L Pharmacology ita “mm NERVOUS | an ye SYSTEM Some basic facts about the : / nervous system and how drugs4] Pharmacology Drugs & the nervous system ™ 1.1. THE NERVOUS SYSTEM A brief introductory description of the Central Nervous System and the Peripheral Nervous System. Synonyms for underlined expressions are found on the right. Use them when describing the CNS. A common distinction is made between the Central Nervous | itis possible to distinguish between System (CNS) and the Peripheral Nervous System (?NS). The smadeup ot Central Nervous system is composed of the brain and spinal | comprises cord. The Peripheral Nervous System, lying wholly oxtside the | CNS, is made up of the motor and sensory nerves and is usually | js found divided into two divisions: the afferent and the efferent. Afferent fibers convey sensory information from organs to the | CNS, while efferent fibers are axons that convey impulses from } transport the CNS toward outlying organs and viscera located within the PNS. Many pharmacologic products owe their effect to their action on the CNS and PNS. The efferent division is further subdi- vided into two systems: the motor nervous system and the autonomous nervous system. _ Efferent Division “AUTONOMOUS: NERVOUS SYSTEM © regulation of body homecs @ under uncon- @ under conscious | scious control control s cn Neurons can be clearly seen in this photograph. ™ PRACTICE 1: Describe the ANS. Fill in the blanks below, then look at the diagram on the next page and continue your descrip- tion. (This is also an opportunity to practice making a simple presentation). The efferent division can be into . The motor division skeletal muscles and movement. The ANS body homeostasis.Pharmacology Drugs & the nervous system [5 The Autonomous Nervous System PARASYMPATHETIC Fibers to iris of eye; salivary glands, heart, Jungs, stomach and other digestive organs SYMPATHETIC Fibers to iris, salivary glands, heart and lungs THORACIC. DIVISION. SYMPATHETIC Fibers to liver, stomach, pancreas, intestines, ‘adrenals and kidneys \ SYMPATHETIC PARASYMPATHETIC TP fi UF a SYMPATHETIC Fibers to bladder, colon, rectum and genitals LUMBAR DIVISION Zp / t SYMPATHETIC eh Fibers to blood vessels, Hy ‘sweat glands and hair fol- licles of lower limbs PARASYMPATHETIC Fibers to bladder, colon, rectum and genitals Only one-half of the system is represented here; it exists on both sides of the spinal cord. The sympa- thetic system (in dark) is characterized by chains of ganglia on either side of the cord and by other large genglia (shown as large circles). The parasympathetic system (lightly shaded) has its ganglia (not _ shown) nearer the organs stimulated so that it acts in a more piecemeal fashion.6} Pharmacology rugs & the nervous system Words to keep in mind yy VOCABULARY EXTRACT: ™ Adjectives and adverbs common: commonly: ™ Verbs to convey: to lie(lay/lain): to owe: to divide into: = Location within outside on either side on both sides on one side (ORDS TO SAY ALOUD a common word, a common occurrence a commonly found word; Itis commonly thought that. Neurons convey action potentials (signals). Blood conveys oxygen from the lungs to the brain. It lies within the CNS. It owes its effect to... It owes its efficacity to The ANS may be divided into two systems. It is located within the CNS. The peripheral nervous system lies outside the CNS. Located on either side of the spinal cord .. Located on both sides of the spinal cord ... Located on one side of the brain ractice saying the following words aloud, paying particular attention to stress. sympathetic parasympathetic adrenal saliva salivary ganglion afferent efferent si - pa - THET - ik syllables in SMALL capitals receive secondary stress; those in LARGE boldface type a- DREE - nil receive primary stress. suh - LYE - va The a symbol designates a neu- tral sound: the final ain sofa. PAR - 9 - si - pd - THET - ik SAL - 2 - vER - ee GANG - lee - on A-fer-ant EH-fer-ant ™ ENLARGING YOUR VOCABULARY AND PRONOUNCING THE WORDS CORRECTLY Below are the verbs and nouns used on the preceding pages. Write in their missing forms, saying both noun and verb out loud. Use each in one or two original sentences. VERBS NOUNS VERBS NOUNS 1] to locate 4 innervation 2] to convey 3 regulation 3] to divide 0 representationPharmacology Drugs & the nervous system | 7 @ 1.2. NEUROTRANSMITTERS Neurotransmitters enable and facilitate interneuronal communications via slight alterations in trans- membrane potentials. Cholinergic synapses release acetylcholine (ACh). Roughly half the amount of this neurotransmitter is found within the cell's cytoplasm, with the remaining half located in synaptic vesi- cles. A single synaptic vesicle may contain several thousand molecules of ACh. A single synaptic knob will contain a million vesicles. (See the figure.) THE TRANSMISSION OF IMPULSES The following is a simplified description of how neurons convey impulses (action potentials) synaptic cleft membrane synaptic knob ‘An action potential arrives, altering the knob’s, transmembrane potential. This results in depolar- ization of the membrane. @ Membrane depolarization causes Ca?* (calcium ions) to penetrate and enter the neuronal cytoplasm. © synaptic vesicles now fuse with the presynaptic membrane leading to the release of neurotransmit- ter molecules into the synaptic cleft. @ Ca?* ions are gradually eliminated from the knob's cytoplasm, chiefly by the endoplasmic retic- ulum. As the Ca?* concentration falls, the release of the neurotransmitter comes to a stop. endoplasmic reticulum vesicles © The neurotransmitter molecules diffuse across the cleft, bind to receptors located on the postsynap- tic surface and bring about an alteration in the transmembrane’s potential that increases permeability and allows sodium ions (Na+) to enter from the surrounding medium. This in turn triggers an action potential in the postsynaptic membrane. © The removal of the neurotransmitter ACh is ensured by means of enzymatic breakdown which results in the formation of acetate and choline, both reabsorbed by the synaptic knob. The enzyme is acetylcholinesterase (AChE) — also called cholinesterase. ™ PRACTICE 2: SPEAKING ‘Make complete sentences using the key words. 1. Neurotransmitters / interneuronal communication 2. 1/2 ACh in cytoplasm / 1/2 in vesicles in synaptic knob 3. arrival of an action potential / change in transmembrane potential / depolarization Answer these questions. 4. What happens when the neurotransmitter (here ACh) binds to receptors on the postsynaptic membrane? 5. What is responsible for the action potential triggered in this membrane? 6. What happens to the residual ACh in the synaptic cleft following this last event? For more work on cause and effect relation- ships see page 9.Pharmacology Drugs & the nervous system ™ ENLARGING YOUR VOCABULARY AND PRONOUNCING THE WORDS CORRECTLY Below you will find most of the verbs used thus far. Working with your instructor, say each verb aloud paying par- ticular attention to the stress pattern (primary and secondary stress). Then write in the corresponding noun forms, again saying each aloud. Note that in some cases the stress changes (as in the first, done as an example)! secondary stress primary stress T]t0 Miter \Xa/-ter-&-tion _ [B]tofuse 2] to arrive 13] to increase 3] to cause 14] to locate 4] to contain 5] to liberate 5] to convey 16] to penetrate 8] to depolarize 17] to release 7] to diffuse 18] toremain [8] to distinguish 19] toremove 9] to eliminate [20] to result 10] to form 21] to surround 2] to facilitate [22] to transmit WORDS TO SAY ALOUD: PRONUNCIATION PRACTICE Here are some words related to this unit. Practice pronouncing them and the words related to them, again paying careful attention to stress patterns. Read from left to right. jon jons synapse synapses enzyme enzymes depolarize — depolarizes regulate regulates jonize fonization synaptic synaptically enzymatic enzymatically depolarizing depolarization regulatory regulation SAY IT RIGHT: Practice pronouncing these words. catecholamine preganglionic acetylcholine norepinephrine adrenergic cholinergic acetylcholinesterase cholinesterase cat-a-KOHL 3 meen PREE-gang-lee-ON-ik a-set-al-KOH-leen nor-a-pih-NEF-rin ab-reh-NER-jik xou-leh-NER-jik a-seT-al-xou-la- NES-t0-RACE KOH-la-NES-ta-RACEPharmacology rugs 8 the nervous system | 9 Pi GRAMMAR SYNTHESIS By Cause and Effect Relationships 1, TO CAUSE: ‘The action potential causes depolarization of the transmembrane. The action potential causes it to depolarize. 2. TO RESULT IN: ‘The action potential results in depolarization of the transmembrane. 3. TO RESULT FROM: Depolarization results from the arrival of the action potential. 4, TOBRING ABOUT: The action potential brings about depolarization of the transmembrane. 5, TO INDUCE: The action potential induces depolarization of the membrane. 6. TO TRIGGER: The effect of the neurotransmitter is to trigger an action potential in the postsynaptic membrane. 7. TO LEAD TO: The alteration of the transmembrane leads to the influx of Ca?+. ™ PRACTICE 3 Describe the steps involving neurotransmitter release by the presynaptic neuron and its uptake by the postsynaptic neuron. Action potential i Jey | Depolarization with arrives at synaptic 1 ‘accompanying influx knob a of calcium ions. binding of neuro- transmitter to recep- tors Release of neu- rotransmitter from presynaptic! neuron into synaptic cleft Influx of sodium 7“, 4 : Elimination of ions. Result: i remaining neuro- depolarization cs transmitter via enzy- and action |: _matic action potential10| Pharmacology Drugs & the nervous system ™ PRACTICE 4: FLUENCY PRACTICE. IN OTHER WORDS. Rephrase each idea below using the indicated word or expressions. In some cases you will need to make significant syntactic changes. ACTION POTENTIALS RELEASE OF NEUROTRANSMITTER 1] An action potential arrives, altering the synaptic knob's transmembrane potential and causing depolarization of the membrane. 2] The neurotransmitter diffuses across the cleft, and, making contact with the postsynaptic membréne, induces an alteration in the mem- brane’s potential. Upon the arrival of an action potential... a. b. When an action potential arrives ...it ¢. First, an action potential arrives and d. The depolarization of the membrane is brought about by ACETYLCHOLINESTERASE 3] Tae enrects oF ACHE (acervecuounvestenase). This enzyme is found in the synaptic cleft and ‘postsynaptic membrane and is responsible for the breakdown of ACh molecules into acetate and choline and therefore prevents sustained synaptic stimulation. ACh produces.. The effect of ACh is to cause... ACh causes the membrane .. When ACh binds to receptors on the postsynaptic membrane ... e. An excitatory postsynaptic potential is a graded change which results aoge SAY IT RIGHT: Practice saying tl a. Diffusing across the cleft, .. b. The contact of the neurotransmitter and the exterior surface of the membrane causes ... ¢. The alteration in the postsynaptic membrane’s potential... Located in ... The enzymatic effect of ACHE is The role of ACHE is to ... ACh molecules. Without this enzymatic action If ACh is not eliminated, The non elimination of ACh ACETYLCHOLINE 4] The effect of ACh on the postsynaptic mem- ‘brane. ACh =» depolarization of the membrane and permeability to Nat. This depolarization is an excitatory postysnaptic potential (EPSP). It is a graded change, meaning that it occurs gradually over tim and not in one sudden step. an excitatory postsynaptic potentialDrugs & the nervous system 11 Pharmacol; Eyodting ... or ikilcting Some neurotrans- 9} exciting * e Others are nothing to get excited about. In fact, they're inhibiting. INHIBITORS 5] Some neurotransmitters result in ahyper- | a... exert an inhibitory effect on a ee eee b. When other neurotransmitters bind to recep- This hyperpolarization inhibits or prevents the tors on the postsynaptic membrane formation of action potentials and is called an An inhibi synaptic potential is pro- inhibitory postsynaptic potential (IPSP). Foie Bore re BY sane Dopamine, gamma aminobutyric acid (GABA) and serotonin are three examples of such neu- rotransmitters. ALTERED MEMBRANE PROPERTIES 6] Barbiturates, like the local anesthetics ben- a. Anesthetics such as .. produce their effects by b. Anesthetics such as ..., and like alcohol, inhibit... c. The inhibitory effect of ... causes zocaine and lidocaine and nitrous oxide, and also like alcohol, exert an inhibitory effect mak- ing the membrane less responsive to stimuli, and the transmission of action potentials. For pronunciation and vocabulary work see the next page.2] Pharmacology Drugs & the nervous system ™ ENLARGING YOUR VOCABULARY AND PRONOUNCING THE WORDS CORRECTLY Working with your instructor, say each verb aloud paying particular attention to the stress pattern (primary and secondary stress). Then write in the corresponding noun forms, again saying each aloud. Note that in some cases the stress changes (as in the first, done as an example)! secondary stress primary stress ae Ce 1) to alter (Al-ter-a-tion to excite 2] to block to increase 3] to break down to induce [4] to contact to inhibit to contract to present 6] to designate to prevent WORDS TO SAY ALOUD: PRONUNCIATION PRACTICE Read the following phrases and sentences out loud. Be careful of stress patterns. It excites... It’s exciting It has an excitatory effect It inhibits ... It's inhibiting It has an inhibitory effect. It has a noticeable inhibitory effect. It has a noticeable and long-lasting inhibitory effect. Depolarization results in an excitatory effect while hyperpolarization of the postsynaptic membrane produces the contrary — an inhibitory effect. SAY IT RIGHT: the three neurotransmitters dopamine DOH-pa-meen dopaminergic pox-pa-mee-NER-jik gamma aminobutyric GAM-2 a-MEEN-oh-byou-TIR-ik acid A-sid serotonin seR-oh-TOHN-inPharmacology rugs & the nervous system 13 Pw GRAMMAR SYNTHESIS: Bi Sentence construction ==M— using the verb MAKE MAKE + NOUN + ADJECTIVE © The drugs make the membrane less responsive. © It makes the process easier to understand. MAKE + NOUN + VERB (bare infinitive) © The drugs make the muscles contract. © What make dv 2 ™ PRACTICE 5: SPEAKING Restate the ideas using the verbs and expressions shown. See page 15 for information on how these verbs are used. 3 ways in which drugs can act on information transmission at synapses action on the rate of Prevention of neuro- prevention of neurotransmitter 2 transmitter 3 ‘neurotransmitter released (increase or inactivation binding to receptors decrease) accelerate prevent interfere slow down interfere block augment disrupt hinder decrease inhibit impede block Here are two drugs and one chemical product, a toxin, which affect transmission of action potentials. Practice the expressions above in providing a complete description (use expressions of cause and effect as well). See the preceding sections for information concerning neurotransmitters. neostigmine Qe (blocks acetyl- +holinesterase action) atropine © orocks binaing to ostsynaptic receptors) © orocks ach release rom presynaptic mem- toxin14) Pharmacology rugs & the nervous system ™ 1.3. THE AUTONOMOUS NERVOUS SYSTEM + Working in pairs if possible, read through the description below and fill in the box with the appropriate informa- tion. The autonomous nervous system (ANS) is composed of two subdivisions: the sympathetic and the parasympathetic, each with preganglionic and postganglionic neurons. Preganglionic neurons origi- nate in the CNS, (in the brain stem or spinal cord) and synapse with one or more postganglionic neurons whose cell bodies are found in the autonomic ganglia. Postganglionic fibers innervate internal organs but not skeletal muscle. ‘Two neurotransmitters requiring special attention are acetylcholine (ACh) and norepinephrine (NE), the latter also being referred to as noradrenaline. Both play important parts in the ANS, though not the same. All preganglionic neurons of the parasympathetic division are known to release ACh, while the neuro- transmitter liberated by the postganglionic neurons of the sympathetic division is norepinephrine. ‘Two other designations are often used when speaking of pre- and postganglionic neurons. These are cholinergic and adrenergic, referring to ACh- and NE-releasing neurons respectively. ANS DIVISION Parasympathetic OTHER TERMS USED Neurons releasing ACh are termed cholinergic neurons; receptors at synapses are nicotinic or muscarinic preganglionic postganglionic Neurons which release norepinephrine are called adrenergic neurons; receptors at synapses are alpha, beta or dopaminergic, all having subtypes (such as beta, and beta). ™ PRACTICE 6 Decide whether the following 4 statements are true or false. Justify your answers. All preganglionic neurons are cholinergic. Only adrenergic neurons are found in the parasympathetic division. No adrenergic neurons release ACh. No adrenergic neurons lie within the sympathetic division RWNoPharmacology Drugs & the nervous system} 15 Ei GRAMMAR SYNTHESIS: Hi Special Verbal patterns: Prevent/Hinder/Inhibit | PREVENT The substance prevents DNA synthesis. The substance prevents the DNA strands from separating. The drug prevents the spread of infection. It prevents the infection from spreading. = BLOCK ‘The substance blocks DNA synthesis. ™ Usual patterns for DISRUPT, INHIBIT, HINDER and IMPEDE disrupts inhibits The substance | pinders DNA synthesis. impedes = INTERFERE WITH The substance interferes with DNA synthesis (but does not necessarily block it alto- gether). ™ PRACTICE 7: PREPOSITION REVIEW Put an appropriate preposition in each blank. 1. Neurotransmitters are released the presynaptic knob and diffuse the synaptic cleft to bind receptors located the postsynaptic neuron 2. Action potentials are conveyed the length of the neuron. 3. Acetylcholinesterase is an enzyme which is involved the breakdown of the neurotransmitter. 4. Natural products and drugs act neurons and their ability to convey impulses. 5. The sympathetic division of the autonomous nervous system is concerned many voluntary functions, with the parasympathetic division generally devoted unconscious or involuntary func- tions such as heartbeat and respiration. 6. The ANS is responsible the regulation of homeostasis.