Psychopharmacology

⚫ Psychopharmacology is important field of

PRINCIPLES OF Neuroscience. It is relevant with the study
PYSCHOPHARMACHOLOGY of the effects of drugs on affect, cognition,
and behavior.
DR. SHAZIA HABIB ⚫ This field is responsible for the development
ASSISTANT PROFESSOR
DEPARTMENT OF APPLIED PSYCHOLOGY
of psychotherapeutic drugs used to treat
GCUF various psychological and behavioral
disorders

4.2

⚫ Thechemicals of interest here are those The term drug has many meanings:
which alter the functions of cells within ⚫ Medication to treat a disease
the nervous system. ⚫ 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)

Drugs
 ⚫ Drug effects: Changes that we observe in
⚫ Chemical messengers produced by the human physiological processes and
body are not drugs’ while synthetic behavior due to use or abuse of a drug
chemicals that mimic their effects are e.g. effect of morphine or heroin----
classified as drugs (sedation, muscle relaxation, euphoria
⚫ Essential nutrients (proteins, fats, etc)
carbohydrates, minerals and vitamins) are ⚫ Site of Action: Are the point at which
necessary constituents of healthy diet molecules of drugs interact with molecules
⚫ Effective in low doses because large located on or in the cell body and effect
quantity of every substance will somehow some biochemical process of these cells
alter the function of the cell e.g. molecules of opiates and their specific
receptors in the membrane of certain
Drnuegureffsects and site of action
on

Pharmacokinetics
a. Pharmacokinetics (movement of drugs)
b. Pharmacodynamics
⚫ Drug molecules interact with target sites to
Pharmacodynamics is the study of how a effect the nervous system
drug effects an organism and their ◦ The drug must be absorbed into the bloodstream
mechanism and then carried to the target site(s)
⚫ Pharmacokinetics is the study of drug
Pharmacokinetics is the study of how the absorption, distribution within body,
organism effects the drug. metabolized and drug elimination
⚫ Both together influence dosing, benefit, ◦ Absorption depends on the route of administration
◦ Drug distribution depends on how soluble the drug
and adverse effects. molecule is in fat (to pass through membranes) and
on the extent to which the drug binds to blood
proteins (albumin)
Principles of ◦ Drug elimination is accomplished by excretion into
psychopharmachology urine and/or by inactivation by enzymes in the liver
4.8
⚫ Drugs vary widely in their effectiveness Drug Effectiveness

⚫A small dose of a relatively effective drug ⚫ Dose-response (DR)

can equal or exceed the effects of larger curve:
⚫ Depicts the relation between
amount of a relatively ineffective drug. drug dose and magnitude of
drug effect
⚫ Wayto measure the effectiveness of the ⚫ Drugs can have more than
one effect e.g. opiates such
drug is dose- response curve. as morphine and codeine
produces analgesia along
with high dose depressing
the activity of neurons in
medulla (side effects)
Drug effectiveness
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⚫ The effectiveness of a drug is considered relative ⚫ For example if the toxic dosage is five times
to its safety higher than the effective dose, the TI is 5.0.

⚫ Therapeutic index: is one of the measure of a ⚫ The lower the TI, the more care/caution must be
drug’s margin of safety. taken in prescribing the drug. e.g. TI of
⚫ The therapeutic index of a drug is the ratio of the barbiturates is low as 2 or 3 while tranquilizers
lethal dose to the effective dose (Librium or Valium) has TI well over 100
⚫ Obtained by two numbers
TI= drug dosage producing the desired effect in ⚫ The larger the therapeutic index, the safer the
50% of subjects : drug dosage producing toxic drug is.
effects in 50 % of the subjects
⚫ Think about consequences of over dosage of
barbiturate?????
Drug effectiveness Drug effectiveness
⚫ The larger value of TI indicates that there Drugs vary in effectiveness
is a wide margin between the toxic and a. Different sites of action:
effective dose, whereas a smaller value (e.g. though having same analgesic effects
indicates that there is a narrow margin (pain relieving effects) a given dose of
between the effective and toxic dose. morphine produces much more pain
⚫ In case of drugs that have a low TI, even reduction than the same dosage of aspirin)
a small increase in the dosage can
produce toxic effects among patients. Morphine and aspirin both have analgesic
effects

Drug effectiveness

b. Different affinities for receptors: ⚫ The most desirable drug has a high
Drugs vary widely in their affinity for the affinity for sites of action that produces
molecules to which they attach - the therapeutic effects and a low affinity for
readiness with which the two molecules join the sites of action that produces toxic side
together. A drug with high affinity will effects
produce effects at a relatively low dose,
whereas one with a low affinity must be
administered in high doses.

Drug effectiveness Drug effectiveness

 ⚫ Tolerance: Repeated drug administration results
❖ If drugs are repeatedly administered the
in diminished drug effect (or requires increased
effects will not remain constant.
dosage to maintain similar/ constant effects)
❖ Repeated administration of a drug can ⚫ Tolerance can reflect decreased drug-receptor
alter its subsequent effectiveness binding or reduced postsynaptic action of the
drug
⚫ Withdrawal effects are often the opposite of the
drug effect itself and often accompanies
tolerance. When we stop taking drug after its
prolonged and high usage to acquire desired
effects e.g. heroin usually produces euphoria
withdrawal from it produces dysphoria
Effects of repeated administration

Tolerance & Withdrawal

⚫ Sensitization:It is opposite of tolerance. ⚫ Placebois an innocuous substance that

Repeated drug administration results in has no specific side effects.
heightened drug effectiveness and drug
produces larger and larger effects. Like in
drug addiction.

Sensitization Placebo Effects

 Routes of Drug Administration ⚫ Intramuscular (IM): into a large muscle
Routes of drug administration into the body (upper arm, thigh or a buttocks)
⚫ Intravenous (IV): into a vein---blood ➢ Drug initially absorbed into blood stream
stream---brain in few sec (rapid through capillaries that supply it to
absorption). E.g. injections in veins muscles, role of drug (ephedrine) for slow
absorption.
◦ Intraperitoneal (IP): into the gut (abdominal wall
into peritoneal cavity) (used in lab animals)
⚫ Inhalationof the drug into the lungs
◦ Subcutaneous (SC): under the skin (when small (Nicotine, cocaine, marijuana). Very short
amounts of drug needs to be administered)
route from lungs to brain and cause rapid
effects

4.21

lungs provide the route. Nicotine, freebase ⚫Oral administration: via the mouth
cocaine and marijuana are usually smoked. Some drugs/ chemicals cann’t be
Also to treat lungs disorders. Short route administered orally. E.g. insulin
and rapid effects ⚫ Sublingual: beneath the tongue
(Nitroclycerine for patients with angina
⚫ Topicaladministration: absorbed through pectoris)
the skin/ mucous membrane (sniffing). ⚫ Intrarectal: at the opposite end of the
Natural/ artificial steroid hormones can be digestive tract rectum/
administered in this way. This route vagina(suppositories). Rectal
delivers the drug to the brain very rapidly. suppositories are used to administer
Cocaine hydrocholaride often sniffed in drugs that might upset a person’s
this way. stomach.
⚫ Intracerebral: injected direct in the brain ⚫ Several factor determining the rate at which
ventricles or the CSF. To achieve a drug in the bloodstream reaches sites of
action within the brain.
widespread distribution of drugs in the
1. Lipid solubility: ( fast effect of heroine than
brain. morphine, crossing BBB)
2. Depot binding: binding of drugs with
⚫ Intacerebroventricular (ICV) injecting into various tissues of the body or with proteins
cerebral ventricles (very rare in humans in the blood not directly with target site.
to treat certain brain infections through As long as the drug molecules bound to the
depot, they can't reach their site of actions and
insertion of antibodies) exert their desired effects.

Distribution of drugs within the

body

⚫ One source of depot binding is albumin ⚫ Drugs don’t remain in the body indefinitely
⚫ Are deactivated by the enzymes and
(a protein found in blood made by the liver)
eventually excreted by the kidneys
⚫ Depot binding can both delay and prolong
⚫ Liver is important in the enzymatic
the drug effects deactivation of drugs, some deactivating
⚫ Other source of depot binding is fat enzymes found in the blood and brain.
tissues, bones muscles and the liver. ⚫ In some cases enzymes transform drug
Drugs bind with these depots more slowly molecules into another more biologically
active form. More active than the
than do with the albumin because they administered ones----- more long duration
must leave the blood vessels to do so drug effects

Inactivation and Excretion

 Synaptic Transmission Sites of Drug Action
1. Effects on production of neurotransmitters
(agonists and antagonists)
⚫ Transmitter substances are
◦ Synthesized, stored, released, and terminated
◦ Most drugs effect behaviors by effecting synaptic a. Synthesis of neurotransmitters from its
transmission precursors. The rate of synthesis and release
◦ Direct agonist: a drug that binds to and of NT is increased when a precursor is
activates a receptor (the precursor served as administered (precursor ----- agonist)
agonists)
◦ Antagonist: a drug that binds to but does not a. Synthesis of NT are controlled by enzymes. If a
activate a receptor drug inactivate one of these enzymes , it will
🞄Indirect antagonists are drugs that interfere with prevent the NT from being produced (drug-----
the normal action of a neurotransmitter without
binding to its receptor site antagonist)

4.29

2. Effects on storage and release of ⚫ Other drugs have opposite effects. They
neurotransmitters act as agonists by binding with these
⚫ Some of the transporter molecules that fill proteins and directly triggering the
the synaptic vesicles are capable of being release of NT (drug----- agonist)
blocked by a drug.
⚫ Molecules of the drug bind with the
particular site on the transporter and
inactivate it.
⚫ Synaptic vesicles remain empty----noting
released against presynaptic membrane
(drug ------ antagonist)
3. Effects on receptors (both pre and post ⚫ Drug mimicking the effects of NT act as
synaptic receptors) (direct agonist)
⚫ Most important and complex site of action
of drugs are receptors (pre and post ⚫ Drugs that prevent the NT from opening
synaptic) in the NS. the ion channels by occupying the
⚫ NT released----stimulate postsynaptic receptor’s binding sites (direct antagonist/
receptors. Some drugs bind with the receptor blockers)
receptors as the NTs does. Once a drug
bound with the receptor ------ serves as
either agonist or antagonist

⚫ Binding of molecules with the alternative 4.Effect on reuptake or destruction of NT

sites (non competitive binding): drug Stimulation of post synaptic potential-----
attaching to one of the alternative sites termination of postsynaptic potential
preventing the opening of ion channels is Two processes involved
(indirect antagonist). Its ultimate effect is ⚫ Molecules of NT taken back into the TB through
similar to that of direct antagonist but its the process of reuptake, or destroyed by an
site of action is different. enzyme (enzymatic deactivation)
⚫ Drug act as either by blocking the reuptake
process (inactivating the molecules), and prevent
⚫ Drug attaching to one of the alternative the enzyme form working by binding with them
sites and facilitates the opening of ion both cases drug work as-----agonist---prolong
channels (indirect agonist) the presence of NT in synaptic cleft
Drug Action on Synaptic
Transmission 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

Agonist drugs are in red, Antagonists are in blue

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