pharma sheet # 25 - Khaled Rashydah

بسم الله الرحمن الرحيم

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بسم الله الرحمن الرحيم
Pharma sheet
* Benzodiazepines
- used for sedative & hypnotic activities
- Mechanism of action :
. increase affinity of GABA receptors toward GABA aminobenzoic acid
. increase the frequency of opening the chloride channels --- increase hyperchloridism across the membrane -- become away
from the action potential ( inhibitory activity )
. this inhibitory activity affect all the body - so increase the dose ---- the drug may become muscle relaxant for patient
- Dosing effect of benzodiazepines :
. little dose -- antianxiety . higher dose - sedative
- the most important common & used drugs of benzodiazepines is around 9-10 drugs
- drugs of benzodiazepines share the same: 1) mechanism of action
2) effects
but they differ in : 1) Pharmakinetics 2) Dosing
- to prescribe the appropriate drug from benzodiazepines group , you
must understand the situation of your patient , so pharmakinetics for these drugs is very important
$ Examples :
. patient can't sleep (enter sleep state) but he hasn't problem in the duration of sleep - give him short acting benzodiazepine drug like Triazolam ( just induce sleep)
. patient can't sleep & he has frequent wakening during sleep ( problem in duration of sleep )- need a drug to induce sleep &
continues active during sleep ( to solve frequent wakening problem)
- give him long acting drug

. patient can't sleep & he has problem in duration of sleep ( but frequent wakening is less like he awaken after 2 hours of his sleep
- give him intermediate drug
- actions of benzodiazepines :
1) Antianxiety 2) Muscle relaxant 3) Hypnotic ( sedative )
4) Antiepileptic ( Diazepam is the drug of choice in case of grand mal
epilepsy )
5) Anterograde amnesia ( VERY IMPORTANT in DENTISTRY because
the patient didn't remember the dental procedure ,so he would not
feel fear & anxiety
- Tolerance of benzadiapenes :
. there is idea of addiction for these drugs , so don't prescribe those drugs for susceptible patient , for example :
شخص مدمن بده يضحك عليك وبيجي عالعيادة وبعمل حاله انه بخاف من شغل الاسنان وانه
ما بيعرف ينام قبل يوم من الموعد , فبتوصفله دواء مثل Valium و طبعاً الدواء ما بيجي حبة
ولكن باكيت كامل , فلازم تتأكد من حالته وتشوف وضعه العام وتصرفاته
SO TAKE CARE OF THESE CONDITIONS
- Flumazenil is the only antidote for benzodiazepine overdose
. mainly benzodiazepine overdose linked with I.V adminesteration
. Flumazenil idea like the idea of Naloxone ( antidote for opoid overdose)
. Flumazenil blocks GABA aminobenzoic acid receptors
- benzodiazepines mainly used in Oral-surgery not in normal dentistry


* Zolpidam :-
- Benzodiazepine alternative in sedation (hypnotic) condition not for antianxiety and there is another drug which is Zopiclone but Zolpidam the most important
- it is not from Benzodiazepines or Barbiturates groups
-Currently the most prescribed drug in USA ……why? bcz idea of tolerance is minimal ,& little or no withdrawal symptoms during prolonged use -
means no addiction

- although advantages of Zolpidam is over benzodiazepines but our
experience about it is very little
-Adverse effects of Zolpidam :
nightmares , agitation , headache , daytime drowsiness ( hung over
problem )
$ Examples of Zolpidam nightmares :
. شخص في استراليا عايش في ناطحة سحاب شرب حبة ونام فصحي مشى عالبرنده وقع مات
. شخص شرب حبة وصحي طبخ سمك اكل ورجع نام وهو مش موعي عحاله
- لذلك هذا الدواء بدخلك بحاله لا انت نايم ولا انت صاحي وهذا يحدث في عدد قليل من المرضى


* Buspirone :
- drug B , not used in dentistry - hypnotic & antianxiety drug
- need long time ( more than week ) to be established in body so it's
drug B


* Barbiturates group :
- for example Thiopental ( Ultra short acting drug ) which was very common & used in surgical operations
اول ما يخدروك ما بتعدّ لل 10 الا وانت نايم
- very active hypnotic & it is not anesthetic ,but it used in operations
to sedate the patient before the beginning of operation & after that they put anesthesia with oxygen ( like halogenated hydrocarbons)
- it's similar to benzodiazepines but the difference is in the duration of opening the chloride channel but the end result of both is same
- at clinical symptoms level barbiturate more active than benzodiazepines at the level of respiratory centre
- Therapeutic index of benzodiazepines is very wide but of barbiturates is very narrow ,so barbiturates may lead to death , & was used for suicide in sixties & seventies
- Barbiturates overdose cause arrthrymia & problems in CNS & the most important one is CO2 Respiratory centre depression
- Today , barbiturates have been largely replaced by the benzodiazepines primarly because they induce tolerance , physical dependence & are associated with severe withdrawal symptoms ,& their ability to cause
coma in toxic doses & also respiratory depression
- short acting barbiturates is still used to induce anesthesia & very minimal use in dentistry ( oral surgery ) like pentobarbital & secobarbital (6-8 hrs)
- DON'T USE :
. LONG ACTING BARBITURATES drug for dentistry procedures because the patient become drowsed for 1-2 days
. ULTRA SHORT ACTING BARBITURATES drug because induction is within 30 seconds & that is not enough to make procedure & it's max. activity is just 20 minutes
- Nowadays the only use for them is anticonvulsant
. Phenobarbital has been regarded the drug of choice for treatment of young children with recurrent febrile seizures ( children with very high temperature don't develop chills as normal but they develop febrile seizure
. Phenobarbital is still used as long acting drug for tonic –clonic seizure ( grand mal seizure )
- Nowadays Barbiturates & Benzodiazepines don't used for antianxiety & sedation
- Never prescribe these drugs because they cause respiratory depression & death & they are easy to get & use them ,so may be used for suicide
- Barbiturates problems :
1) physical dependence is very high
2) hung over is very strong
3) very strong affect on CNS
4) respiratory depression ( the most important )
5) problems in enzyme induction



* Chloral hydrate : sedative drug near to benzodiazepines group (increase affinity toward GABA receptors & frequency of receptor opening)


* Dentistry applications of hypnotic & antianxiety drugs :
- Benzodiazepines the main used in dentistry ,& don't prescribe barbiturates unless you don't have benzodiazepines
- Zolipediam : hypnotic for patient before day of dental procedure
- Buspirone : one of the agent that is antianxiety but doesn't have applications in dentistry (need time to induce clinical effect )
- Sedation dentistry ( Relaxation dentistry ) :
. patient with panic ,fair & anxiety from dental procedure ,so we use it to manage this pain& fair
. it's idea comes from the idea of conscious sedation which used a lot in Angioplasty
.Conscious sedation : minimal depress level of consciousness ,due to we want to maintain patient's airway , because unconscious patient his tongue dropped in his pharynx
. advantages of conscious sedation (relaxation dentistry ):
1) reduce pain ( actually it doesn't directly reduce pain ,but it makes
the patient relax ,& more the patient relax as more his pain feeling is less
2) the patient is able to speak & respond to puerperal cues throughout the procedure ( like open or close your mouth )
3) Anterograde amnesia ( temporary memory lost)


* 3 types of sedation :
1) I.V sedation 2) Internal conscious sedation
3)Inhalation conscious sedation

* 1) I.V sedation ( deep conscious sedation )
- near unconsciousness
- given by oral-surgeon & specialized training dentist (60 hours )
- not used in dental clinics , it's common in hospitals
- it's advantage that you can give the patient the drug & you can notice his situation immediately ,if he doesn't sleep well you can raise the dose (titration )
- higher amnesia in I.V administration more than the oral one
- I.V has higher activity & more profound activity bcz it doesn't have the first pass metabolism & there is not variation in absorption like what happened with oral forms

* 2) Internal conscious sedation (sedation dentistry )
- the patient take pill before the procedure - patient relax & you can wake him up easily
- some degree of amnesia
- disadvantages :
1) Variability :level of sedation from oral form is not predictable ( bioavailability is different from patient to another )
2) Defect in fine motor activity ,so he must be driven by another person to the dental clinic
- most common medication of these activity is Triazolam ( short acting
benzodiazepines drug )
- you can prescribe intermediate acting drug ( such as lorazepam) if
the patient has dental procedure at 8 a.m for example so he can take
pill before the day of procedure
- Amnesia profound (very strong amnesia) in Triazolam although it is in the oral form but in other drugs of this group like Diazepam ,the amnesia profound is less than Triazolam if you take it orally
- so Triazolam : short acting , very quick activity , amnesia profound & don't given for children

- Mediazolam is:
.alternative for (Triazolam ) & similar to it ,used for children because it can found in syrup form (child can't take tablet) . the only one of benzodiazepines that found in liquid form
. drug of choice in case of children if you want to give them one of benzodiazepines drugs ,but usually we use Chloral Hydrate
- Depending on TABLE IN THE LECT. SLIDES :
. Triazolam , Mediazolam , Lorazolam , Temazepam ,Flurazepam
. حكى الدكتور احفظوهم مثل اسمكم
. the major difference between them is in the duration (pharmakinetics), and that determines their indication especially
in dentistry
. Triazolam : >onset 15-30 minutes
> peak after 1 hour
> activity 1-3 hours ((so that why Trizolam widely used in dentistry ))
>2uses --- before bed time (patient afraid from dental procedure) --- patient can't sleep but if you make indication for sleep he will sleep well
>used in USA dental offices bcz of rapid onset action &
good enterograde amenesia
. Mediazolam : > toward children > onset 15-30 minutes
> peak less than that of Triazolam
> Trade name : VERSED
. Lorazepam : rarely use
. Temazepam : >it's problem in it's long activity duration (6-8 hrs)
> good alternative for Triazolam in cases of long procedures
. NOT ALL BENZODIAZEPINES HAVE THE SEDATIVE EFFECT AT THE SAFE DOSE


* Depending on ANOTHOR TABLE IN LECT. SLIDES ( the table that contains drugs that are more toward antanxiety like Diazepam ,Oxazepam & Alprazolam)
- Diazepam (Valium ) = ( Happy Pill ):
. if the procedure was easy & the patient is afraid & you don't need to sedate the patient -- you need just antianxiety - Valium
. > onset 36 hours > peak 1-2 hrs > duration 24 hrs
يعني المريض بيقدر يؤخذوهم قبل ساعتين , او يوم , مثل ما بدك
. الدكتور حكى لازم نعرف كل شيء عن Valium والادوية الاخرى من الجدول ما نهتم الها باستثناء Oxazepam
- Oxazepam : . it's duration is less (6-12 hrs ) so the patient can recover faster from antianxiety & fine motor disadvantages
- Alprazolam : drug of choice in case of panic disorder ( very very high fear ) like fear from wars
. شخص من البوسنة (عنده هاي الحاله ) كان يدرس في استراليا قبل عام 2000 فلما يسمع العاب نارية او صوت فيه
boom يتخبئ تحت التخت


* 3) Inhalation conscious sedation
- Nitric oxide ( laughing gas )
. given with oxygen
. it was the most common used drug in dentistry for sedation but now it is not drug of choice for sedation
.inhalation sedation was used in dentistry for long time & it's the most frequently method for sedation used in dentistry
. 2 problems : some dentists can't use it
some patients fear from put it on their nose
. Disadvantages :
>deep level of sedation if the patient has severe anxiety
> can't be given to patients with COPD, emphysema…… (respiratory system problems)
> can't be given to claustrophobic patients ( patients fear from covering their nose )

* Chloral Hydrate :
- similar to benzodiazepines & come in syrup form for children
- onset 30-45 minutes
- long period of sedation & length variability
-not used for emergency situation bcz need time to be active
* Dentistry Sedation for children :
1st drug of choice is Chloral Hydrate
2nd drug of choice is Mediazolam
. أخر سلايدين في المحاضرة غير مهمين لكن لازم نعرف عن ال chloral hydrate


THE END



Done By : Khaled Rashydah
Week # 10
Date of lect.:Tuesday 23\11\2010
Dr. Malek Zahlif