PHARMACOLOGY OF VASOCONSTRICTORS

All local anesthetics currently used in dentistry today produce some degree of vasodilatation. This

characteristic results in the increased vascularity of the injected site and results in a shorter duration of local

anesthetic action due enhanced uptake of the local anesthetic into the bloodstream.

- Using a “chemical tourniquet” to prolong the effect of local anesthetics

- The vasoconstrictive action of epinephrine reduces uptake of local anesthetic resulting in a significant increase in the duration of local anesthetic action.

- the addition of vasoconstrictors in local anesthetic solutions will:

1. Prolong the effect of the local anesthetic

2. Increase the depth of anesthesia

3. Reduces the plasma concentration of the local anesthetic

4. Reduces the incidence of systemic toxicity

5. Reduces bleeding at surgical site

Local anesthetics containing epinephrine produce:

1. Localized

VASOCONSTRICTION MEDIATED BY ALPHA RECEPTOR ACTIVATION

 i. Hemostasis at surgical site

 ii. Ischemia of localized tissue

2. Systemic

HEART

 i. Increased heart rate (β1)

 ii. Increased force and rate of contraction (β 1)

 iii. Increased cardiac output

 iv. Increases oxygen demand

 v. Dilation of coronary arteries

 vi. Decreases threshold for arrhythmias 

LUNGS

 i. Bronchodilation (β2 )

SKELETAL MUSCLE
i. Predominately vasodilation (fight or flight response) (β 2 )

CNS

i. Minimal direct effect due to difficulty in crossing the blood-brain barrier. Most effects on the CNS are manifestations of the vasoconstrictor on other organs such as the heart.

Concentrations of vasoconstrictors

1. Epinephrine The most commonly used epinephrine dilution in dentistry today is 1:100000. However it appears that a 1:200000 concentration is comparable in effect to the 1:100000 concentration.

2. Levonordefrin Levonordefrin is a synthetic compound very similar in structure to epinephrine. It is the only alternate choice of vasoconstrictor to epinephrine. It is prepared as a 1:20000 (0.05mg/ml)(50 mcg/ml) concentration with 2 % mepivacaine.

Cardiovascular considerations

The plasma concentration of epinephrine in a patient at rest is 39 pg/ml.1 The injection of 1 cartridge of lidocaine 1:100000 epinephrine intraorally results in a doubling of the plasma concentration of epinephrine.

The administration of 15 mcg of epinephrine  increased heart rate an average of 25 beats/min with some individuals experiencing an increase of 70 beats/min.

Clinical considerations

It is well documented that reduced amounts of epinephrine should be administered to patients with:

HEART DISEASE (ANGINA HISTORYOF MI)

POORLY CONTROLLED HIGH BLOOD PRESSURE

It is generally accepted that the dose of epinephrine should be limited to 0.04 mg (40 mcg) for patients that have these medical diagnoses

Use of local anesthetics during pregnancy

Local anesthetics (injectable)

Drug                                                   FDA category

Articaine                                             C

Bupivacaine                                        C

Lidocaine                                            B

Mepivacaine                                        C

Prilocaine                                            B

Vasoconstrictors

Epinephrine 1:200,000 or 1:100,000 C (higher doses)

Levonordefrin 1:20,000 Not ranked

Local anesthetics (topical)

Benzocaine                                        C

Lidocaine                                            B

Piroxicam:

Half‐life of 45 hrs. Once‐daily dosing. Delay onset of  action.

High doses inhibits PMN migration, decrease oxygen  radical production, inhibits lymphocyte function. 

used to relieve the symptoms of  arthritis, primary dysmenorrhoea, pyrexia; and as an analgesic,non-selective  cyclooxygenase (COX) inhibitor

The risk of adverse side efects is nearly ten times higher than with other NSAIDs. Peptic ulcer (9.5 higher)

AUTOCOIDS

An  organic substance, such as a hormone, produced in one part of organism and transported by the blood or lymph to another part of the organism where it exerts a physiologic effect on that part.

TYPES OF AUTACOIDS:
 Amines : Histamine,5-Hydroxytryptamine.
 Lipids    : Prostaglandins, Leukotriens, Platelet activating factor.
 Peptide : Bradykinin , angiotensin. 

Neurophysiology

Nerve fibers exhibit wide range of sensitivity to nerve blockade-in order of increasing resistance to block are the sensations of pain, cold, warmth, touch, pressure, proprioception and motor function

Nerve Fibers:

Myelinated = faster conducting

Unmyelinated = slower conducting

- Small non-myelinated fibers (C- pain fibers) and smaller myelinated pre-ganglionic B fibers are more readily blocked than are larger myelinated fibers responsible for muscle activity and touch [A-alpha and A-beta].

- Clinically, a person would notice complete lack of sensation to a pinprick, while at the same time still be able to move their fingers.

Angiotensin

It is generated in the plasma from a precursor plasma globulin. It is involved in the electrolyte balance, plasma
volume and B.P

Angiotensin I:
Renin is an enzyme produced by the kidney in response to a number of factors including adrenergic activity (β1-
receptor) and sodium depletion. Renin converts a circulating glycoprotein (angiotensinogen) into an inactive material angiotensin-I. It gets activation during passage through pulmonary circulation to angiotensin II by (ACE). ACE is located on the luminal surface of capillary endothelial cells, particularly in the lungs & also present in many organ (e.g brain).

Angiotensin II:
Is an active agent, has a vasoconstrictor action on blood vessels & sodium and water retention