PHARMACOLOGY - Local Anaesthetics Flashcards
What is the mechanism of action for local anaesthetics?
Local anaesthetics prevent the initiation and conduction of action potentials through blocking the voltage-gated sodium channels of nociceptive afferent (sensory) nerve fibres
What is pain?
Pain is the unpleasant sensory and emotional experience associated with actual or potential tissue damage
Are local anaesthetics weak acids or weak bases?
Local anaesthetics are weak bases
How does the ionisation status of a local anaesthetic drug affect its action?
Local anaesthetics must be lipophilic and thus uncharged to pass through the lipid cell membrane (i.e. B) however local anaesthetics have to be charged to bind to the binding sites within the sodium channels (i.e. BH+)
What are the two pathways used by local anaesthetics to block sodium channels?
Hydrophobic pathway
Hydrophilic pathway
Describe the hydrophobic pathway used by local anaesthetics
The lipophilic, uncharged local anaesthetic molecule (B) passes into the cell membrane and sideways into the sodium channel
Describe the hydrophilic pathway used by local anaesthetics
The lipophilic, uncharged local anaesthetic molecule (B) passes through the cell membrane into the intracellular space and into an open sodium channel
How can local anaesthetics exhibit use dependence?
The binding of local anaesthetics increases due to increased action potential frequency as this increases how often the sodium channels are open to allow the local anaesthetic to bind to and block these channels
Describe how the hydrophillic pathway exhibits use dependence but the hydrophobic pathway does not
The hydrophobic pathway does not exhibit use dependence as the drug moves sideways into the sodium channel which can happen whether or not the sodium channels are open or closed. However, the hydrophilic pathway does exhibit use dependence as this pathway requires the sodium channel to be open in order to enter the sodium channel and carry out an effect
Since local anesthetics are weak bases will they be charged or uncharged at physiological pH?
At physiological pH, local anaesthetics are largely uncharged (unionised) (B)
How does the degree of ionisation affect the speed of onset of local anaesthetics?
Local anaesthetics must be in their lipophilic, uncharged (unionised) form in order to cross the cell membrane so the more drug available in its unionised form and less in its charged (ionised) form, the faster the speed of onset
Why are inflamed tissues resistant to local anaesthetics?
Inflammatory tissue has an acidic environment, which means the equilibrium will shift to the left and more of the local anaesthetic will exist in its charged (ionised) form, reducing the quantity of uncharged (unionised) drug available to cross the cell membrane
How does protein binding influence the duration of action of local anaesthetics?
Local anaesthetics have the ability to bind to local structural proteins. The higher degree of protein binding increases the duration of action as their will be a larger resevoir of drug available
How does lipid solubility influence the potency of local anaesthetics?
Local anaesthetics must be in their lipophilic, uncharged (unionised) form in order to cross the cell membrane so increased lipid solubility will increase the ability of the drug to cross the cell membrane and carry out its effect
Why is bicarbonate sometimes added to local anaesthetics?
Bicarbonate increases the pH causing the equilibrium to shift to the right to increase the quantity of local anaesthetic in its unionised form (uncharged) to increase the quantity of drug that can cross the cell membranes and carry out it’s effect - increasing speed of onset
Why is adrenaline sometimes added to local anaesthetics?
Adrenaline acts on α1 adrenoreceptors on vascular smooth muscle which causes a local vasoconstriction which will limit the blood flow to the area which will decrease the volume of blood that can wash the drug away. This will increase the length of time the local anaesthetic can enter surrounding cells, prolonging it’s effect
(T/F) Adrenaline can be added to local anesthetics for any administration method
FALSE. Adrenaline can only be added to local anaesthestics that are being administered via local infiltration
Describe the chemical structure of local anaesthetics
Local anaesthetics have a lipophillic aromatic group attached to a hydrophilic amine group either by an ester link or amide link
What are the two classes of local anaesthetic structure?
Ester-linked local anaesthetics
Amide-linked local anaesthetics
How are ester-linked local anaesthetics metabolised?
Ester-linked local anaesthetics are rapidly hydrolysed by non-specific cholinesterases
How are amide-linked local anaesthetics metabolised?
Amide-linked local anaesthetics are metabolised by the liver
Why do ester-linked local anaesthetics have a shorter half life compared to amide-linked local anaesthetics?
Ester-linked local aneasthetics are rapidly hydrolysed by non-specific cholinesterases leaving them with short half lives, however amide-linked local anaesthetics are metabolised within the liver and thus are required to be washed away by blood to reach the liver and be metabolised, resulting in a longer half life
When would you use topical anaesthesia?
To desensitise intact skin or mucous membranes
When would you use local infiltration of local anaesthesia?
To desensitise dermal and subcutaneous tissues for minor surgery
