L8 Pharm 1 - Drugs & Toxins Lecture PDF

Lecture 8 Pharmacology 1: Drugs & Toxins PSC 101- Bio Psych February 4th 2025 Lecture 8 Learning Objectives 8.1- Explain how drugs and toxins can be introduced into the body and which factors will determine the effectiveness of those substances. 8.2- Create an argument if botulinum t...

Lecture 8 Pharmacology 1: Drugs & Toxins PSC 101- Bio Psych February 4th 2025 Lecture 8 Learning Objectives 8.1- Explain how drugs and toxins can be introduced into the body and which factors will determine the effectiveness of those substances. 8.2- Create an argument if botulinum toxin is a drug or a poison. Be sure to understand its mechanism of action at the neuromuscular junction. 8.3- Compare and contrast SSRIs and cocaine/methylphenidate. Be sure to mention their neurological and behavioral effects. Also explain how they can be used to help people with certain neurological disorders. Lecture 8 Learning Objectives 8.1- Explain how drugs and toxins can be introduced into the body and which factors will determine the effectiveness of those substances. 8.2- Create an argument if botulinum toxin is a drug or a poison. Be sure to understand its mechanism of action at the neuromuscular junction. 8.3- Compare and contrast SSRIs and cocaine/methylphenidate. Be sure to mention their neurological and behavioral effects. Also explain how they can be used to help people with certain neurological disorders. 8.1- Drug & Toxin Absorption Bloodstream Drugs and toxins must be introduced into the bloodstream to interact with the brain and body The bloodstream will transport the substance around the whole body 8.1- Drug & Toxin Absorption Blood Stream Will only interact with certain tissues Ligands binding to receptors Primary cause of side effects Drug designed to interact with the brain region Activates the same receptors in another part of the brain or body Ex: antihistamine, opioids, etc. 8.1- Drug & Toxin Absorption Substance Breakdown enzymes Once a substance enters the bloodstream, it will start to be broken down by the body Kidneys The substance’s effect is dependent on: Dose Route of administration Liver 8.1- Drug & Toxin Absorption Dose The effectiveness of the substance is directly related to its concentration More of the substance, greater the effect on the body Effective and fatal doses greatly vary between substances 8.1- Drug & Toxin Absorption Dose- Opioids Diverse class of analgesics Pain killers A slight difference to the structure greatly influences how effective each opioid is at pain suppression 8.1- Drug & Toxin Absorption Dose- Opioids Compared Equivalent Opioid Type Dose Codeine (Oral) ~110 mg Morphine (Oral) 10 mg Oxycodone (Oral) 6.67 mg 8.1- Drug & Toxin Absorption Substance Breakdown Most direct path from administration to the target tissue will have the most significant effect Has the least amount of time to be broken down 8.1- Drug & Toxin Absorption Routes of Administration Least Ingestion Absorption Intramuscular injection Inhalation Intravenous injection Most 8.1- Drug & Toxin Absorption Equivalent Dose- Opioid Opioids Type Compared Dose Codeine (Oral) ~110 mg Morphine (Oral) 10 mg Oxycodone (Oral) 6.67 mg Morphine (IV) 3.33 mg Fentanyl (IV) 0.1 mg 8.1- Drug & Toxin Absorption Substance Effectiveness The effect a drug or toxin has on the body is determined by the dose and route of administration Few structures in the body have additional protections to filter out some drugs and toxins 8.1- Drug & Toxin Absorption Blood-Brain Barrier (BBB) Astrocytes tightly wrap around blood vesicles in the brain Materials must pass through the astrocytes before reaching the neurons 8.1- Drug & Toxin Absorption Blood-Brain Barrier (BBB) Allow in good stuff Glucose Oxygen (O2) Water Amino acids More Blocks bad stuff Badu Waste Toxins More 8.1- Drug & Toxin Absorption Blood-Brain Barrier (BBB) Small and uncharged substances can still slip through the BBB to interact with the CNS Drugs and toxins that interact with the brain are able pass through the BBB 8.1- Drug & Toxin Absorption Blood-Brain Barrier (BBB) Pharmaceutical companies take advantage of this fact Design medications to pass through or to be blocked Example: Diphenhydramine (Benadryl) Loratadine (Claritin) 8.1- Drug & Toxin Absorption Benadryl Diphenhydramine Allergy medicine Reduced allergy symptoms Such as excessive mucus production Antihistamine 8.1- Drug & Toxin Absorption Antihistamines Mucus producing cells in our sinuses are regulated by histamine receptors When histamine binds to histamine receptors, mucus is produced 8.1- Drug & Toxin Absorption Antihistamines Antihistamines are antagonists Molecules that bind to a receptor but do not activate the receptor Prevents histamine from binding and activating the receptors 8.1- Drug & Toxin Absorption Antihistamines Antihistamines will block receptors on mucus producing cells in the sinus Reducing mucus production Giving relief from allergy symptoms 8.1- Drug & Toxin Absorption Histamine in the Brain The same molecule is reused in different organs for different functions Histamine is a NT that activates receptors in our brain that keep us awake 8.1- Drug & Toxin Absorption Benadryl Benadryl is a small molecule that can pass through the BBB Antihistamines in the brain will block histamine receptors Resulting in drowsiness and exhaustion 8.1- Drug & Toxin Absorption Claritin Loratadine Allergy medicine Antihistamine Similar ligand Different molecular structure, larger and slightly charged 8.1- Drug & Toxin Absorption Claritin Different structure prevents it from passing through the BBB Antihistamine is unable to access the brain Prevents drowsy side G effects 8.1- Drug & Toxin Absorption BBB Summary Substance must get past the BBB to interact with the brain Small substances are able to get through Self-Assessment Questions Get your iClicker app or web portals ready! Lecture 8 Learning Objectives 8.1- Explain how drugs and toxins can be introduced into the body and which factors will determine the effectiveness of those substances. 8.2- Create an argument if botulinum toxin is a drug or a poison. Be sure to understand its mechanism of action at the neuromuscular junction. 8.3- Compare and contrast SSRIs and cocaine/methylphenidate. Be sure to mention their neurological and behavioral effects. Also explain how they can be used to help people with certain neurological disorders. 8.2- Botox NMJ Introduction The first drugs and toxins we will cover primarily act on the neuromuscular junction (NMJ) Location of communication from the nervous system to the muscles 8.2- Botox NMJ Introduction Skeletal muscles are made of many parallel muscle fibers Muscle fibers contract when stimulated by axons PNS neurons of the somatic efferent division have axons that synapse with each muscle fiber 8.2- Botox Neuromuscular Junction (NMJ) Presynaptic: Axon Functions are identical to neuron-to-neuron synapses Releases acetylcholine (ACh) Postsynaptic: Muscle fiber Contracts when ACh binds to ACh receptors 8.2- Botox catch presynaptic cell gated SNARE NTvesicle I 8.2- Botox Cat Cat I 8.2- Botox A 8.2- Botox Contract 8.2- Botox 8.2- Botox 8.2- Botox Botulinum Toxin Commonly known by commercial name: Botox Neurotoxin poison Produced by bacteria found in mishandled meat “Sausage Poisoning” 8.2- Botox Botulinum Toxin/Botox Mechanism of Action Breaks down the SNARE complex Prevents the SNARE from operating What will happen if the NMJ of a muscle fiber is exposed to Botox? Take 1-minute to think about your answer Pair up with a person next to you and talk about your answer (if you are comfortable) Share your answers with me! (if you are comfortable) What will happen if the NMJ of a muscle fiber is exposed to Botox? Possible Answers: Stop moving No ACh release in cleft 8.2- Botox 8.2- Botox SNARE 8.2- Botox EE Break.fi 8.2- Botox nqsytE.EE 8.2- Botox Botulinum Toxin Effects PNS axon is unable to release NTs without intact SNARE complexes Muscle fiber will not receive NTs when the axon is stimulated Muscle fiber is permanently paralyzed 8.2- Botox Do you think botulinum toxin (Botox) is a poison or a medication? Take 1-minute to think about your answer Pair up with a person next to you and talk about your answer (if you are comfortable) Share your answers with me! (if you are comfortable) 8.2- Botox Do you think botulinum toxin (Botox) is a poison or a medication? Possible Answers: 8.2- Botox Botulinum Toxin Uses It is both! Depends on: Dose Route of administration 8.2- Botox Botulinum Toxin Uses Ingestion of a high dose of botulinum toxin will will allow the toxin to enter the blood stream and circulate to NMJs across the whole body Resulting in: Botulism Possible Death 8.2- Botox Botulinum Toxin Uses Local injection of a low dose of botulinum toxin to a specific muscle will not spread to the blood stream Only the injected muscle will be affected Resulting in: Localized muscle paralytic 8.2- Botox Botox Uses Cosmetic Paralyzes small face muscles Prevents wrinkles in skin when muscles contract i 8.2- Botox Botox Uses Tension Headache Treatment Weakens overly constricted muscles around base of skull Relieving tension causing headache 8.2- Botox Botox Uses Strabismus treatment Aka “lazy eye” Caused by muscles of the eye unevenly pulling on the eye Pulling one eye more to one side than the other Muscles on tenser side are weakened to even tension across eye Self-Assessment Questions Get your iClicker app or web portals ready! Lecture 8 Learning Objectives 8.1- Explain how drugs and toxins can be introduced into the body and which factors will determine the effectiveness of those substances. 8.2- Create an argument if botulinum toxin is a drug or a poison. Be sure to understand its mechanism of action at the neuromuscular junction. 8.3- Compare and contrast SSRIs and cocaine/methylphenidate. Be sure to mention their neurological and behavioral effects. Also explain how they can be used to help people with certain neurological disorders. 8.3- Reuptake Inhibitors Substances in the Brain Botox primarily acts on only synapses in the PNS Can not pass the BBB Substances that pass through the BBB are able to access the brain to influence synaptic transmission 8.3- Reuptake Inhibitors Reuptake Inhibitors Multiple commonly prescribed medications influence synaptic transmission by modulating the activity of NT reuptake proteins 8.3- Reuptake Inhibitors SSRI Selective serotonin reuptake inhibitors (SSRI) Medication commonly prescribed as treatment for: Major Depression Disorder Generalized Anxiety Disorder 8.3- Reuptake Inhibitors 8.3- Reuptake Inhibitors 8.3- Reuptake Inhibitors 5 HT 8.3- Reuptake Inhibitors 5Heaters 8.3- Reuptake Inhibitors C 8.3- Reuptake Inhibitors Clear out will stop 8.3- Reuptake Inhibitors 8.3- Reuptake Inhibitors the BlockReuptake 5 HT proteins 8.3- Reuptake Inhibitors 8.3- Reuptake Inhibitors How and why would postsynaptic activity be influenced if 5-HT receptors are inhibited? Reuptake proteins Take 1-minute to think about your answer Pair up with a person next to you and talk about your answer (if you are comfortable) Share your answers with me! (if you are comfortable) 8.3- Reuptake Inhibitors How and why would postsynaptic activity be influenced if 5-HT receptors are inhibited? Possible Answers: S HT hangs in cleft activating receptors 8.3- Reuptake Inhibitors 8.3- Reuptake Inhibitors 8.3- Reuptake Inhibitors Block I 8.3- Reuptake Inhibitors 8.3- Reuptake Inhibitors SSRI The synapse will take longer to clear all 5-HT out from the cleft Still have: Some functioning 5-HT uptake proteins Degradation proteins Diffusion 8.3- Reuptake Inhibitors SSRI SSRI increases the amount of time 5-HT is in the synaptic cleft Giving 5-HT more opportunities to bind and unbind from 5-HT receptors Resulting in increased postsynaptic activation 8.3- Reuptake Inhibitors Serotonin Hypothesis Working theory of why SSRIs helped people with depression and anxiety Belief that those people had decreased 5-HT signaling Currently being reevaluated 8.3- Reuptake Inhibitors SSRI- Mysteries While the initial mechanism of SSRIs are very well understood, it is unclear how increased 5-HT signaling helps some people with depression and anxiety disorders 8.3- Reuptake Inhibitors SSRI- Mysteries SSRIs do not work for everyone Beneficial behavioral outcomes typically take ~3 weeks to manifest Even though 5-HT levels increase within hours of first dose 8.3- Reuptake Inhibitors SSRI- Mysteries Beneficial outcomes might be due to presynaptic changes following prolonged increase of 5-HT signaling Currently being investigated 8.3- Reuptake Inhibitors SSRI- Mysteries 5-HT is most likely a part of the puzzle, but not the “magic bullet” that it was first thought to be 8.3- Reuptake Inhibitors 5HTT KO Experiment- Paradoxical Finding Flashback to our development lecture Researchers knocked out (KO) a 5-HT transporter (5HTT) which is a reuptake protein! Expected to reduce anxiety because they thought KOing reuptake would increase 5-HT signaling Surprised to see they actually killed off 5-HT producing cells! 8.3- Reuptake Inhibitors 2-Minute Neuroscience: SSRI https://youtu.be/uiXcAbrO8kU?si=pLpqxnCWKxnxvUVR Time: 0:00 – 2:00 8.3- Reuptake Inhibitors 10-Minute Neuroscience: Depression https://youtu.be/1euK8OSIR9E?si=5vmlaez3fkfhKpaI Will not be tested on, just for self education about modern depression research 8.3- Reuptake Inhibitors Reuptake Inhibitors SSRIs are not the only substance that influences synaptic signaling by decreasing the effectives of reuptake proteins. 8.3- Reuptake Inhibitors Cocaine Cocaine is an illegal recreational drug that inhibits the reuptake of: Dopamine (DA) Norepinephrine (NE) Serotonin (5-HT) Near identical mechanism of action as SSRIs 8.3- Reuptake Inhibitors Cocaine Stimulant drug that causes one to experience: Hyperactivity Euphoria Emotional dysregulation 8.3- Reuptake Inhibitors Why do SSRIs and cocaine have very different behavioral effects if they have near identical mechanisms of action on the synapse? Take 1-minute to think about your answer Pair up with a person next to you and talk about your answer (if you are comfortable) Share your answers with me! (if you are comfortable) 8.3- Reuptake Inhibitors Why do SSRIs and cocaine have very different behavioral effects if they have near identical mechanisms of action on the synapse? Possible Answers: Route Dose Mult NT CDA NE mult post synaptic responses which proteins 8.3- Reuptake Inhibitors SSRI vs Cocaine The drugs have different behavioral effects because they influence the signaling of different NTs The increase DA and NE will result in hyperactivity, euphoria, and other symptoms 8.3- Reuptake Inhibitors SSRI vs Cocaine Neural activity is dependent on the activity of the receptors in the brain Modulating different NT signaling in the brain will affect those receptors, thus having different effects on behavior 8.3- Reuptake Inhibitors Cocaine Modulation of the DA system will be a major aspect of our next lecture (Opioids) 8.3- Reuptake Inhibitors Methylphenidate Commonly know by commercial name: Ritalin Commonly prescribed to treat attention-deficit hyperactivity disorder (ADHD) Same activity component as cocaine 8.3- Reuptake Inhibitors Methylphenidate Unclear how and why the increase of DA and NE signaling has a beneficial outcome for some people with ADHD 8.3- Reuptake Inhibitors Reuptake Inhibitors Amazing tool for supporting people with a range of neurological disorders Thought to be a “magic bullet” but in reality, seems to be helping a part of a bigger picture Hot bed of research!!! 8.3- Reuptake Inhibitors 2-Minute Neuroscience: Cocaine https://youtu.be/dBuIliNAixg?si=sTwXAUQ1zCOZcif6 Time: 0:00 – 1:30 Self-Assessment Questions Get your iClicker app or web portals ready! Any questions? Slides were made by Brett M. Bormann, UC Davis Neuroscience Graduate Group