Vasoconstrictors Its Role

8/13/2019 Vasoconstrictors Its Role

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VASOCONSTRICTORSITS ROLE

&CLINICAL

SIGNIFICANCE



INTRODUCTION

All clinically injectable LA’s posess somedegree of vasodilating activity leading tothe following reactions:

1. Increased rate of absorption into CNS

2. Decreased depth & duration of LA

3. Higher plasma levels- LA toxicity4. Increased bleeding due to increased

perfusion.



Vasconstrictors are drugs that constrict bloodvessels – controlling tissue perfusion. These

are important additions to LA for the followingreasons:

1. By constricting blood vessels – decreasesblood flow to the site.

2. Absorption into CVS reduced.

3. LA blood levels lowered – minimizing toxicity.

4. Increased amounts of LA for longer periods –

increased depth & duration.5. Decreased bleeding at the site of

administration.



The commonly used vasoconstrictorschemically identical to sympatheticnervous system mediators – also actions

resemble response if adrenergic nervesare classified as sympathomimetic oradrenergic drugs.

These have many common clinical actionsbesides vasoconstriction.



CLASSIFICATION - According to

chemical structure

Related to the presence or absence of catechol nucleus (orthohydroxybenzene(OH) attached to third or fourth aromatic ring – catechols. If theyalso contain amine group NH2 attached to the aliphatic side chain calledcatecholamines. Vasoconstrictors contain only NH2 group without –OHgroup – non- catecholamines.

Catecholamines:

1. Epinephrine

2. Nor- epinephrine

3. Levonordefrine

4. Iso proterenol

5. Dopamine

Non- catecholamines:1. Amphetamine

2. Methamphetamine

3. Ephidrine

4. Mephentermine

5. Hydroxy amphetamine

6. Metariminol

7. Methoxamine

8. Phenylephrine

Felypressin is a synthetic analogue of polypeptidevasopressin ( anti diuretic hormone) is used as a vasoconstrictor



CLASSIFICATION- according to

modes of action Acting directly on

adrenergicreceptors:

Epinephrine

Nor- epinephrineLevonordefrinIsoproterenolDopamineMethoxamine

Phenylephrine

Acting indirectly:release nor-

epinephrine fromadrenergic nerve

terminals:

Tyramine

Amphetamine

Methamphetamine

Hydroxy amphetamine

Mixed acting:

Metarimnol

Ephedrine



The concept of adrenergic receptors found in mosttissues of the body was proposed by ahlquist in 1948. Alpha & beta receptors.

Activation of a recptor leads to contraction of smooth

muscles in blood vessels (vasoconstriction) furtherdivided into a1 and a2 based on location and function.

A1- excitation post synaptic

A2 – inhibitory post synaptic.

Activation of B receptors – smooth muscle.Relaxation ( bronchodilatation & vasodilatation)

Cardiac stimulants ( increased rate and strength ofcontraction).



B RECEPTORS

B receptors divided into – b1 receptorsfound in heart and small intestinesresponsible for cardiac stimulation and

lipolysis.

B2 – found in bronchi, vascular beds anduterus – bronchodilatation, vasodilatation.



DILUTION OF

VASOCONSTRICTORS

The genesis of vasoconstrictor dilutions in LAbegan with the discovery of adrenaline in 1857by Abel.

Resting plasma epinpehrine level is 36pg/mldoubles after administration of one cartridge(1.8 ml) lidocaine with 1:100000 epinephrine.Elevation is linearly dose dependent – persistsupto half an hour.

Of all the vasoconstrictors availabel like nor-epinephrine, epinpehrine remains the mosteffective and used vasoconstrictor in medicineand dentistry.



EPINEPHRINE

Epinephrine is the most useful agent representsthe best example of drug mimicking thesympathetic activity.

Epinephrine as acid salt is highly soluble inwater. Sodium bisulfite is added to delay thedeterioration.

SOURCE: Available as a synthetic – also

obtained from adrenal medulla of animals existas both levo & dextrorotatory forms. Levo formis 15 times more potent.



MODES OF ACTION: Directly on both A & Breceptors. B actions predominate.

SYTEMIC ACTIONS: Stimulates b receptors ofmyocardium. Positive inotropic ( force ofcontraction) & chronotropic ( Rate ofcontraction). Stimulates B receptors ofpacemaker cells leading to incidence of

dysrhythmias ventricular tachycardias andpremature ventricular contractions are common. Dilatation of coronary arteries – Increases

coronary artery blood flow. Systolic BP is increased. Diastolic BP with small

doses because greater sensitivity to epinephrineof B receptors than A receptors in skeletalmuscle vessels.



Diastolic increase with large doses because ofconstriction of blood vessels supplying skeletalmuscles caused by A receptor stimulation.

Overall action on heart leads to decrease incardiac efficiency.

Vasculature: Primary action is on smallerarterioles & precapillary sphincters of blood

vessels supplying skin, mucous membranes,kidney primarily contain A receptors. Vessels of skeletal muscles contain both A,B2.

with B2 predominates.

Small doses produces dilation due to B2 actions.Large doses produces vasoconstriction due to Aactions.



Haemostais: Predominant A receptor stimulation leadsto haemostasis. As epinephrine decreases action revertsto Vasodilation – B action predominates.

Respiratory system: Due to B2 effect – potent dilatorof bronchiole smooth muscle drug of choice in activeasthmatic episodes(Bronchospasm).

CNS: In large doses stimulates CNS.

Metabolic: increases O2 consumption through B actionstimulates glycogenolysis in liver & skeletal muscle – elevates blood sugar levels – at a concentration of 150to 200 pg/ml equivalent to 7.2 ml (4 cartridges)containing 1:100,000 epinephrine.

Termination of action: 1)Primarily by reuptake. 2)inactivation of enzymes Catechol – O – Methyltransferase and Monoamine Oxidase. 3) Small acountsexcreted unchanged in urine.



Side effects & overdose: Relates to CNSstimulation like fear, anxiety, tension,restlessness, tremor, dizzines, respiratory

difficulty & palpitation. Dramatic increase insystolic B.P. & diastolic >300 mmHg leads tocereberal ischemia. Anginal episodes in patientswith coronary insufficiency stimulatory phase ofoverdose is usually brief because of rapidinactivation of the drug.

Clinical applications: 1) Management activeallergic reactions.

2) Management of bronchospasm & cardiac arrest.

3) Vasoconstrictor for haemostasis & in LA todecrease absorption & increase the depth &duration.

4) To produce mydriasis.



Availability: Available in 1:50,000; 1:80,000;1:100,000; 1:200,000; 1:300,000.

Maximum doses: As per American heartassociation(1964) the least concentration ofvasoconstrictiors contained in LA are not contraindicatedin patients with Cardiovascular diseases providedaspiration and slow injection is practiced.

As per 1954 New York Heart Association maximum dosebe limited to 0.2mgs per appointment.

In cardiovascular compromised patients limit exposuresto vasconstrictors as much as possible If possible include ASA III & IV in the above group.

Haemostasis: the 1:50,000 dilution of epinephrine ismore effective than 1:100,000 or 1:200,000 dilutions.The concentration in ASA III ,IV to be used is 1:100,000



NOR EPINEPHRINE

Properietary name: levophed, noradrenalin.

Official name: Levarterenol.

Relatively stable in acid solution butdeteriorates on exposure to light,air.

Acetone- sodium bisulfite is added to

reatard deterioration. Available in both synthetic & natural forms – 20% catecholamine production byadrenal medulla.



In phaeochromocytoma – it may be 80% nor-adrenaline is synthesized & stored in postganglionic adrenergic nerve terminals.

Actions almost exclusively on A receptorsbutalso stimulate B receptors (10%).One fourth aspotent as epinephrine.

Systemic actions: Positive inotropic action on

myocardium through B1 receptors. Stimulates pacemaker cells leading to greater

incidence of cardiac dysryhthmias.Increasecoronary blood flow.

Produces a decrease in heart rate due to reflexact on carotid & aortic baroreceptors & vagusafter marked increase in both systolic & diastolicpressures.



Systolic & diastolic pressure increases due to Astimulation (leading to peripheral vasoconstriction &concomitant increase in vascular resistance).

Overall effects on heart rate:1) Increased systolic & diastolic BP.

2) Decrease heart rate

3) Increased stroke volume

4) Increased total peripheral resistance Does not relax bronchial smooth muscle.

CNS stimulating effects are not prominent.

After overdose increases BMR, elevates blood sugar,lesser than epinephrine.

Action is terminated by reuptake at adrenergic nerveterminals by MAO. Exogenous norepinephrine isinactivated by COMT.



Side effects: Less severe thanepinephrine. Excessive levels markedly

increase systolic & diastolic BP with risk ofhemorrhage, stroke, headache etc.,

Clinical applications: Used with LA as avasoconstrictor & for management of

hypotension. Available with LApropoxycaine & procaine in a 1:30,000dilution. No longer available in US.

In Germany with lidocaine & mepivacaineor in combination with epinephrine or nor-epinephrine or tolycaine.(Japan)



Maximum dose: Should be used for paincontrol & not for hemostasis. 25% as

potent as vasopressor as epinephrine.Hence used as a 1:30,000 dilution.

Normal healthy patient: 0.34mg/APPT or

100ml of 1:30,000 solution. Clinically significant cardiovascular disease

(ASA III or IV) 0.14mg/APPT or approx

4ml of 1:30,000 solution.



LEVONORDEFRIN

Proprietary name: Neo-cobefrin. Synthetic vasoconstrictor acts through direct A

receptor stimulation (75%) B activity (25%)lesser than epinephrine 15% as potent as

epinephrine. Less cardiac stimulant and CNS than

epineprhine. Pacemaker cells & coronary arteries same as

epinpehrine. Heart rate & on vasculature same as epinephrine

but to a lesser degree.



Respiratory system: brochodilatation but tolesser degree.

Eliminated through actions of COMT & MAO.

Side effects: lesser than epinpehrine.

As a vasoconstrictor it is 1/6th as effective asepinephrine.

Used in 1:20,000 dilution.

Maximum dose: 1mg/APPT or 20 ml of 1:20,000

In the concentration at which it is available it

has the same effects on clinical activity as of LAas epinpehrine in 1:50,000 or1:100,000concentration.



PHENYLEPHRINE

HYDROCHLORIDE

Proprietary name: Neo synephrine.

Synthetic sympathomimetic amine.

Direct A receptor stimulation(95%) – long

duration. No B actions on heart.

It is only 5% as potent as epinephrine.

CVS: Increase systolic & diatolic pressure.

Reflex bradycardia

Slightly decreased cardiac output.

Powerful vasoconstriction without marked



Powerful vasoconstriction without markedvenous congestion.

Bronchodilatation to a lesser degree.

CNS: Minimum effect. It undergoes hydroxylation to epinephrine then

oxidation to metanephrinw then same asepinephrine.

Used as a vasoconstrictor in LA, management ofhypotension, as a nasal decongestant , inopthalmic solutions to produce mydriasis.

Was used with 4% procaine in 1:25000 dilution

(no longer available in dental cartridges) It is 1/20 as potent as epinpehrine.

Its use in 1:2500 dilution equal to 1:5000epinpehrine.

Excellent vasoconstrictor with few side effects.



Normal healthy patient 4mg/APPT (100mlof 1:2500 solution).

Patient with ASA III or IV 1.6mg/APPTequal to 4ml of 1:2500 solution.



FELYPRESIN - OCTAPRESSIN

Synthetic analogue of antidiuretic hormonevasopressin- non-sympathomimetic aminecategorized as a vasoconstrictor.

Direct stimulant of vascular smooth muscle –

more pronounced on the venous than onarteriolar microcirculation.

No direct effect on myocardium. It is a non-dysrhythmic drug.

In high doses felypressin induces constriction ofcutaneous blood vessels may produce facialpallor.



It has no effect on adrenergic nerve stimulation – can safely be administered to hyperthyroidpatients & to those receiving MAO inhibitors &tricylic antidepressants.

It is contraindicated in pregenant patients due toits oxytocic actions.

The incidence of systemic reaction is minimal.

It is used as a vasoconstrictor in LA to decreasetheir absorption & duration of action. Used in 0.03IU/ml with 3% prilocaine in some

countries. Maximum dose: Not recommended for use

when hemostasis is required becausepredominant action is on venous system. Forpatients with ASA III or IV maximum dose is0.27IU ; 9ml of 0.013IU/ml.



SELECTION OF

VASOCONSTRICTOR

In the selection of an appropriatevasoconstrictor the following factors must beconsidered:

1)

Length of dental procedure.2) Need for hemostasis during or after

3) Requirement for post operative pain control.

4) Medical status of the patient.

Vasoconstrictors are important additions to LAepinpherine added to short or mediumduration LA’s. slows absorption. Delays peakblood levels. Prolongs duration & depth.

Reduces incidence of systemic toxicity.



In modern dentistry all the above aredifficult to achieve without inclusion of

vasoconstrictor unless specificallycontraindicated inclusion of avasoconstrictor should be considered.

Care always must be taken to avoiduintended intravascular administration ofvasoconstrictor & LA through multipleaspirations & slow administration ofminimum concentrations of bothvasoconstrictor & LA.

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Vasoconstrictors Its Role