Pharmacology Of Vasoconstrictors

•Factors Required for drug dose calculations

-ASA I or II no contraindications -ASA III or IV contraindications with lowered MRD

alpha receptors

-Alpha receptors are found on blood vessel walls: smooth muscles •contraction of blood vessels

•Information necessary to calculate MRD

-Concentration-1- 100;000 ( 1 drop epi with 100,000 drops water) -Dilution- no epi=full strength -Standard Cartridge Volumes 1.8ml -Defined MRD for each Drug- need to know each drugs MRD -Relevant patient factors. ASA

Epinephrine

-Naturally occurring catecholamine -Trade name Adrenaline •Neurotransmitter along with norepinephrine and dopamine. •Drug of choice to treat ANAPHYLAXIS. -Anaphylaxis produces peripheral dilation- hypersensitivity reaction -And produced bronichal constriction. •Added to local anesthetic in concentrations of: -1:50,000 ~ produces more hemostasis (more concentrated) -1:100,000~ used in dentistry. -1:200,000 -Sodium bisulfite added to prevent oxidation 1:1,000 is the concentration of an epi pen.

Epinephrine Actions on Specific Systems and Tissues BP effects

-Small doses = increase systolic pressure -Higher doses = increase diastolic pressure

Epinephrine Actions on Specific Systems and Tissues •Vasculature: Both alpha & beta 2

-Smaller doses = (beta 2) vasodilatation -Higher doses = (alpha) vasoconstriction

LA plain may not provide profound anesthesia, what are the potential effects of LA plain?

-Unmanaged pain for patient -Leads to spikes of blood pressure due to endogenous release of body's epinephrine which can exceed the amount of epi in the Local Anesthetic. -Endogenous release can increase adverse effects. (no way of knowing how much is released) -Endogenous epi into circulation is difficult to predict. -Most adverse events are short lived- rapid biotransformation and elimination. Endogenous=Body's production of epi or nor epi.

Beta receptors

-found on bronchial vessels: smooth muscles •Relaxation of bronchial vessels:vasodilation -Beta Receptors on cardiac vessels: cardiac stimulation.•(Increased heart rate and increased strength of contraction

Recommended Max. Dose of Epi A 1.7 ml cartridge of LA with Epi 1:100,000 contains

0.017 mg

Max dose for Cardio (ASA III-IV)

0.04 mg Epi •0.04mg / 0.017 = 2 cartridges max dose for Cardio ASA III & IV

_____________ may be preferable to 1:100K in patients with cardiovascular disease and in those taking drugs that reportedly enhance the systemic effects of epi., what drugs are they?

1:200K Such drugs are: MAO inhibitors (increase hypertension), Phenothiazines (may reduce the pressor effects), and Tricyclic antidepressants ( pressor effects may be enhanced).

Andrenergic Receptors types

Alpha and beta

Street drugs are sympathomimetic amines:

Ephedrine, amphetamine, methamphetamine, and phenylephrine have effects on adrenergic receptors.

the most used vasoconstrictor in LA used in medicine and dentistry is:, why

Epinephrine . Epinepherine has a profound effect on the heart and blood vessels, as one might experience after moderate to heavy exercise. The Epinepherine sympathomimetic reaction: apprehension, tachycardia, sweating, and pounding in the chest (palpitation). Intravenous injection of 0.015 mg of epi with lidocaine results in an increase in heart rate of 20 to 70 beats per min. and increase in systolic blood pressure of 20 to 70 mm Hg.

Epinephrine Actions on Specific Systems and Tissues Metabolic

Inhibits insulin secretion

Vasoconstrictos have the following effects:

Lungs- dialation, heart constriction

Why is nor epiniephrine not used?

Norepinepherine is not used because of intense peripheral vasoconstriction and elevation of BP.

Epinephrine Actions on Specific Systems and Tissues •Cardiovascular system: Beta 1 effects

Overall decrease in cardiac efficiency

Vasoconstrictors are drugs that constrict the size of blood vessels and thereby control:

Tissue perfusion, Also reduce toxicity, prolong duration of LA, delay absorption into vascular system, and increase concentration of LA at nerve membrane.

What is the purpose of VC being added to epi?

Vasoconstrictor in LA to decrease absorption •Vasoconstrictor to increase depth of anesthesia •Vasoconstrictor to increase duration of anesthesia also to produce mydriasis: pupil dilation

Hemostasis

arrest bleeding. Epi is effective in preventing or minimizing blood loss during surgical procedures... such as tooth extraction and subgingival scaling / root planing or debridement.

Sympathomimetic

drugs that activate adrenergic receptors and the sympathetic system.

Why does BP increase with VC?

may increase with vasoconstrictors to make heart pump more blood.

Where is epi normally produced?

normally released from the adrenal medulla at a basal rate of 2-8 nanograms per kilogram (1 kg. = 22 lbs.) per minute and may increase 20 - 40 fold during severe stress. ..... umm Injection of 18 micrograms of epi (one cartridge of epi 1:100,000) may increase 3 fold within seven minutes. Two dental cartridges of epi 1:100,000 (18-36 micrograms) has been shown to increase plasma levels of epi to an equivalent of the physiological activities of public speaking and moderate exercise. injection of the maximum dose of epi 1:100,000 ( 18mL or nine cartridges of LA) may increase plasma levels found after strenuous exercise...Not appropriate for those who are medically compromised. Inadvertent intravascular injection may result in even higher plasma epi concentrations.

Adrenegic

receptors in the body stimulated by catecholamines: epinephrine, norepinephrine and levonordefrin.

Epinephrine The increased risk is most significant in patients with:

severe cardiovascular disease or patients taking medications that interact with epi.

Vasoconstriction:

temporary action on smooth muscle walls of blood vessels where adrenergic receptors are located at the site of the injection, the duration increases LA effects

Why are vasoconstrictors added to LA?

to oppose the vasodilation properties of LA.

Vasopressor

vasoconstrictors epinephrine and norepinephrine. (both naturally in body)

Max dose for Healthy (ASA I-II) is

•0.2 mg Epi •0.2mg / 0.017 = 11 1/2 cartridges max dose for healthy ASA I & II

Concentrations of Vasoconstrictors

•1:1000 = 1mg/ml epinephrine to treat anaphylaxis •1:2,500 = 0.4mg/ml phenylphrine •1:20,000 = .05mg/ml levonordefrin •1:50,000 = .02mg/ml epinephrine •1:100,000 = .01mg/ml epinephrine •1:200,000 = .005mg/ml epinephrine •One dental anesthetic cartridge is 1.7 ml of total solution- .01mg/ml= 1.7X.01=.017mg per cart. •1ml = 1cc

Vasoconstrictor drugs provide beneficial effects that include:

•A decrease in the blood flow by constricting the blood vessels at the injection site •An increased duration of the anesthetic's effects •Reduction in systemic toxicity due to the increased duration of the anesthetic, requiring a lower administered dose •Hemostasis at the injection site

Dilation of the blood vessels causes an increase in blood flow to the site of injection, which in turn causes

•An increased rate of anesthetic absorption into the bloodstream •A decrease in the duration of the anesthetic's action •Higher plasma levels of local anesthetics; increasing the risk of toxicity •Increased bleeding in the area because of increased perfusion.

Overdose to Epi

•Cardiovascular compromised are: uncontrolled arrhythmias, uncontrolled hypertension, unstable angina, or M.I. (heart attack) within six months - Postpone elective treatment •Overdose: increasing fear, apprehension, anxiety, tension, throbbing headache, tremor, weakness, dizziness, pallor, respiratory difficulty, & palpatation •Increased BP, both systolic & diastolic, may precipitate anginal attack in patients with coronary insufficiency

Vasoconstrictor actions in LA

•Decrease blood flow (perfusion) at injection site •Slower absorption rate of LA into circulatory system •Lower blood levels of LA = less risk of toxicity •Increased amount of LA remain in and around the nerve, thus increase the duration of action •Decrease bleeding at the site of injection •Vasoconstrictors are sympathomimetic or adrenergic drugs. •Chemically like sympathetic nervous system mediators epinephrine and norepinepherine

Dilutions of Vasoconstrictors

•Dilution expressed as a ratio of vasoconstrictor to sterile water in grams per milliliter •Presented as milligrams (mg) per milliliters (ml) of solution. •1:1000 = one gram (1000mg) of vaso in 1000 milliliters (ml) of solution = 1.0 mg/ml •1:100,000 = 0.01 mg/ml •1:10,000 = 0.1 mg/ml •1:1000 is more concentrated than 1:100,000

Five Vasoconstrictor Drugs

•Epinepherine •Levonordefrin •Norepinepherine •Phenylephrine •Felypressin

Medical Status of the Patient

•Few contraindications to vasoconstrictor in the concentrations used in dental cartridges •Must weigh risk over vasoconstrictors for patients with significant cardiovascular disease, thyroid dysfunction, diabetes, and sulfite sensitivity and patients receiving MAO inhibitors, tricyclic antidepressants, and phenothiazines 1:200K may be preferable to 1:100K in patients with cardiovascular disease and in those taking drugs that reportedly enhance the systemic effects of epi. Such drugs are: MAO inhibitors (increase hypertension), Phenothiazines (may reduce the pressor effects), and Tricyclic antidepressants ( pressor effects may be enhanced).

Phenylphrine HCl Adverse Events

•Local effects- include ischemia and necrosis •Systemic effects- blood pressure increases, palpitations, syshrythmias and ventricular fibrillation, heart attack or stroke. -Adverse effects are short lived. -Effcient reuptake in synapses. -Rapid removal and biotransformation -Extreme care to avoid intravascular injection.

Epi manages what 3 things?

•Management of acute allergic reactions •Mgt. of bronchospasm •Mgt. of cardiac arrest

Clinical Signs and Symtoms of Vasoconstrictor Overdose and Anxiety/Fear Anxiety

•Nausea & restlessness •Heart racing •Intense anxiety •Weakness •Tremor •Headache •Hyperventilation •Palpitation •Shakiness •Fainting (sycope)

Clinical Signs and Symtoms of Vasoconstrictor Overdose and Anxiety/Fear Overdose

•Nausea & restlessness •Heart racing •Intense anxiety •Weakness •Tremor •Severe headache •Hyperventilation •Palpitation •Shakiness

Systemic Reactions

•Systemic reactions include: apprehension, pounding in chest, tachycardia, sweating, & arrhythmia •LA Cocktail to reduce systemic reactions: -First inject series of LA with epi 100K or 200K -Second series of LA plain - no epi -Total number of cartridges is same -Say, "I'm individualizing my TX for you." -Or do less areas of TX: •Sextant instead of quadrants •Quadrants instead of half mouth

Norepinephrine

•Trade name is Levarterenol or Noradrenalin •Naturally occurring catecholamine •Used in LA to treat hypotension •1/4 as potent than epinephrine, therefore use higher concentration (1:30,000) •Not available in U.S. in dental cartridges •Is a potent vasoconstrictor with documented cases of tissue necrosis & slough. Not recommended in dentistry as a vasoconstrictor •Not available in North America for dentistry use.

Levonordefrin

•Trade name is Neo-Cobefrin -Synthetic catecholamine: not made by the body. •Both Levonordefrin and epinephrine stimulate adrenergic receptors in tissues and are called sympathomimetic drugs. •Sympahomimetric drugs used in LA: Epinephrine, Levonordefrin, and Phenylephrine. •One/sixth the potency as epi, therefore it is used in higher concentration (1/6 potent-1:20,000 concentration) -Used in mepivacaine LA at 1:20,000 conc. -Mepivivaine 2% -Maximum dose is 1 mg per appointment = 20 ml of a 1:20,000 concentration (11 cartridges) for all patients •Less cardiac & CNS stimulation than epi

Phenylphrine HCl

•Trade name is Neo-Synephrine •Is the weakest vasoconstrictor •Used at 1:2,500 concentration in procaine LA •Maximum dose 4mg per appointment or 10 ml of a 1:2,500 solution for healthy patient. •Max dose 1.6 mg per appointment or 4 ml of a 1:2,500 solution •Not available in dental cartridge •Excellent vasoconstrictor with few side effects Phenylphrine used with procaine an ester LA.

Felypressin

•Trade name is Octapressin •Synthetic hormone •Used in prilocaine in Germany & Japan, not available in U.S. •Acts on venous side of vessels not arteriolar side like other vasoconstrictors •Very little effect on myocardium- safe for patients with dysrhythmias and hyperthyroidism and when patient is taking tricyclic antidepressants. •Max dose for cardiac patients (ASA III or IV) is 9 ml of 0.03 IU/ml solution = 5 cartridges

Epinephrine on body Systems and Tissue.

•↑ systolic & diastolic BP •↑ cardiac output, heart rate, and coronary artery blood flow. •↑ heart dysrhythmias. •↑ vasoconstriction on peripheral vasculature •↑ vasodilation in skeletal muscle vasculature •↑ initial hemostasis, after 6 hours then vasodilation. •↑ oxygen consumption of cardiac muscle •↑ bronchial smooth muscle vasodilation. •↓ in overall cardiac efficiency •Not a potent CNS stimulant in therapeutic doses -The risks of adverse reactions or toxicity from epi are minimal with single injections, but increases with multiple injections.

Actions of Levonordefrin on the Body Systems and Tissue

•↑ systolic & ↓ diastolic BP (except in high doses) •↑ cardiac output, heart rate, and coronary artery blood flow. (less than epinephrine) •↑ heart dysrhythmias. (less than epinephrine) •↑ vasoconstriction on peripheral vasculature •↑ vasodilation in skeletal muscle vasculature •↑ hemostasis (less than epinepherine). •↑ oxygen consumption of tissue and muscles. •↑ bronchial smooth muscle vasodilation(less than epinephrine) •↓ in overall cardiac efficiency •Less potent CNS stimulant than epinephrine.