4223201
| Frage | Antworten |
| What is the mechanism for Local Anaesthetics? | Block the conduction of action potentials in nerve axons |
| Which pathway carries pain and temperature information? | Lateral spinothalamic tract |
| How is the strength of a pain signal encoded? | Frequency of action potentials |
| What determines how easily a LA blocks the transmission of an AP? | Diameter of the nerve fibre. |
| What type of information is carried in a: 1) Aa 2)Ab 3)Ad 4) C | 1) Proprioception 2) Touch 3) Pain (mechanical and thermal) 4) Pain (mechanical, thermal and chemical) |
| Which of the four classes of nerve fibres isn't myelinated? | C fibres |
| What is the order of size of nerve fibres? (LARGEST TO SMALLEST) | 1) Aa 13-20uM 2) Ab 6-12uM 3)Ad 1-5uM 4)C 0.2-1.15uM |
| Which nerve fibres are most sensitive to block by LAs | Ad and C fibres |
| Describe the 3 main parts of a LA | 1) Aromatic group (lipophilic, hydrophobic) 2) Ester or Amide 3) Amino Group |
| Describe the structure of an Ester | |
| Describe the structure of an Amide | |
| What determines the percentage of an LA which is ionised? | 1) pH of solution 2) pKa of LA |
| What do pH and pKa equate to? | pH = -log10[H+] pKa = -logtoKa (acid dissociation constant) |
| When does pKa = pH (or Ka = [H+]) | when LA + H+ >>>>>> LAH+ <<<<<< Are both at 50% |
| What happens to the percentage of ionised LA as the pH decreases (becomes more acidic)? | Percentage of ionised LA increases |
| HENDERSON-HASSLEBATCH EQUATION | pKa - pH = log [LAH+]/[LA] |
| What happens to the acidity of an inflamed tissue? | Acidity increases |
| What are the two pathways LAs can take to block sodium channels? | Hydrophobic and Hyrdophilic |
| Which pathway is most prevalent? | Hydrophilic |
| Describe the Hydrophobic (Lipophilic) pathway. | Unionised LA molecules enter the membrane and interact with membrane proteins (sodium channels) preventing them from functioning. |
| Describe the Hydrophilic pathway | Most hydrophobic (10-20%) molecules pass through the membrane and enter the cytoplasm. Majority become ionised (80-90%) because pH cytoplasm = 7.4. Block sodium channel at intracellular side. |
| Where do LAs bind in sodium channels? | Bind at the S6 segment in domain IV of a subunit. |
| Which states do LAH+ have high affinity for? | Open and inactive |
| Why don't LAs affect normal channel APs? | LAs are use-dependent >> the more active the channel the more they bind (as in high frequency of pain APs) |
| What is the pKa of procaine? | 8.98 |
| Why is procain hardly used? | 1) poor tissue penetration 2) short plasma half life 3) readily hydrolysed by non-specific esterases in plasma |
| What is the pKa of Lidocain (Lignocaine) | pKa=8.0 |
| What is the plasma half life of lidocaine? | 2hr |
| How is lidocaine removed from the system? | Metabolised by the liver |
| What is the time taken for onset? | 5-10 minutes |
| What can be injected to prolong the effect of LAs? Give two examples of this | Vasoconstrictors 1) Adrenaline 2) Felypressin |
| Why do vasoconstrictors prolong the action of LAs? | Circulation terminates action of LAs. Constricting blood vessels keeps LA active at site for longer. |
| Give an example of two other LAs containing an ester group | tetracaine (amethocaine) cocaine |
| Give an example of another two LAs containing an amide group | Bupivacaine Prilocaine |
| What are the two Atypical LAs? (NUMBER 1) | |
| NUMBER 2 | |
| Why is benzocaine an Atypical LA? | No amine group >> always unprotonated Can only take hydrophobic pathway |
| Why is QX-314 an Atypical LA? | Permanently 100% ionised. Has to be introduced into cytoplasm of cells experimentally (via pipette). |
| Which LAs are used as surface anaesthetics and in what form? | Lidocaine-Spray (nose, mouth, upper RT) Lidocaine & Tetracaine - Solution (cornea of eye) Cocaine: solution/spray (ear/nose/throat) Lidocaine, tetracaine - gel/ointment (urethra/skin) |
| What is infiltration anaesthesia used for? (And which LAs?) | Most LAs, injected into tissues to block conduction in fine nerve terminals for minor surgery. Never toes or fingers (ischaemic damage) |
| What is intravenous regional anaesthesia used for? And which LAs are used? | Limb surgery - lidocaine or prilocaine Injected distal to pressure cuff. |
| What is nerve-block anaesthesia used for? Where is it injected? | Dentistry, surgery and analgesia. Injected close to nerve trunk |
| Where is a spinal anaesthesia injected? What is it used for and which LAs are used? | Injected into subarachnoid space between 2 & 5 lumbar vertebrae (inhibit nerves innervating lower body) Used for surgery on abdomen, pelvis or leg Lidocaine or bupivicaine. |
| Where is an epidural injected? What is it used for? Which LAs are injected? | Epidural space of spinal cord. Childbirth. lidocaine, bupivacaine and ropivacaine. |
| How would you treat neuropathic pain? | With I.V lidocaine |
| What are the 3 Adverse effects of LAs? *NUMBER 1 | High plasma conc (accidental injection into artery or vein) CNS: Stimulation>>confusion>convulsions> respiratory depression CVS: DECREASE blood pressure due to: i) decrease heart contractility ii)Vasodilatio |
| *NUMBER 2 | Hypersensitivity (allergic reaction) |
| *NUMBER 3 | Methaemoglobinaemia - due to toxic metabolite produced from prilocaine |
| What are the other clinical uses of LAs? | Treatment of ventricular dysrhythmias Potentially treatment of epilepsy |
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