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1. INTRODUCTION TO CNS

2. • The central nervous
system consists of
the brain and spinal
cord
• It is referred as
"central" because it
combines
information from
the entire body and
coordinates activity
across the whole
organism

3. INTRODUCTION TO CNS
• There are two reasons why understanding the
action of drugs on the central nervous system
(CNS) presents a particularly challenging
problem
• The first is that centrally acting drugs are of
special significance to humankind
• The second reason is that the CNS is
functionally more complex than any other
system in the body, and this makes the
understanding of drug effects very much more
difficult

4. CHEMICAL SIGNALLING IN THE
NERVOUS SYSTEM
• The brain is basically a chemical machine; it
controls the main functions of a higher animal
across timescales ranging from milliseconds to
years.
• The chemical signaling mechanisms cover a
wide dynamic range
• Currently, we understand much about drug
effects and neuromodulation

5. Chemical transmission in the central
nervous system
• In the nervous system, a synapse is a structure
that permits a neuron (or nerve cell) to pass an
electrical or chemical signal to another neuron or
to the target efferent cell
• Glial cells (support cells), particularly astrocytes,
participate actively in chemical signaling
• The terms neurotransmitter, neuromodulator and
neurotrophic factor refer to chemical mediators

6. # Neurotransmitters are released by presynaptic
terminals and produce rapid excitatory or inhibitory
responses in postsynaptic neurons
# Fast neurotransmitters (e.g. glutamate, GABA)
operate through Gated ion channels
# Slow neurotransmitters and neuromodulators
(e.g. dopamine, neuropeptides, prostanoids)
operate mainly through G-protein-coupled
receptors

7. # Neuromodulators are released by neurons, and
produce slower pre- or postsynaptic responses
# Neurotrophic factors are released mainly by
non-neuronal cells and act on tyrosine kinase-
linked receptors that control neuronal growth
# Glutamate, 5-hydroxytryptamine,
acetylcholine may act through both ligand-gated
channels and G-protein-coupled receptors and
act as both neurotransmitter & neuromodulator

8. # Many chemical mediators, including glutamate,
nitric oxide and arachidonic acid metabolites, are
produced by Glial cells as well as neurons
# Many mediators (e.g. cytokines, growth factors,
steroids) control long-term changes in the brain
mainly by affecting gene transcription

9. PSYCHOTROPIC DRUGS
• Psychotropic drugs are defined as those that
affect mood and behavior
• Because the assessment of brain function are
difficult to define and measure, there is no
consistent basis for classifying psychotropic
drugs
• The following classification is based on that
suggested in 1967 by the World Health
Organization

10. 1) Anesthetic agents
Definition: drugs used to produce surgical
anesthesia
Examples: halothane, propofol
2) Anxiolytics and sedatives
(hypnotics, minor tranquillizers)
Definition: cause sleep and reduce anxiety
Examples: barbiturates, benzodiazepines

11. 3) Antipsychotic drugs
(neuroleptic drugs, antischizophrenic drugs,
major tranquillizers)
Definition: drugs that are effective in relieving
the symptoms of schizophrenic illness
Examples: chlorpromazine and haloperidol
4) Antidepressant drugs
Definition: drugs that alleviate the symptoms of
depressive illness
Examples: monoamine oxidase inhibitors, and
tricyclic antidepressants

12. 5) Analgesic drugs
Definition: drugs used for controlling pain
Examples: opiates, carbamazepine
6) Psychomotor stimulants
(psychostimulants)
Definition: drugs that cause wakefulness and
euphoria
Examples: amphetamine, cocaine and caffeine

13. 7) Psychotomimetic drugs
(hallucinogens)
Definition: drugs that cause disturbance of
perception (particularly visual hallucinations)
and of behavior in ways that cannot be simply
characterized as sedative or stimulant effects
Examples: lysergic acid diethylamide and
mescaline

14. 8) Cognition enhancers
(Nootropic drugs)
Definition: drugs that improve memory and
cognitive performance
Examples: acetylcholinesterase inhibitors (e.g.
donepezil, rivastigmine)

15. EXCITATORY AMINO ACIDS
• EAA are known as neurotransmitters of the
CNS in the last decade
• The most important EAA are glutamate and
aspartate
• GLU and ASP are fast neurotransmitters
used in neuronal transmission
• EAA generate synchronous oscillatory
activity, which probably is essential for the
maintenance of consciousness

16. Alzheimer's disease
• AD is a progressive neurologic disorder
that causes the brain to shrink (atrophy)
and brain cells to die
• Current therapies are aimed at either
improving cholinergic transmission
within the CNS or preventing excitotoxic
actions resulting from overstimulation of
N-methyl-D-aspartic acid (NMDA)-
glutamate receptors in selected brain
areas.

17. 1- Mild/Moderate AD
# Cholinesterase inhibitors increase the
levels of acetylcholine in the brain, which
plays a key role in memory and learning
# Cholinesterase inhibitors most commonly
prescribed for mild to moderate AD including
donepezil, galantamine (orally), rivastigmine
(orally and transdermal patch) and tacrine.
# Common adverse effects include nausea,
diarrhea, vomiting, anorexia, tremors,
bradycardia, and muscle cramps.

18. 2- Moderate/Severe AD
# Memantine regulates glutamate by blocking the
NMDA receptors.
# Memantine is well tolerated, with few dose-
dependent adverse events. Expected side effects are
confusion, agitation, and restlessness. It is often
given in combination with an AChE inhibitor.

19. Parkinson's disease
PD is a degenerative disorder of the CNS that
often impairs the motor skills and speech
The disease is correlated decrease of dopamine
and overproduction or of acetylcholine , resulting
in loss of the control of muscle movements.

20. 1.Enhancement of dopaminergic
activity by drugs as:
a) Levodopa, which is its natural precursor
b) Dopamine agonists (Bromocriptine, and
Apomorphine)
c) Prolong the action of dopamine
(Selegiline)
d) Release dopamine from stores and inhibit
reuptake (Amantadine)

21. 2.Reduction of cholinergic activity
by antimuscarinic drugs
a) Natural belladonna
b) Synthetic atropine substitutes
c) Antihistamines
d) Phenothiazine

22. Depression
• Depression" is a very common
psychiatric disorder that is related to
the "mood" (affective disorder).
• Changes in mood are associated with
depression and/or mania.
• It is due to Neurotransmitter
Imbalances & dysregulation creates a
state of deficiency in monoamines

23. • 5-HT deficiency may cause the sleep
problems, irritability and anxiety associated
with depression
• Decreased level of NE regulates mood.
alertness, appetite, reward & drives,
• Dopamine is important for pleasure, sexual
function & psychomotor activity.
• Drug is aimed to increase the levels of
these amines.

24. Classification of antidepressants based on site
of action
A ) Drugs that block the reuptake of NE and 5-
HT (Most tricyclics like Imipramine,
Desipramine,
B) Drugs that Inhibit MonoAminoxidase (MAOIs,
Phenelzine, Tranylcypraine
C) Drugs that selectively block reuptake of 5-HT
(SSRIs) (Fluoxetine; Paroxetine; Sertraline
D) Drugs that Block Presynaptic α2-adrenoceptors
(Mirtazapine, Mianserin).

25. 25
Epilepsy
# Epilepsy is a chronic neurological
disorder characterized by recurrent
seizures
# A seizure is a brief disturbance of
electrical activity in the brain

27. Therapeutic management:
• The goal of treatment is to:
Control or reduce the frequency of
seizures
Minimize side effects
Allowing the patient to live as normal life
as possible

28. Anti-epileptic drugs
Strategies
• blockade of voltage-gated channels (Na+ or
Ca2+).
• Enhance inhibitory GABAergic (Neurons that
produce GABA) transmission.
• Interference with excitatory glutamate
transmission.

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During the past 15 years, new antiepileptic drugs have been
introduced, some of which have potential advantages in
terms of pharmacokinetics, tolerability, and lesser risk for
drug-drug interactions when compared with the older agents
used to treat epilepsy. These new drugs, which include
gabapentin, lamotrigine, topiramate, levetiracetam,
oxcarbazepine, zonisamide, are labeled as second generation
when compared with older antiepileptics, such as
Benzodiazepines, phenobarbital, phenytoin, carbamazepine,
ethosuximide and valproic acid.

30. 30
Examples of antiepileptics:
1. Benzodiazepines (Old antiepileptic)
2. Sodium valproate (Broad spectrum antiepileptic
drug against all types of seizures except status
epilepticus (emergency case of epilepsy),
because it is prepared as oily solutions → not
available for i.v. injection)
3. Phenobarbital (is used in the treatment of status
epilepticus).
4. Examples of Second generation antiepileptics :
Gabapentin and Pregabalin