pharma sheet #11 - by thara'a mualla

IN THE NAME OF GOD

Last lecture we talked about the cholinergic agonists ,, nd we categorized them into :

** direct cholinergic agonists
** indirect cholinergic agonists

And we talked about the DIRECT ones nd discussed three drugs which are :
1. Bethanecol
2. Carbechol
3. Pilocarbine
We also said that the pilocarbine is our drug of choice in cases of glaucoma nd when we need to increase the salivation..

We talked also about the indirect tye nd said they were 2 drugs :

1. Neostigmine
2. Physostigmine
We emphasized the fact that the blood brain barrier is an important factor bcz physostigmine can enter the brain whilst neostigmine can’t .. SO this will change the chemical indications of the 2 drugs compared to each other.. meaning … physostigmine can be used to antagonize a drug that can enter the brain but we can’t do the same thing in case of Neostigmine ..

MOSTLY neostigmine is used to adverse the effect of muscle relaxants ..



Amma blnsbeh la “Today’s lecture” it was about the CHOLINERGIC ANTAGONISM :
It is the opposite of the agonism ,, we just want to reduce the cholinergic activity in the body ,, we need this in some cases like when want to decrease the salivation.. (3aks el pilocarbine .. that was used to increase salivation) ,, sometimes we want to work with a dry mouth ,, or in other cases like patients who suffer from bradycardia (low HR) due to action of the vagus nerve … (as we know it serves a parasympathetic activity) so we want to increase the HR by giving antagonist of the cholinergic effect ..

Recall that the vagus nerve gives parasympathetic action to 75% of the body including the face.. heart .. abdominal parts … etc

So if we want to oppose the cholinergic activity we just give an anticholinergic agent to reduce the Ach.. so we could increase the HR in cases of emergency..

Mechanism of action of the anticholinergic drugs is that they bind to the cholinergic receptors without activating them,, yet it prevents Ach from binding to its receptors so it slowers its activity..

Now imp note .. hl2 when we give an Ach antagonist we r also giving antagonist for some sort of sympathetic activity that is controlled by Ach nd not by adrenalin.. like process of sweating (it is considerd with the sympathetic system yet it is controlled by the activity of Ach. )

So we give Ach  we increase the para.sym activity  so we increase the sweating … nd vice versa..

☺ The prototype nd the most imp. Drug in the cholinergic antagonism system is the ATROPINE ..  CONSIDERED AS DRUG “A” … :D

☺ Atropine is extracted from a plant named “atropa belladonna” >> set el7oson wl jamal :P

So as indicated in the name it was used in cosmetics bcz atropine caused dilatation of the pupil (3alameh jamalyyeh *_* ) so here the atropine opposed the action of the Ach. That caused constriction of the pupil to treat glaucoma as we said b4 ..

☻ It was used in suicidal crimes ..
☻ It is very specific.. y ?? bcz it acts only on the muscurinic receptors SOOO forget about the nicotinic receptors here  so the activity against muscles 7tkoon mam7yyeh 

Now if we inhibited the muscurinic receptors we`ll obtain an opposite result if we did activation .. “”here Ach activity will decrease .. Hr will increase ,, motility of the GIT will decrease.. pupil will dilate.. urinary constriction >> 3ks 3mal el bethanecol,, and salivation will decrease .. leading to dry mouth .. “”

So atropine is mostly used in emergencies when we need to increase the HR for bradycardia patients or when we need to decrease the motility of the GIt as in cases of colitis patients..  those are given benzoatropine..

So ob9omo :::::: 
☺ Atropine  dilation of the pupil
☻ Ach  constriction of the pupil..

When we need to make dilatation of the pupil ???
For the ophthalmologist to see the retina,, but this can cause many side effects such as blurring of the vision nd stinging ( bcz we played with the muscles of the eye)

Bardo el atropine is used to decrease Ach on the bronchial muscles that will cause dilatation of the respiratory muscles ..

For the previous case we could use 2 drugs we`ll discuss them later on .. but they are given generally to emphysema nd bronchitis patients ..

Atropine in dentistry : we have 2 types of treatments  normal treatment and emergency treatment..

Generally any dental clinic should have an emergency kit that should include atropine nd other important drugs as well in cases of hypotension , bradycardia , and allergic patients..

If the heart beats reached a level < 60 usually (40 – 45 ) here we should give the patient 0.5 mg of atropine (IV)  ND THIS IS THE MAX. DOSE .. nd the loading dose as well bcz its ana emergency case and we can’t wait ..

**The loading dose must be given intravenous .. nd should be a high dose .. so it goes to the heart and increase the beats there .. now if there was no response we may give an (IM) sustaining dose >> 0.1 mg every 5 min. but we musn’t give more than 3 mg >> cz this will cause toxicity nd overdosing ..
We have 2 options here .. : IV & IM ,,, 1st IV is given in emergency cases as a loading dose the we may use the IM .. but its not optional to use the IM first .. 

We may give adrenaline if the patient had a cardiac arrest..

So till now the most imp. Use of atropine in dentistry is to diminish the salivation ,, sometimes we use the suction machines to make the mouth dry in cases of applying restorations or any procedure that needs a very dry workin’ field .. here the atropine is given to patients an hour b4 treatment begins (0.4 mg tablet )  el doses msh 7efez bs lel 2amaneh el 3lmyyeh :P


Another type of drugs is the scopolamine .. it’s a B drug 
Could be used in mouthwashing materials .. nd maybe to produce the “dry mouth” effect ..

It has a v. high activity on the brain nd it waz widely used in suicidal crimes.. so it CAN enter the brain nd penetrate the blood brain barrier ..

It also could be used as an aniti motion sickness drug (la3ayan )  commonly used for this purpose..

Motion sickness .. is due to increase in Ach .. soOo we give an anticholinergic drug .. such as scopolamine but at very ow doses bcz its very dangerous ,, usually given in form of patches .. with 0.3 mg (300 micrograms) ..

Scopolamine is also given to aid in blocking the short memory (also due to its ability too enter the brain) ,, it was given to women during delivery to let them forget the pain .. + valium .. this one is also used in putting stints (shabakat) in the heart to block the short term memory in coward patients .. :D

SiDe EffeCtS !!  it is very dangerous on children they would die if a dose of 0.4 mg was taken .. bcz it has a very narrow therapeutic index.. also it can cause tachycardia , blur vision , dry mouth , confusion, convulsion , CNS excitation like in morphine addiction …)

Atropine side effects were described >> “” hot as a hare ,, blind as a bat ,, dry as a bone ,, red as beet ,, and mad as a hatter “”

As dentists ..we won`t give 0.8 mg of atropine to a patient .. cz the max is 0.5 mg..


Now we will talk about muscles :

We said it’s a somatic system that is the somatic nerve has no ganglia.. it goes out from the brain and ends in the muscle in the affected organwhere It produce Ach.

As we said tubocurarine was used was used in killing animals by causing paralysis in their muscles ..

These drug agents acts by blocking the cholinergic transmission between …….. (check this plz :S) & nicotinic receptors on the neuromascular end plate ..

** here we are talking about NICOTINIC receptors not muscurinic receptors,, nicotinic where the Na+ enters and the K+ goes out of the cell and action potential evolves causing muscular contraction 

… paralysis may occur due to antagonism (undepolarizing effect) or by an depolarizing effect … how ????
By increasing the Action potential nd causing muscle fatigue or somehow end of receptors ,, or long acting effect on these receptors so there won`t be any new binding or any new action potential ..

In orofacial surgeries we need to use muscle relaxants >> to relax the patient ..

Here when we give the relaxant we will not need to give a high dose of anesthesia bcz using high anesthetic doses may be lethal nd cause death .. 

>> so we can see the synergistic effect between if we can say the inhaled anesthetics and the muscle relaxants .. :D

Tubocurarine is widely used in hospitals for the previous purpose ,, there is another derivatives but this is the prototype ..

Tubocurarine acts by binding to the end plate nicotinic cholinergic receptors ,, thus exciting them .. si it acts as a competitive antagonist toward the Ach . >> causing relaxation of the muscle .

>> Good thing about tubocurarine that it doesn’t penetrate the CNS ..
>> it given intravenous ..

We have the antidote choline esterase Inhibitor  neostigmine .. we give it to the patient if he didn’t wake up or it took him too long so we can give him neostigmine to increase Ach.. acting as a competitive antagonist (inhibitor)

Another type is the rocuronium  it is the fastest it acts within 30 sec. nd stay for 30-45 min.

** succinylcholine  drug B   depolarizing agent ..
The difference between acetylcholine and succinylcholine is that the 2nd one is not degraded by the Ach esterase ,, so it stays bound .. nd thos persistent binding makes persistent depolarization so the muscle stayz depolarized so there is no new binding nd no new action potential .. and the muscle stay flacit nd cause wt is called flacit paralysis

SEE THE SLIDES ………

The importance of this drug is that it works and ends the action quickly so we can finish the titration bardo quickly … so it is favorable in the emergency cases ..

Maybe used also after it is injected intravenously in the patient then relaxation of chest muscles will occur so we can apply the endotrachial incubator easily nd we don’t need to apply the mechanical ventilator ,, the action of the drug would end in 1 min. nd muscles will go back to their normal state without causing any risk on the patient 

Lect.11
12-10-2010
Corrections are over welcomed 


Done by : ThaRa2 M3aLLa 




A SMILE  IS A CURVE .. THAT SETS EVERYTHING STRAIGHT .. 

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