the body, thus affecting
some biochemical processes of these cells.

3. CLASSIFICATION
 Structure- Tricyclics
 Mechanism of Action – MAOI
 History – First generation, traditional.
 Uniqueness – atypical antipsychotics
 Major clinical applications
 Anti depressent
 Anti psychotics
 anxiolytics

4. PHARAMCOLOGICAL ACTIONS

5. PHARMACODYNAMICS
 What the body does to the drug
 Receptor mechanism
 Dose response curve
 Therapeutic index
 Development of tolerance
 Dependence
 Withdrawal phenomenon

6. MECHANISM
• Four sites of action
o Receptors (those sites to which a
neurotransmitter can specifically adhere to
produce a change in the cell membranes)
o Ion channels
o Enzymes
o Carrier Proteins
• Biologic action depends on how
its structure interacts with a
receptor

7. Neurotransmitters Go
through 7 steps
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)

9. RECEPTORS
• Types of Action
o Agonist: same biologic action eg benzodiazepines act
benzodiazepine recognition site in the benzodiazepine
GABA receptor complex
o Antagonist: opposite effect eg Flumazenil
o Partial Agonist :Buprenorphine
o Inverse agonist
• Interactions with a receptor
o Selectivity: specific for a receptor
o Affinity: degree of attraction
o Intrinsic activity: ability to produce a biologic response
once it is attached to receptor
o Medications treating anti psychotics - blocks dopamine 2
receptors

10. MECHANISM
 Poorly understood
 Drugs alter synaptic concentration of dopamine,
serotonin, nor epinephrine , histamine, gamma
amino butyric acid or acetylcholine
 Results from
 Receptor agonist, antagonist
 Interference with neurotransmitter uptake

11. ION CHANNELS
• Drugs can block or
open the ion channels
• Example:
benzodiazepine drugs
facilitate GABA in
opening the chloride
ion channel

12. ENZYMES
• Enzymes catalyze specific biochemical reactions
within cells and are targets for some drugs
• Monoamine oxidase is an enzyme that breaks down
most bioamine neurotransmitters (NE, DA, 5-HT)
• Enzymes may be inhibited to produce greater
neurotransmitter effect.
• Eg Lithium binds directly to enzyme inositol 1
phosphatase

13. CARRIER PROTEINS
• Transport neurotransmitters
across cell membranes
• Medications may block or
inhibit this transport
• Example: antidepressants
(SSRI) on serotonin
transporter protein
/

14. SIDE EFFECTS
 Unavoidable risks of medical treatment
 Probability of its occurence
 Impact on quality of life
 Cause

15.  TCA‟s – most common side effect caused by
blockade of muscarinic acetylcholine receptors or
histamine 2 receptors.
 SSRI‟s serotonion reuptake – cause nausea and
sexual dysfunction
 Anti psychotics – D2 blockage of drugs – Extra
pyramidal side effects.
 Benzodiazepine – agnostic action ataxia and
daytime sleepiness.

16.  Time course
adverse effects differ in terms of time of onset and
duration . Some appears ate the end of the
treatment
Nausea occuring with SSRI‟s or venlaxafine eg
Sedation occuring with mirtazapine of
onset
Long term complications – Dopamine and other
Dopamine receptor antagonists – Tardive
Dyskinesia

17. MOST COMMON SIDE EFFECTS
 Somnolence - desirable adverse effect
 GI Disturbances - Sertraline most likely to cause
loose stools, Fluvoxamine most likely to cause
nausea
 Movement disorder
 Sexual dysfunction – most commonly associated
with the use of SSRI.
 Weight gain - atypical antipsychotics bec. of
disturbance in glucose and insulin metabolism

18. SIDE EFFECTS
 Glucose changes- atypical antipsychotics because
of disturbance in glucose and insulin metabolism
 Hyponatremia – elderly patients more common by
oxcarbamazepine
 Cognitive impairment
 Sweating
 Cardiovascular
 Rash
 Urinary retention

19. POTENTIAL ADVERSE EFFECTS OF
ANTIDEPRESSANT THERAPY
10/5/2012
Central Nervous System
Cardiac
Dizziness, cognitive impairment,
Orthostasis
sedation, light-headedness,
19
hypertension
somnolence, nervousness,
heart block,
insomnia, headache, tremor,
tachycardia
changes in satiety and appetite
Gastrointestinal
Nausea, constipation,
Urogenital
vomiting, dyspepsia,
Erectile dysfunction, diarrhea
ejaculation disorder,
anorgasmia, Autonomic Nervous System
priapism Dry mouth, urinary retention,
blurred vision, sweating

20. IDIOSYNCRANTIC AND
PARADOXICAL RESPONSE
 When a patient expresses particularly unusual or
rare effects from a drug
 Eg some patients may be agitated when given a
benzodiazepine
 Spontaneous orgasm instead of anorgasmia
 Behavioural disinhibition - benzodiazepines

21. SAFETY
 Therapeutic index relative measurement of toxicity
or safety of a drug and is defined as ratio of median
toxic dose to median effective dose.
 High therapeutic index: wide range between
dose at which the drug begins to take effect and
dose that would be considered toxic eg SSRI
 Low therapeutic index: low range eg LITHIUM

22. OVERDOSE
 Newer drugs have a wide margin of safety.
 Safest drug can have severe medical complication
especially when combined with other drugs
Suicide is a major concern
Attempt made to verify that the medicine is not
hoarded.
Random pill container
Asking family members to dispense daily might be
helpful.
Possible of accident ingestion of medication by
children in household.

23. PHARMACOKINETIC
ACTION
 What the body does to the drug
 Time course of drug concentration in different
parts of the body such as plasma , adipose
tissue and CNs.
 Explains or predicts the onset and duration of
drug activity and intention between drugs that
alter their metabolism or excretion.

24. ABSORPTION
• From site of administration into the plasma
• Oral - (tablet and liquid)
o Most Convenient
o Most variable (food and antacids)
 First pass effect
 Decreased gastric motility (age, disease, medication)
• IM - Short-and long acting
• IV - Rarely used outside hospital

25. BIOAVAILABILITY
• Amount of drug that reaches systemic circulation
unchanged
• Often used to compare one drug to another, usually
the higher the bioavailability, the better

26. DISTRIBUTION
• Amount of drug found in various tissues,
especially the intended ones
• Psychiatric drugs must pass through blood-brain
barrier (most fat-soluble)
• Factors effecting distribution
o Size of organ (larger requires more)
o Blood flow (more, greater concentration)
o Solubility (greater, more concentration)
o Plasma protein (if bound, slower distribution, stays in body
longer)
o Anatomic barriers (tissues surrounding)

27. CROSSING THE BLOOD BRAIN
BARRIER
• Passive diffusion
o Drug must dissolve in the structure of the cell
o Lipid solubility is necessary for drugs passing through
blood brain barrier (then, can also pass through
placenta)
• Binding to other molecules
o Plasma protein binding
o The more protein binding, the less drug activity.
o Can bind to other cells, especially fat cells. Then are
released when blood level decreases.
Image Source Page: http://www.nanowerk.com/spotlight/spotid=19339.php

28. METABOLISM
• Process by which the drug is altered and broken
down into smaller substances (metabolites) that are
usually inactive.
• Lipid-soluble drugs become more water soluble, so
they may be more readily excreted.
• Most metabolism is carried out in the liver

29. CYTOCHROME P450 (CYP)
Largest class of enzymes catalyzing oxidation of
organic substances in all living things
• 11,550+ identified ; 57 in humans
• High affinity for fat-soluble drugs
• Involved in metabolism of most psychiatric medications
• Inactivate drugs (or in some cases activate them)
• Chemicals may increase or decrease CYP activity
• Example:
o SSRIs inhibitors of the subfamily CYP2D6
o Compounds in grapefruit juice inhibit CYP3A4
o Tobacco induces CYP1A2

30. ELIMINATION
• Clearance: Total amount of blood, serum, or
plasma from which a drug is completely
removed per unit time
• Half-life: Time required for plasma
concentrations of the drug to be reduced by 50%
• Only a few drugs eliminated by kidneys (lithium)
• Most excreted via the liver
o excreted in the bile and delivered to the intestine
o may be reabsorbed in intestine and “re-circulate” (up
to 20%)
o BILE, FECES, and URINE are major routes of
excretion.

31. SUCCESS OF MEDICATIONS
 Patient related factors
 Diagnosis
 Past history of diagnosis
 Concurrent medical disorder
 Lifestyle
 Overall medical stats
 Genetic factor

32.  Diagnosis
 failure to diagnose a disorder diminishes the
likelihood of optimal drug selection.
 Produces worsening of symptoms
 Treatment failure for exacerbation of symptoms
should promp a reassesment of diagnosis
 Post treatment response
 Response in faulty members

33.  Concurrent medical / psychiatric illness
 Thyroid disease not adequately treated
 Sleep apnea produces depression and cognitive
impairment.
 Kleine levin syndrome – mimics bipolar disorder
 Recreational drug, alcohol consumption and frequent
consumption of coffee can undermine psychotropic drug
treatment.

34. DOSING AND STEADY STATE
• Dosing: Administration of
medication over time, so that
therapeutic levels can be
achieved.
• Steady-state:
o drug accumulates and plateaus
at a particular level
o rate of accumulation determined
by half life
o reach steady state in about five
times the elimination half-life

35.  Duration
 varies
 High rates of chronicity and relapse
 Therapeutic trial
 Continuation therapy
 Frequency of visits
 Determined by clinical judgment.
 Maintenance therapy needs monitoring.

36. TREATMENT OUTCOMES
 Remission
 Degree of improvement to below the syndromal
threshold is defined as remission.
 Response
 50 percent or greater decrease from baseline on a
standard rating scale.
 Treatment failure
 Anticipate
 Prompt reassesment
 Intolerance to side effects
 Appropriate dosage for sufficient for a length of time?
 Drug non compliance

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

38. TREATMENT RESISTANCE
 Some patients fail to respond to repeated trials of
medication.
 Tolerance
 Marked by a need, over time , to use increased
doses of drug for it to maintain a clinical effect.
 Decreased responsiveness occurs after
repeated doses.
 Sensitization
 Reverse of tolerance
 Sensitivity to a drug effect increases over time.

39.  Withdrawal
 Development of physiological adaptation of a
drug
 „side effect‟
 More abruptly it is stopped and the shorter its
elimination half life more likely the clinically
significant withdrawal symptoms occur
 Gradual tapering of medication.
 Benzodiazepines, SSRI (paroxetine)

40. COMBINATION OF DRUGS
 “use of mutiple drugs should be avoided as
possible”
 When two psychotropics drugs with the same
approved indications are used concurrently , this is
termed as combination therapy.
 Adding another drug with another indication is
termed as augmentation.
 Almost all patients with bipolar disorder take more
than one psychotropic agent.
 Medications are also given to counteract the side
effects , to treat specific symptoms and as a
temporary measure to transition from one drug to
another.

41. SPECIAL POPULATION
 Children
 high metabolism, low – slow, /kg
 Pregnant and nursing women
 Avoid administering in them unless the psychiatric
disorder is severe.
 Paroxetine – FDA warning – cardiac malformation.
 Lithium – ebstein‟s anomaly
 Carbamazepine, valproic acid – neural tube defects.
 Lamotrigine – oral clefts.
 Psychotherapeutic drugs – overly sedated at delivery
 ECT is good

42.  Elderly patients –
 more susceptible to adverse effects and may metabolize
and excrete drugs more slowly.
 low metabolism , 1/3 adult dose, drug interaction and
medical state
 Medically ill patients
 Medical disorder should be ruled out as a cause of
psychiatric symptoms
 Taking other medications can result in pharmacodynamic
and pharmacokinetic interaction
 Potentially increased sensitivity to adverse effects
including increased or decreased metabolism and
excretion of the drug.

43. NON APPROVED DOSAGES AND USES
 Treat psychiatric disorders with drugs that are
approved for non psychiatric conditions.
 Propanolol – social anxiety and lithium induced
tremor
 Verapamil for mania and treatment of MAOI
induced hypertensive crisis.
 Clonidine and guanificine for ADHD and PTSD.
 Levothyroxine for antidepressent augmentation

44. BLACK BOX WARNING
 Prescribing information sometimes contains a black
box warning to warn physicians about potentially
important safety information
 Strongest warning – more serious than just bolded
text

45. THANK YOU