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CNS PHARMACOLOGY
Introduction to CNS drugs
Lecturer Name: Dr. A. Yiaile
Lecture Outline
• Action of drugs on CNS
• General characteristics of CNS drugs
• Classification of CNS drugs
Action of drugs on CNS
• Drugs may:
• Modify synthesis, storage, release or metabolism of
the inhibitory or excitatory neurochemical
transmitters eg MAO- inhibit monoamine oxidase
and thus inhibit degradation of noradrenaline hence
used as antidepressants
• Act by modifying ion fluxes across the cell
membrane eg phenytoin sodium
Action of drugs on CNS
• Drugs may:
• Specifically act as antagonists at post-synaptic
receptors eg chlorpromazine etc
• Act as neuromodulators
• Modify energy supply of the CNS eg by local
inhibition of synthesis of high energy phosphate
bonds
Action of drugs on CNS
Specificity and Non-specificity of
CNS Drug Actions
 The effect of a drug is considered to be specific in the CNS
when it affects an identifiable molecular mechanism unique to
target cells that bear receptors for that drug.
 Conversely, a drug is regarded as nonspecific when it produces
effects on many different target cells and acts by diverse
molecular mechanisms.
 Even a drug that is highly specific when tested at a low
concentration may exhibit nonspecific actions at higher doses.
Specificity and Nonspecificity of
CNS Drug Actions
 Conversely, even generally acting drugs may not act equally on
all levels of the CNS.
 For example, sedatives, hypnotics, and general anesthetics
would have very limited utility if central neurons that control the
respiratory and cardiovascular systems were especially
sensitive to their actions.
 Drugs with specific actions may produce nonspecific effects if
the dose and route of administration produce high tissue
concentrations
Classification of CNS Drugs
Drugs acting in the CNS are generally classified as:
General non-specific CNS Depressants
General non-specific CNS Stimulants
Drugs that selectively modify CNS function
General non-specific CNS
depressants
This category includes the anesthetic gases and vapors, the
aliphatic alcohols, and some hypnotic-sedative drugs.
These agents share the capacity to depress excitable tissue at
all levels of the CNS, leading to a decrease in the amount of
transmitter released by the nerve impulse, as well as to general
depression of postsynaptic responsiveness and ion movement.
General non-specific CNS
depressants
At sub-anesthetic concentrations, these agents (e.g., ethanol)
can exert relatively specific effects on certain groups of neurons,
which may account for differences in their behavioral effects,
especially the propensity to produce dependence
General (Nonspecific) CNS
Stimulants
The drugs in this category include pentylenetetrazol and related
agents that are capable of powerful excitation of the CNS, and the
methylxanthines, which have a much weaker stimulant action.
Stimulation may be accomplished by one of two general
mechanisms:
(1) by blockade of inhibition or
(2) by direct neuronal excitation (which may involve increased
transmitter release, more prolonged transmitter action,
labilization of the postsynaptic membrane, or decreased
synaptic recovery time).
Drugs That Selectively Modify
CNS Function
The agents in this group may cause either depression or
excitation.
In some instances, a drug may produce both effects
simultaneously on different systems.
Some agents in this category have little effect on the level of
excitability in doses that are used therapeutically.
Drugs That Selectively Modify
CNS Function
The principal classes of these CNS drugs are:
 opioid and non-opioid analgesics
anticonvulsants,
drugs used in treating Parkinson's disease,
appetite suppressants,
antiemetics,
analgesic-antipyretics,
tranquilizers,
sedatives, and hypnotics
Drugs That Selectively Modify
CNS Function
The principal classes of these CNS drugs are:
Certain stimulants
Neuroleptics (antidepressants and antimanic and
antipsychotic agents),
 Medications employed in the treatment of Alzheimer's
disease (cholinesterase inhibitors and antiglutamate
neuroprotectants) and
Compounds promising in the symptomatic treatment of
Huntington's disease (tetrabenazine for the depletion of
monoamines and reduction in tremor).
Drugs That Selectively Modify
CNS Function
Although selectivity of action may be remarkable, a drug usually
affects several CNS functions to varying degrees.
When only one constellation of effects is wanted in a therapeutic
situation, the remaining effects of the drug are regarded as
limitations in selectivity (i.e., unwanted side effects).
General Characteristics of CNS
Drugs
The effect of a CNS drug is additive with the physiological state
and with the effects of other depressant and stimulant drugs.
For example, anesthetics are less effective in a hyper-
excitable subject than in a normal patient; the converse is true
for stimulants.
In general, the depressant effects of drugs from all categories
are additive (e.g., the fatal combination of barbiturates or
benzodiazepines with ethanol), as are the effects of stimulants.
General Characteristics of CNS
Drugs
The effect of a CNS drug is additive with the physiological state
and with the effects of other depressant and stimulant drugs.
Therefore, respiration depressed by morphine is further
impaired by depressant drugs, while stimulant drugs can
augment the excitatory effects of morphine to produce vomiting
and convulsions.
General Characteristics of CNS
Drugs
Antagonism between depressants and stimulants is variable.
Some instances of true pharmacological antagonism among
CNS drugs are known; for example, opioid antagonists are very
selective in blocking the effects of opioid analgesics.
Some instances are variable, for example, an individual
whose CNS is depressed by an opiate cannot be returned
entirely to normal by stimulation by caffeine.
General Characteristics of CNS
Drugs
The selective effects of drugs on specific neurotransmitter
systems may be additive or competitive.
This potential for drug interaction must be considered
whenever such drugs are administered concurrently.
To minimize such interactions, a drug-free period may be
required when modifying therapy, and development of
desensitized and supersensitive states with prolonged therapy
may limit the speed with which one drug may be halted and
another started.
General Characteristics of CNS
Drugs
An excitatory effect is commonly observed with low
concentrations of certain depressant drugs due either to
depression of inhibitory systems or to a transient increase in the
release of excitatory transmitters.
Examples are the stage of excitement during induction of
general anesthesia and the stimulant effects of alcohol.
The excitatory phase occurs only with low concentrations of
the depressant; uniform depression ensues with increasing
drug concentration
General Characteristics of CNS
Drugs
An excitatory effect is commonly observed with low
concentrations of certain depressant drugs due either to
depression of inhibitory systems or to a transient increase in the
release of excitatory transmitters.
The excitatory effects can be minimized, when appropriate,
by pretreatment with a depressant drug that is devoid of such
effects (e.g., benzodiazepines in preanesthetic medication).
 Acute, excessive stimulation of the cerebrospinal axis
normally is followed by depression, which is in part a
consequence of neuronal fatigue and exhaustion of stores of
transmitters
Classification of CNS drugs
Opioid/Narcotic
Non-opioid analgesics
Anticonvulsants,
 Anti- Parkinson's ,
Appetite suppressants,
Antiemetics,
Tranquilizers,
Anesthetics
Sedatives, and hypnotics
Antipsychotics
Antidepressants
Anxiolytic agents
Degenerative Disorders

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INTRODUCTION TO CNS DRUGS.pptx

  • 1. CNS PHARMACOLOGY Introduction to CNS drugs Lecturer Name: Dr. A. Yiaile
  • 2. Lecture Outline • Action of drugs on CNS • General characteristics of CNS drugs • Classification of CNS drugs
  • 3. Action of drugs on CNS • Drugs may: • Modify synthesis, storage, release or metabolism of the inhibitory or excitatory neurochemical transmitters eg MAO- inhibit monoamine oxidase and thus inhibit degradation of noradrenaline hence used as antidepressants • Act by modifying ion fluxes across the cell membrane eg phenytoin sodium
  • 4. Action of drugs on CNS • Drugs may: • Specifically act as antagonists at post-synaptic receptors eg chlorpromazine etc • Act as neuromodulators • Modify energy supply of the CNS eg by local inhibition of synthesis of high energy phosphate bonds
  • 6. Specificity and Non-specificity of CNS Drug Actions  The effect of a drug is considered to be specific in the CNS when it affects an identifiable molecular mechanism unique to target cells that bear receptors for that drug.  Conversely, a drug is regarded as nonspecific when it produces effects on many different target cells and acts by diverse molecular mechanisms.  Even a drug that is highly specific when tested at a low concentration may exhibit nonspecific actions at higher doses.
  • 7. Specificity and Nonspecificity of CNS Drug Actions  Conversely, even generally acting drugs may not act equally on all levels of the CNS.  For example, sedatives, hypnotics, and general anesthetics would have very limited utility if central neurons that control the respiratory and cardiovascular systems were especially sensitive to their actions.  Drugs with specific actions may produce nonspecific effects if the dose and route of administration produce high tissue concentrations
  • 8. Classification of CNS Drugs Drugs acting in the CNS are generally classified as: General non-specific CNS Depressants General non-specific CNS Stimulants Drugs that selectively modify CNS function
  • 9. General non-specific CNS depressants This category includes the anesthetic gases and vapors, the aliphatic alcohols, and some hypnotic-sedative drugs. These agents share the capacity to depress excitable tissue at all levels of the CNS, leading to a decrease in the amount of transmitter released by the nerve impulse, as well as to general depression of postsynaptic responsiveness and ion movement.
  • 10. General non-specific CNS depressants At sub-anesthetic concentrations, these agents (e.g., ethanol) can exert relatively specific effects on certain groups of neurons, which may account for differences in their behavioral effects, especially the propensity to produce dependence
  • 11. General (Nonspecific) CNS Stimulants The drugs in this category include pentylenetetrazol and related agents that are capable of powerful excitation of the CNS, and the methylxanthines, which have a much weaker stimulant action. Stimulation may be accomplished by one of two general mechanisms: (1) by blockade of inhibition or (2) by direct neuronal excitation (which may involve increased transmitter release, more prolonged transmitter action, labilization of the postsynaptic membrane, or decreased synaptic recovery time).
  • 12. Drugs That Selectively Modify CNS Function The agents in this group may cause either depression or excitation. In some instances, a drug may produce both effects simultaneously on different systems. Some agents in this category have little effect on the level of excitability in doses that are used therapeutically.
  • 13. Drugs That Selectively Modify CNS Function The principal classes of these CNS drugs are:  opioid and non-opioid analgesics anticonvulsants, drugs used in treating Parkinson's disease, appetite suppressants, antiemetics, analgesic-antipyretics, tranquilizers, sedatives, and hypnotics
  • 14. Drugs That Selectively Modify CNS Function The principal classes of these CNS drugs are: Certain stimulants Neuroleptics (antidepressants and antimanic and antipsychotic agents),  Medications employed in the treatment of Alzheimer's disease (cholinesterase inhibitors and antiglutamate neuroprotectants) and Compounds promising in the symptomatic treatment of Huntington's disease (tetrabenazine for the depletion of monoamines and reduction in tremor).
  • 15. Drugs That Selectively Modify CNS Function Although selectivity of action may be remarkable, a drug usually affects several CNS functions to varying degrees. When only one constellation of effects is wanted in a therapeutic situation, the remaining effects of the drug are regarded as limitations in selectivity (i.e., unwanted side effects).
  • 16. General Characteristics of CNS Drugs The effect of a CNS drug is additive with the physiological state and with the effects of other depressant and stimulant drugs. For example, anesthetics are less effective in a hyper- excitable subject than in a normal patient; the converse is true for stimulants. In general, the depressant effects of drugs from all categories are additive (e.g., the fatal combination of barbiturates or benzodiazepines with ethanol), as are the effects of stimulants.
  • 17. General Characteristics of CNS Drugs The effect of a CNS drug is additive with the physiological state and with the effects of other depressant and stimulant drugs. Therefore, respiration depressed by morphine is further impaired by depressant drugs, while stimulant drugs can augment the excitatory effects of morphine to produce vomiting and convulsions.
  • 18. General Characteristics of CNS Drugs Antagonism between depressants and stimulants is variable. Some instances of true pharmacological antagonism among CNS drugs are known; for example, opioid antagonists are very selective in blocking the effects of opioid analgesics. Some instances are variable, for example, an individual whose CNS is depressed by an opiate cannot be returned entirely to normal by stimulation by caffeine.
  • 19. General Characteristics of CNS Drugs The selective effects of drugs on specific neurotransmitter systems may be additive or competitive. This potential for drug interaction must be considered whenever such drugs are administered concurrently. To minimize such interactions, a drug-free period may be required when modifying therapy, and development of desensitized and supersensitive states with prolonged therapy may limit the speed with which one drug may be halted and another started.
  • 20. General Characteristics of CNS Drugs An excitatory effect is commonly observed with low concentrations of certain depressant drugs due either to depression of inhibitory systems or to a transient increase in the release of excitatory transmitters. Examples are the stage of excitement during induction of general anesthesia and the stimulant effects of alcohol. The excitatory phase occurs only with low concentrations of the depressant; uniform depression ensues with increasing drug concentration
  • 21. General Characteristics of CNS Drugs An excitatory effect is commonly observed with low concentrations of certain depressant drugs due either to depression of inhibitory systems or to a transient increase in the release of excitatory transmitters. The excitatory effects can be minimized, when appropriate, by pretreatment with a depressant drug that is devoid of such effects (e.g., benzodiazepines in preanesthetic medication).  Acute, excessive stimulation of the cerebrospinal axis normally is followed by depression, which is in part a consequence of neuronal fatigue and exhaustion of stores of transmitters
  • 22. Classification of CNS drugs Opioid/Narcotic Non-opioid analgesics Anticonvulsants,  Anti- Parkinson's , Appetite suppressants, Antiemetics, Tranquilizers, Anesthetics Sedatives, and hypnotics Antipsychotics Antidepressants Anxiolytic agents Degenerative Disorders