27760080
Description
Flashcards by Majd Fawaz, updated more than 1 year ago
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Created by Majd Fawaz
over 3 years ago
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| Question | Answer |
| True or False LA and Analgesics work in a similair way with almost identical effects | - False - Unlike Analgesics, LA do not interact with pain receptors and dont interfere with the biosynthesis or release of pain mediators - They don't cause loss of consciousness |
| How do Local Anesthetics work? | - LA binds to Na+ channels --> Block nerve conduction: No action potential generated + Decrease excitation of nerve - Cause loss of motor fucntion - Channel preference: Inactivated>Open>Closed |
| Tetradotoxin Saxitoxin | - Marine neurotoxins - They bind IRREVERSIBLY to Na+ channels --> No depolerization until a new channel is synthesised - Cause paralysis of the resperatory muscle - Relaxtion of the VSM --> Hypotention |
| - Tetradotoxin (TTX) - Left is lactone form - Right is hemiacetal form | |
| Centruriodes | - Scorpion venom - Not toxic to humans - Not addictive - Showed efficacy in Neuroblastoma |
| - Saxitoxin (STX) | |
| - Cocaine - Has anesthitc properties - Addictive, Allergies, Chemical Instability, Toxic - Many side effects - Causes withdrawl when discontinued | |
| - All inactive metabolites | |
| - Atropine - Cocaine analogue - Has little anesthetic activity - Causes eye irritation at doses that cause local anesthesia | |
| - Homatropine | - More potent than atropine - Less irritating to the eye - Still a weak anesthetic agent |
| - Benzoyltropine - Strong LA - No addicition (no 2-carbomethoxy) | |
| - Benzocaine - Good anesthetic properites + Low toxicity - No basic 3-N --> Not water solubility --> No paranteral use --> Topical use only | |
| - Procaine - Prototype for LA - Low potency + Short DOA - Needs vasoconstrictor - Is synthesized in slight acidic medium to preserve shelf life - No autoclaving | |
| - Isogramine - Has LA activity (serendipitous) - Led to the synthesis of Lidocaine | |
| What are the 3 parts that make up the structure of most LA | 1) Lipophilic aromatc ring 2) Linker of various lenght 3) Amino group |
| SAR: Intermediate Chain | - Short alkyl chain (1-3 carbons) - Linked to aromatic ring via functional group (ester or amide) - Branching hinders hydrolysis => Longer DOA |
| SAR: Aromatic Ring | - Essential for binding - More lipophilic subs. --> More potent - For amino-esters: *ortho/para e- donating subs. --> Inc. potency * e- withdrawing groups dec. potency - For amino-amides: *o,o dimethyl subs --> Inc. DOA |
| Analyze its LA activity | - The methyl group between the ester and the ring prevents resonance --> Less potent |
| - Proparacaine - Amino group (meta) doesn't do resonance | |
| - Benoxinate - Alkyloxy group (meta) doesn't do resonance | |
| - 2-Chloroprocaine - Chloro is e- withdrawing --> ester is more susceptible to hydrolysis + Less zwitterion --> Short DOA + Less potent | |
| - Propoxycaine - Propoxy group protects the ester from hydrolysis --> Long DOA | |
| - Tetracaine - x50 Procaine: * Increase lipophilicity --> Increase topical potency * N-butyl is e- donating --> Longer DOA - Overdose may produce CNS toxicity and seizure activity - Hypersensitivity | |
| SAR: Hydrophilic Portion | - 3-amine --> Water soluble salts - Can be 2nd or 3rd amine or part of a cycle - Onium ion produced is involved in the binding to Na+ channel (necessaty debatable) |
| - Hilles Theory - 1 binding site for un/ionized N - Ionized (external) binds to hydrophilic BS (when channel opens) - Lipid soluble LA: * Diffuse --> Bind to hydrophobic BS (nonbasic LA) *Diffuse --> Protonate --> Bind to Hydrophilic BS | |
| - Lidocaine - Most comman LA (amino amide) - Very lipophilic --> Very rapid onset - Lipophilic --> Central effect + CNS toxicity - Has antiarrhythmatic effect - Causes vasodilation (give vasoconstrictor) - More stable in aqueous solution | |
| - Mepivacaine - Pharmacological and toxicological profile similair to Lidocaine - Slight longer DOA - No vasodilation (no need for vasoconstrictor) | |
| - Bupivacaine - Increased potency and DOA - Cardiotoxic (affinity to cardiac tissue) | |
| - Levobupivacaine - Same LA activity as Bupivacaine - Less cardio/CNS toxicity - More selective to sensory compared to motor neuron | |
| - Ropivacaine - Propyl analogue of Mepivacaine and Bupivacaine - Has the LA potency and DOA of Bupivacaine - Less cardio/CNS toxicity - More selective to sensory compared to motor neuron - Has inherent vasoconstriction ability (no need for vasoconstrictor) - Not used as a racemic mix | |
| - Articaine - Used in dentistry: * Fast onset (Very Lipo) * Short DOA (ester) - Gives inactive metabolite (water-soluble CA) | |
| Name the LA with chiral centers | - Bupivacaine - Etidocaine - Mepivacaine - Prilocaine |
| Name the LA that are marketed in their Levo form | - Ropivacaine - Levobupivacaine |
| True or False The Levo isomer shows significant decrease in CNS and cardiotoxicity | - True - Ex: Levobupivacaine |
| True or False Amide and ester type LA can be sterilized using heat | - False - Ester bond is too weak in terms of hydrolytic stability to withstand high temperature |
| - Describe the relationship between lipophilicity and 1) Onset of Action 2) Water Solubility 3) Potency 4) DOA 5) Toxicity | 1) Fast onset 2) Decreased water solubility (paranteral unavailability) 3) Increased potency 4) Short DOA 5) Increased toxicity |
| - Administration of LA in a carbonic acid-carbondioxide solution as suppose to hydrochloride salt would improve time of onset and DOA, however it is unpractical...Why? | - Being unionized, it will not be water soluble and will precipitate, inhibiting it from being injected. |
| - PABA (para amino benzoic acid) - Responsible for the hypersensitivity reaction patients have to ester-type LA | |
| Side effects of LA | - Hypersensitivity (ester-type) - Cardiovascular depression - Block NMJ - Relaxation of non/vascular smooth muscle - Amide-type LA: convulsion followed by sever CNS depression - Prilocaine: metabolised into o-toluidine --> methemoglobinemia |
| - Tocainide - Used as antiarrhythmatic - Was prepared to minimmize the CNS toxicity of Lidocaine - No subs on N - a-methyl to prevent MOA metabolism - Has LA activity (not used) | |
| - Tolycaine - Used as antiarrhythmatic - Prepared to minimize CNS effects of Lidocaine - The ester is hydrolyzed into polar carboxylate group --> No BBB penetration --> No CNS | |
| DDI | - Ester-type LA and cholinesterase inhibitors: They will prolong LA activity and/or toxicity - Ester-type LA and Sulfonamide: It will prevent antibiotic from working |
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