Drugs acting on CNS

Drugs acting on the CNSlecture 1 Dr. Ghada Taqa

Al-Hamadi , Drugs acting on the CNSII. 4medstudents.com 2003

Nervous System

CNS
PNS
Somatic
Autonomic
Parasympathetic
Sympathetic


Most drugs that affect the central nervous system (CNS) act by altering some step in the neurotransmission process. Drugs affecting the CNS may act presynaptically by influencing the production, storage, release of N.T or termination of action of neurotransmitters. Other agents may activate or block postsynaptic receptors.


In many ways, the basic functioning of neurons in the CNS is similar to that of the autonomic nervous system (ANS) For example, transmission of information in both the CNS and in the periphery involves the release of neurotransmitters that diffuse across the synaptic space to bind to specific receptors on the postsynaptic neuron. In both systems, the recognition of the N.T by the membrane receptor of the postsynaptic neuron triggers intracellular changes.



However, several major differences exist between neurons in the peripheral ANS and those in the CNS. The circuitry of the CNS is much more complex than that of the ANS, and the number of synapses in the CNS is far greater. The CNS, unlike the peripheral ANS, contains powerful networks of inhibitory neurons that are constantly active in modulating the rate of neuronal transmission.

In addition, the CNS communicates through the use of multiple neurotransmitters (serotonin , dopamine , Noradrenaline, Acetylcholine, Opioid peptides Substance P, Nitric oxide ). whereas the ANS uses only two primary neurotransmitters, acetylcholine and norepinephrine.

Drugs acting on the CNS include

1- Anxiolytic and hypnotic . 2- Antidepressants 3- Antieplipsy

Anxiolytic and

Hypnotic Drugs

Definitions Sedative & Hypnotics

Disorders involving anxiety are among the most common mental disorders . Anxiety is an unpleasant state of tension, apprehension, or a fear that seems to arise from either a known or an unknown source). Anxiolytics : Drugs that clam the patient and reduce anxiety without inducing normal sleep. Hypnotics : Drugs that initiate and maintain the normal sleep. Anxiolytic (anti anxiety drugs) hypnotic (sleep-inducing agent)

The physical symptoms of severe anxiety are similar to those of fear (such as tachycardia, sweating, trembling, and palpitations) and involve sympathetic activation.

Episodes of mild anxiety are common life experiences and do not warrant treatment. However, severe, chronic, anxiety may be treated with antianxiety drugs

Types of anxiety disorders

Generalized anxiety disorder— persistent state of heightened anxiety with increased levels of motor tension and autonomic hyperactivity.Panic disorder— recurrent, discrete periods of sudden and intense fear or discomfort accompanied by autonomic arousal.


Classification of hypnotic drugs 1. Benzodiazepines ( BDZ ) 2. Barbiturates 3. Miscellaneous ( non BDZ non barbiturate drugs). Zolpidem Zaleplon 4. H1-antihistamines with sedative activity

Benzodiazepines

are widely used anxiolytic drugs. They have largely replaced barbiturates in the treatment of anxiety and insomnia, because benzodiazepines are generally considered to be safer and more effective


Though benzodiazepines are commonly used, they are not necessarily the best choice for anxiety or insomnia. Certain antidepressants with anxiolytic action, such as the selective serotonin reuptake inhibitors, are preferred in many cases, and non benzodiazepine hypnotics and antihistamines may be preferable for insomnia.

1- Benzodiazepines

Benzodiazepines are the most widely used anxiolytic drugs. Benzodiazepines are more effective and safer

Benzodiazepines receptors

There are 3 types of BZ receptors : 1-BZ1 central receptor linked to sleep 2-BZ2 central receptor linked to cognition & motor function 3-periphral BZ receptors (not our field here)

Benzodiazepines Mechanism of action

The benzodiazepines bind with high affinity to specific benzodiazepine-binding sites ( BZ1 and BZ2 receptors subtypes) on Gamma-aminobutyric acid (GABA), which is the major inhibitory neurotransmitter in the mammalian brain.

Gamma-aminobutyric acid receptor (GABA)

Mechanism of Action Benzodiazepines combine with BZ receptors  increase GABA action on GABA receptors  chloride channels opening   chloride influx to the cell  cell membrane hyperpolarization  inhibition of propagation of action potential  inhibitory effect on different sites of the brain especially motor cortex & limbic system.

Benzodiazepines Pharmacokinetics

Benzodiazepines are usually given orally and are well absorbed by this route. Absorption from the small intestine. Diazepam and lorazepam are available for intravenous administration. benzodiazepines are converted in the liver to one or more active metabolites. In several cases the active metabolites have a much longer half-life than the parent

Benzodiazepines therapeutic uses

Anxiety disorders : Both acute and chronic anxiety , Diazepam is used for long period. Muscular disorders: Diazepam in muscle spasms & spasticity in degenerative disorders .

Amnesia: short acting agents endoscopy, bronchoscopy & angioplasty. Seizures: Clonazepam in chronic epilepsy Diazepam is the drug of choice in grand mal and status eplipticus Diazepam used in treatment of alcohol withdrawal.

Benzodiazepines therapeutic uses

Sleep disorders: Reduced REM and Slow-Wave sleep. leads to REM rebound when drug is discontinued.
Effective drugs Triazolam. Temazepam. Flurazepam Zolpidem. Zaleplon.
Nonbenzodiazepens
Benzodiazepines


Triazolam : Short acting Induce sleep in patient with recurrent insomnia Rebound insomnia Better to be used intermittently (because tolerance develops within a few hours )


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