Drugs acting in the
Central Nervous System
(CNS DRUGS)
“Drugs acting in the central nervous system (CNS) were among the first to be discovered by primitive humans and are still the most widely used group of pharmacologic agents. In addition to their use in therapy, many drugs acting on the CNS are used without prescription to increase one’s sense of well-being. Evolution is tireless in the development of natural toxins.
1. INTRODUCTION TO CNS PHARMACOLOGY
1.1 Drugs acting on the CNS
1.1.1 Introduction
Drugs acting on the CNS influence the lives of everyone almost every day. The non-medical use of CNS drugs including coffee, alcohol, and drugs of abuse such as marijuana, cocaine, and opiates is widespread. Drugs affecting the CNS are important therapeutically because they may relieve pain or fever, suppress disorders of movement or seizures, induce sleep or arousal, and reduce the desire to eat, inhibit motion sickness, and treat anxiety, mania, depression, or schizophrenia.
1.1.2 Non-specific CNS depressants
1. Anesthetic gases and vapors, aliphatic alcohols, barbiturates and many but not all sedative-hypnotics.
1.1.3 Non-specific CNS stimulants
· Pentylenetetrazol
· Methylxanthines.
1.1.4 Drugs that selectively modify CNS function
1. Agents in this class may cause either depression or excitation, or potentially both effects simultaneously in different systems. They include, anticonvulsants, antiparkinsonian drugs, opioids and nonopioid analgesics, appetite suppressants, antemetics, analgesic-antipyretics, antidepressants, antimanic, and antipsychotic drugs, and some sedative-hypnotics.
1.1.5 “Approaches to the elucidation of the sites and mechanisms of action of CNS drugs demand an understanding of the cellular and molecular biology of the brain. Although knowledge of the anatomy, physiology, and chemistry of the nervous system is far from complete, the acceleration of interdisciplinary research on the CNS has led to remarkable progress (Bloom, 1996)” This lecture introduces guidelines and fundamental principles for the comprehensive analysis of drugs the affect the CNS.
1.2 An introduction to Central Nervous System
The central nervous system (CNS) consists of a brain and spinal (nerve) cord. Most invertebrates and all vertebrates have sensory and motor neurons that are linked by way of a CNS. Most invertebrates have a CNS that is organized into a brain and a longitudinal nerve cord that is ventral to the digestive system, whereas chordates have a spinal cord that is hollow and dorsal to the digestive system. The CNS processes input from the internal and external environments, integrates information, and controls the body’s responses through efferent pathways to the body.
The brain is protected by the skull in vertebrates. The head is usually first to make contact with changes in the environment (for example, changes in light through the eyes, sound through the ears, and olfactory encounters through the nose), so it is beneficial to have the information-processing tissues of the nervous system concentrated there.
The nerve cord, or spinal cord, serves as a connection between the peripheral nerves and the brain. It receives sensory information from the periphery, relays it to the brain for interpretation and feedback, and coordinates many reflexes. It also contains the cell bodies of many of the neurons that control the body’s glandular and muscular responses by way of the peripheral nervous system.
1.3 Schematic Organization of the Gross Anatomy of the CNS
1.3.1 The spinal cord
The spinal cord is composed of four main groups of segments, ie the sacral, lumbar, thoracic, and cervical segments passing from caudal to rostral. Ascending and descending tracts are located peripherally in the white matter, while cells and synaptic connections are concentrated in the H-shaped central gray matter. Sensory information flows into the dorsal horns of the spinal cord, and motor information leaves via the ventral horns. Preganglionic sympathetic neurons are found in the intermediolateral cell columns of the thoracolumbar spinal cord. Preganglionic parasympathetic neurons are found in an analogous area of the sacral spinal cord (and the brain). The spinal cord receives sensory information from the periphery, processes that information locally via sensory-motor reflexes and sends sensory information to the brain. The brain transmits motor commands to the spinal cord for the regulation of motor neurons found in the ventral horns that permit voluntary motor function.
1.3.2 The medulla, pons, and midbrain
These regions of the brain serve as bridges between the spinal cord and more rostral structures. They contain most of the nuclei of the cranial nerves (optic, oculomotor, trochlear, trigeminal, abducens, facial, vestibular, glossopharyngeal, vagus, spinal accessory, hypoglossal) (but not olfactory). Major sensory and motor tracts reciprocally interconnecting the spinal cord with higher structures pass through this part of the brain. In the central core of this region is located the reticular formation, which is a region of gray matter which receives afferent collaterals from ascending sensory tracts and relays this information rostrally for the maintenance of arousal and regulation of sleep. These regions also contain nuclei for the coordination of numerous reflexes including coordination of eye movements, regulation of blood pressure, control of breathing, vomiting, and swallowing.
1.3.3 The limbic system
This includes structures such as the hippocampus, septum, amygdala, hypothalamus, and olfactory lobes. These structures lie beneath the cortex and integrate emotional states with motor and visceral responses. The hippocampus is also crucial to the formation of recent memories and is often injured in Alzheimer’s disease. The hypothalamus is a principal integrating region for the autonomic nervous system, and regulates body temperature, water balance, intermediary metabolism, sexual cycles, secretions of the pituitary gland, and circadian cycles.
1.3.4 The extrapyramidal motor system
This includes the basal ganglia, such as the caudate nucleus, globus pallidus, substantia nigra and subthalamic nucleus. This system complements the functions of the pyramidal or voluntary motor pathways and is involved in diseases such as Parkinsons and Huntingtons diseases.
1.3.5 The thalamus and cerebral cortex
The thalamus lies in the center of the brain, above the hypothalamus, and serves as a region for relay of ascending sensory information to various regions of the cerebral cortex. The cerebral cortices constitute the largest division of the brain in man. The human cortex contains approximately 50 billion neurons, each of which can make and receive thousands of synapses, thereby providing astronomical numbers of potential synaptic interactions. The cortex is divided into frontal, parietal, occipital, and temporal lobes. The cortex processes sensory information, controls voluntary motor functions, and is responsible for higher cortical functions such as abstract thought, consciousness, and memories.
1.4 Schematic Organization of Brain Microanatomy
1.4.1 The CNS is composed of excitable cells that conduct information ie neurons, and of supportive cells such as various types of glia. Most neurons have one axon which transmits an action potential away from the cell body, and many dendritic processes which receive synaptic contacts from other neurons. Synaptic relationships are most commonly seen to be axo-dendritic or axo-somatic, however evidence has been presented that indicate the presence of axo-axonic, dendro-dendritic and soma-somatic synapses.
1.4.2 There are three main patterns of organization of neuronal connections.
1. Long hierarchical patterns are typically found in the primary sensory and motor pathways. The essential feature of this is that chains of neurons provide a precise flow of information, but destruction of any link in the chain incapacitates the entire system. Few transmitters are known in the major links of sensory and motor pathways. SP is a transmitter of primary afferents, and ACh is the transmitter of alpha motor neurons innervating skeletal muscles.
2. The second pattern of organization involves neurons whose connections are established locally ie interneurons or local circuit neurons. They regulate flow of information through their own small spatial domain. Important transmitters include the inhibitory transmitters GABA and Glycine, and excitatory transmitters glutamate and aspartate.
3. The third pattern of organization involves neurons which, from a single anatomical location, send multiple branched and divergent connections to many target cells located at great distances. However, there is no apparent hierarchy of organization such that destruction of one link causes major disruption of function. Typical examples include NE neurons of the locus coeruleus, which project to the cortex and spinal cord etc.
1.4.3 Neuroanatomy at a glance
The telencephalon gives rise to the striatum (caudate nucleus and putamen), the hippocampus and the neocortex, its cavity becomes the lateral ventricles (first and second ventricles). The diencephalon gives rise to the subthalamus, hypothalamus, thalamus and epithalamus, its cavity to the third ventricle. The mesencephalon gives rise to the tectum, pretectum, cerebral peduncle and its cavity develops into the mesencephalic duct or cerebral aqueduct. Finally, the rhombencephalon gives rise to the pons, the cerebellum and the medulla oblongata, its cavity becomes the fourth ventricle.
1.5 The Blood-Brain Barrier
1.5.1 The concentration of many drugs in the blood will differ substantially from its concentration in the brain. The Blood-Brain Barrier is a semipermeable barrier to the passive diffusion of macromolecules, and charged molecules including neurotransmitters , their precursors and metabolites, and some drugs from the blood stream into various regions of the brain.
1.5.2 Windows in the barrier
The efficacy of the BBB varies. It is much less effective as a barrier in the regions of the median eminence, area postrema, pineal gland, subfornical organ, and subcommissural organ.
1.5.3 Active transport of some substances occurs across the BBB in either direction. For example many transmitter metabolites are cleared from the brain into the CSF by an acid transport system in the choroid plexus. Cerebral ischemia and inflammation can modify the BBB and permit access of some molecules which ordinarily are excluded.
1.6 Synaptic Transmission
1.6.1 Definitions
1. A neurotransmitter is a chemical contained in a neuron which is released by an action potential, crosses the synaptic cleft, and interacts with a post-synaptic target to cause excitation or inhibition of that target.
a. There are multiple criteria which a molecule must meet in order to be considered a neurotransmitter.
1. The transmitter must be shown to be present in the presynaptic terminals of the synapse and in the neurons from which those presynaptic terminals arise.
2. The transmitter must be released from the presynaptic nerve concomitantly with presynaptic nerve activity.
3. When applied experimentally to target cells, the effects of the putative transmitter must be identical to the effects of stimulating the presynaptic pathway.
2. A neuromodulator is a chemical which does not by itself cause excitation or inhibition postsynaptically, but which influences the probability that a neurotransmitter released from the same cell will cause a post-synaptic response.
3. A neurohormone is a substance released from a neuron which travels far beyond the synapse, ie into the blood, to influence the activity of distant targets.
1.6.2 There are three major classes of neurotransmitters/neuromodulator in the CNS
1. Monoamines: ie DA, NE, EPI, 5-HT, ACh
a. DA particularly important in CNS pharmacology of schizophrenia, affective disorders, Parkinsons disease, and neuroendocrine dysfunction.
2. Amino acids: ie GABA, Glycine, Aspartate, Glutamate
3. Peptides: ie SP, NPY, VIP, Enkephalins etc etc
a. SP is the transmitter of primary afferents carrying pain? Enkephalins are the body’s own morphine.
1.6.3 Considerable evidence indicates co-localization of multiple neurotransmitters in individual neurons
1. NPY and NE in sympathetic postganglionics, and in the CNS we have colocalization of PNMT (EPI) and NPY in the C1 nucleus.
1.6.4. Examples of drug sensitive sites in synaptic transmission
1. Microtubules responsible for orthograde and retrograde transport of macromolecules between the soma and distal processes. Drug: colchicine
2. Electrically conductive axonal membranes. Drug: local anesthetics.
3. Terminal sites for synthesis, storage, and release of transmitters: Drugs: alpha methyl para tyrosine, reserpine, tyramine.
4. Sites for active reuptake of released transmitters. Drugs: Cocaine, tricyclic antidepressants.
5. Pre- and post-synaptic receptor sites. Drugs: clonidine, NE, ACh.
1.7 Severe side effects
CNS side effects can lead to or exaggerate clinical depression, including suicidal feelings and clinical paranoia. It is very important therefore that you are aware that such moods swings can be related to efavirenz and that you are not ‘going mad’.
Why these symptoms are associated with efavirenz is not understood. It is also not possible to predict who will experience more severe symptoms.
Some studies have cautioned against using efavirenz if you are already depressed or have a history of psychiatric illness, but people without such a history have also found symptoms difficult.
Several reports have been published of severe reactions in people with no previous psychiatric symptoms or illness.
Some studies have linked higher efavirenz levels to low body weight. Importantly, research in 2004 showed that race may be an important factor. Several studies showed that a higher percentage of African women metabolize efavirenz more slowly. This results in higher doses than they need.
Often side effects are related to high blood levels of efavirenz. Measuring drug levels with TDM can allow dose reductions without reducing the HIV effect of the combination or risking resistance.
Several studies showed that some poeple, particularly African women, clear efavirenz more slowly from their bodies. This results in higher doses than they need.
Symptoms include:
· Impaired concentration, confusion and abnormal thinking.
· Mood swings including anxiety, agitation, depression, paranoia (feeling very anxious or nervous) and euphoria (feeling very happy).
· Sleep disturbance including insomnia, drowsiness, vivid dreaming and nightmares.
Measuring efavirenz levels with <href=”#tdm”>therapeutic drug monitoring (TDM) can allow dose reductions without reducing the HIV effect of the combination or risking resistance.
1.8 Central nervous system infection
Central nervous system infections are those infections of the central nervous system (CNS). There are four main causes of infections of the nervous system: bacterial, viral, fungal and protozoal.
1.8.1 Bacterial infections can be pyogenic infections (e.g., meningitis; brain abscess; subdural and epidural abscesses), tuberculosis, neurosyphilis, or leprosy.
1.8.2 Viral infections may be meningitis, encephalitis, poliomyelitis, slow virus infections, acquired immune deficiency syndrome (AIDS), and post-infectious syndromes.
1.8.3 Fungal infections may be meningitis or meningoencephalitis, brain abscess, or spinal epidural infection.
1.8.4 Protozoal infections include toxoplasmosis, malaria or amoebic infection.
1.9 CNS DRUG DISCOVERY
Modern CNS drug discovery began with Daniel Bovet at the Pasteur Institute in Paris. He wanted to understand the physiological role of histamine, and realized the actions of neurotransmitters such as acetylcholine and adrenaline could be investigated much more effectively with receptor antagonists: atropine and ergotamine, respectively. Using guinea pig intestine, he therefore screened compounds that had previously been synthesized at the Institute for antihistamine activity. None of the compounds identified were sufficiently safe for human use, but in 1941 phenbenzamine was found suitable for clinical use, which led the way for a large number of antihistamine medications. Henri Laborit (a French surgeon) was one of the first to use antihistamines to prevent the traumatic consequences of shock caused by circulatory collapse during surgery. This led him to discover the important effects that antihistamines, particularly promethazine, had on the CNS. He used promethazine and found that it made patients less anxious. Laborit visited the manufacturers, Rhone-Poulenc, at Vitry-sur Siene, near Paris, and persuaded them to synthesize analogs. In the spring of 1951, Laborit was given samples of chlorpromazine. So pleased was he with the “beatific quietude” it produced that he recommended it for use in calming agitated patients. Two Parisian psychiatrists (Jean Delay and Piere Denikeer) observed clear-cut benefits in a variety of patients including agitated and/or anxious patients, hyperactive manics, and schizophrenics.Insight into the biochemical basis of this efficacy emerged from Sweden in 1962 when Arvid Carlsson demonstrated that chlorpromazine (and other neuroleptics) increase dopamine turnover. Carlsson, who was subsequently awarded the Nobel prize for his contribution to our understanding of transduction in the nervous system, suggested that they work by blocking dopamine receptors. This was subsequently confirmed by many groups worldwide. The first generation of neuroleptic drugs was shown to block D2 receptors and have made a substantial contribution to the management of schizophrenia. However, such compounds have a number of serious limitations. Firstly, they are not always effective. Secondly, positive psychopathological symptoms may benefit more than negative or deficit symptoms. Thirdly, antipsychotics are generally associated with a variety of adverse neurological effects; these effects were first seen with chlorpromazine, which caused persistent abnormal facial movements (tardive dyskinesia). A major advance in this area emerged in 1988 with the description, by Kane and colleagues in the United States, of a compound (clozapine) with a much reduced propensity to induce adverse neurological effects. This “atypical” antipsychotic was active at other receptor types, including D4 receptors and led to the emergence of a new generation of “atypical” antipsychotics during the 1990s, which have been further refined during this decade, e.g., aripiprazole.
2. Drug Classification
(According to their primary pharmacological activity)
This section describes several common schemes for classifying drugs with psychoactive properties.
Chemical Structure
Compounds are often classified according to their chemical structures. Although this is useful for medicinal chemists, it does not provide a meaningful classification scheme for categorizing drug effects. Some compounds with similar chemical structures produce very similar biological effects (e.g., morphine, heroin), but others which belong to the same chemical class often produce much different effects (e.g., apomorphine, nalorphine). Furthermore, compounds which differ in chemical structure often produce similar biological effects (e.g., amphetamine, cocaine).
Pharmacological Activity
This scheme classifies drugs according to their primary pharmacological activity. All compounds produced multiple effects, so what is consider the primary effect and what is considered the secondary effect varies as a function of reference point. Often the primary therapeutic use of a compound is considered its primary effect and thus used to classify it pharmacologically.
The classification scheme given below focuses on each compound’s main psychotropic effects which in some cases classifies it differently from what might be considered its primary pharmacological effect (i.e., based on therapeutic use). For example, pseudoephedrine is a popular decongestant that has mild stimulatory properties. Pseudoephedrine’s decongestant effect might be considered its primary effect, while its stimulatory effect would be considered a secondary side-effect. However, from a psychopharmacological perspective, pseudoephedrine’s stimulatory effect is its primary effect and its decongestant action is a secondary (although therapeutically more useful) effect. Therefore, pseudoephedrine is classified below as a mild stimulant like caffeine and nicotine.
2.1 Classification of CNS DRUGS
(According to their primary pharmacological activity) These are classified into the following classes:
· Anti Parkinson’s drugs
· Anti Alzheimer drugs
· Anxiolytic and hypnotic drugs
· CNS stimulants
· Anesthetics
· Antidepressant drugs
· Neuroleptic drugs
· Opioids analgesics and antagonist
· Antiepileptic drugs
· Analgesics
· Anti convulsants
· Psychotropic drugs
· anti psychotropic drugs
These different classes of drugs acting on CNS are further classified as:
1. Antiparkinsonian drug:
a. Drugs affecting brain dopaminergic system
1. Dopamine precursor: Levodopa.
2. Dopaminergic agonist: Bromocriptine, Lisuride, Pergolide, Piribedil.
3. Peripheral decarboxylase inhibitors: Carbidopa, Benserazide.
4. Facilitate dopaminergic transmission: Amantadine, Selegiline/Deprenyl.
b. Drugs affecting brain cholinergic system
1. Central anticholinergics: Trihexyphenidyl, Procyclidine, Biperiden.
2. Antihistaminics: Orphenadrine, Promethazine.
2. Antialzheimer drugs
· Donepezil
· Galantamine
· Memantine
· Rivastigmine
· Tacrine
3. Sedative (Anxiolytic):
1. A sedative agent should reduce anxiety.
2. A sedative should exert a calming effect with little or no effects on motor or mental functions.
3. Depression of CNS should be the minimum consistent with therapeutic efficacy.
Hypnotic:
1. A hypnotic drug should produce drowsiness.
2. Should encourage the maintenance of a state of sleep that resembles the natural sleep states.
3. CNS depression should be more pronounced than sedation.
Classification of anti anxiety drugs:
- Barbiturates:
- Long acting: Phenobarbitone, Mephobarbitone.
- Intermediate acting: Amytobarbitone.
- Short acting: Hexobarbitone.
- Ultra short acting: Thiopental-Na.
- Benzodiapines: Diazepam, Lorazepam, Oxazepam.
- Aldehyde derivatives: Paraldehyde.
- Alcohol derivatives: Ethanol, Chloral hydrate.
- Cabamets: Ethinmate.
- Inorganic: KBr, NaBr.
- Miscellaneous: Scopolamine, Antihistamine.
- Newer agents: Zopiclone, Zolpidem.
Classification of Barbiturate:
According to chemical structure:
Þ Oxybarbiturates: Oxygen present in position C2.
Þ Thiobarbiturates: Sulfur present in position C2.
According to duration of action:
Long acting:
1. Duration of action: >6 hours.
2. Main use: As anticonvulsant
3. Examples: Phenobarbitone, Barbital.
Intermediate acting:
1. Duration of action: 3 – 5 hours.
2. Main use: As hypnotic.
3. Examples: Amobarbital, Butabarbital.
Short acting:
1. Duration of action: 2 hours.
2. Main use: As sedative.
3. Examples: Pentobarbital, Hexobarbital, Secobarbital.
Ultra-short acting:
1. Acts within few seconds.
2. Duration of action: 30 minutes.
3. Main use: As intravenous anaesthetic.
4. Examples: Thiopental-Na.
According to therapeutic activity:
Anticonvulsant and sedative:
1. These are long acting barbiturates.
2. Duration of action: >6 hours.
3. Examples: Phenobarbitone, Barbital.
Sedative and hypnotics:
1. These are intermediate and short acting barbiturates.
2. Duration of action: 2 – 5 hours.
3. Examples: Amobarbital, Pentobarbital, Hexobarbital, Secobarbital.
General anaesthesia:
1. These are ultra short acting barbiturates.
2. Acts within few seconds.
3. Duration of action: 30 minutes.
4. Examples: Thiopental-Na.
4. CNS STIMULANTS
A. Psychomotor stimulants
· Amphetamine
· Caffeine
· Cocaine
· Methylphenidate
· Nicotine
· Theobromine
· Theophylline
B. Psychotomimetic drugs
· Lysergic acid diethylamide
· Phencyclidine
· Tetrahydrocannabinol
5. ANESTHETICS
a. Preanesthetic medication
· Anticholinergics
· Antiemetics
· Anti histamines
· Barbiturates
· Benzodiazepines
· Opioids
b. Muscle relaxant
· Atracurium
· Succinylcholine
· Vecuronium
C. General anesthetics
Route: inhaled
· Enflurane
· Halothane
· Isoflurane
· Methoxyflurane
· Nitrous oxide
· Svoflurane
Route: intravenous
· Methohexital
· Thiamylal
· Thiopental
· Diazepam
· Lorazepam
· Midaxolam
· Etomidate
· Fentanyl
· Morphine
· Droperidol+fentanyl
· Ketamin
· Propofol
D. Local anesthetics
· Bupivacaine
· Lidocaine
· Procaine
· Tetracaine
6. Anti depressants
A. Tricyclic/polycyclic
· Amitriptyline
· Amoxapine
· Desipramine
· Doxepin
· Imipramine
· Maprotilin
· Nortriptyline
· Protriptyline
· Trimipramine
B. Selective serotonin reuptake inhibitors
· Fluoxetine
· fluvoxamine
· Nefazodone
· Paroxetine
· Sertraline
· Trazodone
· Venlafaxine
C. Mono amine oxidase inhibitors
· Isocarboxazid
· Phenelzine
· Tranylcypromine
D. Drugs used to treat mania
· Lithium salts
7. NEUROLEPTIC DRUGS
a. Phenothiazines
· Chlorpromazines
· Fluphenazine
· Prochlorperazine
· Promethazine
· Thioridazine
b. Benzisoxazoles
· Risperidone
c. Dibenzodiazepines
· Clozapine
d. Butyrophenones
· Haloperidol
e. Thioxanthenes
· Thiothixene
8. Opoid analgesics and antagonists
a. Strong agonists
· Fentanyl
· Heroin
· Meperidine
· Morphine
· Sufentanil
b. Moderate agonists
· Codein
· Propoxyphene
c. mixed agonist antagonist
· Buprenorphine
· Pentazocine
d. Antagonists
· Naloxone
· Naltrexone
9. Antiepileptic drugs
· Carbamazepine
· Clonazepam
· Clorazepate
· Diazepam
· Ethosuximide
· Gabapentin
· Lamotrigine
· Phenobarbital
· Phenytoin
· Primidone
· Tiagabine
· Topiramate
· Valproic acid
· Vigabatrin
Classification of antiepileptic drugs:
1. Barbiturates:
o Phenobarbitone
o Mephobarbitone
2. Deoxybarbiturate:
o Primidone
3. Hydantoins:
o Phenytoin
4. Iminostilbene:
o Carbamazepine
5. Succinimide:
o Ethosuximide
6. Aliphatic carboxylic acid:
o Valproic acid
7. Benzodiazepines:
o Clonazepam
o Diazepam
8. Newer drugs:
o Lamotrigine
9. Miscellaneous:
o Trimethadione
10. Analgesics:
Analgesics are the agents which relieve pain without impoting degree of conciousness analgesics act on the pathway of pain perception.
a. narcotic analgesics
(i) Natural: – 1.opium alkaloids (morphine ,codeine )
(ii) Semi synthetic opiates: – oxy morphine, heroin
(iii) synthetics-analgesics:-
· Meperidine,
· Methadone,
· Naloxone,
· Phenazocine
b. non narcotic analgesics :-
(i) Drugs with analgesics but with negligible anti inflammatory action eg. Acetaminophen, Phenacetin
(ii) Drugs with analgesics and mild to moderate anti inflammatory action eg.
· Ibuprofen
· Ketoprofen
· Mefenamic acid
· Diclofenac
(iii) Drugs with analgesics and marked anti inflammatory action eg.
· acetyl salicylic acid (aspirin)
· aloxiprin
· feprazone
11. Anti convulsants:
Anticonvulsants are the agents which stops convulsion
eg.
· tetanus
· strychnine
· poisoning
· Eclampsia,
· barbiturates
· diazepam
· paraldehyde
· mephenesin
· tobucuranine,
Therapeutic indications for anticonvulsant agents:
1. Simple partial:
o Phenytoin
o Carbamazepine
o Phenobarbital
o Primidone
2. Complex partial:
o Phenytoin
o Carbamazepine
o Primidone
3. Tonic clonic:
o Phenytoin
o Carbamazepine
o Phenobarbital
o Primidone
o Valproic acid
4. Absence:
o Ethosuximide
o Valproic acid
o Clonazepam
5. Myoclonic:
o Valproic acid
o Primidone
6.Infantile:
o Phenobarbital
o Primidone
7. Status:
o Phenytoin
o Diazepam
o Phenobarbital
12 Psychotropic drugs:
Psychotropic drugs are defined as those that affect mood and behavior.
Types of psychotroic drugs:
Depending on the primary use, the psychotropic drugs may be grouped into –
1. Antipsychotic (neuroleptics, major tranquillizer): Useful in all types of psychosis, especially schizophrenia.
2. Antianxiety (anxiolytic-sedative, minor tranquillizer): Used for anxiety and phobic states.
3. Drugs for affective disorders:
o Antidepressants for minor as well as major depressive illness, phobic states, and obsessive-compulsive behaviour.
o Antimanic (mood stabilizer) to control mania and break into cyclic affective disorders.
4. Psychotomimetic (psychedelic, psychodysleptic, hallucinogen): These are seldom used therapeutically but produce psychosis like states, majority are drugs of abuse.
13. Antipsychotic drugs: Antipsychotic drugs are used to treat schizophrenia.
Classification of Antipsychotic drugs:
a. Phenothiazines:
o Aliphatic side chain: Chlorpromazine, Triflupromazine.
o Pilperidine side chain: Thioridazine.
o Piperazine side chain: Triflupromazine, Fluphenazine.
b. Butyrophenones: Haloperidol
c. Thioxanthenes: Flupenthixol.
e. Others: Pimozide, Reserpine.
f. Atypical neuroleptics: Clozapine, Risperidone.
DEA Drug Schedules
The Controlled Substances Act of 1970 divided substances to be regulated into 5 schedules. These schedules govern the legal distribution and use of most substances with a significant abuse liability. (For details of the Controlled Substances Act and its revisions, see Appendix C, Agents Manual–DEA SENSITIVE.) The Drug Enforcement Administration is the primary federal agency charged with enforcing these regulations and with coordinating national and international efforts to reduce illicit drug supply. Hence, this classification scheme is often refereed to as the DEA Schedules.
- Schedule I substances have a high abuse liability and no approved medical use. These substances are available for investigational purposes only, and the research protocol must be approved by the Food and Drug Administration (FDA) prior to granting a license for handling Schedule I compounds. Drugs are provided by manufactures under federal contract. Pharmacies do not sell these compounds nor can physicians write prescriptions for them. Special record-keeping and storage procedures are required for all Schedules I substances.
- Schedule II-IV substances have decreasing abuse liabilities (II is the highest) and approved medical uses. Physicians are licensed to prescribe these compounds and pharmacies can dispense them, although pharmacies do not stock all of these substances. Schedule II compounds have more stringent record-keeping and storage requirements than do Schedule III and IV substances.
- Schedule V substances have a recognized abuse liability (and approved medical uses) but are generally not regulated (e.g., they are available without prescription). Many of these substances are used in common, over-the-counter medicines. Including compounds on this schedule facilitates state and local regulations deemed appropriate in some jurisdictions (e.g., An individual state may impose restrictions on some substance considered to have an unexpectedly high abuse liability.).
| Schedule | Abuse
Liability |
Approved
Medical Use |
Availability | Examples |
| Schedule I | High | No | investigational
use only |
|
| Schedule II | High | Yes | written
prescription with no refills |
|
| Schedule III | Moderately High | Yes | written or
telephone prescription with refills |
|
| Schedule IV | Moderate | Yes | written or
telephone prescription with refills |
|
| Schedule V | Low | Yes | prescription
not necessary |
Robitussin A-C (contains less than 100 mg codeine per 100 ml) |
| Note: Drugs are continually being reclassified. The above listing (except for Schedule V) is from the information contained on the DEA’s license application/renewal form (DEA-225) dated April 1988. | ||||
CNS Drugs (Generic) available in Bangladesh
1. Hypnotics
· Benzodiazepines
· Barbiturates
· Chloral hydrate & its derivatives
· Paraldehyde
· Miscellaneous Hypnotics
2. Sedative and Tranquillisers : Anxiolytics
· Benzodiazepines
· Diazepam
· Alprazolam
· Bromazepam
· Chlordiazepoxide
· Clorazepate
· Lorazepam
· Oxazepam.
3. Antipsychotic and Related drugs
a) Antipsychotic drugs:
§ Phenothiazines
§ Thozanthenes
§ Butyrophenone
§ Dihydroindolone
§ Dibenzoxazepine
b) Atypical Antipsycholic dmgs:
· Amisulpride
· Aripiprazole
· Clozapine
· Olanzapine
· Quetiapine
· Risperidone
· Sertindole
· Ziprasidone
· Zotepine.
c) Antimamic drugs: Lithium salt.
4. Antidepressants
a. Tricyclic & related antidepressants
b. MAOIs
c. SSRI and related antidepressants
d. Miscellaneous Antidepressants
5. Drugs used in Nausea, Vomiting & Vertigo
a. Drugs used in vestibular disorders-
· Cinnarizine
· Meclizine
· Promethazine
b. Drugs used for Meniere’s disease-Beta histamine,
c. Drugs used in mausea & vomiting in pregnancy.
6. Anticonvulsant /antiepileptic drugs.
| a) Carbama Zepine | f) Clobazam |
| b) Clonazepam | g) Diazepam |
| c) Lamotrigine | h) Oxcarbazepine |
| d) Phenobarbitone | i) Phenytoin |
| e) Sodium Valporate |
7. Drugs used in Rigidity & Tremor: Parkinsonism
a) Dopaminergic Drugs-
· Levodopa,
· Co-carbidopa
· Bromocriptine
· Entacapone
· Selegiline,
b) Antimuscarinic drugs Procyclidine,
c) Drugs used in essential tremor, Choreatics and related disorders Haloperidol.
8. Psychotropic drugs- Piracetam.
9. CNS Stimulants- Caffeine
10. Appetite Suppressants / Antiobesity drugs
· Pancreatic lipase inhibitor
· Centrally acting- Sibutramine
11. Durgs for dementia
a) donepezil,
b) Rivastigmine
12. Analgesic
13. Drugs used in substance dependence
a) Alcohol & Opioid dependence-Naltrexone,
Classification of CNS drugs available in Bangladesh with their trade names
1. Hypnotics
| Brand Name | Generic Name | Company Name | Pac Size | Price (MRP TK.) |
| 1. Aluctin cap. | Flurazepam | Ambee | 100’s | 354 |
| 2. Anquil tab, | Midazolam | General | 7.5mg x 30’s 15mg x 10’s | 240
135 |
| 3.Dormicum Inj. | -do- | Roche | 15mg/3ml
3ml x 5′ |
843.75 |
| 4. Dormicum Tab. | -do- | -do- | 7.5mg x 30’s | 297.00 |
| 5. Milam Tab | -do- | Sk+F | 7.5 x 30’s mg
15x 10’s mg |
240
150 |
| 6.Amoctin Tab | Nitrazepam | Sk+F | 100’s | 60 |
| 7. Eplon cap. | Zaleplon | Beximco | 5mg x 30’s
10mgx 30’s |
180
300 |
| 8. Natsin Tab | Melatonin | Incepta | 100’s | 300 |
| 9. Imovane Tab | Zopiclone | Imovance | 30’s | 227.70 |
2. Sedative & Tranquillizers:
| Brand Name | Generic Name | Company | Pacsize | MRP |
| 1. Sedil Tab | Diazepam | Square | 100’s | 22 |
| 2. Diazimet Tab | -do- | Medinet | 100’s | 22 |
| 3. Easium Tab | -do- | Opsonin | 100’s | 21 |
| 4. Phasmapam Tab | -do- | Phasmadesh | 250’s | 62.50 |
| 5. Sedil Inj. | -do- | Square | 10 amps | 110 |
| 6. Sedulin Tab | -do- | Jayson | 100’s | 21 |
| 7. SerelamTab | Alprazolam | General | 100’s | 200 |
| 8. Zolium | -do- | Incepta | 100’s | 200 |
| 9. Laxyl Tab | Bromazepam | Square | 50’s | 100 |
| 10. Nightus Tab | -do- | Beximco | 100’s | 150 |
| 11. Detens Tab | Clobazam | Orion | 30’s | 75 |
| 12. Keolax Tab. | -do- | Beximco | 100’s | 275 |
3. Antipsychotic Drugs
| Brand | Generic Name | Company | Pacsize | MRP |
| 1. Opsonil Tab | Chlorpromazine Hcl | Opsonin | 100mg x 50’s | 45 |
| 2. Modecate Inj. | Eluphenazine | Kapsicorn | 1ml amp | 116.55 |
| 3. Melleril Tab | Thiosidazine | Novartis |
04. Drugs used in Nausea, Vomiting & Vertigo
| No. | Brand Name | Generic Name | Company Name | Packs | Mrp |
| 01. | Cinarin Tab. | Cinnarizine | Nipa | 15 mg/tab
100’s Pack |
27 |
| 02. | Vertina Tab. | Meclizine | Square | 50mg/tab
50’s Pack |
125 |
| 03. | Stemitil Tab. | Prochlorperazine | Sanofi Aventis | 5mg/tab
500’s Pack |
150 |
| 04. | Menaril Tab. | Betahistine | Incepta | 8mg/tab
100’s Pack |
200 |
| 05. | Maxil Tab. | Metoclopramide | Nipa | 10mg/tab
100’s Pack |
34 |
| 06. | Naurif Tab. | Granisetron | Square | 1mg/tab
20’s Pack |
560 |
| 07. | Onset 8 Tab. | Ondansetron | beximco | 8mg/tab
30’s Pack |
300 |
05. Anticonvulsant/ Antiepileptic drugs
| No. | Brand Name | Generic Name | Company Name | Packs | Mrp |
| 01. | Carbazin Tab. | Carbamazepine | Sk +F | 200mg/tab
50’s Pack |
152 |
| 02. | Arotril Tab. | Clonazepam | Aristopharma | .5mg *50’s &2mg *30’s | 100
120 |
| 03. | Lamitrin Tab. | Lamotrigine | ACI | 50mg/tab
30’s Pack |
240 |
| 04. | Trileptal Tab. | Oxcarbazepine | Novartis | 300mg*50’s,
600mg*50’s |
1250
2250 |
| 05. | Diphedan Tab. | Phenytoin | Ambee | 100mg/tab
100’s Pack |
101 |
| 06. | Valex Tab. | Sodium valproate | Incepta | 200mg/tab
50’s Pack |
125 |
| 07. | Neuropen Tab. | Gabapentin | Drug Int. | 300mg/tab
30’s Pack |
480 |
06. Drug used in rigidity & tremor: Parkinsonism
| No. | Brand Name | Generic Name | Company Name | Packs | Mrp |
| 01. | D –Dopa Plus Tab. | Levodopa | Drug Int. | Levodopa 250 & carvidopa 25mg
30’s Pack |
225 |
| 02. | Serocryptin Tab. | Bromocriptine | Serono/janata | 2.5mg/tab
30’s Pack |
647 |
| 03. | Jumex Tab. | Selegiline | Chinoin/city overseas | 5mg/tab
50’s Pack |
725 |
| 04. | Kdrine Tab. | Procyclidine | Opsonin | 5mg/tab
100’s Pack |
42 |
07. Psychotropic drugs
| No. | Brand Name | Generic Name | Company Name | Packs | Mrp |
| 01. | Neurolep Tab. | piracetam | square | 800mg/Tab
40’s Pack |
240 |
08. Appetite Suppressants/Antiobesity Drugs
| No. | Brand Name | Generic Name | Company Name | Packs | Mrp |
| 01. | Xenical Cap. | orlistat | Roche | 120mg/cap
84’s pack |
3543.75 |
| 02. | Obenil Cap. | sibutramine | square | 5mg/cap
30’s pack |
150 |
09. Drugs for Dementia
| No. | Brand Name | Generic Name | Company Name | Packs | Mrp |
| 01. | Elzer Tab. | donepezil | Square | 5mg/tab
30’s pack |
300 |
| 02. | Exelon Cap. | Rivastigmine | Novartis | 1.5,3,4.5,6mg/cap
60’s pack |
4920 |
10. Drugs used in substance dependence
| No. | Brand Name | Generic Name | Company Name | Packs | Mrp |
| 01. | Nodict tab. | naltrexone | Sun pharma | 50mg/tab
10’s pack |
550 |
Description of some CNS products of General Pharmaceutical and Beximco Pharmaceuticals
GENERAL Pharmaceuticals Ltd
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