pharma sheet # 27 - Ruba Jassar

بسم الله الرحمن الرحيم

In the previous lecture, we discussed general anesthesia, and we mentioned that as dentists we’re not going to apply it to our patients, but we may need it in case of wars! So, we’ll quickly revise it first…
When mentioning general anesthesia, we’re concerned with 3 aspects:
Induction, maintenance and Recovery.
INDUCTION
Is the stage in which the patient enters anesthesia (becomes unconscious) by injection or inhalation. In other words, it’s the stage were anesthesia is induced.
If we use a gas for general anesthesia (such as halothane, isoflurane, influrane…etc) this will take long time (up to 30 minutes) and you can’t balance between the concentration of the used gas and the response of the patient. So the solution is to give him IV drug which has a quick effect (propofol, barbiturates).
Consequently it is better to perform general anesthesia by injection rather than inhalation.
There are 2 drugs that can be used in inhalation:
1. Halothane
The problem is that it may cause irreversible hepatitis especially in females (1 per 350,000), it doesn’t cause it in children so we can use it with them.
2. Isoflurane
Also causes hepatitis but much more less than halothane, that’s why it’s the drug of choice
We use it in combination with oxygen 70% or 60% (i.e. Isoflurane is either 30% or 40%, repectively) during ventilation.

- We can also mix oxygen, halothane and Nitrous Oxide (NO) which results in analgesia besides anesthesia.

Now, as you do this, you let the patient enter steady state anesthesia.
This state must remain during all the procedure; surgery for example.
Sometimes the patient wakes up or feels the pain or even moves, in this case we should give the patient an analgesic beside the aforementioned anesthetic, and this achieved by the oxygen-halothane-NO combination.
Note: NO can be only used as an anesthetic in large doses which will cause toxicity so we use it as an analgesic as above
Note: the strongest drug in analgesia is fentanyl, which is even stronger than opioids.
- There is another way to guarantee that the patient is relaxed without giving him large doses of isoflurane, which is by giving him muscle relaxants (the one we talked about is ….) we need the muscles to be relaxed to prevent the patient from making weird actions or movements while we are working.
- People have variable responses under anesthesia, some may wake up suddenly, some may feel the pain, in these cases you repeat the induction.
MAINTENANCE
Removal of the gases or drugs and only oxygen is left, so this is mechanical ventilation. After the removal of these gases, they need 5-10 minutes depending on the drug to be expired from the patient’s body, but he remains dizzy and not completely stable.
RECOVERY
Now the patient is under control and management, the respiratory center is switched on, this requires ~3 hours, but this varies according to the patient, that’s why patients are moved to the recovery room (غرفة الإنعاش) till they regain full consciousness.
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Now we’ll be talking about local anesthesia.
- As dentists this is what we use in clinic.
- The most important drug used for anesthesia is Lidocaine (Xylocaine)
- All drugs of local anesthesia come into two groups; esters and amides.
1- Esters
They are not used in dentistry because they result in allergic reactions.
Once they get metabolized in the body, they bind to certain molecules, the result is production of haptin (leads to allergy).
2-Amides
We use them in dentistry because they rarely cause allergic reactions, but they might cause syncope. Patients sometimes get confused and think that syncope is due to allergy, so if the patient reported allergy to amides, you should be sure what they mean by that.
Extra: symptoms of allergy are rash, fever, cough; so ask the patient about those symptoms. It may get complicated to “shock”, but that’s a different entity than syncope and is more dangerous. Check Wikipedia for more info.



Mechanism of action
Injection (or let’s say: entrance) of the anesthetic in a normal pH media  it should be lipophilic to this point, which allows it to  cross the axon barrier and enter the axon  should get ionized (basic): gets attached to the Na receptor from the intracellular end  NERVE INHIBITION
In cases of inflammation or cancer, the media in which the anesthetic is administered becomes more acidic (as inflammation reduces pH), thus the above sequence will be disturbed:
Injection of the anesthetic in a reduced-pH media  it should be lipophilic to this point, becomes more positive (because it’s a weak base) which allows it to  cross the axon barrier and enter the axon  should get ionized (basic): gets attached to the Na receptor from the intracellular end  NERVE INHIBITION reduced effect  more concentration (build up or accumulation of the local anesthetic) required.

Route of administrations
Topical or Injection.
Topical agents: tetracaine, proparacaine
Injectebale agents: tetracaine, bupivacaine, lidocaine (most used)
- Lidocaine has different dosage forms with specific concentration at each:
• Sterile injection (with or without epinephrine) 1-2%
• Topical ointment 5%
• Topical jelly 2%
• Topical oral spray 10%

- In surgery and dental practice, lidocaine is used for topical anesthesia, infiltration, and nerve block.
• Nerve block : by applying anesthetic at or close to nerve endings by injection. This is usually very harmful to patient
• Infiltration: away from nerve, that’s why it’s easier and less harmful
So, we usually try the first 2 methods (topical, infiltration), if they don’t work we use nerve block.

- Its ability to cause vasodilation after injection is countered with the aforementioned addition of epinephrine, in concentrations of 1:100,000 or 1:200,000.
- Side effects: Patients may experience some sedation, shivering, and positional headaches following exposure to lidocaine. Headache occurs due to vasodilation activity which leads to hypotension and thus when the patient stands up they feel dizzy and suffer from headache.
- Using a 2% solution, for infiltration and nerve block, the expectation for local anesthesia can break down as follows:
• Pulpal anesthesia: 5-10 minutes
• Soft tissue anesthesia: 1-2 hours
- Adding epinephrine to the solution yields the following expectations:
• Pulpal anesthesia: 60-90 minutes
• Soft tissue: 2-4 hours
Note: lidocaine leads to soft tissue anesthesia which can be reversed by phentolamine. We use this wich patients when anesthesia persists more than 2 hours, since some of them find it annoying.

- There are several alternatives to lidocaine, all of them members of the amide class of local anesthetics:
• Articaine is available in solutions of 4%, or with epinephrine dilutions of 1:100,000 or 1:200,000. Its use is nearly exclusively in dental practice, for infiltration and nerve block anesthesia.
One of its advantages is that you can increase the dose up to 4% without having side effects. It can be used instead of lidocaine which affects the heart at high doses.
• Bupivacaine With its extended duration of action, its 0.5% solution is useful for dental procedures requiring anesthesia forlonger than 90 minutes. It is used in prolonged operations that last more than 90 minutes. It is also used for post operative analgesia.This effect can reduce the need for post-operative analgesic use.






Anesthetic pKa Onset Duration (with Epinephrine) in minutes Max Dose (with Epinephrine)
Procaine 9.1 Slow 45 - 90 8mg/kg – 10mg/kg
Lidocaine 7.9 Rapid 120 - 240 4.5mg/kg – 7mg/kg
Bupivacaine 8.1 Slow 4 hours – 8 hours 2.5mg/kg – 3mg/kg
Prilocaine 7.9 Medium 90 - 360 5mg/kg – 7.5mg/kg
Articaine 7.8 Rapid 140 - 270 4.0mg/kg – 7mg/kg

Notes:
- pKa: equilibrium between charged and uncharged forms of amides.
- We use the pKa to measure the ability of drug to penetrate.
- pKa decreased  this is better because the amount of uncharged (lipophilic) is more  more peneteration and effect
- lowest pKa here is for Articane
- Prilocaine has the disadvantage of causing methemoglobinemia
Extra: Methemoglobinemia is a disorder characterized by the presence of a higher than normal level of methemoglobin (metHb) in the blood. Methemoglobin is a form of hemoglobin (Fe that has extremely high affinity to oxygen, resulting in almost no oxygen delivery to the tissues. When its concentration is elevated in red blood cells, tissue hypoxia can occur. Hypoxia is presented as cyanosis (patient becomes bluish)

Special thanks for my brother Dr. Hamza Jassar ^_^ for typing this sheet

Ruba M. Jassar
Lec of : 29/11/2010

#27