Dr.

Mehwish Waseem
DPT, MS-CPPT
• The CNS:brain and spinal cord

• Cerebrum: largest ,bilateral hemisphere…several lobes (frontal,

temporal, parietal, and occipital). The outer cerebrum, or cerebral
cortex, is the highest order of conscious function and integration in
the CNS…sensory and motor functions as well as intellectual and
cognitive abilities. ..short-term memory and speech.
• supervisory capacity regarding lower brain functioning and may
influence the control of other activities such as the autonomic
nervous system.
• CNS drugs…tend to affect cortical function indirectly by first
altering the function of lower brain and spinal cord structures.
• An exception is the group of drugs used to treat epilepsy; these
drugs are often targeted directly for hyperexcitable neurons in the
cerebral cortex.
• In addition, drugs that attempt to enhance cognitive function in
conditions such as Alzheimer disease might also exert their primary
effects in the cerebrum.
 located deep within the cerebral hemispheres
 caudate nucleus, putamen, globus pallidus,

lentiform nucleus, and substantia nigra.

 control of motor activities; deficits in this area

are significant in movement disorders such as

Parkinson disease.
 The area of the brain enclosing the third ventricle
is the diencephalon…thalamus and hypothalamus.
 The thalamus contains distinct nuclei that are

crucial in the integration of certain types of

sensations and their relay to other areas of the
brain (such as the somatosensory cortex).
 The hypothalamus is involved in the control of

diverse body functions including temperature

control, appetite, water balance, and certain
emotional reactions…control over the function of
hormonal release from the pituitary gland.
• a bridge between the higher areas of the brain
(cerebrum and diencephalon) and the brainstem.
• Brainstem: pons and the medulla oblongata.
• locations of centers responsible for controlling
respiration and cardiovascular function (vasomotor
center).
• The reticular formation is also located in the midbrain
and brainstem. ..collection of neurons that extend from
the reticular substance of the upper spinal cord
through the midbrain and the thalamus.
• regulating the amount of arousal or alertness in the
cerebral cortex.
• CNS drugs that affect the arousal state of the individual
tend to exert their effects on the reticular formation…
Sedative-hypnotics and general anesthetics…CNS
stimulants (caffeine, amphetamines)
• lies posterior to the brainstem and is separated
from it by the fourth ventricle.
• … two hemispheres…three lobes (anterior,
posterior, and flocculonodular).
• Plan and coordinate motor activity
• Concerned with the vestibular mechanisms
responsible for maintaining balance and posture.
• Therapeutic medications are not usually targeted
directly for the cerebellum, but incoordination and
other movement disorders may result if a drug
exerts a toxic side effect on the cerebellum.
• The limbic system is comprised of several structures
that are dispersed throughout the brain but are often
considered as a functional unit or system within the
CNS.
• Major components of the limbic system include
cortical structures (such as the amygdala,
hippocampus, and cingulate gyrus), the hypothalamus,
certain thalamic nuclei, mamillary bodies, septum
pellucidum, and several other structures and tracts.
• control of emotional and behavioral activity.
• Certain aspects of motivation, aggression…
• CNS drugs affecting these aspects of behavior,
including some antianxiety and antipsychotic
medications, are believed to exert their beneficial
effects primarily by altering activity in the limbic
structures.
• The spinal cord is cylindrically shaped and consists of centrally
located gray matter that is surrounded by white matter.
• The gray matter serves as an area for synaptic connections
between various neurons.
• The white matter consists of the myelinated axons of neurons,
which are grouped into tracts ascending or descending between
the brain and specific levels of the cord.
• Certain CNS drugs exert some or all of their effects by
modifying synaptic transmission in specific areas of gray
matter, while other CNS drugs, such as narcotic analgesics, may
exert an effect on synaptic transmission in the gray matter of
the cord as well as on synapses in other areas of the brain.
• Some drugs may be specifically directed toward the white
matter of the cord.
• Drugs such as local anesthetics can be used to block action
potential propagation in the white matter so that ascending or
descending information is interrupted (i.e., a spinal block
 unique structure and function of CNS capillaries.
 Certain substances are not able to pass from the

bloodstream into the CNS, despite the fact that

these substances are able to pass from the
systemic circulation into other peripheral tissues.
 caused primarily by the tight junctions that occur

between capillary endothelial cells; in fact, CNS

capillaries lack the gaps and fenestrations that are
seen in peripheral capillaries.
 as a selective filter and seems to protect the CNS
• drugs targeted for the CNS must be able to pass from
the bloodstream into the brain and spinal cord.
• In general, nonpolar, lipid-soluble drugs are able to
cross the blood-brain barrier by passive diffusion.
• Polar and lipophobic compounds are usually unable to
enter the brain. Some exceptions occur because of the
presence of carrier-mediated transport systems in the
blood-brain barrier…(such as glucose) are transported
via facilitated diffusion, while other compounds
(including some drugs) may be able to enter the brain
by active transport.
• the typical manner by which most drugs enter the
brain is by passive lipid diffusion.
 The majority of neural connections in the human
brain and spinal cord are characterized as chemical
synapses
 The chemical synapse indicates that a chemical

neurotransmitter is used to propagate the nervous

impulse across the gap that exists between two
neurons.
 excitation or inhibition of the other neurons.
• found in many areas of the brain as well as in the
periphery (skeletal neuromuscular junction, some
autonomic synapses).
• In the brain, acetylcholine is abundant in the
cerebral cortex, and seems to play a critical role in
cognition and memory.
• Neurons originating in the large pyramidal cells of
the motor cortex and many neurons originating in
the basal ganglia also secrete acetylcholine from
their terminal axons.
• In general, acetylcholine synapses in the CNS are
excitatory in nature.
 Monoamines are a group of structurally similar CNS
neurotransmitters that include the catecholamines
(dopamine, norepinephrine) and 5-hydroxytryptamine
(serotonin).
• Dopamine exerts different effects at various locations
within the brain.
• Within the basal ganglia, dopamine is secreted by neurons
that originate in the substantia nigra and project to the
corpus striatum. As such, it is important in regulating
motor control, and the loss of these dopaminergic neurons
results in symptoms commonly associated with Parkinson
disease
• Dopamine also influences mood and emotions, primarily
via its presence in the hypothalamus and other structures
within the limbic system. Although its effects within the
brain are very complex, dopamine generally inhibits the
neurons onto which it is released.
 is secreted by neurons that originate in the locus
caeruleus of the pons and projects throughout the
reticular formation.
 generally as an inhibitory transmitter within the

CNS, but the overall effect following activity of

norepinephrine synapses is often general
excitation of the brain, probably because
norepinephrine directly inhibits other neurons that
produce inhibition. This phenomenon of
disinhibition causes excitation by removing the
influence of inhibitory neurons.
 is released by cells originating in the midline of the
pons and brainstem and is projected to many
different areas, including the dorsal horns of the
spinal cord and the hypothalamus.
 strong inhibitor (painfull stimuli)
 Involved in controlling many aspects of mood and

behavior, and problems with serotonergic activity

have been implicated in several psychiatric
disorders, including depression and anxiety.
 glycine and gammaaminobutyric acid (GABA)
 Inhibitory transmitters…at presynaptic and

postsynaptic neurons in the brain and spinal cord.

 Other amino acids such as aspartate and glutamate

have been found in high concentrations

throughout the brain and spinal cord; these
substances cause excitation of CNS neurons.
 These excitatory amino acids have received a great

deal of attention lately because they may also

produce neurotoxic effects when released in large
amounts during CNS injury and certain neurologic
disorders (epilepsy, amyotrophic lateral sclerosis,
and so forth).
 substance P…excitatory transmitter that is involved
in spinal cord pathways transmitting pain
impulses.
 Increased activity at substance P synapses in the

cord serves to mediate the transmission of painful

sensations, and certain drugs such as the opioid
analgesics may decrease activity at these synapses.
 endorphins, enkephalins, and dynorphins…

endogenous opioids…inhibit painful

sensations. ..decrease the central perception of
pain.
 Recent evidence has implicated substances
such as adenosine and adenosine
triphosphate (ATP) as transmitters or
modulators of neural transmission in specific
areas of the brain and in the autonomic
nervous system.
 CNS drugs increase or decrease transmission at
specific synapses.
 psychotic behavior…overactivity dopamine as a

neurotransmitter . Drug therapy…decrease activity

at central dopamine synapses.
 Parkinson disease…decrease in dopamine

synapses… Antiparkinsonian drugs attempt to

increase dopaminergic transmission .
 AP… at the presynaptic terminal…neurotransmitter
release.
 local anesthetics, block propagation along neural

axons so that the action potential fails to reach the

presynaptic terminal.
 the amount of depolarization or the height of the

action potential arriving at the presynaptic terminal

is directly related to the amount of transmitter
released… presynaptic inhibition,…GABA is
believed to exert some of its inhibitory effects via
this mechanism.
 metyrosine (Demser).. inhibits an enzyme that is
essential for catecholamine biosynthesis in the
presynaptic terminal.
 Treatment with metyrosine results in decreased

synthesis of transmitters such as dopamine and

norepinephrine.
 A certain amount of chemical transmitter is stored
in presynaptic vesicles. Drugs that impair this
storage will decrease the ability of the synapse to
continue to transmit information for extended
periods.
 antihypertensive drug reserpine , which impairs the

ability of adrenergic terminals to sequester and

store norepinephrine in presynaptic vesicles.
 Certain drugs will increase synaptic activity by
directly increasing the release of neurotransmitter
from the presynaptic terminal.
 Amphetamines…increasing the presynaptic release

of catecholamine neurotransmitters
 Conversely, botulinum toxin (Botox)…impair the

release of acetylcholine from the skeletal

neuromuscular junction.
 movement of the transmitter molecule back into
the presynaptic terminal.
 A drug that impairs the reuptake of transmitter

allows more of it to remain in the synaptic cleft and

continue to exert an effect…tricyclic
antidepressants impair the reuptake mechanism
that pumps amine neurotransmitters back into the
presynaptic terminal, which allows the transmitter
to continue to exert its effect and prolong activity
at the synapse.
 Cholinesterase …myasthenia gravis… functional
decrease in activity at the skeletal neuromuscular
junction.
 Anticholinesterase drugs such as neostigmine and

pyridostigmine inhibit acetylcholine breakdown,

allowing more of the released neurotransmitter to
continue to exert an effect at the neuromuscular
synapse.
 chemical antagonists… block the postsynaptic
receptor, thus decreasing synaptic transmission.
 use of beta blocker..beta-adrenergic receptors on

the myocardium, and they are frequently used to

treat hypertension, cardiac arrhythmias, and
angina pectoris.
 Other drugs may improve synaptic transmission…

improved receptor–effector coupling,…

benzodiazepines (e.g., diazepam
 [Valium],appear to enhance the postsynaptic

effects of the inhibitory neurotransmitter GABA.

 receptors on the presynaptic terminal of some
types of chemical synapses…negative feedback in
controlling neurotransmitter release.
 clonidine (Catapres), may exert some of its

antihypertensive effects by binding to presynaptic

receptors on sympathetic postganglionic neurons
and impairing the release of norepinephrine onto
the peripheral vasculature.
 Drugs may alter synaptic transmission by affecting
membrane organization and fluidity(amount of
flexibility/mobility of lipid bilayer).
 Alcohol(ethanol) or general anaesthetics.