Neuropharmacology Principles - Wong Chun Keung - 16 Sep 2024 PDF

PHARMACOLOGY AND TOXICOLOGY PRINCIPLES OF NEUROPHARMACOLOGY WO N G C H U N K E U N G 16 SEP 2024 1 DRUGS THAT ALTER AXONAL CONDUCTION - LOCAL ANESTHETICS 1 P B TFF I Local anesthetics stop the nerves in part of body sending signals to brain Unable to feel pai...

PHARMACOLOGY AND TOXICOLOGY PRINCIPLES OF NEUROPHARMACOLOGY WO N G C H U N K E U N G 16 SEP 2024 1 DRUGS THAT ALTER AXONAL CONDUCTION - LOCAL ANESTHETICS 1 P B TFF I 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 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 #zE A 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 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 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 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 A 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 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 adrenerge - acetylcholine Narcolepsy acetylcholiness evase 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