pharma sheet #9 - by Zaid Alzo3bi

Adrenergic receptors:
• The adrenergic receptors (or adrenoceptors) are a class of G protein-coupled receptors that are targets of the catecholamines, especially noradrenaline (norepinephrine) and adrenaline (epinephrine). Although dopamine is a catecholamine, its receptors are in a different category.
• Many cells possess these receptors, and the binding of an agonist will generally cause a sympathetic response (e.g. the fight-or-flight response). For instance, the heart rate will increase and the pupils will dilate, energy will be mobilized, and blood flow diverted from other non-essential organs to skeletal muscles.

• They are divided into:
A)  (Alpha) receptors: their agonists in general are the epinephrine and norepinephrine. They are subdivided into two categories :
1) 1 receptors: found on the smooth muscles and on all blood vessels causing constriction.
• Important point here: As a dentist, when you give an anesthetic shot, it will be accompanied with adrenaline, why do you think so??
- The answer is that, adrenaline causes vasoconstriction, this constriction will localize the anesthesia around the tooth area and prevent it to spread out through the blood stream, and getting diluted by the blood, and as a result loses its effect.
• Also, adrenaline causes dilation of the eye pupil during stimulation.

2) 2 receptors: presynaptic are found at adrenergic and cholinergic nerve terminals. Postsynaptic are found in the blood vessels and in the CNS.
- 2 receptor provides feedback inhibition; when stimulated, causes inhibition of the adrenergic effect.

B)  receptors: their agonists are epinephrine and norepinephrine, while the antagonist is propranolol, and they are subdivided into:
1) 1 adrenergic receptors: found on the heart, they increase the heart rate and the contraction force.
2) 2 adrenergic receptors: have a dilation effect on the smooth muscles (blood vessels) and bronchial muscles as well.
 Note: you may find some of the 2 receptors on the heart.



• Drugs that we are going to learn about are 4 kinds:
1- Cholinergic agonists ( stimulate the cholinergic effect)
2- Cholinergic antagonists ( inhibits the effect)
3- Adrenergic agonists
4- Adrenergic antagonists

Cholinergic agonists:
- Stimulate the cholinergic (parasympathetic) effect through the neurotransmitter acetylcholine.
- Acetylcholine (ACH) is stored in vesicles in nerve endings. When an action potential reaches a nerve ending, vesicles fuse with the membrane and the contents are exocytosed, i.e. discharged outwards, into the synaptic cleft.
- Also as dentists, you need to stimulate the parasympathetic in order to increase the salivation by the patient, especially those who have dry mouth, or the cancer patients who usually have dry mouth because of the chemotherapy.
- We can also use these agonists with many patients who suffer from several cases:
a) Constipation, parasympathetic increases the motility of the GI tract and facilitates the defecation process.
b) Patients with urinary retention, who face difficulties in urination because of the muscle contraction, are given cholinergic agonists to relax the muscles.
 Note: usually ladies after delivery suffer from this case.
- Acetylcholine does not affect the normal situation; instead, it revises the normal situation in case of abnormalities occur.
So if a person is in the rest, normally his heart rate is around 72 beat/minute, if we give him a cholinergic agonist, it will not decrease the rate that much and it will almost stay the same.
While if the rate is 90 and we took acetylcholine, it will decrease it to 72!


• The first drug we are going to talk about is
1- Bethanechol (A): “A” means that is used as a dental application. Bethanechol is the muscarinic agonist most used to mimic the muscarinic effects of acetylcholine as it has very little nicotinic action, and is not rapidly hydrolyzed by cholinesterase as is acetylcholine itself.
- It causes increasing of the intestinal motility and tone.
- Stimulates the muscles of the bladder causing explosion of the urine.
- Therapeutic uses:
In urologic treatment, Bethanechol is used to stimulate the atonic bladder, particularly in or postpartum or postoperative, non-obstructive urinary retention.
- This drug can also be used for paralytic ileus or abdominal distension (which common post-operatively) as it stimulates gastrointestinal contractions.


- The side effects of this drug could be :
a) Decreased blood pressure
b) Salivation
c) Sweating
d) Bronchospasm
- We should be aware of all the possible side effects of any drug we will perscribe, because even it is very little change in the normal situation that may occur with the person who is taking this drug ( the bethanechol in our example), (this change) could be considerable with the patients of hypotension or asthma or COPD diseases as emphysema…etc.

- The general adverse effects of the drugs are abbreviated in the word SLUD which stands for:
a. salivation
b. lacrimation
c. urination
d. defecation
- The effect and the side effects actually are relative, if a person took bethanechol for example, to stimulate the salivation, then the urination and the defecation will be considered as side effects and the salivation is the effect, on the other hand, if he took it because of constipation, then the salivation will be the side effect, and the defecation is the effect that he needs.
- An example of dental prescription that you may prescribe to your patient in future who suffers xerostomia: Bethanechol, tablets 25 mg
30 tablet, take 1 tablet up to 5 times daily.
• (do not memorize doses)
 Note: the diabetic patients (as well as hypertensive patients) usually have a dry mouth, and since the percentage of the diabetes and hypertension in Jordan are relatively high, I think we will prescribe this drug a lot later on!!! So keep it in your minds!


The second drug we will talk about is the carbachol:
- It’s a “B” kind, means not used for dental patients.
- A small problem with this drug that it has a poor selectivity, so it has both actions; muscarinic and nicotinic.
- Has a little use at the internal or systematic level.
- Topically, it is used in the eye as a miotic agent, to treat glaucoma by causing pupillary constriction and decrease in intraocular pressure.

 Note: glaucoma means the increase of the intraocular pressure, carbachol, used to reduce this pressure by stimulating the parasympathetic, which will cause constriction of the eye muscles, leading to lacrimation, which in turn, decreases the eye pressure.


The third drug is Pilocarbine (A):
- Has better effect in healing the glaucoma than the carbachol does.
- Though it is more powerful than the mentioned drugs in causing salivation, lacrimation and sweating, it’s not that much used because of its poor selectivity.
- It’s also used as an antidote for scopolamine poisoning.
- Its adverse effect: may cause disturbances in the brain.



- Here is another example of a dental prescription:

• Pilocarpine HCl (Salagen) Tablets 5 mg,
21 tablets, take 1 tablet “t.i.d” (Latin abbreviation stands for: three times a day), 1/2 hour prior to meals. Dose may be titrated to 2 tablets t.i.d.
Some authors recommend using 1 tablet of pilocarpine 4-5 times daily.

 Note: the dr. said that t.i.d stands for “twice a day”, but I checked it in the Wikipedia, and found that it’s three not twice.
- Keep in minds that patients differ from each other in their response to the medication, some need a tablet twice a day, others need three … etc.


• Contraindications of cholinomimetics (cholinergic agonists):
1) Asthma; cause bronchoconstriction thus precipitate asthma attack.
2) Hypotension; vasodilation may result in reduction of coronary blood flow.
3) Peptic ulcer; stimulate gastric acid secretion and gastrointestinal motility both of which slow wound healing.

The End
Best wishes,
ZAID M. AL-ZU’BI
Lecture #9: 5/10/2010