CPT1: local anaesthetics Flashcards
What do local anesthetics do?
Cause the complete loss of sensation in a limited region of the body
What is the general mechanism of action of local anesthetics?
Block intiation and propogation of AP by reversibily inhibiting VG Na+ channels
What is the (1) mechanism of action of LAs?
The LA directly plugs the Na+ channel from the inside.
LA must penetrate nerve sheath and nerve fibre and penetrate the neuron in an unionized form. Inside the neuron it becomes ionised as the pH is slightly acidic. The LA cannot leave now so directly plugs the Na+ channel therefore Na+ can’t leave and no AP can be produced.
Recovery from drug infuced recovery is slower so it so refracotry period is longer and less frequent impulses proudced so AP can’t be produced so neurons are non-conducitng
What is the order of nerve fibres in which LA will have an effect on first?
- Small mylelinated axons (Adelta & B)
- Non- myleninated (C)
- large myleinated (Aa, Ab, Ax)
Nocieception and sympathetic transmission blocked first
What is the (2) mechanism of action of LA?
- Explained by critical volume theory
- Drug dissolves in phospholipd membrane of neuron
- Results in increased pressure within the membrane
- small expansion of membrane
- Distortion of channel protein
- Blockage of Na+ channel
What does use dependance mean?
The degree of block is propotional to rate of nerve stimulation
Describe the affinity LAs have for the NA+ channels depending on their states
- Open state - acess more easily
- Inactive - higher affinity
- Closed - not easily bind
LA has biggest effect when Na+ channel is open or inactive
- What is the onset of action dependent on?
- What is that dependent on?
- What does potenct reflect?
- What is potency determined by?
- Rate of tissue penetration and Na+ channel interaction
- This ^ is determined by lipid solubility and molecular weight
- Potency reflect the degree of Na+ channel activation
- This is determined by lipid solubility, lenght of alkyl chain and substituents on alkyl chain
What is the structure of a local anesthetics?
What difference do the different linkages make?
Determines how it will be metabolised. E.ester = hydrolysis. Amide = CYP450s
Which form of the drug is most acrtive?
Ionized/ charged form
Are LA acids or bases? what form are they used in?
Weak bases use in the form of salts
What equation is used to work out the concentratio of charged and uncharged forms of LA?
log ( cation/ uncharged) = pKa - pH
What effects the duration of action?
How is each class of LA metabolised/ excrected?
- Metabolism
- Excretion
Ester - hydrolysed very rapidly by plasma esterases in plasma so half life is very short
Amides - metabolised in liver and have a longer half life
Excretion mainly occurs via the kidney
How can duration of action be increased?
- Increase dose
- add a vasoconstrictor to maintain in local area for longer e.g. A or NA
What is rate of onset dependent on?
- Potency
- protein binding
- metabolism
- vascularisation
- concentration
Describe metabolism of esterase LA refering to specific examples
Procaine tertacaine are metabolised by liver and plasma cholinesterases and have short half lifes
Describe protein binding while referring to specific examples and the effect this can have
Bupivacaine and etidocaine are bound to plasma proteins extensively. This can cause increased toxicity in patients with existing liver disease
Compare rates of onsets and duration of action between LAs
- Lignocaine - Rapid onset and moderate duration
- PDP - procaine, Dibucaine, prilocaine - moderate onset (pro - short, Dib - long, pri - moderate)
- BA - Bupivacaine, amethocaine - slow onset, long duration
What are clinical uses of LAs?
- Gynaenocological procedures
- Investigation and treatment of conditions of the eyes, ears. nose and throat
- Treatment of painful condition of mouth and throat
- skin biopises
- examination and surgical proccedures of the urinary tract
- antipuritics
What types of LA are there?
- topical
- infiltaration (e.g. SC)
- peripheral nerve block
- Spinal
- epidural
*
What LA is oly used for surface anaesthesia?
Benzocaine
Which LA has low toxicity
prilocaine
What is their progression in loss of when using LA?
- pain
- cold
- warmth
- touch
- deep pressure
- motor function
What are adverse effects caused by and what are these?
- caused by drugs entering the systemic circulation
- CVSL Agitation, confusion, respiratory depresion, tremor
- CVS: myocaridialdepression and vasodilation - hypotension - caridac arrest
- hypersensitivity -
- allergic dermatitis - PABA
- , mucosal mitation - cocaine and dibucaine
- methaemoglobin anemia - large doses of prilocaine
what are precautions off LAs?
•Adrenaline/noradrenaline combinations should not be used where circulation may be compromised by vasoconstriction
–fingers
–toes
–ears
–nose
–penis
