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

PLASMA FRACTIONS:

a) Fresh frozen plasma.

b) Platelets.

c) Plasma concentrates.

d) Non-plasma recombinant factor concentrates.

Drugs Used in Diabetes

Goals of diabetes treatment

lower serum glucose to physiologic range
keep insulin levels in physiologic range
eliminate insulin resistance

best initial step in management: weight loss, contractile-based exercise weight loss is more important for insulin sensitivity than is a low-carb diet

Modalities of diabetes treatment

Type I DM

insulin
low-sugar diet

Type II DM
exercise
diet
insulin

6 classes of drugs 

Insulin
Sulfonylureas -    Glyburide
Meglitinides  - Nateglinide
Biguanides    Metformin    
Glitazones (thiazolidinediones)    Pioglitazone
α-glucosidase inhibitors    Acarbose
GLP-1 mimetics (incretin mimetics)    Exenatide
Amylin analog    Pramlintide

Amoxicillin

a moderate-spectrum

β-lactam antibiotic used to treat bacterial infections caused by susceptible

Mode of action Amoxicillin acts by inhibiting the synthesis of bacterial cell walls. It inhibits cross-linkage between the linear peptidoglycan polymer chains that make up a major component of the cell wall of Gram-positive bacteria. microorganisms. It is usually the drug of choice within the class because it is better absorbed, following oral administration, than other beta-lactam antibiotics. Amoxicillin is susceptible to degradation by  β-lactamase-producing bacteria, and so is often given clavulanic acid.

Microbiology Amoxicillin is a moderate-spectrum antibiotic active against a wide range of Gram-positive, and a limited range of Gram-negative organisms

Susceptible Gram-positive organisms : Streptococcus spp., Diplococcus pneumoniae, non β-lactamase-producing Staphylococcus spp., and Streptococcus faecalis.

Susceptible Gram-negative organisms  Haemophilus influenzae, Neisseria gonorrhoeae, Neisseria meningitidis, Escherichia coli, Proteus mirabilis and Salmonella spp.

Resistant organisms Penicillinase producing organisms, particularly penicillinase producing Staphylococcus spp. Penicillinase-producing N. gonorrhoeae and H. influenzae are also resistant

All strains of Pseudomonas spp., Klebsiella spp., Enterobacter spp., indole-positive

Proteus spp., Serratia marcescens, and Citrobacter spp. are resistant.

The incidence of β-lactamase-producing resistant organisms, including E. coli, appears to be increasing.

Amoxicillin and Clavulanic acid Amoxicillin is sometimes combined with clavulanic acid, a β-lactamase inhibitor, to increase the spectrum of action against

Gram-negative organisms, and to overcome bacterial antibiotic resistance mediated through β-lactamase production.

Quinolone

Quinolones and fluoroquinolones form a group of  broad-spectrum antibiotics. They are derived from nalidixic acid.

Fluoroquinolone antibiotics are highly potent and considered relatively safe.

MOA : Quinolones act by inhibiting the bacterial  DNA gyrase enzyme. This way they inhibit nucleic acid synthesis and act bacteriocidically.

Drugs  :Nalidixic acid, Ciprofloxacin , Levofloxacin,  Norfloxacin ,Ofloxacin,  Moxifloxacin  , Trovafloxacin

On the basis of Receptors, drugs can be divided into four groups,

a. agonists

b. antagonists

c. agonist-antagonists

d. partial agonists

a. Agonist

morphine fentanyl pethidine

Action : activation of all receptor subclasses, though, with different affinities

b. Antagonist

Naloxone , Naltrexone

Action :  Devoid of activity at all receptor classes  

c. Partial Agonist: (Mixed Narcotic Agonists/Antagonists)

Pentazocine, Nalbuphine, Butorphanol , Buprenorphine

Action: activity at one or more, but not all receptor types

With regard to partial agonists, receptor theory states that drugs have two independent properties at receptor sites,

a. affinity

The ability, or avidity to bind to the receptor
Proportional to the association rate constant, Ka

b. efficacy

or, intrinsic activity, and is the ability of the D-R complex to initiate a pharmacological effect

Drugs that produce a less than maximal response and, therefore, have a low intrinsic activity are called partial agonists.

These drugs display certain pharmacological features,

a. the slope of the dose-response curve is less than that of a full agonist

b. the dose response curve exhibits a ceiling with the maximal response below that obtainable by a full agonist

c. partial agonists are able to antagonise the effects of large doses of full agonists