Pharma sheet #13 - yasmin Hzayyen

بسم الله الرحمن الرحيم
Lecture # 13
Dr. Malik Zihlif
17.10.2010
Adrenergic Agonists:
 As said before adrenaline has many applications; one of its most important ones is that it works as a vasoconstrictor with the local anesthesia. We also talked about its uses, dilutions, adverse effects and publications. The main purpose for using a vasoconstrictor is to reduce the spread of the anesthesia from the local sag, plus to minimize/prolong the effect of the local anesthesia.
-Lodacaine Tetracaine minimizes the spread in our bodies; to minimize it under the effective dose for the adverse effect (arrhythmia, weakness…etc.)
-Local anesthesia SHOULDN’T be given intravenously, otherwise it will dilute; we aspirate after injecting the needle before pushing the medicine in (aspiration means pulling out or sucking out) and if there was blood that means that we’ve reached a vein, if nothing comes out that means it’s ok to inject the medicine now; all that to avoid side effects.
-Adrenaline SHOULDN’T be given to patients suffering from hyperthyroidism, hypertension and cardiovascular disease; high load on the heart.
-Adrenaline’s side effects: Anxiety, palpitation, irregularity in the heart beats…etc,
Check the slides : )
 Other adrenergic agonist is norepinephrine/noradrenaline: used by the dentists for a long time now. Same as the adrenaline; it’s used as a vasoconstrictor. It’s still used occasionally in cardiac shock; it’s used in the septic shock and neurogenic shock. Neurogenic shock paralyzes the sympathetic nervous system; it becomes flaccid…dead, vasodillation happens and hypotension. Alpha1 elevates the blood pressure by vasoconstring the vessels.
-Vasodilation happens in consequence of: (1) septic shock: is a serious medical condition caused by decreased tissue perfusion and oxygen delivery as a result of infection and sepsis. (2) neurogenic shock.
-Earlier the drug of a choice was noradrenaline for all kinds of hypotension shocks but problems occur; nowadays it’s used for the two kinds of shocks mentioned before. It was also used with the local anesthesia until problems occurred again.
-Dillution for adrenaline 1:80,000 while for noradrenaline 1:25,000.
**The doctor discussed cases concerning the subject, so don’t forget to read the paper that will be given to us… here is what he said:
“This is a paper from 1992, it’s important to know about these cases; if u observe similar symptoms you’ll know that this patient could be overdosed or has some other kinds of problems:
Adverse reaction associated norepinephrine in local ansthesia
Case 1: An otherwise healthy 40 years old Caucasian woman, reported to her private dentist for restorative work; maxillary injection with one cartridge and left inferior alveolar nerve block with two cartridges of Xylestesin (please check the name of the medicine from the paper) total of 5.4ml of 3% Lidocaine anesthesia with 1:25,000 norepinephrine were given to this patient. Seconds after receiving the last cartridge about five times after the first injection, the patient complained of severe headache, the pain was pulsating and primarly located on the right side of her head and of the severity quite unlike any headache she had ever experienced. She was pale, cold and cried for about 10mins. the blood pressure taken about 15mins. later was slightly elevated. All these symptoms stopped after administrating Paracetamol (acetaminophene), then the patient was taken home after 30mins.
The reason for her headache and other symptoms was that vasoconstrictors (especially the epinephrine) cause problems; side effects and interactions. That’s what happens in pharmacology, after administrating drugs to the patients, you have to observe them and their reactions to the medicine. It may happen with adrenaline in high doses; for example, 1:50,000 we notice that problems occur if the patient has hypertention…
Due to its side effects, nerepinephrine is contraindicated and rarely used nowadays. It causes irritation and tissue necrosis.
 Those were two of the non-selective, direct acting, adrenergic agonists ( adrenaline/epinephrine and noradrenaline/norepinephrine).
-Non-selective, adrenergic agonist means that these drugs act directly on Alpha1, Beta1, Alpha2, Beta2 receptors.
-Adrenaline is better than noradrenaline in some situations because the non-selectivity is different. Although they act directly on the same receptors, but their agonist activity differs between both of them.
-Noradrenaline is a better vasoconstrictor but with the local anesthesia, it needs more average.
-Domination of the site; Alpha1 is on the human skin, Beta2 on the internal arteries like coronary artery. But on the site of the receptors beta2 is the one that responds to the epinephrine.
-When epinephrine is given to a patient, vasoconstriction occurs in the peripheral and dilatation around the vital organs.
 Phenylephrine is drug A!
Now we’ll talk about Alpha1 and Alpha2 Selective Drugs.
**(Please refer to the “Identification of Adrenoreceptor” 3rd slide Hand out 8#)
The phenyleprine is a component of a number of cold medications, where it acts as a nasal decongestant by virtue of its vasoconstrictor ability; cold medications like Lemsip. Medications containing anitihistamine, vasoconstrictor and Panadol; nasal decongestant some of them have phenyleprine.
**(Please study the slides that talk about phenyleprine 13# and 14# in the same hand out).
-One of its adverse effects: Rebound nasal congestion can occur with chronic use as a nasal decongestant; it means that in this case if we prescribe for a patient phenyleprine, we have to inform the patient to take the medicine for only4-5 days to avoid rebound congestion caused by the tolerance that occurred in the patient’s organism, the receptors degrade. You can also prescribe another drug called pseudoephedrine (more popular).
-The other adverse effect is that large doses can cause cardiac irregularity; it has an effect on the Beta receptors but the cardiac irregularity is because pseudoephedrine changes hypertension or the patient’s blood pressure.
 TAC-4 Alternate Dental Gel!
(Prilocaine/Lidocaine/Tetracaine/Phenylephrine)
-Prilocaine -> cholinergic agonist, it causes salivation in the mouth. (Possible mistake will be corrected in the next lecture).
-Lidocaine and Tetracaine -> local anesthesia.
-Phenylephrine -> helpsshrink blood vessels, which in turn may help with the prevention of bleeding; as an injection it works as a vasoconstrictor, and in the TAC-4 gel it shrinks the blood vessels, it’s used in the mouth by dentists to reduce bleeding while working in the patient’s mouth.
-Cautions similar to adrenaline.
**(Please study the slide 16# from the same hand out).
-Xerostomia is a dental side effect.
 Dopamine is drug B!

It is the best vasopressor, it causes (regular) cardiac stimulation with little increase in myocardiac oxygen consumption.
** (Again study from the slides “Dopamine” in the same hand out).
-One of the side effects of the adrenaline and noradrenaline, that they may reduce the perfusion toward the kidney causing kidney necrosis, on the other hand, Dopamine cause no problems as the artery that feeds the kidney has adrenergic receptors all over it.
-Dopamine is given to the patient’s that have hypotension shock.
-It is less common used by the dentists and it has no side effects concerning our specialty.
-Atropine increases the heart rate while Dopamine is a vasopressor.

 Dobutamine is drug B!
It’s a good example of the Selective Drugs; it’s selective for the Beta1 receptors (agonist). It increases the heart rate, rarely used by dentists; it’s a hospital drug.
 Selective Beta2 stimulants:
• Sulbutamol is drug A!
-Used for asthma patients; it’s has a relaxant effect on smooth muscles (bronchi muscles).
** ( Study the slides that talk about “Selective Beta2 stimulants” from the same hand out).
-It causes xerostomia with inhaler usage; related to dental practice side effects.
-Inhalers are used by adult patients suffering from asthmatic attack, spacers are added to the inhalers for the children to use. If the spacer doesn’t work, we give adrenaline.
 Ephidrene is drug A!

It’s a mix-acting sympathomimatic agent, it is a releasing agent (weak).
-It cause the release of norepinephrine.
-In psycho-depression patients, we are concerned for the balance between norepinephrine, acetyl choline, dopamine and serotonin that are situated in the central nervous system.
-Ephidrene is used to increase the euphoria effect in the patients.
-It’s also used to increase the sympathetic activity in the organism; it increases the consumption of the energy (metabolism), causing a lot of side effects.
** (Study the slides that talk about “Ephedrine”).
-It’s used commonly by the dentists.
-It’s better than the phenyleprine.

Yasmin Hzayyen -=)
Corrections are more than welcomed
Don’t forget to study the slides-=) Good Luck all