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Lesson B.1 Notes

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Pharmacology and Toxicology
PHAR 100
Bill Racz

Lesson B. 1 - Physiological & Pharmacological Aspects of the Central & Peripheral Nervous System Nervous System • Divided into two main components: • Central nervous system (brain and spinal cord) and Peripheral nervous system • afferent or sensory nerve fibres which carry messages to the brain and efferent nerve fibres which carry messages from the brain and spinal cord to tissues • efferent system is divided into motor nerves ( skeletal muscle), and the autonomic nervous system Nervous System Central Peripheral Afferent Efferent Motor Autonomic Parasympathetic Sympathetic Nicotinic Muscarinic Alpha Beta Dopamine Nicotinic Beta1 Beta2 The Central Nervous System • Controls all bodily functions • Consists of a central part (the brain and spinal cord) linked to a peripheral part (nerve fibres). The sensory nerve fibres carry messages from tissues to the brain or spinal cord, and the motor nerve fibres carry messages from the brain or spinal cord to the tissues. Parts of the Brain and its functions: Three main parts: 1. Forebrain 2. Midbrain 3. Hindbrain 1. The Forebrain Lesson B. 1 - Physiological & Pharmacological Aspects of the Central & Peripheral Nervous System (a) Cerebral cortex (cerebrum): This is the largest part of the brain which is very rich in nerve cells. It is composed of grey matter (outside) and white matter (inside); it is divided into lobes or regions, each with specific functions. There are two halves or hemispheres to the cerebral cortex with numerous fibres connecting them. The functions of the cerebral cortex are: sensory and motor coordination, mental processes, intelligence, memory, vision, judgement, thought, speech, emotions, and consciousness. The cerebral cortex can be stimulated (excited) or depressed (inhibition) by drugs. (b) Thalamus: A relay centre; from here impulses are relayed to the cerebral cortex. The thalamus coordinates information. Its function is the coordination and filtration of incoming signals. It is also involved in appreciation of painful sensation. (c) Hypothalamus: A very important area; consists of various specialized regions of nuclei located near the base of the skull. The functions are to control the involuntary functions of the body that are necessary for living, e.g. regulation of heart, blood pressure, body temperature, and metabolism. It also controls feeding, drinking, sexual, and emotional responses. The hypothalamus forms a very important part of the limbic system. Neurons in the hypothalamus produce substances called releasing factors which travel to the pituitary gland and modify this gland. A number of drugs can affect the hypothalamus. (d) Pituitary: A small gland located at the base of the brain which secretes hormones that control growth, behaviour and metabolism of the body through the action of these hormones on peripheral tissues, e.g. follicle stimulating hormone stimulates follicle maturation in the ovaries. Thyroid stimulating hormone stimulates the thyroid gland to synthesize and release thyroid hormone. 2. The Midbrain The midbrain is the area that links the forebrain with the hindbrain. It is a relay centre for visual (eye) and auditory (ear) stimuli or signals. 3. The Hindbrain The hindbrain has many components. Only two, the medulla and the cerebellum, are described here. (a) Medulla (the bulb): This is the site of origin of many cranial nerves. It is where regulation of respiration (breathing centre) and regulation of heart and blood pressure occurs. It also exercises control over some involuntary activity (the autonomic nervous system). A number of drugs which depress respiration and blood pressure will do so by depressing the medulla, e.g. barbiturates. (b) Cerebellum: The cerebellum is a large, highly convoluted structure connected to the brain stem by large fibre tracts. It is responsible for coordination and posture. It does not initiate Lesson B. 1 - Physiological & Pharmacological Aspects of the Central & Peripheral Nervous System movement, but is an organizer of voluntary activity initiated elsewhere. Drugs which affect the cerebellum will cause ataxia (drunkenness), e.g. alcohol. The Brain Nerve Cell (The Neuron) : The functional unit of the brain is the neuron. The brain contains about 10 billion nerve cells, which differ from each other in shape and size. Basically, each nerve cell or neuron has three parts: 1. The cell body or soma contains a nucleus and surrounding cytoplasm which is packed with rough endoplasmic reticulum, a network of smooth endoplasmic reticulum, and abundant vesicles which can be secreted. These are characteristic of cells active in protein synthesis and secretion of substances. Neurons have two types of projections – dendrites and the axon. 2. The dendrites function as the receiving antennae for incoming information, are usually short, and can have highly complex branching patterns. The incoming information is accepted or picked up through a receptor located on the dendritic membranes. Upon receipt of a "signal" from another cell, an electric current is generated and transmitted to the axon. 3. The axon, a single fibre that extends from the cell body and ends at a synapse. The axon carries signals away from the cell body. The dendrites and cell body receive information in the form of pulses from other neurons. The neuron responds (or it does not respond) by sending its own pulses through its axon to another neuron. Some neurons are activated by other neurons; many neurons can activate themselves spontaneously. Organization The following schematic diagram depicts the organizational structure of the central nervous system. Neurons + Axons Tracts or Pathways Networks DRUGS Systems Behaviours Cognition Mood Sensory Motor Visceral Function The Synapse and the Concept of Synaptic Transmission In order for the brain to function properly, the nerve cells (neurons) must communicate with each other. The neurons are not continuous with each other, but simply touch each other only at Lesson B. 1 - Physiological & Pharmacological Aspects of the Central & Peripheral Nervous System certain places or junctions. The junction between two neurons is called the synapse. The synapse is commonly formed by contact of the axon belonging to one neuron with a dendrite or the cell body of another neuron. Each neuron may have thousands of synapses on its cell body or dendrites. An impulse (signal), when it reaches the synapse, has to be communicated to another neuron if it is to produce further effect. The passage of a signal from one neuron to another neuron is called synaptic transmission. Synaptic transmission is usually chemical in nature. Substances mediating synaptic transmission are synaptic transmitters. Synapses are usually unidirectional and one synapse makes one connection between two cells. However, a single cell can make synaptic connections with many other cells. In chemical transmission, the release of a transmitter substance is required in order to activate the other cell or pass on the message. The following diagram depicts the concept of synaptic transmission: The nerve impulse (electrical activity) passes down a nerve axon and releases a chemical substance into the synaptic cleft. The postsynaptic membrane contains binding sites for the chemical transmitter. These binding sites are called receptors. The binding of the chemical transmitter to the receptor usually provokes a change in the permeability of the membrane and ions (calcium) move across the membrane, causing a change in electrical activity of the membrane and this electrical activity is passed along to the next cell. The continuous presence of a transmitter in the synaptic cleft would prevent other impulses from getting through. To prevent the synapses from becoming non-functional, the chemical transmitter is removed by one of two major mechanisms: broken down by enzymes or taken back up into the presynaptic structure. The process of synaptic transmission is very rapid. The synapses can be a target site for many drugs. Some drugs can interrupt synaptic transmission, whereas others can enhance or facilitate it. There are many different ways in which drugs can interfere with this process, thereby modifying the activity of the brain. Concepts of Receptors The diagram depicts the concept of receptors and how agonists (stimulators of receptors) and antagonists (inhibitors of receptors) act. As stated above, after release into the synaptic Lesson B. 1 - Physiological & Pharmacological Aspects of the Central & Peripheral Nervous System cleft, the neurochemical transmitter or messenger binds to specific molecules known as receptors. Receptors are proteins synthesized in the rough endoplasmic reticulum, transported to different parts of the cell and inserted into the cell membrane of the cell body, dendrites and axons. (Some receptors can be inside the cell). Receptors have specificity for endogenous transmitters and this specificity or differences in the binding properties of receptors has been exploited in drug development. Stated another way, each endogenous transmitter usually has its own specific receptor. When the transmitter binds to the receptor, it elicits a specific response. Drugs can either stimulate a receptor (called agonists) or inhibit action on a receptor (called antagonists). In the human brain, there are hundreds of different types of receptors and receptor subtypes for a large number of transmitter substances, such as norepinephrine, dopamine, gamma- aminobutyric acid (GABA), glutamate, histamine, acetylcholine, opioids, and serotonin. A brief description of some of these transmitters and their receptors follows. Acetylcholine: Cholinergic synapses and receptors are found in both the peripheral nervous system (neuromuscular junction, autonomic ganglia and parasympathetic postganglionic synapses) and in the brain and spinal cord. Cholinergic receptors have two broad classifications. Those that are stimulated by nicotine are called nicotinic receptors. Nicotinic receptors are found in all autonomic ganglia, at the neuromuscular junction, and in certain regions of the brain. Muscarinic receptors are stimulated by
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