Results for "acetylcholine"

# Synaptic transmission and the vesicle cycle ILO: - the two fundamental synaptic mechanisms by which excitable cells and in particular neurones can affect one another's function: electrical or chemical synaptic communication - how a neurotransmitter supporting chemical synaptic communication is defined and the diversity of types of small molecules that can be defined as being a neurotransmitter - how these are stored in small membranous vesicles, what constitutes the classical vesicle cycle and full collapse vesicle fusion during release - the experimental evidence for this full collapse fusion release model and how the vesicle membrane is recycled - further experimental evidence for an alternative to this model: the "kiss and run" model of vesicle cycling - the proteins that make up the release machinery and how they are readied for release during "docking" and "priming" - what happens to these proteins during the release process and the subsequent retrieval of vesicle membrane following full collapse fusion # Types of synapse - **chemical synapse** - molecules stored in vesicles - molecules diffuse across a gap - relatively slow - unidirectional - majority of synaptic transmission in the nervous system - **electrical synapse** - holes in adjoining cell membranes - linked by channels - gap junctions or connexons - signalling is very fast - bidirectional - direct electrical coupling between cells - electrical synchronisation in the heart - relatively rare in the nervous system - inhibitory interneurons or local networks # Chemical synapse Key functional roles - Neural computation - integration of many input +/- - Exhibit plasticity - development, learning and memory - Act as targets for drug action - neurotransmitter synthesis, release, receptors, uptake, degradation to produce a broad range or complex series of effects - inc functional flexibility ## Neurotransmitter 6 criteria :  ### Types  - amino acids - amines - purines - peptides - **dales principle** - neurons release just one transmitter at all of its synapses - how is dales principle challenged? - challenged by co existence and co release of small molecule transmitter and peptides by interneurons eg GABA and enkephalins - and more than one small molecule transmitter in some projection pathways eg L glutamate and dopamine ## Vesicles - neurotransmitters are likely to be stored in one type of vesicle ### Types  For LDCVs - concentration is lower because of the relatively proximity to the voltage gated channels - only seen when there is sustained AP in a more global manner rather than restricted to synaptic active zone ### Cycling  1. vesicle is filled with neurotransmitter with appropriate transporter which uses ATP as an energy source to drive against conc gradient and fill the vesicle 2. vesicle collected in to reserve pool, mobilised to active zone for docking 1. atp dependent process 3. primed to be sensitive to calc conc to initiate membrane fusion 1. also atp dependent 4. exocytosis following inc in intracellular conc of calcium 5. vesicle membrane fully collapses into the membrane 6. loss of membrane recovered with endocytosis, calcium dependent with coated pits 1. uncoating requires atp 7. small vesicles become part of endosome, all recycled 8. then pinched off again to start the cycle ### Evidence for full fusion/collapse - slam freezing - rapidly cooling of the neuromuscular junction on a metal block after electrical stimulation of motor neurone axon fibres to initiate acetylcholine release - sections of the presynaptic membrane were visualised at different types after electrical stimulation to follow any changes in presynaptic membrane - activity led to increase in membrane surface area - therefore vesicle recycling ### Step 1 - docking - close association with plasma membrane - synaptic vesicles only dock at active zone - presynaptic area adjacent to signal transduction machinery - active zones differ between neurons by vesicle number ### Step 2 - priming - ready for release - maturation of synaptic vesicle - made competent to release transmitter - requires ATP - conformational change in proteins that drive release ### Step 3 fusion/exocytosis - full fusion of synaptic vesicle and presynaptic terminal membrane - requires calcium - calcium sensor protein - fusion induces exocytosis - takes 1ms ### Step 4 endocytosis - recovery of fused membrane - triggered by inc intracellular calcium - involves cytoskeletal protein lattice formation from clathrin monomers - this helps to pinch off membrane with clathrin coated pits - takes about 5 seconds - ATP dependent ### Step 5 - recycling - mechanism to conserve synaptic vesicle membrane via endosome - decoating of clathrin coated pits is also atp dependent - vesicles refill with transmitter - atp dependent ### Kiss and Run Model? - fast recycling and low capacity, favoured at low frequency stimulation - may be majority of glutamate release in hippocampus - whereas classical is slow, high capacity, favoured at high frequency stimulation - full vesicle fusion may not be required - neurotransmitter leaks out of small fusion pores - SSVs recycled intact - and not recycled as clathrin coated vesicles via the endosome Functional evidence - flickering capacitance changes instead of up stepping capacitance - capacitance dependent on surface area ### Targeting vesicles Vesicle associated proteins - synaptobrevins VAMP - synaptotagmins Plasma membrane associated proteins - SNAP-25 - syntaxins ### Snares for release - synaptobrevin - single transmembrane spanning - t snare - syntaxin - single transmembrane spanning - SNAP-25 - anchored to membrane by S-acylation ### Release machinery in the different steps     Syntaxin regulatory domain is important in maintaining a tight connection to the cell membrane Snares form a tighter complex during priming - atp dependent - Habc domains binding assisted by Munc18 - zippering - formation of the SNARE pins What is the Ca2+ sensor? - synaptotagmin - found on vesciles - binds to SNARE pins in absence of Ca2+ - during priming - binds to phospholipids in C region in presence of Ca2+ - Ca2+ binding may cause synaptotagmin to pull vesicle into membrane Why must SNAREs disassociate? - to allow internalisation of empty vesicles - re docking of another vesicle - involves NSF - ATPase which binds to the SNARE-pin complex to facilitate disassociation

Lecture 3: Block 2: Acetylcholine and Nicotine

NICOTINIC ACETYLCHOLINE RECEPTOR DRUGS

ACETYLCHOLINE

acetylcholine

Neurotransmission and Acetylcholine: Brain and Medical Insights

Ch 7: Acetylcholine

Medicinal Chemistry of Acetylcholinesterase Inhibitors and Alzheimer’s Treatments

2.7 - Acetylcholine, Nicotine, and Muscarine

ch 7: acetylcholine

2. Acetylcholine & Amino acids

Acetylcholine

Unit 10 – Drugs for Central Nervous System (CNS) Problems (Comprehensive Study Guide – Nursing Pharmacology) ⸻ 🧩 Central Nervous System (CNS) Overview • CNS = Brain + Spinal Cord • Controls body movement, behavior, and cognitive function. • Neurotransmitters are chemicals that transmit signals between neurons. • Excitatory: Acetylcholine (ACh), epinephrine, norepinephrine • Inhibitory: Dopamine, serotonin, gamma-aminobutyric acid (GABA) ⚖️ Balance of dopamine and acetylcholine is critical for smooth movement. An imbalance leads to disorders like Parkinson’s Disease. ⸻ 🧍‍♂️ Parkinson’s Disease (PD) Cause • Progressive CNS disorder due to low dopamine production in the substantia nigra. • Too little dopamine → too much acetylcholine, causing impaired motor control. Key Symptoms Motor: • Tremors (“pill-rolling”) • Bradykinesia (slow movements) • Muscle rigidity, stiffness • Stooped posture, shuffling gait • Difficulty rising, “freezing in place” • Masklike facial expression Nonmotor: • Constipation, urinary frequency • Depression, anxiety, hallucinations • Sleep issues, fatigue • Memory problems ⸻ Drug Classes for PD Goal: Restore balance between dopamine and acetylcholine. 1️⃣ Dopamine Agonists Action: Mimic or increase dopamine. Improve movement, coordination, and muscle control. Examples: • carbidopa/levodopa (Sinemet, Rytary) • pramipexole (Mirapex ER) • ropinirole (Requip) • rotigotine (Neupro patch) Nursing Implications & Teaching: • Give 30–60 min before meals (empty stomach). • Avoid protein-rich foods (reduces absorption). • Monitor for orthostatic hypotension — rise slowly. • Don’t crush extended-release tablets. • Neupro patch: rotate sites, don’t reuse within 14 days. • Avoid vitamin B6 unless taken with carbidopa. • Takes 2–3 weeks for full effect. Side Effects: • Hypotension, headache, nausea, insomnia • Dyskinesia (abnormal movements) • “On/off effect” – medication wears off quickly • Long-term use → hallucinations, impulse control problems Adverse Effects: • Neuroleptic malignant syndrome: fever, rigidity, confusion • Psychosis, severe hypotension ⸻ 2️⃣ COMT Inhibitors Action: Block COMT enzyme → prolong dopamine activity. Examples: • entacapone (Comtan) • tolcapone (Tasmar) Nursing Implications: • Always give with carbidopa/levodopa. • Monitor liver function (q6 months) – risk of liver failure (especially tolcapone). • Harmless side effect: brown-orange urine. • Rise slowly to prevent hypotension. ⸻ 3️⃣ MAO-B Inhibitors Action: Inhibit MAO-B enzyme → prevents dopamine breakdown. Examples: • selegiline (Eldepryl) • rasagiline (Azilect) • safinamide (Xadago) Teaching: • Avoid foods high in tyramine → hypertensive crisis risk. (Aged cheese, wine, beer, cured meats, soy sauce, yogurt, avocados, bananas) • Monitor BP closely. • Avoid OTC decongestants or stimulants. • Can cause insomnia, dizziness, dry mouth, or constipation. ⸻ 🧠 Alzheimer’s Disease (AD) Cause • Progressive neurodegenerative disorder leading to memory loss, confusion, and poor judgment. • Loss of acetylcholine (ACh) and buildup of amyloid plaques and neurofibrillary tangles in the brain. Symptoms • Early: forgetfulness, confusion, mood changes. • Late: loss of reasoning, personality changes, inability to perform ADLs. ⸻ Drug Classes for AD 1️⃣ Cholinesterase Inhibitors Action: Block enzyme acetylcholinesterase (AChE) → increases ACh → improves memory and function. Examples: • donepezil (Aricept) • rivastigmine (Exelon) • galantamine (Razadyne) Side Effects: • Nausea, vomiting, diarrhea • Loss of appetite, GI discomfort • Drowsiness, headache, insomnia • Muscle cramps, bradycardia Adverse Effects: • Dysrhythmias, GI bleeding, hallucinations • Overstimulation of parasympathetic system (too much ACh) Nursing Implications: • Give at bedtime to reduce nausea. • Monitor weight, HR, and mental changes. • Report black/tarry stools or vomiting blood. • Avoid OTC anticholinergics (they reduce effectiveness). ⸻ 2️⃣ NMDA Blockers Action: Block NMDA receptor → decreases glutamate activity → prevents neuron death. Example: • memantine (Namenda) Used in: Moderate to severe AD (often combined with donepezil). ⸻ ⚡ Epilepsy / Seizure Drugs (AEDs) Purpose Reduce excessive electrical activity in the brain and prevent seizures. Common AEDs: • phenytoin (Dilantin) – prevents neuron excitation • topiramate (Topamax) – broad-spectrum seizure control Topiramate Key Points: • Side effects: dizziness, drowsiness, taste changes, paresthesias (“pins and needles”) • Adverse: metabolic acidosis, ↑ ammonia → confusion, lethargy, vomiting • Monitor: serum bicarbonate & ammonia levels • Teaching: stay hydrated, report mental status changes, don’t crush tablets • Contraindicated in pregnancy (teratogenic) ⸻ 💥 Multiple Sclerosis (MS) Pathophysiology • Autoimmune disease where the immune system attacks myelin (fatty sheath around neurons). • Leads to nerve signal disruption → muscle weakness and loss of coordination. • Common type: Relapsing-Remitting MS (RRMS) – periods of flare-ups and remission. Common Symptoms • Fatigue, weakness, difficulty walking • Double vision or blurred vision • Tingling or numbness • Bladder/bowel dysfunction • Depression, poor concentration ⸻ Drug Therapy for MS 1️⃣ Biological Response Modifiers (BRMs) Action: Modify immune system activity and slow disease progression. Examples: • beta-interferons (Avonex, Betaseron, Rebif, Extavia, Plegridy) • glatiramer (Copaxone) • fingolimod (Gilenya) • teriflunomide (Aubagio) Side Effects: • Flu-like symptoms, headache, fatigue • Elevated liver enzymes, slow HR • Thinning scalp hair Nursing Teaching: • Rotate injection sites. • Monitor liver enzymes, CBC, and heart rate. • Avoid live vaccines. ⸻ 2️⃣ Monoclonal Antibodies Action: Destroy lymphocytes that attack myelin. Examples: • alemtuzumab (Lemtrada) • natalizumab (Tysabri) • ocrelizumab (Ocrevus) Side Effects: • Increased risk of infection • Headache, rash, fatigue • GI upset Nursing Teaching: • Given IV every few months to yearly. • Monitor for infusion reactions and infection signs. ⸻ 3️⃣ Neurologic Drugs Examples: • dimethyl fumarate (Tecfidera) – reduces CNS inflammation • dalfampridine (Ampyra) – improves walking by increasing nerve conduction Teaching: • Take daily; don’t crush tablets. • Watch for GI symptoms and dizziness. ⸻ 💪 Amyotrophic Lateral Sclerosis (ALS) Description • Progressive, fatal disorder destroying motor neurons → paralysis. • Death usually occurs within 3–5 years of diagnosis. Drug Therapy Glutamate Antagonists Example: • riluzole (Rilutek, Tiglutik) Action: Inhibits glutamate release → slows neuron damage → prolongs life by months. Side Effects: • Weakness, nausea, dizziness • Liver toxicity (↑ liver enzymes) • Neutropenia, anemia Nursing Implications: • Monitor liver enzymes before and during therapy. • Report jaundice or dark urine. • Take on an empty stomach (1 hr before or 2 hrs after meals). • Avoid alcohol. • Don’t breastfeed while on this med. ⸻ ⚙️ Myasthenia Gravis (MG) Description • Autoimmune disease destroying acetylcholine receptors at neuromuscular junction. • Causes muscle weakness and fatigue, especially in eyes, mouth, throat. Symptoms • Ptosis (drooping eyelids) • Difficulty chewing/swallowing • Weakness in arms, legs, or respiratory muscles • Worsens with activity, improves with rest ⸻ Drug Therapy Acetylcholinesterase Inhibitors Action: Prevent breakdown of acetylcholine → improves nerve–muscle communication. Example: • pyridostigmine (Mestinon) Dosage: Usually every 4–6 hours, depending on patient response. Side Effects: • Nausea, vomiting, abdominal cramps, diarrhea • Increased salivation, sweating • Bradycardia, hypotension Adverse: • Cholinergic crisis (too much medication): → extreme weakness, bradycardia, bronchospasm, respiratory arrest. Nursing Implications: • Use with caution in asthma, COPD, bradycardia. • Give doses at same time each day to maintain muscle strength. • Monitor for myasthenic vs. cholinergic crisis. • Give meds 30–45 min before meals to prevent aspiration. Patient Teaching: • Take missed dose ASAP (but skip if close to next dose). • Don’t double dose. • Avoid alcohol and sedatives. • Report muscle weakness or breathing difficulty. • Keep atropine available (antidote for cholinergic crisis)

MUSCARINIC ACETYLCHOLINE RECEPTOR DRUGS

W3: Ligand gated ion channels - nicotinic acetylcholine receptors

Acetylcholine

What does the bicep flex at the elbow?: Forearm What fluid is serving as a shock absorber for central nervous system?: Cerebrospinal fluid The heart is located in which cavity?: Pericardial Mitochondria, lysosomes, ribosomes are examples of?: Organelles What regulates light entering the pupil?: Iris What layer of the skin contains spiny-shaped cells?: Stratum Spinosum Which direction do abductor muscles move an extremity?: Away What is the spinal cord a continuation of?: Medulla oblongata What system brings oxygen to and eliminates carbon dioxide from blood?: Respiratory ‘ Transcription occurs in which organelle?: Nucleus By late 70’s, what percent of muscle mass has disappeared?: 50% Eccrine glands are the most common type of what?: Sweat gland What is an individual bundle of muscle cells called?: Fascicle Which division of the autonomic nervous system prepares the body from stress?: Sympathetic Stomach and bladder are in which cavity?: Abdominopelvic Smallest living units of biological organization?: Cells Has a cuticle, cortex, and medulla?: Hair What is the oily substance excreted onto the skin?: Sebum What kind of muscles are found inside the digestive tract, blood vessels, and uterus?: Smooth First contraction in labor is an example of what process?: Positive feedback Which type of muscle is found only in the heart?: Cardiac Chondrocytes are found in what cavities?: Lacunae Neurotransmitter at the neuromuscular junction?: Acetylcholine What is the stratum germinativum?: Regenerative layer of the skin Lactic acid builds up in muscles when this molecule is converted in the absence of oxygen?: Pyruvic acid Which part of the autonomic nervous system operates under non stressful conditions?: Parasympathetic What converts food into simpler substances for absorption?: Digestive system What restores resting membrane potential?: Repolarization Brain is located in which cavity?: Cranial The loss of what makes the elderly more sensitive to the cold?: Circulation Phosphocreatine provides cells with what energy producing molecules?: ATP Brain decreases in size and mass due to loss of what?: Neurons How many nuclei does heart muscle contain?: Uninucleated Which glands are ductless and secrete hormones?: Endocrine Process correcting change to bring body back to normal?: Negative feedback

indirect cholinomimetics/acetylcholinesterase inhibitors/anticholinesterases

Acetylcholine

NPP Acetylcholine