PHAR 100 Module 1 PDF

MODULE 1 Section 1 Drugs: Any substance received by a biological system that is not received for nutritional purposes, and which influences the biological function of the organism. This broad definition means that chemicals, biological agents and herbal products are all...

MODULE 1 Section 1 Drugs: Any substance received by a biological system that is not received for nutritional purposes, and which influences the biological function of the organism. This broad definition means that chemicals, biological agents and herbal products are all considered drugs. Pharmacology: The science of drugs, including their uses, effects and mechanisms of action. Introduction to the History of Drug use and Development - Human have used drugs since before recorded history - Records from early china and egypt showed ancient use of drugs - The majority of clinically useful drugs have been developed over the past 250 years with the development of experimental biological sciences (and pharmacology) Historical Influences and modern pharmacology Key historical influences that have shaped modern pharmacology: 1. Ancient Civilization discoveries - Healers existed historically in traditions and cultures of ancient times - Ancient Greece, Egypt, and China formed modern pharmacology and have shaped history Ancient Greece Ancient Egypt Ancient China - 380 B.C.E Theophrastus; a - One papyri (document), in - Earliest recorded drug pupil of Aristotle wrote a egypt, (Ebers Papyrus) was experiments are those that textbook on therapeutics that from the year 1550 B.C.E, emerged from China in the included opium poppy was intended to be a year 2700 B.C.E. (papaver somniferum). textbook of drug use for - Reported that the emperor Serturner pharmacist in 1803 medical students. Shen Ning classified all isolated crystals of morphine - Scholars proved this drugs according to taste from opium and testest the pure document contains true - The drug Ma Huang was substance on himself 3 others, observations on the use of classified as a "medium and discovered its pain drugs specifically drug”, and was widely used relieving abilities. purgatives (they cause in Chinese medicine for use bowel movement) against coughs, influenza, - Senna was one of the and fevers. recommended drugs in this - Modern day: ephedrine has  document and it is still been isolated from Ma used today. Huang, and has been used to treat asthma, and a version of ephedrine is used as a decongestant. Opium 1. Morphine: Opium has 10% morphine. Serturner coined the name morphine from Morpheis (god of dreams). Morphine is able to relieve intense pain. → Acetylsalicylic acid (Aspirin) and Acetaminophen (Tylenol), only relieve mild to moderate pain. 2. Codeine: Opium contains 0.5%. Codeine is a component of Tylenol-3, a prescription drug in Canada. 2. Role of poisons in history Influence of Poisons - Use of poisons in ancient times has resulted in the discovery and development of drugs still used today. - “All substances are poisons. There is one which is not a poison. The right dose differentiates a poison and a remedy”. - Paracelsus, 16th century swiss physician. Examples of poisons that have led to the development of drugs: 1. Curare: A plant derived drug that was used by indigenous peoples from regions of the amazon rainforest in South America. As a poison: Indigenous peoples dipped their arrows in curare for hunting so when an animal was struck, it caused paralysis and eventually death by respiratory paralysis. As a drug: Used as an anesthetic during surgery by administering a small dose to induce muscle relaxation. The structure of curare has been modified to make it safer, and new versions are still used by anesthetics today. 2. Ergot: Poisonous fungus that grows on the heads of rye during wet seasons. - In the middle ages, Ergot was ground together with the rye, which got into bread. Because of the accidental mixing, terrible epidemics occurred, killing 20,000 people in one region of russia. Ergot Poisoning: - Use impacts nervous, cardiovascular, and reproductive systems. Nervous Systems: - Targets nervous system and and results in symptoms such as mental frenzy, hallucinations and convulsions Cardiovascular System - Ergot can cause the constriction of blood vessels leading to starvation of blood in fingers, toes and limps, resulting in a burning sensation. - Limbs become black and die→ extreme cases, they can fall off Reproductive System - Poisoning can cause violent contractions of the uterus. - 16th century→ midwives recognized ergot could be used in small amounts to hasten labor. - 1800’s→ physicians used ergot to expedite labor - Could result in death. Ergot as a drug → these two compounds can be used derived from ergot that have pharmacological uses 1. Ergotamine - Useful in treatment of migraines - Theory: Migraines are caused by pulsations of arterial blood vessels that carry blood to the head - Ergotamine contracts these blood vessels reducing the amplitude of the pulsation 2. Ergonovine - Used to be used to hurry childbirth but it is no longer used this way as the effects may be too strong and the mother could be injured by rapid delivery. - Now can be used to stop uterine bleeding after childbirth 3. Influence of religion - Therapy was heavily influenced by religion and magic (healers were physicians and priests). - Intoxicating substances in plants were used by traditional healers to alter conscious state and facilitate communication with their gods. Peyote - The peyote cactus was used in Mexico to achieve a mystical state which was connected to spiritual and ritualistic use. - Contains the substance escaline that causes hallucination, a feeling of well being and perception distortion. – similar to LSD Drug discovery  - 25% of drugs used today are derived from plant sources, with the active substances being purified and potentially modified to be more effective or less toxic. - 19th century was a time of chemical synthesis - At this time, drugs discovered or introduced to therapy were small molecules derived from chemical synthesis in the lab. 1. Drugs that act on the brain - Alter normal chemical signaling in the brain - LSD (lysergic acid diethylamide) is one of the most potent hallucinogenic drugs LSD Albert Hoffmann in 1943, synthesized LSD which was similar in chemical structure to ergotamine and ergonovine The discovery of the hallucination effects of LSD led to the discovery that certain mental illnesses might be due to the potent substances in the brain that produce psychic disturbance. Research on therapeutic effects of LSD stopped around the 1970’s, but recently evidence has shown that LSD might be effective in treating depression, anxiety and addiction. 2. Drugs that act against disease - Infectious disease: any disease caused by an organism like bacteria, viruses, fungi or parasites. - Many drugs were introduced to combat infectious disease: 1900’s: Organo Arsenicals - Paul Ehrlich designed complexes of arsenic and organic molecules (organoarsenicals), which selectively bind to parasites. This led to a cure for syphilis (std), in the early 20th century. 1930’s: Sulfa Drugs - Gerhard Domagk introduced Sulfa Drugs in germany - First successful synthetic drugs for treatment of bacterial disease. - Now called Antibacterial compounds → antibiotic refers to chemical substances produced by microorganisms. 1940’s: Penicillin - Alexander Fleming discovered first antibiotic Penicillin - Used in therapy of Gram Positive (bacteria with thick cell walls and no outer membrane) disease. 1950’s: Streptomycin - Selman Waksman discovered streptomycin. - Changed the treatment of gram-negative bacterial diseases (bacteria with thin cell walls and an outer membrane) Section 1 QUIZ: How has Historical use of chemicals contributed to the advancement of pharmacology? - Sulfa drugs led to the development of the first synthetic antibacterial compounds. Which one of the historical drugs listed is still used clinically today? - Morphine Section 2: Drug development and Drug Trials Drug development is divided into five key steps: Drug Discovery 1. Basic Research and Drug Discovery Step 1: Identification of Target for drug Identify a target for a new potential drug (could be a receptor), that when activated causes relief of pain. → when a compound is found that binds well to target its pharmacological effects are studied at the molecular, cellular, organ, and animal level. Step 2: Studying the Target If a compound is proved to be effective in initial studies it is identified as a lead compound and undergoes more studies for safety and efficacy (the max pharmacological response that can be produced by a specific drug in that biological system). Eg. When developing a new drug that relieves pain, the effect of the drug on pain would be studied. 2. Pre clinical trials - Molecular and Cellular studies conducted prior to testing in humans divided into 2 studies: 1. Pharmacology Studies Determines the detailed mechanism of the action of the new drug. If a drug has been developed to treat high BP, how the drug specifically lowers BP would be studied. 2. Toxicology Studies Determines potential harm and risk associated with the new drug  Studies look at acute, and chronic toxicity and effects on reproductive, carcinogenic, and mutagenic potential. (3-6 years) Drug Development 3. Clinical Trials (6-7 years) Initial steps: Step 1: Proof Of Safety Pharmaceutical manufacturer submits proof of safety and efficacy through tests via animal species → proof is sent in Canada to the Health Products and Food Branch, and in The US, the Food and Drug administration (FDA) Step 2: Methodology Steps of method used to test in human clinical trials. Step 3: Investigation Submissions are evaluated by qualified scientists to investigate use of drugs in humans because animal testing isn't necessarily reliable in predicting human reactions. Phases 1-3: Happen on Humans Phase 1: - Trials test 1 or 2 doses of the new drug to determine tolerability. - Evaluates absorption, distribution, elimination and bad effects of new drugs. - Uses 20-80 healthy volunteers Phase 2: - Tests effectiveness of treating conditions it’s meant for, while monitoring safety - Uses 100-500 people who have the disease the drug is tested for Phase 3: - Randomized Controlled Trials (RCT) → used for licensing and marketing of drug - Uses 1000+ people who are affected by the disease the drug is meant for - Tests the safety and effectiveness of drugs in comparison to o therapy/pre-existing therapy for disease. - Tested at multiple centers in cities, for months-years - Cost can vary from 1-50 million dollars. Design of Phase 3 clinical Trials: Stages:  1. Enrollment: Determining enrollment prior to the study - Must find target population (group of patients who the drug is intended for) - Study population: Group of target population that meets all required criteria for study 2 factors that influence who can be included in study: 1. Inclusion/Exclusion Criteria - Identifies who can/can’t be included in study population - Study population is carefully defined ro eliminate variables other than the drug in the study that can affect results. (eg. diseases have different levels of severity like cancer, and a patient with a mild form may see greater benefit than a patient with a more severe cancer) - Patients with conditions that may influence the results are typically excluded, but some people are included who have common comorbidities to be representative of the target population. 2. Consent - Informed consent must be obtained by form of document written in non-scientific language that outlines purpose of study, procedures used, and potential risks/benefits that could occur. - Trial methodology and informed consent documents are reviewed by an independent Institutional Ethics Review Board, to protect rights of participants. 2. Treatment Allocation: allocating participants to treatment groups and conducting trial 1. Double Blind Design - Studies are conducted in a double blind manner where neither the investigator or subject is aware of the treatment the subject is assigned too. - Eliminates Biases 2. Randomization (Treatment) Treatment: Experimental Treatment Group - Patients are assigned to either an experimental treatment (receives a new drug) or control group. - Patients are assigned by randomization by computer generated system - Randomization ensures that confounding principles (known and unknown) are distributed equally amongst groups. → removes biases. Control Group: the efficacy and safety of experimental drugs has to be compared to a control drug which is divided into a placebo or gold standard drug. 1. Placebo - Fake drugs that look the same in appearance, color, taste and administration. 2. Gold Standard  - Best available treatment for specific disease at the time - If available, the control group receives the GD drug 3. Results: Outcome: - Find if the experimental treatment drug was more/less effective then the control group. - Outcome of trials that measure effectiveness of drugs in each participant needs to be measured and compared. (in an objective and reliable manner). Compliance, Quality of Life and statistics 3 factors influence interpretation of phase 3 clinical trial 1. Compliance - Patient compliance must be determined: refers to how often the patient actually took the drug when they were supposed too. - To measure, patients are asked to return unused drugs to count and compare, and for intravenous drugs, compliance is measured by checking the administrator sign off of the drug. 2. Quality of Life - Measure the impact of the drug or treatment on the quality of life of participants - Some help, some don’t 3. Statistics - Experimental vs control is measured using statistics - Differences can be as small as 2% but only statistics can determine whether this was real or happened by chance. Health Canada Review - After successful completion of initial phase 3 trials, the manufacturer submits a new drug application containing detailed results of clinical trials. - Results are reviewed by regulatory scientists Manufacturing (0.5-2 years) - Once the regulatory agency has reviewed the new drug application, manufacturing begins - Manufacturers come up with a drug name (generic) and brand name for the drug. Generic vs Brand Name - Generic name is equivalent to chemical name - Manufacturer applies for a patent with a brand name for that drug giving a company rights to market that drug for 20 years. (Brand Name) eg. Acetaminophen is Tylenol generic name and Tylenol is the brand name. - After a patent expires, other manufacturers can make copies of the original brand name drug and sell it under their own name. - Post-Market surveillance/Phase IV clinical trials (continuous) Bioequivalence - Comparative bioavailability study is conducted to ensure that all marketed drugs are as effective as original brand name drugs. Post Market Surveillance (Phase 4 clinical trials) - Closely monitor effects they may have when taken with other medication. - Surveillance the effects the drugs have to highlight warnings. - SECTION 3 Drug Targets - Drugs are designed to act with one selected target in the body which are usually receptors or other drug targets. 1. Receptors: A molecule or complex of molecules on the inside or outside of the cell that has a regulatory function in the organism. - Receptors are normally bound to and activated by endogenous ligands which are substances found in the body like hormones and neurotransmitters. - Receptors are in locations all around the body, and these locations determine where a drug will act and whether the response from a drug-receptor interaction will be beneficial or not. 2. Other Drug Targets : some drugs interact non-specifically with the biological system and not via receptors. Chemical reactions: Antacids neutralize stomach acid through neutralization reaction Physical Chemical Forces: Cholestyramine (lowers cholesterol in blood), chemically binds to bile acids in the GI tract, preventing their absorption and increasing elimination of bile salts that are used to make cholesterol. Drugs and Receptors: - Most drugs mimic the action of or block the effect of the endogenous ligand at receptor - Agonists: Drugs that bind to and stimulate receptor - Antagonists: Drugs that bind to but block the receptors response Drug Response - Intensity of pharmacological effects increases in proportion to the dose→ called the dose-response relationship. Cannabis and Alcohol - Study reported that marijuana was safer than alcohol. - It is insufficient to just ask whether cannabis is more or less harmful than alcohol without further specification. Other questions need to be asked like:  1. Quantity: How much alcohol was compared to how much cannabis 2. Frequency of use: Used how often? 3. User demographics: By what people? 4. Environmental factors: Under what circumstances? Dose-Response relationships - For a drug to achieve the correct response, many receptors need to be activated at once: Low doses: very little response observed because not many receptors are activated. Threshold: A certain number of receptors need to be activated before an effect will be seen. Therapeutic Doses: Once this point is reached, a small increase in dose results in a large increase in response. Dose- Response Curve - Dose/Concentration and percent response an individual will have - Dosing occurs within linear region of dose-response curve - A graphical representation of how much drug you need in the body to see a specific effect. Y-axis: effect of drug→ max response is 100% X-axis: dose of drug (logarithmic scale) Low doses: Receptor threshold has not yet been reached Therapeutic Range: Dose is directly proportional to response ED50: Dose of drug that results in 50% of max effect Maximal Response: Max response has been reached and further dose increase has no further effects. Efficacy and Potency Efficacy: max pharmacological response that can be produced by a specific drug in that biological system. Potency: - Dose of a drug that is required to produce a response of a certain magnitude (usually 50% of that max response) ED50 - Refers only to the amount of drug that must be given to obtain a particular response. - The more drug you need, the less potent the drug *efficacy is more important then potency Therapeutic range:  - The aim of drug therapy is to give a dose that keeps the blood [] of a drug above the minimum concentration that produces the desirable response but below the concentration that produces an unacceptable toxicity. - The range of blood concentration where the drug is effective but toxicities usually do not occur. SECTION 4: Pharmacokinetics - Refers to the movement of a drug into, through and out the body. - After administration of a drug, 4 key processes occur: Absorption, Distribution, Metabolism, Excretion. Routes of Administration: 1. Topical: refers to drugs that are applied directly to a place i or outside of the body On the skin - Can treat mild-moderate severe skin conditions - Can produce a systemic effect: some topical steroids can be absorbed and cause toxicities elsewhere in the body. Through the skin - Transdermal: application of a drug to skin for absorption into the general circulation for systemic effect. Inhalation - Through lungs for both local and systemic effects - Avoids toxicity 2. Enteral: Administration through GI tract, then delivered to liver which contains enzymes that can decrease amount of active drug left to enter the general circulation (first pass effect) Mouth Advantages: commonly used, convenient and inexpensive, non invasive Disadvantages: variable absorption due to differences in intestinal motility and disease Rectum Advantages: Systemic or local effect, less invasive, digestive enzymes are bypassed Disadvantages: limited medications are suitable, absorption from rectal mucosa is slow, incomplete and variable. Under the tongue (sublingual) In the cheek (Buccal) Advantages: enzymes of stomach, intestines and liver are bypassed Disadvantages: not all drugs are well absorbed from this route, drug may be swallowed, and behaves as if taken orally. 3. Parenteral: administration bypassing the GI tract. - Injected into body and directly enter bloodstream Intravenous: - immediate effects - Used for drugs that are poorly absorbed - Response is irreversible→ high risk of drug reactions - Needs nursing - Prep has to be sterile and free of pyrogens Intramuscular - Drug is injected deep into a muscle - Volume of drug is limited to 2-3 mL in an adult Subcutaneous - Injected into deepest layer of skin - Allows for modification of drug preparations to control timing of the release of the drug from the injection site. - Administration and Bioavailability - Bioavailability differs between drugs - Bioavailability: The fraction of an administered dose that reaches the systemic circulation (blood) in an active form. - A drug dose given intravenously is considered to be 100% bioavailable as it does not require absorption. 4 major processes are involved in Pharmacokinetics 1. Absorption - Movement of drug from site of administration into blood - Drug must be able to cross biological membranes Drug movement to be absorbed 1. Diffusion through aqueous pores 2. Diffusion through lipids 3. Active or Carrier mediated transport 2. Distribution - Movement of drug from blood to the site of action and other tissues - Most drugs reach all tissues and organs regardless of target site - Concentration of drug and blood are equal at sites of distribution (if concentration in blood drips below concentration at any distribution sites, the drug will move from that site to the blood to maintain equilibrium) - The greater the blood flow to an organ, the drugs reach faster Distribution and Termination of drug effect: example using thiopental - Administration: after injection, drug concentration is high, and is high in the brain (high blood perfusion) which will make patients fall asleep. Concentration of thiopental is low in muscle and fat (low blood perfusion). - Distribution: After elapsed time, concentration of drug in muscle and fat increases and the concentration in blood decreases, causing the drug to leave the brain and move into the blood→ as C decreases in brain, the patient wakes up. - Termination of effect: Action of drug has been terminated by the distribution of the drug from the brain into muscle and fat. 3. Metabolism - Drug metabolism (biotransformation) is the conversion of a drug into another compound in order to eliminate it. - After metabolism, metabolites are left and are usually functionless - Drugs are converted to be more water soluble to be eliminated by the kidneys - Biotransformation occurs in love and sometimes, kidneys, intestines, lungs, skin etc. Biotransformation reactions - Phase 1: Addition or unmasking of a functional group - Phase 2: Addition of a large water soluble moiety to the product from phase 1 - P450’s: enzymes that are responsible for the majority of biotransformation drugs → found mostly in tissues within liver 4. Excretion - Moving the drug and metabolites out of the body, through bodily fluids. Through:  1. Kidney: eliminates majority of drugs, through urine (if not water-soluble, the kidney can reabsorb back into the blood) 2. GI tracts: After biotransformation in the liver, some drugs can be excreted by the gastrointestinal tract via feces. 3. Lungs: Volatile or gaseous drug forms can be excreted through lungs 4. Breast Milk: Excreted through the breast of nursing parents. 5. Saliva and Sweat: Drugs can be found in saliva and sweat. Variation in Drug Response - Dose of a drug is the amount of a drug that will cause a desired effect in most people but not all people. - Different people have different responses to drug dosage which is why doses sometimes need to be adjusted based on the individual. - Due to genetic factors, environmental factors, disease states, altered physiological states, presence of other drugs. 1. Genetic: genetic variability in receptors that drugs bind too 2. Environmental Factors: exposure to certain chemicals 3. Other disease states: Presence of diseases like liver disease metabolize drugs at a slower rate. 4. Physiological states: Age reduces the functions of certain organs therefore making individuals more susceptible to drug action. 5. Other drugs present: One drug can change the biological effect of a second drug leading to variability in drug response. SECTION 5: DRUG TOXICITY AND DRUG INTERACTIONS Adverse Effects of Drugs - Any effect produced by a drug that was not the intended effect 1. Extension of Therapeutic effect - Too much drug is in the blood. → overdose 2. Unrelated to the Main drug action: a drug can cause unrelated effects from the pharmacological action of the drug. 3. Allergic reaction: mediated by the immune system→ antibody - antigen combination provokes an adverse reaction in a patient. 4. Withdrawal and Addiction: unwanted physiological and psychological effects of the drug 5. Teratogenesis: produced effects in developing fetus 6. Biotransformation reaction: occurs when a drug is converted to a chemically reactive metabolite that can bind to tissue components and cause tissue/organ damage. Predicting Adverse Drug Reactions - After usage of drug, some effects may begin to appear due to a couple reasons:  1. Rarity of Occurence: Toxic reaction can be rare, and so it is difficult to predict adverse drug reaction. 2. Length of Use: Toxic reaction may appear after prolonged use 3. Detectability in animals: Toxic effects aren't detectable in animals and therefore are only seen once tested on humans. 4. Time period specificity: Toxic effect may be unique to a particular period in time→ pregnant women Assessing Drug Toxicity - Drug toxicity is assessed using a measure called the therapeutic index Therapeutic index (TI) = TD50 (dose of drug that is toxic in 50% of population) ED50 (dose of drug that is effective in 50% of the population) Therapeutic index tells you how safe a drug is by relating the dose required for a beneficial effect to the dose required to produce an adverse effect. Higher= Safer, Lower = Less safe. Drug-Drug Interactions - Occurs when one drug change the pharmacological effects of a second drug - Occur at many points during drugs journey through the body During: 1. Absorption: Drg can increase movement, speeding a second drug through the intestine, and decreasing constant of second drug therefore decreasing absorption. 2. Metabolism: Drugs can block inactivation of a second drug in the liver, increasing the blood level and pharmacological effect of the second drug. 3. Excretion: A drug can facilitate the excretion of a second drug by the kidney decreasing the blood level and pharmacological effect of the second drug. Drug-Food Interactions - Drug food interactions involve the interference of food with drugs taken concurrently 1. Tyramine: - Class of antidepressant drugs inhibit an enzyme (monoamine oxidase) used to break down Tyramine (found in cheese) → if a patient is being treated with an MAO inhibitor and consumes food containing tyramine, it cannot be broken down and it will cause intense high blood pressure. 2. Grapefruit: - A component of grapefruit inhibits enzymes that carry out biotransformation, which can result in higher blood levels of the drug than expected. SECTION 6- PHYSIOLOGICAL AND PHARMACOLOGICAL ASPECTS OF THE CENTRAL NERVOUS SYSTEM The central Nervous System Cerebral Cortex (cerebrum) - Largest part of the brain and rich in neurons - Functions include: Sensory and motor coordination, mental processes, intelligence, memory, vision, judgment, thought, speech, emotion and consciousness. - Neurons in CC are stimulated or inhibited by drugs. Limbic System - Region of brain that integrates memory, emotion, and reward - Together with the hypothalamus, they control emotion and behavior - Houses dopaminergic reward centers, which are targets for misused drugs and are associated w/ addictions. The neuron - Functional unit of brain - Nerve cell that generate and transmits electrical signals - 90 billion neurons each different in shape and size - Neurogenesis: process that continuously generates new neurons - Neuroplasticity: Process that reshapes connections between neurons Structure of neuron 1. Dendrites - Short complex branches - Act as receiving antennae for incoming information through receptors on dendritic membranes - Receives info then sends an electric current down the neuron. 2. Cell Body - Largest part of neuron and contains a nucleus and surrounding cytoplasm’ - Cytoplasm contains lots of pre packages neurotransmitters which can be secreted 3. Axons - Single fiber that extends from cell body to synapse - Axon continues to carry incoming information away from dendrites and cell bodies by electric pulses. Info is then sent to other neurons. Synapse - Junction between two neurons, where one neuron's axon ends and another neuron's dendrite or cell body begins. Synaptic Transmission - The passage of a signal from one neuron to the other - Very rapid and chemical in nature → substance is released the quickly activates the next neuron - Endogenous chemicals that transmit signals are called neurotransmitters - One synapse connects 2 neurons, but a single neuron can make synaptic connected with many other neurons Drugs and Synaptic Transmission - Synapse is a target site for many drugs - Drugs can interrupt synaptic transmission, and others can enhance or facilitate it, modifying the activity of the brain. Neurotransmitters and Receptors 1. Glutamate - Primary excitatory neurotransmitter in the CNS and is found in almost all neurons - Acts on receptors called the glutamatergic receptors→ important for learning 2. Serotonin - Hyperactivity of the serotonergic system is involved in anxiety and hypo-activity has been implicated in depression. - Some classes of CNS stimulants act by increasing serotonin at the synapse 3. Catecholamines 1. Dopamine - Involved in the control of some hormonal systems, motor coordination and motivation and reward. 2. Norepinephrine - Can bind to alpha and beta receptors - Activation of these receptors leads to excitation of the cell. 4. Acetylcholine  - Produces an excitatory response in the CNS. 2 types of receptors can bind to it: 1. Nicotinic Receptors: - Found in certain regions of brain and are stimulated by acetylcholine or nicotine 2. Muscarinic receptors: - Found in many regions of brain - Involved in learning, memory, and cognitive function - Stimulated by acetylcholine on muscarinic - Drugs that block the action of acetylcholine at these receptors produce amnesia. - Loss of these neurons is thought to be associated with Alzheimer's. 5. Gaba - Gamma-amino butyric acid is the primary inhibitory neurotransmitter in the CNS 6. Opioid Peptides - Main classes of opioid peptides: enkephalins, endorphins, dynorphins