Local Anesthetics Flashcards
MoA of Local Anesthetics
Act directly on nerve cells to block their ability to transmit impulses –> by blocking action potential propagation of nociceptive neurons (sodium channels) –> eliminate sensations of pain.
*The molecular targets –> voltage-gated sodium channels –> reduce the influx of sodium ions.
*Local anesthetics have to get intracellularly to exert their action – at the intracellular site of the receptor.
The 2 categories of local Anesthetics
1) Amides (longer duration of action)
2) Esters (shorter duration of action)
*end in -caine
PK of short-acting Local Anesthetics
- Short-acting local anesthetics –> readily absorbed into the blood from the injection site after administration.
- Limited duration –> unless blood flow to the area is reduced (in case of a vasoconstrictor)
PK of long-acting Local Anesthetics
less dependent on the co-administration of vasoconstrictors, unlike short-acting agents
Clinical uses of local Anesthetics
Minor surgical procedures often in combination with vasoconstrictors (e.g. epinephrine)
What agent is used to increase the onset of action of local anesthetics –> to enhance intracelluar access
Sodium biocarbonate
MoA of cocaine
cocaine –> has intrinsic sympathomimetic actions –> Reduces influx of NE
reuptake at nerve terminal. (no need for vasoconstrictor)
Adverse effects of local Anesthetics
1) CNS effects
- light-headedness
-sedation
-restlessness
-Nystagmus
-Tonic-clonic convulsions
* sever convulsions –> Coma with respiratory and cardiovascular depression
2) Cardiovascular effects
- Vaodilation (Excpet for Cocaine)
- Heart block is susceptible patients
Drugs used as Local Anesthetics
1) Bupivacaine (Amide)
2) Lidocaine (Amide)
3) Cocaine (Ester)
4) Procaine (Ester)
5) Benzocaine (Ester)
end -caine
PK of Ester Local Anesthetics
(Cocaine, Benzocaine, Procaine)
–> short-half life
–> matabolised by plasma Cholinesterases
PK of Amide local Anesthetics
(Bupivacaine, Liodcaine)
–> Longer half-life
–> Undergo Hepatic metabolism by CYP450 isoenzymes
* Lidocaine – < 2h.
* Bupivacaine – 3-4 h.
Administration of Lidocaine and Bupivacaine
- Analgesia via topical use.
- Analgesia via injection –> for epidural,
perineural and subarachnoid.
Administration of Cocaine, Procaine and Benzocaine
- Analgesia.
- Topical use only for cocaine and benzocaine.
Adverse Effects of Cocaine abuse
Cardiovascualr toxicity: (vasoconstriction)
1) Hypertension
2) Cerebral Heamorrahge
3) Arrythmia
4) MI
Adverse effects of Bupivacaine
1) Arrythmias
2) Vasodilation
3) Hypotention
Why does the treament of Infection increase the effectivness of local anesthetics?
Infection and inflammation lower tissue pH, reducing the diffusion of the agent into the nerve, thus reducing its effectivness
How does liver Dysfunction result in toxicity when administrating an Amide local Anesthetic?
Liver Dysfunction–> increases the emlination half-life of amide local Anethetics–> risk of toxicity
PK of Cocaine
causes Euphoria and Enhanced mental Alertness
