4. LA pharmacology of vasoconstrictors Flashcards
(32 cards)
Which LA can be used as plain LA?
Prilocaine and mepivacaine, as they have minimal vasodilating activity.
(procaine has the highest VD activity)
Vasoconstrictors are added to LA to:
- constrict blood vessels and decrease blood perfusion to site of injection
- decrease LA absorption into circulation and decrease plasma concnetration of LA
- decrease systemic effect of LA and toxicity
- increase duration of action
- decrease bleeding (useful when bleeding is anticipated)
Chemically, vasoconstrictors can be classified into…?
- Catecholamines
- naturally occuring (adrenaline, noradreanline and dopamine)
- systhetic (isoproteronol and levonordefrin)
- Non-Catecholamines
- meth
- felypressin
Vasoconstrictors can be classified by the mode of action into…?
- Direct action on adrenergic receptors
- indirect action by releasing of noradrenaline from adrenergic nerve terminal
- mixed effect
Describe the effect of alpha and beta receptors (1&2)
- alpha 1 : vasoconstraction
- alpha 2 : inhibition of norardrenaline release (but constriction effect in terms of LA)
- beta 1 : increase heart rate, force of contraction (lypolysis in GIT)
- beta 2 : mainly bronchodilation (not much of importance in LA)
What is techyphylaxis and what are its clinical effects
depletion of noradrenaline from pre-synaptic storage, no clinical effect.
produced by indicrect/mixed acting vasoconstrictors
not seen in direct acting vasoconstrictors
convert 1:3,754,234 into mg/ml
1:3,754,234 = 1g per 3754234ml of solvant
1000mg/3754234ml
0.000267mg/ml
Why is it relatively safe (relatively contraindicated) to adiminster lidocaine (1:100,000 adrenaline) to patients with CVS problems?
The plasma concentration of exogenous adrenaline is 2 times as high after injection
the plasma concentration for endogenous adrenaline due to pain is 40 times as high
thus the risk of triggering CVS problems due to pain outweighs the adverse effects on the heart due to LA injection
adrenaline in one cartridge of LA only has moderate effect on CO and stroke volume, minimal effects on BP and HR
Name the mode of action (alpha or beta activation or other) for the following drugs:
adrenaline
noradreanline
levonorderfin
phenylephrine hydrochloride
felypressin
adrenaline: predominate β, some α
noradreanline: 90% α, 10% β
levonorderfin: 75% α, 25% β
phenylephrine hydrochloride: 95% α, 5% β
felypressin: hormone, stimulant of vascular smooth muscle, more effects on veins
Describe the effect of adrenaline on:
myocardium
pacemaker cells
coronary arteries
blood pressure
haemostasis
respiratory system
CNS
Metabolism
Termination of action
Myocardium: Stimulate β1, increase force of contraction and rate
pacemaker cells: β1, increased incidnce of dysrhythmias, ventrcular tachycardia and ventricular contractions
coronary arteries: dilation
Blood pressure: increase systolic and decrease diastolic at small doses (due to more sensitivity to β receptors of BV in skeletal muscles), increased pulse pressure, smaller load on the heart
At higher doses, increased diastolic pressure (due to activation of α receptor)
Overall: incrased CO (SV + HR), strength of contraction, oxygen consumption of heart, DBP/SBP
this leads to decrease in cardiac efficiency
Haemostasis: initially activation of α in the BV, vasoconstriction. as concentration decreases, β2 is predominant leading to postoperative bleeding after ~6hrs
Respiratory system: bronchodilation
CNS: Stimulation in overdose
Metabolism: increase in oxygen consumption, glycogenesis in liver and skeletal muscle, raised blood sugar
Terminaion of action: reuptake by adrenergic nerves and by enzyme COMT and MAO, small amount is excreted in the urine unchanged
Describe the side effects of adrenaline of overdose
CNS: fear, anxiety, restlessness, tremor, weakness, dizziness, respiratory difficulty and palpitation
CVS: dysrhythimias or rarely fibrillation, dramatic increase in SBP and DPB ,ay lead to cerebral haemorrhage
Anginal episodes may be precipitated
stimulatory phase of overdose is brief because of rapid inactivation of adrenaline
What are the available concentration of LA in dentisitry
and
What is the guideline for maximum dose of vasiconstrictor use in LA
1 in:
50,000
80,000
100,000
200,000
300,000
least concentrated solution that produce effective pain control sould be used, all concentration is equivalent in duration and effects in pulpal anaesthesia
1:100,000 is recommended in extended pain control
exposure to vasoconstrictors is to be limited or avoided in poorly controlled patients with CVS disease
if adrenaline to be used for haemostasis, 1:50,000 is effective, however, 1:100,000 is preferred as it has been shown that it can still produce effective haemostasis
What is the effect of noradrenaline (Levarterenol, Levophed) on
Myocardium
Pacemaker
Coronoary arteries
HR
BP
Respiratory system
CNS
metabolism
terminal effects
myocardium: increase force of contraction (ß1)
pacemaker: stimulaition, cardiac dysrhythmias (ß1)
conronary arteries: vasodilation
HR: decreased due to reflex after increase in SBP/DBP
BP: increase in SBP/DBP, systolic greater
overall unchanged CO, increased SV and increased TPR
respiratory: predominantly ∂ activation, so no bronchodilation
CNS: same as adreanline but not as severe and less frequent
Metabolism: same, but less blood sugar
Terminal effect: same
Describe the side effects of noradrenaline
due to intense ∂ activation, produce necrosis and sloughing upon extravascular injection (palate)
should not be used for haemostasis
used only for pain control (in LA), used in higher concentration than adreanaline 1:30,000 due to only 25% potency (to adrenaline)
What is the effect of Levonorderfin (Neo-Cobefrin) on
Myocardium
Pacemaker
Coronoary arteries
HR
BP
Respiratory system
CNS
metabolism
terminal effects
describe the mode of action of Pheynlephrin hydrochloride (Neo-Sunephrine)
availability in dentistry
direct alpha receptor stimulus, littole or no beta actions on the heart
longer duration
dilation of coronary arteries
bradycardia (reflex) and dysrhythmias (at large dose)
powerful vasoconstriction
overall CVS effects: increased SBP/DBP and slight decrease in CO due to reflex
minimum effects on CNS
used with 4% procaine in a 1:2500 dilution (5% potency of adrenaline)
What is the effect of felypressin (Octapressin) on
Myocardium
Pacemaker
Coronoary arteries
Respiratory system
CNS
Uterus
availability in dentistry
It’s a synthetic analogue of antiduretic hormone vasopressin , direct stimulant of fascular smooth muscle, more pronounced effects on venous than arteriole circulation
myocarium: no effect
pacemaker: no dysrhythmias
coronary artery: high doses may impair blood flow
vasculature: facial pallor in high doses
CNS: no effects, can be administered safely to hyperthyroid and hypertensive pt. recieving MAOI or tricyclic antidepressants
uterus: antidiuretic and oxytocic actions (contraindicated in pregnant pt.)
0.03UI/ml with 3% prilocain
What are the factors affecting selection of a vasoconstrictor?
1. length of dental procedure
- to achieve consistently reliable pulpal anaesthesia (lidocaine alone 10min, lidocaine+adrenaline 60min)
2. requirement to haemostasis
- mainly through the alpha actions of vasoconstrictors (adrenaline has a beta rebound after alpha ceases) (phenylephrin has no beta rebound) (noradrenaline is a potent alpha stimulator, local tissue necrosis)
- felypressin has minimum value of haemostais
3. medical status of patients
- weigh the risk and benefits of using LA with vasoconstrictor
- LA+adrenaline are generally not absolutely contraindicated in pt. with well controlled medical conditions with proper precautions of negative aspiration and slow administration of vasoconstrictors
- minimal dose of adrenaline should be used
- felypressin is recommended instead of adrenalin to avoid undesirable sympathetic stimulation but contraindicated in pregnant women
Name the amide and ester based LA
amide: lignocaine (Xylocaine), Prilocaine (Citanest), Bupivacaine (Marcaine), Mepivacaine (scandonest)
ester: Procaine
what is the function of antioxidants, stabilisers and vehicle in LA solutions
antioxydants: preservative, preventing oxydation of vasoconstrictors (sodium bisulfate)
Stabilisaers: increase solubility of LA which is weak organic base) NaCl, HCl
Vehicle: distilled water, increase volume of solution
What are the factors affecting the duration of LA
- individual response to LA
- pain threshold and different type of responders, normal, hyper and hypo)
- accuracy in administering LA
- deposition close to the nerve
- the status of tissue into which LA is administered
- vascularity (inflammation? anatomy?)
- anatomical variations
- shape and thickness of mandible
- locations of lingula
- type of injection used
- nerve block has longer duration than infiltration
what are the absolute contraindications of LA
allergic to a type of LA (ester or amide)
allergic to bisulfate
Why does lignocaine has short onset of acition?
it is highly lipophic and absorbed rapidly
what is the maximum dose of lignocaine
4.4mg/kg plaine
7mg/kg with adrenaline
