Principles Of Neuropharmacology PDF

PHARMACOLOGY AND TOXICOLOGY PRINCIPLES OF NEUROPHARMACOLOGY WO N G C H U N K E U N G 16 SEP 2024 1 CENTRAL NERVOUS SYSTEM Made up of the brain and spinal cord The brain – Controls how we move, feel, think and learn The spinal cord – Carries messa...

PHARMACOLOGY AND TOXICOLOGY PRINCIPLES OF NEUROPHARMACOLOGY WO N G C H U N K E U N G 16 SEP 2024 1 CENTRAL NERVOUS SYSTEM Made up of the brain and spinal cord The brain – Controls how we move, feel, think and learn The spinal cord – Carries messages back and forth between the brain and the nerves – The nerves run throughout the body https://www.zygote.com/assets/img/products/poly-models/3d-male-nervous-system-3.jpg 2 SUBDIVISIONS OF THE CENTRAL NERVOUS SYSTEM Central nervous system - Brain and spinal cord Have seven basic parts: – Medulla, pons, cerebellum, midbrain, diencephalon, cerebral hemispheres and spinal cord Brainstem – The medulla, pons, and midbrain Forebrain – The diencephalon and cerebral hemispheres https://www.ncbi.nlm.nih.gov/books/NBK10926/ 3  SUBDIVISIONS OF THE CENTRAL NERVOUS SYSTEM Medulla Midbrain Necessary for vision and hearing – Manages heart, circulation and breathing Role in motor movement and – Cardiovascular and respiratory systems link sleep/wake cycle together into a united system Pons Diencephalon Coordinating with the endocrine – Part of brainstem linking the brain to spinal system to release hormones cord Relaying sensory and motor signals to – Handles unconscious processes and jobs the cerebral cortex – Point for control muscles and carry Cerebral hemispheres information from senses in the head and Controls muscle functions, speech, face emotions, thought, learning and reading Cerebellum Spinal cord – Coordinating movement and balance Carries nerve signals from brain to – Important in language and attention body and vice versa Important in feeling of sensations and – Assist with vision and eye movement moving the body 4  WHAT IS NEUROPHARMACOLOGY? Study the effects of drugs on the nervous system Focus on actions of medications for neurologic and psychiatric disorders and drugs of abuse Uses the tools of drugs for better understanding of normal function of the nervous system https://www.zoomtesting.co.uk/amphetamine-drug-testing/ 5 COMMON ACTING MECHANISMS FOR NEUROPHARMACOLOGICAL AGENTS Influence the process under neuronal control Alter one of the two basic neuronal activities: synaptic transmission or axonal conduction Only a few neuropharmacological agents alter the axonal conduction. Most neuropharmacological agents act by altering the synaptic transmission. https://basicmedicalkey.com/basic-principles-of-neuropharmacology/ 6 DRUGS THAT ALTER AXONAL CONDUCTION Nonselective inhibition of axonal conduction Suppress transmission in any nerve they reach Reason: Process of impulse conduction along the axon is essentially the same for all neurons Consequence: Cannot produce selective effects. Affect conduction in all nerves of access https://basicmedicalkey.com/basic-principles-of-neuropharmacology/ https://biology.stackexchange.com/questions/8282/why-is-saltatory-conduction-in- Nerve Impulse Conduction in Myelinated Axons myelinated-axons-faster-than-continuous-conductio 7 DRUGS THAT ALTER AXONAL CONDUCTION - LOCAL ANESTHETICS Local anesthetics stop the nerves in part of body sending signals to brain Unable to feel pain after application of local anaesthetic May still feel some pressure or movement Work by decreasing axonal conduction Nonselective inhibition of axonal conduction Suppress transmission in any nerve get reach of Local anesthetics are valuable but with limited indications https://basicmedicalkey.com/basic-principles-of-neuropharmacology/ https://decisionsindentistry.com/article/trends-in-local-anesthesia-delivery/ 8 DRUGS USED AS LOCAL ANESTHETIC Amino amides –Commonly used includes bupivacaine, etidocaine, lidocaine, mepivacaine, prilocaine, and https://en.wikipedia.org/wiki/Amide ropivacaine, etc. Amino esters –Commonly used includes benzocaine, chloroprocaine, https://en.wikipedia.org/wiki/Ester cocaine, procaine, and tetracaine 9 HOW LONG DOES LOCAL ANAESTHETIC STAY IN YOUR SYSTEM? Some local anaesthetics last longer than others Some can stay in the body up to18 hours after being administered Some anaesthetic can even stay in the body for up to 24 hours How long the effects of local anaesthetic last depends on the exact drug used and how much is https://www.sciencephoto.com/media/93011/view given 10 AN EXAMPLE OF STRONG LOCAL ANESTHETIC Tetracaine One of the most potent anesthetics Of the ester-type anesthetic group Widely applied in ophthalmology As a topical anesthetic agent https://koper.gr/wp-content/uploads/2019/04/tetracain.jpg 11 ADVANTAGES AND DISADVANTAGES OF LOCAL ANESTHESIA Advantages Convenience, simplicity and safety Patient is awake during the treatment May be a few postoperative complications Minimize the affect to normal physiological condition of the patients Disadvantages Allergic reaction in rare situation Some patients may develop cardiac arrest (heart stops pumping blood around the body) in rare cases 12 DRUGS THAT ALTER SYNAPTIC TRANSMISSION Synapses, unlike axons, differ from one another Synapses of different sites have different transmitters Drug can selectively influences a specific type of neurotransmitter, alter one neuronally regulated process, while leaving most others unchanged. Effects are thus highly selective and these kind of drug have many uses https://basicmedicalkey.com/basic-principles-of-neuropharmacology/ https://bio.libretexts.org/Bookshelves/Introductory_and_General_Biology/Introductory_Biolo gy_(CK-12)/13%3A_Human_Biology/13.19%3A_Nerve_Impulses 13 ROLE OF RECEPTORS IN SYNAPTIC TRANSMISSION Neuron in synapse alters receptor activity on the target cell by releasing transmitter molecules These transmitter molecules diffuse across the synaptic gap and bind to receptors on the postsynaptic cell Neuropharmacological drugs act by altering the receptor activity on target cells https://basicmedicalkey.com/basic-principles-of-neuropharmacology/ https://www.nursinghero.com/study-guides/wmopen-biology1/signaling-molecules-and-cellular-receptors 14  SYNAPTIC TRANSMISSION STEPS Step 1: Transmitter Synthesis There is synthesis of transmitter (T) from some precursor molecules (Q, R, and S) Step 2: Transmitter Storage Transmitter (T) stored in vesicles Step 3: Transmitter Release When an action potential arrives, the vesicles fuse with terminal membrane and release the transmitter into the synaptic gap https://basicmedicalkey.com/basic-principles-of-neuropharmacology/ 15  SYNAPTIC TRANSMISSION STEPS (CONTINUE) Step 4: Receptor Binding On the postsynaptic cell, the transmitter binds reversibly to the receptor that causes a response in the cell Step 5: Termination of Transmission Transmitter dissociates from the receptor and is removed from synaptic gap by (a) Reuptake into the nerve terminal (b) Enzymatic degradation, or (c) Diffusion away from the gap https://basicmedicalkey.com/basic-principles-of-neuropharmacology/ 16 EFFECTS OF DRUGS ON STEPS OF SYNAPTIC TRANSMISSION? Multiple steps in synaptic transmission – Provides a number of potential targets for drugs When a drug influences receptor function – It can either enhance the receptor activation, or reduce the receptor activation Receptor activation – The drug produce an effect on the receptor equivalent to those of the natural neurotransmitter for that particular synapse Decrease receptor activation – The drug produce an effect on the receptor equivalent to decreasing the amount of natural transmitter available for the receptor binding 17 AMINO ACIDS NEUROTRANSMITTERS Glutamate –Important role in cognitive functions – Memory, thinking and learning –Too much glutamate – Lead to excitotoxicity, traumatic brain injury or the death of neurons –Most common and abundant excitatory neurotransmitter 18 AMINO ACIDS NEUROTRANSMITTERS (CONTINUE) Gamma-aminobutryic acid –Most common inhibitory neurotransmitter, particularly in the brain –Inhibit neural signaling –The “learning chemical” for successful learning Glycine –Most common inhibitory neurotransmitter in the spinal cord –Involved in pain, auditory processing and metabolism 19 MONOAMINES NEUROTRANSMITTERS What is monamines? – Monoamines is a compound containing a single amine group in its molecule. One example is the neurotransmitter (e.g. serotonin, noradrenaline). Serotonin – Calming chemical: Regulate mood, anxiety, sleep patterns, appetite, sexuality and pain – Serotonin imbalance: Depression, anxiety, depression and chronic pain – Medications: Increase the levels of Serotonin by inhibiting the reuptake after their functioning at the postsynaptic receptor sites – Facilitating memory and assists in decision- making behavior https://study.com/academy/lesson/amine-definition-structure-reactions-formula.html 20 MONOAMINES NEUROTRANSMITTERS (CONTINUE) Dopamine Act as “pleasure chemical” - Released when receiving a reward in response to some behavior; such as reward relating to food and drugs Involves feelings of pleasure, focus of attention, mood, sleep, concentration, memory and motivation Diseases relating dysfunctions of the dopamine system - Parkinson’s disease, etc Some highly addictive drugs (cocaine, amphetamines, etc) - Act on brain's dopamine circuits 21 MONOAMINES NEUROTRANSMITTERS (CONTINUE) Histamine Regulates body functions such as wakefulness, feeding behavior and motivation Epinephrine Also called adrenaline Together with norepinephrine - Responsible for the “fight-or-flight response” to fear and stress Activating the sympathetic nervous system 22 MONOAMINES NEUROTRANSMITTERS (CONTINUE) Norepinephrine Also called noradrenalin Linked to memory, mood and stress Increases alertness, heart rate, blood pressure and attention Both a neurotransmitter and a hormone Many medications such as the stimulants and depression medications – Increase norepinephrine for promoting concentration and focus – For reducing symptoms of depression and treating Attention- Deficit/Hyperactivity Disorder (ADHD) 23 WHAT IS ADHD? Attention-deficit/hyperactivity disorder (ADHD) One of the most common mental disorders among children Symptoms include: Inattention - Unable to keep focus Impulsivity - Rash acts occurring with moment without thought Hyperactivity - Excess movement which is unfit to the setting https://foto.wuestenigel.com/doctor-holding-clipboard-with-medical-report-text/ 24 PEPTIDE NEUROTRANSMITTERS Endorphins Short chains of amino acids Natural pain killers Release of endorphins –Elevates mood –Reduces pain https://www.newsfilter.gr/2018/03/23/i-syntagi-tis-eytychias/ 25 ACETYLCHOLINE Found in the central and peripheral nervous systems Specifically in the – Autonomic nervous system and – Spinal motor neurons releasing acetylcholine onto skeletal muscles producing movements Involved in sleeping, learning, memory, motivation, and sexual desire, etc Abnormalities in acetylcholine levels are associated with Alzheimer’s disease Helping direct attention https://assignmentpoint.com/acetylcholine/ 26 EXAMPLE OF OTHER NEUROTRANSMITTERS Oxytocin and vasopressin –Made from the hypothalamus –Linked to drug addiction Estrogen and testosterone –Hormones and work as neurotransmitters –Influence synaptic activity 27 WHAT MEDICATIONS HELP NEUROTRANSMITTERS? Donepezil, galantamine and rivastigmine Block the enzyme acetylcholinesterase – Acetylcholinesterase breaks down the neurotransmitter acetylcholine This medications are used to – Stabilize and improve cognitive function and memory – Management of people with Alzheimer's disease – Management of other neurodegenerative disorders https://www.youtube.com/watch?v=yD4W-iAHfUo 28 WHAT DRUG INCREASES THE RELEASE OF NEUROTRANSMITTERS? Cocaine or amphetamine Cause neurons releasing abnormally large amounts of neurotransmitters Or prevent the normal recycling of these brain chemicals by interfering with transporters Amplifies or disrupts the normal communication between neurons https://www.theblackberrycenter.com/what-is-the-most-addictive-drug/ 29 WHAT DRUG INHIBITS NEUROTRANSMITTER RELEASE? Phencyclidine and related drugs – Inhibit the reuptake of the monoamine neurotransmitters A common street drug – With significant mind-altering effects and mainly used recreationally – Cause distorted perceptions of sounds, hallucinations and violent behavior https://mypaper.pchome.com.tw/show/article/ takk/A1274119728 – Adverse effects may result in an increased risk of suicide, coma, addiction and seizures Typically smoked, but may be taken by mouth or injected 30 CENTRAL NERVOUS SYSTEM PHARMACOLOGY Sub-classifications Sigma (σ) receptors able to bind, with high affinity, a variety of pharmacologically active Narcotic analgesics: drugs, named σ ligands – Act on the sigma and mu The mu (μ) receptors involve in receptors in the body neuromodulating different physiological – Reduce the patient’s perception functions. Primarily affecting nociception of pain but also memory, mood, motivation, stress, temperature, respiration, endocrine and Non-narcotic agents: gastrointestinal activity – Decrease the level of Prostaglandins are hormone-like substances prostaglandin synthesis affecting several bodily functions, including Reduce the inflammatory inflammation, pain and uterine contractions response 31 CENTRAL NERVOUS SYSTEM PHARMACOLOGY Sub-classifications (Continue) Acetylcholine is an amino acid and acts as a neurotransmitter sending messages from one The cholinergic agents: neuron to another – Pharmaceutical agents either increase Acetylcholinesterase is a cholinergic enzyme or decrease the amounts of available found at postsynaptic neuromuscular junctions. acetylcholine or acetylcholinesterase It breaks down or hydrolyzes acetylcholine Adrenergic agents: Sympathetic nervous system helps the body – Affect the sympathetic nervous activate its “fight-or-flight” response on alert. Parasympathetic have opposite but system complementary roles that carries signals for – Adrenergic agents are site specific returning those systems to their standard activity levels CNS stimulants: Norepinephrine (noradrenaline) is a – Increase the available amount of the neurotransmitter of the brain that roles in neurotransmitter norepinephrine regulation of arousal, attention, cognitive – Increase cellular impulse transmission function, and stress reactions 32 CENTRAL NERVOUS SYSTEM PHARMACOLOGY Sub-classifications (Continue) GABA - It slows down the brain and producing a Anti-convulsants: calming effect. It works by blocking specific signals in central nervous system – Either increasing Na+ evacuation or preventing its entry into the cell, elevating Thalamus and cortex -Thalamus is the body's gamma aminobutyric acid (GABA) levels information relay station. All the information – or decreasing acetylcholine levels from body's senses (except smell) must be Sedatives and hypnotics: processed through the thalamus before being – Reduce the activity in the thalamus and the sent to the cerebral cortex of the brain for cortex. Hypnotics induce sleep while the interpretation. Besides, the thalamus also plays sedatives induce calmness in the recipient a role in consciousness, wakefulness, sleep, learning and memory Anti-depressants, either: – Either increase the norepinephrine and Serotonin, also known as 5-hydroxytryptamine serotonin levels in the brain or (5-HT), is a monoamine neurotransmitter. It is – Inhibit the production of monoamine called as the “happy” chemical because it oxidase (MAO) which breaks down the contributes to happiness and well-being. neurotransmitter Serotonin appears to affect mood, emotions, digestion as well as appetite 33 CENTRAL NERVOUS SYSTEM PHARMACOLOGY Sub-classifications (Continue) Dopamine receptors - a class of G protein- coupled receptors that are prominent in the Antipsychotics: vertebrate central nervous system (CNS). It acts like an inbox for messages in form of – Block the dopamine receptor sugars, lipids, peptides and proteins sites in the brain or The limbic system - part of the brain – Decrease the responsiveness involved in emotional and behavioural responses, especially for survival such as of the medulla feeding, reproduction and caring for our young, and fight or flight responses Anxiolytics: – Alter the responses in the limbic center or – They increase GABA levels 34 CENTRAL NERVOUS SYSTEM PHARMACOLOGY ANALGESICS OPIOID AGONISTS Mechanism: Binds to opioid receptor sites. It depresses and/or alters the patient’s pain response. Most also provide a euphoric effect Indication: Pain Side effects: Dizziness, Lightheadedness, Constipation Examples: Codeine, Hydromorphone, Oxycodone, Propoxyphene, Morphine https://www.adph.org/ems/assets/StudentManual_CentralNervousSystemAgents.pdf 35 CENTRAL NERVOUS SYSTEM PHARMACOLOGY Opioid receptor Is G protein-coupled receptors (GPCRs) Mediate the human body's response to Most drugs, hormones and neurotransmitters Involved in sensory perception of taste, vision and olfaction Euphoric effect A feeling of intense excitement and happiness https://www.adph.org/ems/assets/StudentManual_CentralNervousSystemAgents.pdf 36 CENTRAL NERVOUS SYSTEM PHARMACOLOGY ANALGESICS OPIOID AGONIST-ANTAGONIST Mechanism: Binds to the opioid receptor sites. It also exhibiting a mild narcotic antagonist action. Prevents further binding of the receptor site Indication: Pain Side effects: Dizziness, Lightheadedness, Constipation Examples: Buprenorphine, Butorphanol, Nalbuphine, Pentazacine https://www.adph.org/ems/assets/StudentManual_CentralNervousSystemAgents.pdf 37 CENTRAL NERVOUS SYSTEM PHARMACOLOGY Narcotic antagonists are often used either to Reverse toxicity associated with overdose of opioid agonist analgesics or Prevent relapse among patients who are dependent on opioid agonist analgesics https://www.adph.org/ems/assets/StudentManual_CentralNervousSystemAgents.pdf 38 CENTRAL NERVOUS SYSTEM PHARMACOLOGY ANALGESICS NON-OPIOID ANALGESICS Mechanism: Three major classes, salicylates (aspirin), para-aminophenal (Tylenol), and Non-steroidal anti-inflammatory drugs (NSAIDS, e.g., Ibuprofen). All inhibit prostaglandin synthesis which may increase the body’s response to pain. They exhibit an anti- pyretic effect by either peripheral vasodilation or by acting on the thermoregulatory center Indication: Pain, Fever Side effects: GI problems, Headache, Dizziness Examples: Aspirin, Acetaminophen, Ibuprofen, Naproxen sodium https://www.adph.org/ems/assets/StudentManual_CentralNervousSystemAgents.pdf 39 CENTRAL NERVOUS SYSTEM PHARMACOLOGY Prostaglandins Hormone-like substances affecting several bodily functions, including inflammation, pain and uterine contractions Anti-pyretic effect Class of medicines used to reduce the fever 40 CENTRAL NERVOUS SYSTEM PHARMACOLOGY Peripheral vasodilation Act on the most distal parts of the vascular system Dilate the blood vessels such as arterioles and venules Lower the blood pressure Ease the heart for pumping blood through these peripheral blood vessels, and therefore whole body Thermoregulatory center The human body's thermostat The hypothalamic thermoregulatory center Located in the preoptic area of the hypothalamus. Adjusts the body's set point and regulates temperature homeostasis 41 CENTRAL NERVOUS SYSTEM PHARMACOLOGY CHOLINERGIC CHOLINERGIC AGONISTS AGENTS (PARASYMPATHOMIMETIC) Mechanism: Activate the cholinergic system by either inducing parasympathetic activity or by inhibiting the release of acetylcholinesterase (the enzyme required to break down acetylcholine) Indication: Glaucoma, Myasthenia gravis, to increase bladder and intestinal function Side effects: Hypotension, Headache, Nausea and Vomiting, Diarrhea, Bradycardia Examples: Cholinergic activators: Bethanechol, Pilocarpine Acetylcholinesterase Inhibitors: Edrophonium, Neostigmine, Physostigmine https://www.adph.org/ems/assets/StudentManual_CentralNervousSystemAgents.pdf 42 CENTRAL NERVOUS SYSTEM PHARMACOLOGY Glaucoma A common eye condition Damage to optic nerve, which connects the eye to the brain Caused by fluid building up in front part of eye Increases pressure inside the eye May lead to loss of vision 43 CENTRAL NERVOUS SYSTEM PHARMACOLOGY Myasthenia gravis Causes muscles under voluntary control to get weak and tired quickly Communication between nerves and muscles breaks down Develops when antibodies in body attack normal receptors on muscle Blocks the chemical needed to stimulate muscle contraction Bradycardia Slow heart rate Heart beat of adults between 60 and 100 times per minute For bradycardia, heart beat fewer than 60 times a minute 44 CENTRAL NERVOUS SYSTEM PHARMACOLOGY CHOLINERGIC CHOLINERGIC ANTAGONISTS AGENTS Mechanism: Inhibits the effect of acetylcholine on the muscarinic sites Indication: Bradyarrhythmias, Parkinsonism Side effects: Tachycardia, Constipation, Dry mouth Examples: Atropine, Benztropine, Glycopyrrolate https://www.adph.org/ems/assets/StudentManual_CentralNervousSystemAgents.pdf 45  CENTRAL NERVOUS SYSTEM PHARMACOLOGY Bradyarrhythmias A heart rate slower than typical May not pump blood and oxygen to the brain as efficiently Can lead to symptoms such as shortness of breath, fatigue and dizziness Parkinsonism Refers to brain conditions causing slowed movements, rigidity and tremors May be due to genetic mutations, infections and reactions to medications Tachycardia A heart rate over 100 beats a minute Many types of irregular heart rhythms, named arrhythmias, may cause tachycardia 46 CENTRAL NERVOUS SYSTEM PHARMACOLOGY ADRENERGIC ADRENERGIC AGONISTS AGENTS Mechanism: Stimulates the alpha and/or beta responses of the sympathetic nervous system. Alpha1 causes vasoconstriction; Beta1 increases the rate, force and automaticity of the heart; Beta2 produces bronchodilation and vasodilatation. Indication: Bronchospasm, Hypotension due to chronic heart failure or Heart rate deficiency, Vasoconstriction Side effects: Arrhythmias, Tachycardia, Angina, Nervousness, Tremors Examples: Albuterol, Dobutamine, Dopamine, Epinephrine, Isoproterenol, Norepinephrine https://www.adph.org/ems/assets/StudentManual_CentralNervousSystemAgents.pdf 47 CENTRAL NERVOUS SYSTEM PHARMACOLOGY Bronchospasm Muscles lining the bronchi tighten and cause the airways to narrow Limits the amount of oxygen the body receives Chronic heart failure (CHF) Heart has trouble pumping blood through the body May develop over a long period of time Symptoms include shortness of breath, swelling of the feet, ankles, and abdomen and fatigue 48 CENTRAL NERVOUS SYSTEM PHARMACOLOGY Arrhythmias A heart rhythm that is not normal May be harmless or serious. The outlook varies depending on the type of arrhythmia Angina Squeezing, heaviness, pressure, tightness or pain in the chest Like a heavy weight lying on the chest 49 CENTRAL NERVOUS SYSTEM PHARMACOLOGY ADRENERGIC ALPHA ADRENERGIC BLOCKING AGENTS DRUGS Mechanism: Usually block alpha receptors, leading to a muscle relaxation and a widening of the blood vessels Indication: Reynaud’s disease, Vascular headache Side effects: Orthostatic hypotension, Tachycardia, Dizziness, Numbness Examples: Phenoxybenzamine, Phentolamine https://www.adph.org/ems/assets/StudentManual_CentralNervousSystemAgents.pdf 50 CENTRAL NERVOUS SYSTEM PHARMACOLOGY Reynaud’s disease Feel numb and cold in response to cold temperatures or stress In some areas of the body — such as fingers and toes Smaller arteries that supply blood to the skin get narrow Limits blood flow to affected areas Numbness A loss of feeling in a part of the body. Changes in sensation with burning or a pins-and-needles feeling 51 CENTRAL NERVOUS SYSTEM PHARMACOLOGY Vascular headache Pain with throbbing and pulsatile in nature Pain intensity often described as intense Cluster headache with a deeper burning quality Orthostatic hypotension Postural hypotension Form of low blood pressure happening when standing after sitting or lying down May cause dizziness or lightheadedness and possibly fainting 52 CENTRAL NERVOUS SYSTEM PHARMACOLOGY ADRENERGIC BETA ADRENERGIC BLOCKING AGENTS DRUGS Mechanism: Blocks or displaces the agent from the receptor sites Indication: Hypertension, Angina, Glaucoma Side effects: Arrhythmias, Bradycardia, Bronchospasm, Nausea and Vomiting Examples: Acebutolol, Atenolol, Esmolol, Labetalol, Metoprolol, Pindalol https://www.adph.org/ems/assets/StudentManual_CentralNervousSystemAgents.pdf 53 CENTRAL NERVOUS SYSTEM PHARMACOLOGY CENTRAL NERVOUS SYSTEM STIMULANTS Mechanism: Exact mechanism is unknown. It is believed that these agents stimulate the release of norepinephrine leading to an increase in nerve impulse transmission from cell to cell Indication: Narcolepsy, Attention Deficit Disorder Side effects: Nervousness, Tremors, Irritability, Hypotension, Arrhythmias Examples: Dextroamphetamines, Doxapram, Methylphendiate hydrochloride, Pemoline https://www.adph.org/ems/assets/StudentManual_CentralNervousSystemAgents.pdf 54 CENTRAL NERVOUS SYSTEM PHARMACOLOGY Narcolepsy A rare long-term brain condition May prevent the people from choosing when to sleep or wake The brain is unable to regulate sleeping and waking patterns May lead to excessive daytime sleepiness Drowsy throughout the day difficult to concentrate and stay awake Attention-deficit hyperactivity disorder Common for kids with hyperactive behaviors 55 CENTRAL NERVOUS SYSTEM PHARMACOLOGY ANTI-CONVULSANTS Depresses the discharge of abnormally fired neurons by a number of Mechanism: different mechanisms. These mechanisms range from promoting Na+ exit from the cell, inhibiting Na+ from entering the cell, increasing the inhibitory effect of gamma-amino butyric acid (GABA), prevention of release of glutamate and aspartate, and decreasing acetylcholine released by the nerve impulses Indication: Seizures Side effects: Nystagmus, Drowsiness, Hypotension, Respiratory depression Examples: Hydantoins (ethtoin, felbamate, phenytoin) Barbiturates (phenobarbital, mephobarbital, primidone) Benzodiazepines (clonazepam, clorazepate, diazepam) https://www.adph.org/ems/assets/StudentManual_CentralNervousSystemAgents.pdf 56 CENTRAL NERVOUS SYSTEM PHARMACOLOGY Seizures A burst of uncontrolled electrical activity between brain cells Causing temporary abnormalities in muscle tone or movements Resulting in twitching and stiffness Abnormalities sensations, behaviors and states of awareness Nystagmus A vision condition that make repetitive and uncontrolled movements of eyes Resulting in reduced vision and depth perception May also affect balance and coordination Involuntary eye movements can ranges from up and down, side to side or in a circular pattern 57 CENTRAL NERVOUS SYSTEM PHARMACOLOGY SEDATIVES AND HYPNOTICS Mechanism: Decreases the amount of neurotransmissions form the thalamus and the cortex of the brain Indication: Wide ranging; from sedation and insomnia to treatment of alcohol withdrawal symptoms. Side effects: Drowsiness and respiratory depression Examples: Thiopental sodium, Pentobarbital, Phenobarbital, Alprazolam, Cloracepate, Diazepam, Quazepam, Chloral Hydrate https://www.adph.org/ems/assets/StudentManual_CentralNervousSystemAgents.pdf 58 CENTRAL NERVOUS SYSTEM PHARMACOLOGY Sedation A state of calmness, relaxation, or sleepiness caused by drugs May be applied to help relieving anxiety during medical or surgical procedures or Assist to cope with very stressful events Alcohol withdrawal symptoms Feeling low or depressed Shakiness or trembling Anxiety or jumpiness Loss of appetite Fatigue 59 CENTRAL NERVOUS SYSTEM PHARMACOLOGY ANTI-DEPRESSANTS Mechanism: Two primary mechanisms prevail. The first Tricyclic antidepressants (TCAs), is to cause an increase in the amount of norepinephrine and serotonin in the central nervous system. This is accomplished by inhibiting the reabsorption of these two substances in the presynaptic membrane. The second is a monoamine oxidase inhibitor (MAO) that prevents the central nervous system’s neurotransmitters from being metabolized Indication: Depression Side effects: Hypotension, Tachycardia, Blurred vision, Dry mouth, Restlessness, Insomnia, Nausea and Vomiting Examples: TCA & others: Amitriptyline, Clomopramine, Doxepin, Bupraprion MAO Inhibitors: Phenelzine, Tranylcypromine https://www.adph.org/ems/assets/StudentManual_CentralNervousSystemAgents.pdf 60 CENTRAL NERVOUS SYSTEM PHARMACOLOGY ANTIPSYCHOTICS Mechanism: The majority of agents block the post synaptic dopamine receptors which, in turn, inhibit the transmission of nerve impulses. Some others also have the effect of decreasing the cells responsiveness at the medullary chemoreceptor zone Indication: Psychosis, Alcoholism Side effects: Extrapyramidal reactions, Tardive dyskinesia, Sedation, Blurred vision, Dry mouth, Heat intolerance Examples: Chlorpromazine, Mesoridazine, Perphenazine, Thioridazine, Droperidol, Haloperidol https://www.adph.org/ems/assets/StudentManual_CentralNervousSystemAgents.pdf 61 CENTRAL NERVOUS SYSTEM PHARMACOLOGY Psychosis People lose some contact with reality May involve seeing or hearing things while other cannot see or hear (hallucinations) Believing things that are not actually true (delusions) May also involve confused (disordered) thinking and speaking Alcoholism Alcohol use disorder People cannot stop drinking Drinking affects their health Making safety at risk Damages personal relationships 62 CENTRAL NERVOUS SYSTEM PHARMACOLOGY Extrapyramidal reactions  A variety of movement disorders Suffered as a result of taking dopamine antagonists, usually antipsychotic (neuroleptic) drugs Often used to control illness such as psychosis, etc Tardive dyskinesia A condition where the face, body or both make sudden, irregular movements Unable to control movements Commonly developed as a side effect of medications 63 CENTRAL NERVOUS SYSTEM PHARMACOLOGY ANXIOLYTICS Mechanism: Majority appear to effect some level of the limbic or subcortical areas of the brain. One other major mechanism appears to be in the potentiation of GABA, which is an inhibitory neurotransmitter Indication: Anxiety, Alcohol withdrawal, Partial seizure disorder Side effects: Drowsiness, Respiratory depression Examples: Alprazolam, Chlordiazepoxide, Hydroxyzine, Midazolam https://www.adph.org/ems/assets/StudentManual_CentralNervousSystemAgents.pdf 64 CENTRAL NERVOUS SYSTEM PHARMACOLOGY Partial seizure disorder Commonly referred to as "focal seizures" Affecting a single brain area, commonly at the temporal lobes They are associated with epilepsy Majority of partial seizures being harmless, sometimes the condition may be severe Respiratory depression Hypoventilation Breathe too slowly or shallowly Preventing proper gas exchange in the lungs such as Oxygen moves from the air sacs (alveoli) of the lungs to the blood and Carbon dioxide (CO2) moves from the blood to the lungs 65 TUTORIAL Neuroscience https://www.youtube.com/watch?v=WhowH0kb7n0 ADHD Medication - Stimulants vs. Nonstimulants https://www.youtube.com/watch?v=IdPL2w4kolU Opioids https://www.youtube.com/watch?v=NPlNCqBHPnE&list=PLNZqyJn svdMpkVaovOst1bKxaNgBCsTBK 66 PRINCIPLES OF NEUROPHARMACOLOGY 67