before prescribing any drug you should know how does it work what is its effect and side effect to obtain the best result of medication

1. +
Introduction to
Psychopharmacology
Ismail Sadek
Mind and
Brain

2. +
Preview
Principles of Psychopharmacology
 Pharmacokinetics
 Pharmacodynamics
 Sites of Drug Action

3. +
Introduction
Psychopharmacology
The study of the effects of drugs on the
nervous system and behavior
Drug effects – the changes a drug
produces in an animal’s physiological
processes and behavior
Sites of action – the locations at which
molecules of drug interact with molecules
located on or in cells of the body, thus
affecting some biochemical processes of

4. +
Principles of Psychopharmacology
Pharmacokinetics
The process by which drugs are:
 absorbed,
distributed within the body,
metabolized, and
excreted.

5. +
Principles of Psychopharmacology
Routes of Administration
 Oral Administration – administration of a
substance into the mouth so that it is swallowed.
 Sublingual Administration – administration of
a substance by placing it beneath the tongue.

6. +Routes of Drug Administration
Oral Drug Administration
Advantages:
relatively safe, economical, convenient,
practical
Disadvantages:
Blood levels are difficult to predict due to
multiple factors that limit absorption.
Some drugs are destroyed by stomach
acids.
Some drugs irritate the GI system.

7. +
Principles of Psychopharmacology
 Routes of Administration
 Intravenous (IV) Injection – injection of a substance
directly into a vein.
 Drug enters bloodstream immediately and reaches the
brain in seconds

8. +
Principles of Psychopharmacology
 Routes of Administration
 Intraperitoneal (IP) Injection – injection of a substance
into the peritoneal cavity, the space that surrounds the
stomach, intestines, liver, and other abdominal organs.
 Most common route for small laboratory animals

9. +
Principles of Psychopharmacology
 Routes of Administration
 Intramuscular (IM) Injection – injection of a substance
into a muscle.

10. +
Principles of Psychopharmacology
 Routes of Administration
 Subcutaneous (SC) Injection – injection of a substance
into the space beneath the skin.

11. +
Principles of Psychopharmacology
Routes of Administration
Intrarectal Administration –
administration of a substance into the
rectum.
Inhalation – administration of a
vaporous substance into the lungs.
Topical Administration –
administration of a substance directly
onto the skin or mucous membrane.
Insufflation – sniffing drugs; contacts
mucous membranes of the nasal

12. +
Principles of Psychopharmacology
 Routes of Administration
 Intracerebral Administration – administration of a
substance directly into the brain.
 Intracerebroventricular (ICV) Administration –
administration of a substance into one of the cerebral
ventricles.

13. + Routes of Drug
AdministrationAdvantages of Injection Routes
 Absorption is more rapid than with oral
administration.
 Rate of absorption depends on blood flow to
particular tissue site (I.P. > I.M. > S.C.).
Advantages specific to I.V.
injection
 No absorption involved (inject directly into

14. + Routes of Drug Administration
Disadvantages/Risks of Injection
A rapid onset of action can be
dangerous in overdosing occurs.
If administered too fast, heart and
respiratory function could collapse.
Drugs insoluble in water or
dissolved in oily liquids can not be
given I.V.
Sterile techniques are necessary to
avoid the risk of infection.

15. +
Principles of Psychopharmacology
Distribution of Drugs Within the Body
Lipid Solubility – ease with drug molecules are
soluble in fat.
Heroin more lipid soluble than morphine so
gets to brain faster; more intense ”rush”
Depot Binding – binding of a drug with various
tissues of the body or with proteins in the blood.
If drug bound to depot cannot reach site of
action
Albumin – a protein found in the blood; serves
to transport free fatty acids and can bind with

16. +
Depot Binding with
Blood Albumin
Protein

17. +Drug Distribution
Cell Membranes
Capillaries
 Drug affinities for plasma proteins
 Bound molecules can’t cross capillary walls
Blood Brain Barrier
 Tight junctions in capillaries
 Less developed in infants
 Weaker in certain areas, e.g. area postrema in
brain stem
 Cerebral trauma can decrease integrity
Placenta
 Not a barrier to lipid soluble substances.

18. +Termination of Drug Action
Biotransformation (metabolism)
Liver microsomal enzymes in
hepatocytes transform drug molecules
into less lipid soluble by-products.
Cytochrome P450 enzyme family

19. +
Termination of Drug Action
Elimination
Two-stage kidney process (filter,
absorption)
Metabolites that are poorly reabsorbed by
kidney are excreted in urine.
Some drugs have active (lipid soluble)
metabolites that are reabsorbed into
circulation (e.g., pro-drugs)
Other routes of elimination: lungs, bile,
skin

20. +
Termination of Drug Action
Kidney Actions
excretes products of body metabolism
closely regulates body fluids and
electrolytes
The human adult kidney filters approx. 1
liter of plasma per minute, 99.9% of fluid
is reabsorbed.
Lipid soluble drugs are reabsorbed with
the water.

21. +
Termination of Drug Action
Factors Influencing Biotransformation
Genetic
Environmental (e.g., diet, nutrition)
Physiological differences (e.g., age,
gender differences in microsomal
enzyme systems)
Drug Interactions
Some drugs increase or decrease
enzyme activity
e.g., carbamazepine stimulates CYP-

22. +
REMEMBER
No drug
produces a

23. +
Pharmacodynamics
Drug actions at receptor sites and the
physiological/chemical/behavioral
effects produced by these actions:
Studies of drug mechanisms of action at
the molecular level
Provides basis for rational therapeutic
uses and the design of new, superior
therapeutic agents

24. +
Definitions
Efficacy
Degree to which a drug is able to produce
the desired response
Potency
Amount of drug required to produce 50%
of the maximal response the drug is
capable of inducing
Used to compare compounds within
classes of drugs

25. +
Principles of Psychopharmacology
 Dose-Response Curve – a graph of the
magnitude of an effect of a drug as a function of
the amount of drug administered.
Usually defined as mg of drug/Kg of body weight

26. +
Definitions
Effective dose 50% (ED50)
Dose of the drug which induces a
specified clinical effect in 50% of
subjects
Toxic Dose 50% (TD50)
Dose of the drug which induces toxic
effect in 50% of subjects

27. +Dose-Response Curves for Morphine

28. +
Principles of Psychopharmacology
Therapeutic Index – the ratio between
the dose that produces the desired effect
in 50% of the animals and the dose that
produces toxic effects in 50% of the
animals.
If toxic dose is 5 times higher than the
effective dose then the TI = 5
The lower the TI, the more care must be
taken in prescribing the drug

29. +
Principles of Psychopharmacology
Effects of Repeated Administration
 Tolerance – a decrease in the effectiveness of a
drug that is administered repeatedly.
 Withdrawal Symptom – the appearance of
symptoms opposite to those produced by a
drug when the drug is administered repeatedly
and then suddenly no longer taken.
 Sensitization – an increase in the effectiveness
of a drug that is administered repeatedly.

30. +
Sites of Drug Action
Most drugs that affect mental functions
affect synaptic transmission

31. Transmitter
Receptor

32. +Review of steps in synaptic
transmission Neurotransmitters are synthesized and stored in synaptic
vesicles
 Vesicles travel to presynaptic membrane and dock
 Axon fires and voltage-dependent calcium channels open
allowing calcium ions to enter
 Calcium ions interact with docking proteins causing release of
neurotransmitter into synaptic cleft
 Neurotransmitter binds to postsynaptic receptor, ion channels
open, PSPs produced
 Effects of neurotransmitter kept brief by reuptake or
enzymatic degradation


33. +Drug Affects on Synaptic Transmission

34. +
Sites of Drug Action
 Act on Neurotransmitters
 Enzymes control the synthesis of a neurotransmitter from
its precursors.
 Rate of synthesis and release can be increased by
administering the precursor
 The precursor serves as an agonist (step 1 in Figure
4.5)
 If a drug inactivates the enzymes it prevents the
neurotransmitter from being produced
 It serves as an antagonist (step 2 in Figure 4.5)

35. + Drug Affects on Synaptic Transmission

36. +
Sites of Drug Action
 Effects on Storage and Release of
Neurotransmitters
 Drugs may exert their agonistic or antagonistic effects by
influencing the storage and release of neurotransmitters.
 Some drugs can prevent the storage of neurotransmitter
in the vesicles – antagonists (step 3 in Figure 4.5)
 Some drugs can also prevent the release of
neurotransmitters by deactivating proteins that cause
synaptic vesicles to fuse with presynaptic membrane
(step 5 in Figure 4.5)
 Other drugs act as agonists by triggering the release of
neurotransmitter (step 4)

37. + Drug Affects on Synaptic Transmission

38. +
Sites of Drug Action
 Effects on Receptors
 Drugs may exert their agonistic or antagonistic effects by
influencing receptors.
 Direct Agonist – a drug that binds with and activates a
receptor; mimics the effects of a neurotransmitter (step 6
in Figure 4.5).
 Direct Antagonist – a drug that binds with a receptor
but does not activate it; prevents the natural ligand from
binding with the receptor; also called receptor blocker
(step 7 in Figure 4.5).

39. + Drug Affects on Synaptic Transmission

40. +
Sites of Drug Action
 Noncompetitive Binding – binding of a drug to a site on a
receptor; does not interfere with the binding site for the
principal ligand.
 Indirect Antagonist – a drug that attaches to a binding site
on a receptor and interferes with the action of the receptor;
does not interfere with the binding site for the principal
ligand.
 Indirect Agonist – a drug that attaches to a binding site on
a receptor and facilitates the action of the receptor; does
not interfere with the binding site for the principal ligand.

41. + Drug Actions at Binding Sites

42. +
Sites of Drug Action
 Autoreceptors – regulate the amount of
neurotransmitter released
 Drugs that activate these receptors serve as antagonists,
decreasing the amount of neurotransmitter released (step
8 in Figure 4.5)
 Drugs that block the presynaptic autoreceptors increase
the release of neurotransmitter (step 9 in Figure 4.5)

43. + Dendritic Autoreceptors

44. + Drug Affects on Synaptic Transmission

45. +
Sites of Drug Action
 Some terminal buttons form axoaxonic synpases
 Presynaptic Heteroreceptor – a receptor located in the
membrane of a terminal button that receives input from
another terminal button by means of an axoaxonic
synapse; binds with the neurotransmitter released by the
presynaptic terminal button.

46. + Presynaptic Heteroreceptors

47. +
Sites of Drug Action
 Effects on Reuptake or Destruction of
Neurotransmitters
 Drugs can attach to transporter molecules responsible for
reuptake and inactivate them
 Drugs can bind with the enzyme that normally destroys the
neurotransmitter and prevent it from working
 Both types of drugs prolong the presence the
neurotransmitter in the synaptic cleft – agonists (steps 10
and 11 in Figure 4.5).

48. + Drug Affects on Synaptic Transmission

49. + 49
Receptors
Receptors are a target molecule that a drug
molecule has to combine with to produce a
specific effect
Receptors must be compatible.

50. +
Actions at Receptors
 Agonist: binds to receptors and produces pharmacological
action.
 Antagonist: binds to receptors but produces no
pharmacological action
Partial agonists It is possible to produce signal
transduction that is something more than an antagonist yet
something less than a full agonist.
Inverse agonists Inverse agonists are more than simple
antagonists.These agents have an action that is thought to
produce a conformational change in the G-protein linked
receptor that stabilizes it in a totally inactive form.
Binding or localization in the Brain

51. +
Agonist and antagonist interactions with
receptors

52. + A drug binds to a receptor…Then what?
Intracellular action: promotes synthesis or release of an
intracellular regulatory molecule - second messenger.

53. +
Cell Nucleus

54. +
A complex
cascade of
changes
amplify the
effects of the
receptor
within the
neuron.

55. + 55
Types of receptors
 G-protein-couple receptors, seconds
e.g. Muscarinic ACh receptors, adrenoceptors,
histamine receptors
 Kinase linked receptors, hours
e.g. Insulin, Growth factor
 Nuclear intracellullar receptors, hours
e.g. steroid, thyroid hormone

56. + 56
Ion Channels
 Drugs act to affect cellular gating mechanism in
cell wall
Ligand-gated ion channels, milliseconds
e.g GABA benzodiazepines, Nicotinic ACh
Carrier molecules
 Drugs act on carrier transporters which allow
molecules, not lipid soluble to cross cell
membrane

57. +
General Pharmacology
strategies
Indication: Establish a diagnosis and identify the target
symptoms that will be used to monitor therapy response.
Choice of agent and dosage: Select an agent with an
acceptable side effect profile and use the lowest effective
dose. Remember the delayed response for many psych meds
and drug-drug interactions.

58. +
Establish informed consent:The patient
should understand the benefits and risks of
the medication. Make sure to document this
discussion including pt understanding and
agreement. In fertile women make sure to
document teratogenicity discussion.
Implement a monitoring program:Track
and document compliance, side effects,
target symptom response, blood levels and
blood tests as appropriate.

59. +
 Management: Adjust dosage for optimum benefit, safety and
compliance. Use adjunctive and combination therapies if
needed however always strive for the simplest regimen.
Keep your therapeutic endpoint in mind.