Lectures of CNS Pharmachology Last Edition - 1

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Dr. ASMA'A CNS PHARMACOLOGY ALL LECTURES
Anti-depression
Def. of depression: -
Is mental and behavior disorder "mood →always sad" that appears in patient as
addictions, though disorder, and feeling disorder.
‫ والذي يكون فيه مش حابب يخالط أي حد‬،‫ إما المبالغة في اﻻنفعاﻻت او اﻻنطوائية‬،‫المشاعر عنده كلها خاطئة‬
.‫ والحزن مسيطر على المريض في كل الحاﻻت‬.‫بمشاعره‬
Also, anti-depressant treats the anxiety '' ‫''القلق الزيادة‬
Signs or Symptoms of depression: -
 Anxiety.
 "disorder in interaction with society (feeling +thinking)
 Vague pain, that means:
‫ ثم يرجعوها على انها‬،‫ ولما يسوي فحوصات يطلع وﻻفيه حاجه‬،‫ مثال واحد دائما ً مريض‬،‫آلم مجهول‬
.‫اكتأب‬
 Obsessive-compulsive disorder.''‫''الوسواس القهري‬
 Eating disorder, 1- over eating. 2- under eating.
.‫ بل تزداد الشراهة لﻸكل أكثر‬،‫ وبعض الناس ﻻ‬.‫ يمتنع عن الطعام‬،‫بعض المرضى لما يكون متنرفز‬
‫ هذا ﻻ نسميه‬،‫ ساعة او ساعتين( ويسترجع حالته الطبيعية‬،‫لكن إذا كانت حالة مؤقتة )يعني يوم او يومين‬
.‫اكتأب‬
‫ يعني ما عنده شهيه‬anorexia nervosa ً ‫ وتسمى ايضا‬anorexia ‫ يعني دائما ً عنده‬،‫لكن لو هذا سلوك‬
‫ وأي حاجه تدخل بطنه حتى ولو بالقوة هنا تظهر عليه عﻼمات الخوف‬..‫وفوق هذا يحاول ينحف نفسه‬
‫ او‬Laxative ‫ وتﻼقيه دائما ً على ادوية الـ‬،‫ الخوف حتى من انه يرجع لوزنه الطبيعي‬،‫من زيادة الوزن‬
.‫ لتساعده على التقيؤ‬emetic ‫على ادوية الـ‬
 Social phobia.→ tries to be isolate themselves
 Sleeping disorder
Notes: -
- If symptoms \ Signs that persist for at least 2weeks need medical treatment.
- Present of anorexia nervosa is very dangerous because patient suffering from: -
1. Hypokalemia. 2. Hyponatremia.
- And it changes to severe which turns to emergency case and must substitute by
food.
- Percentage of death in anorexia nervosa is 10%.
‫ بس المشكلة انه عارف بأنه يأكل زيادة فيحاول انه يخرج الزيادة فبيسموها‬،bulimia ‫الشراهة للطعام وتسمى‬ -
،‫ لكن عندما تكون سلوك‬،‫ عندما تكون هذه الحالة لساعة او لساعتين فﻼ مشكلة‬.bulimia nervosa
. anti-depressant‫ هنا يعالجوا كﻼ الحالتين بالـ‬،‫كأن يمنع عن نفسه الطعام او يحاول يخرج الزيادة‬
- When the case is chronic anorexia or bulimia, they are treated by anti-depressant.
- All anti-depressant drugs are orally.
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 Concept of treating: -
1\ Depression.→ ↑Serotonin and Dopamine. “Centrally not peripherally”
2\ Psychosis → ↑ Dopamine..
Clinical uses of anti-depressant drugs: -
1- Vague pain.
2- ((‫ اكتأب)) شخص انطوائي‬major depression.
3- Anxiety.
4- Eating disorder. (anorexia or bulimia nervosa ) or extra eating.
5- Social phobia.
6- Dependence and addiction to drugs.
Groups of anti-depressant drugs: -
1. SSRI Selective Serotonin Reuptake Inhibitor.
2. SSNRI Selective Serotonin Norepinephrine Reuptake Inhibitor.

Adjuvant therapy
3. SRI Serotonin Antagonist of Reuptake Inhibitor.
4. MAO inhibitor Mono-Amino-Oxidase Inhibitor.
5. TCA Tricyclic Anti-Depressant.
6. Atypical anti-depressant
- SSRI Selective Serotonin Reuptake Inhibitor.

- First line & main group used for depression treatment, and they are the
most important group.
MOA of SSRI: -
Increase the rate of serotonin by blocking the protein transporter that responsible
for transportation of serotonin only in the process of reuptake.
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Clinical use of SSRI: -

1. Depression (the main and major use)
2. Anxiety disorder. In medical books it's called distress.
3. Vague pain.
4. Addiction of drugs, especially or mainly (Benzodiazepine)
Benzodiazepine, e.g. diazepam and its derivatives.
‫كيف نوقف اﻹدمان لمثل هذه اﻻدوية؟؟؟‬ -
gradual ‫ لكن ﻻزم ان يصاحب الـ‬،gradual decrease ‫ لهذه اﻻدوية وإنما‬sudden stope ‫ﻻ تستطيع ان تعمل‬ -
‫ ونعطي‬،diazepam ‫بحيث نقلل جرعة الـ‬SSRI ‫ فدائما ً الدواء البديل يكون من الـ‬...‫ استخدام دواء بديل‬decrease
.diazepam ‫ الى ان يجدون الدواء البديل في المعالجة بديل تام للـ‬SSRI ‫جرعة اعلى من‬
.(see later) ‫ ان يكون تدريجي خﻼل أربعة أسابيع‬SSRI ‫ايضا ً من شروط إيقاف استخدام الـ‬ -
5. Gambling disorder: - ‫عند ترجمتها تكون )القمر القهري( فماذا تعني؟‬

‫ ويشتي يوقفها لكن ما يعرف يوقفها‬،‫تعني انه يمشي المريض في الحاجة الغلط ومقتنع ايضا ً انها غلط‬
.‫ يعني نوع من أنواع الممارسات الخاطئة وتكرارها‬،(‫)مايقدرش يتوقف عنها المريض‬
6. DOC in Eating disorder: - two types
a. Anorexia nervosa: - more dangerous than bulimia because the
patient doesn’t eat and percentage of death in this case is 10%.
b. Bulimia nervosa: - ↓K , ↓Na , ↓ Ca.
Emetic ‫ بس يحس بتأنيب الضمير ويروح يأخذ أي حاجه تعمل‬،‫هذا يأكل ويريح على نفسه‬
.‫ لكن عاده اهون من الحالة حق النوع اﻷول‬،‫ويخرج اﻻكل‬
7. Obsessive-compulsive disorder: -
.‫ لكن عمل صح ويتكرر عدة مرات‬gambling disorder ‫يعني العمل الذي يسويه صح عكس الـ‬
‫ اذا كان هذا السؤال بيحصل لمرة‬.‫ ويروح يتأكد‬،‫مثﻼً شخص يسأل نفسه او غيره هل غلقت الباب‬
obsessive ‫ هنا تكون الحالة‬،‫ لكن عند تكراره والتأكد عدة مرات‬disorder ‫واحده بس فﻼ يعتبر‬
compulsive.
8. Socialphobia
E.g. of SSRI: -
1- Fluoxetine: -
- The most commonly used for addiction, because it lacks discontinuation
syndrome .
- DOC more in children and adolescent. But if patient needs sedative drug, we
use paroxtine.
.fluoxetine ‫" يفضلوا استخدام مركب الـ‬٢٠،٢١،٢٢" ‫ والمراهقين في عمر‬،‫يعني فترة الطفولة‬
- Long duration of action.
- Can cause insomnia. And may cause hyponatremia.
- No discontinuation. ‫الدواء الوحيد الذي ﻻ يحتاج الى إيقاف تدريجي عن إيقاف استخدامه‬
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Note:
 Prolongation of action is occurred by: -
- Plasma protein binding.
- Activation of inactive metabolite. (the drug)
- T half: time of the drug to reach 1/2 concentration of it in blood.
2- Paroxetine: -
- Sedative.
- The highest one in causing discontinuation syndrome.
3- Citalopram: -
- Used for patient suffering from chronic disease, e.g. D.M patient.
- Preferred in elderly & patient suffering from Alzheimer disease.
- Sedative effect.
- Cause the S.E Prolongation of QT interval, so it may cause tachyarrhythmia.
So, citalopram is taken by elderly that don't have problems in heart or
arrhythmia. ((Sertraline is used in this case))
4- Sertraline: -
- Sedative effect.
- Used for patient suffering from chronic disease.
- Also used with CVS disease, angina, arrhythmia, …etc. why??
Because it's the least one in drug-drug interaction.
i.e. if patient under treatment by warfarin, the best one of anti-depressant in
this case is Sertraline.
3-and 4- both cause discontinuation syndrome if stopped abruptly.
Side effect of SSRI: -
1. The main side effect occurs in GIT e.g. (nausea, vomiting, cramps, and
diarrhea)
2. Sleeping disorder. Some drugs make Insominia, and some make
sedation.
.‫ اثناء النهار تعيق المريض من انجاز أي عمل‬sedation ‫احيانا ً الـ‬
3. Headache.
4. At the first week -the starting- of the treatment, anxiety increase.
.‫عشان كذا المريض دائما ً معه عوده الى عند الطبيب‬
.‫ إذا مافيش أفكار انتحارية‬،‫عودة عند أسبوعين‬
.‫ ﻻزم كل أسبوع يروح زيارة للطبيب‬،‫لكن لو عنده فكر يتوجه لﻼنتحار‬
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In case of suicidal tendency, follow up should be (at least) weekly.
Note: - Drugs of CNS start working and their effect appears when the
serotonin rate increase in the CNS and that start occurring from the 4th week.
increase the anxiety. And drugs start works. ‫ اﻷسبوع الثاني‬-
.‫ تقل تدريجيا ً الى ان تستقر في اﻷسبوع الرابع‬anxiety‫تبدأ الـ‬ ‫ اﻷسبوع الثالث‬-
Full effect .‫تبدأ فعالية الدواء‬ ‫ اﻷسبوع الرابع‬-
5. Discontinuation syndrome/symptoms as result of ((sudden stop))
Q- what is the discontinuation symptoms??
It appears as: -
 In GIT (severe nausea, vomiting, cramps, and diarrhea).
 Then headache appears. "severe"
 Anxiety, paresthesia "numbness", and some patient get tremors. (severe).
 Dizziness.
Note
- Discontinuation starts when the patient stops taking the drugs for (24-48 hs),
and it always starts by GIT disturbances.
- The true stopping of the drug is gradually in four weeks.
6. May cause perforation of stomach (bloody vomiting) specially with
NSAID. Avoid using " NSAID". why??
Because it causes GIT bleeding. But if necessary to use analgesic, proton
pump inhibitor (PPI) should be used before starting treatment.
Notes
.‫ مفعولها متأخرة‬CNS ‫ دائما ً تبدأ ادوية الـ‬
 This group of drugs used for six months at least, then if need to continue,
ok, but if need to stope, the seventh month is added for decreasing the
dose until 0 gradually in four weeks.
2. SSNRI Selective Serotonin Norepinephrine Reuptake Inhibitor.

MOA of SSNRI: -
- Block restorage of Serotonin and Norepinephrine.
 The same characteristic of SSRI, because it inhibits the reuptake transporters of
Serotonin.
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 It also prevents storage of norepinephrine, and because of that, it's used as the
second line treatment. (Adjuvant Therapy)
Clinical Use of SSNRI: -
1- The second line treatment for depression. “Adjuvent therapy”
2- Mainly used for Neuropathy.
E.g. of SSNRI: -
1- Duloxetine. 2- venlafaxine.
1- Duloxetine.
"the first line treatment for diabetic neuropathy, but with no suffering from
BPH"
- When dose the patient of diabetic get diabetic neuropathy???
If patient has uncontrolled blood glucose, and more symptoms are appeared
like "nephropathy, neuropathy, retinopathy and more complication.
But in neuropathy complications, duloxetine is given.
- Duloxetine should NOT be given with: -
 Patient suffering from BPH "difficulty in urination"
 Sympathomimetic drugs.
Because they decrease the urination and making the case worsen.
 Diabetic neuropathy is result of: -
1. Uncontrolled blood glucose.
2. May come as side effect of chronic use for Metformin.
Metformin decrease vit. B12 which responsible for making the myelinated
sheath, and neuropathy occurs.
2- Venlafaxine.
Note
- If the patient under treatment by metformin, we give him/her vit. B12 and
other vitamins that helping in strength of nerves.
Side effect of SSNRI: -

1) The same as SSRI side effects.
2) Hypertension. Caused by NE. " for avoid this side effect, make adjustment
for blood pressure."
3. SRI Serotonin Antagonist Of Reuptake Inhibitor. (Adjuvant Therapy)
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MOA of SRI: -
- Block serotonin receptor. 5HT2 and ↑ effect if serotonin on 5HT1
- Block H1 receptor causing sedation as side effect.
- Block α1 receptor giving the others side effects of the drug.
E.g. of SRI: -
 Trazodone.
 Nefazodone.
Clinical Use of SRI: -
- Second line treatment as adjuvant therapy for depression with patient
suffering from insomnia.
Side effect of SRI: -
- Sedation. (the main side effect)→because blocking H1
- Postural hypotension and reflex tachycardia. →because blocking α1
4. Non selective irreversible MAO inhibitor

Mono-Amino-Oxidase Inhibitor on both (A and B).
- Type A → brain, liver, placenta, GIT.
- Type B → brain, liver, blood platelet.
- 3rd or 4th line treatment of depression.
- The late choice to treat the depression by MAO, because these drugs are
highly effective but more toxic.
MOA of MAO inhibitor: -
- Inhibiting the MAO enzyme.
E.g. of MAO inhibitor: -
 Tranylcypromine
Notes: -
- MAO enzyme is involved in removing "break down" the neurotransmitter
such as adrenaline, noradrenaline, serotonin, and dopamine.
- MAO inhibitors drugs were made to inhibit the MAO enzyme which lead to
accumulation of these neurotransmitter in nervous tissue and in the other
hand it increases the catecholamine production.
.‫ يعني توقف التكسير وتزيد التصنيع‬-
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Side effect of MAO inhibitor: -

1. Hypertensive crisis (emergency or urgency), Because of the increased
catecholamine and the patient has eaten anything that contains tyramine.
2. Drug-food interaction. By food containing Tyramine.
Tyramine is amino acid present in " cheese, smoked meat, smoked fish,
yoghurt and grilled meat.
Tyramine is the precursor of catecholamine, and eating foods that increasing
the catecholamine, so drug-food interaction will lead to sever hypertension.
‫" ان يتجنب اﻷطعمة‬MAO inhibitor" ‫لذلك يجب على المريض الذي يستخدم هذه اﻻدوية‬
.ً‫المذكورة سابقا‬
3. Orthostatic hypotension→ the main side effect in the absence of the
tyramine. Because the MOA inhibitor to interference with transmission in
the sympathetic ganglia.
4. Increase the appetite increasing the weight.
5. TCA Tricyclic Anti-Depressant.
MOA of TCA inhibitor: -

- The same as the second group (SSNRI). Serotonin and NE reuptake inhibitors.
Why drugs of this group aren't added to drugs of the second group (SSNRI)???
- Because this group is very old and it was the first line treatment for depression,
and using this group as anti-depressant need to take large dose of the drug, so
toxicity appear. So, this group is rarely used as anti-depressant.
Nowadays TCA inhibitor used in small dose in the following cases: -
1. Neuropathy like diabetic neuropathy. (if you don't give the patient duloxetine,
give him\her TCA.
2. Vague pain.
3. Obsessive compulsive disorder.
4. Fibromyalgia "pain in the skeletal muscles by unknown cause"→ttt by TCA.
5. Chronic pain "tension headache or migraine that difficult to be treated by drugs
of migraine or analgesic."
6. Urinary incontinence. "in children" by urine retention caused by increasing
norepinephrine. Desmopressin can be used in children.
7. Used in irritable bowel syndrome. ttt→ Buspirone, or TCA or (Duloxetine "last
choice")
Drugs with a long DOA (duration of action) methadone→ long T1/2 life
Diazepam →→ active metabolites.
8. Anti-depressant. (Rarely)
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E.g. of TCA inhibitor: -

- ‫الدواء‬ - ‫بعد تحوله داخل الجسم‬
i. Amitriptyline Nortriptyline.
ii. Imipramine Desipramine
iii. Clomipramine Desmethyl clomipramine.
- i and ii are the 3rd and 4th line of treatment of depressant.

- These drugs are long acting as a result of the active metabolite. And used
once at night.
Side effect of TCA inhibitor: -
1- Atropine like side effect. "Anticholinergic effect"
(dry mouth, dry skin, increase IOP "mydriasis", tachycardia, constipation,
urine retention)
2- Sedation.
3- Arrhythmia. " Torsade de point tachy-arrhythmia"
Torsade de point has two causes (widening of QRS):
a. Electrolyte disturbances.
b. Drug induced.
4- Hypotension. "Because of blocking of α1 receptor." And reflex tachycardia,
BUT norepinephrine is high.
5- Headache.
6. Atypical anti-depressant: It's named by this name because of its MOA. It has
many receptors working on.
MOA of Atypical anti-depressant: -
- Blocking α2 receptor. (antagonist)
- Blocking of H1 receptor.
- Blocking of 5HT2 and 5HT3.
Notes:- -
- Blocking of α2 on the presynaptic cleft lead to increases movement of
all storage of the catecholamine and serotonin to the synaptic cleft.
- Blocking of H1 lead to sedative effect.
- Blocking of 5HT2 lead to prevent and stop the action of serotonin on
this receptor.
- Blocking of 5HT3 lead to prevent the nausea and vomiting which
produced by stimuli from the chemoreceptor trigger zone.
- Action of serotonin still working on the 5HT1 receptor which is responsible as
anti-anxiety.
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E.g. of Atypical anti-depressant: -

1. Mirtazapine: - " orally"
MOA: -
- α2 antagonist.
- Inhibiting 5HT2 and 5HT3
- Inhibiting H1
Clinical use of mirtazapine: -

 Used as 2nd line in Depression but in condition that patient has
insomnia and weight loss "under weight", Why??
- Because blocking of H1 will decrease the insomnia lead to (sedation)
and serotonin action increases the appetite and weight gain occur.
2. Bupropion: -
MOA of Bupropion: -
- Unknown mechanism.
Clinical use of Bupropion: -
o Smoking cessation.
.anxiety ‫يساعد المريض اﻹقﻼع عن التدخين ﻷنه يقلل الـ‬
o ↑dopamine. ↑epinephrine. ↑Serotonin
o leads to hypertension.
o 3rd and 4th line of treatment.
o High effective and high toxic.
S.E of Atypical anti-depressant: -
1. Sedation. → effect H1
2. Weight gain.
Because of serotonin
3. Increase the appetite.
4. Hypertension.
5. Tachycardia. Because of blocking α2 receptor
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Ani-psychotic drugs
Firstly; what is Psychosis: -
It's mental disorder that patient has the most important symptoms "schizophrenia";
appears as: -
- Thought disorder.
- Delusion and hallucination.
‫ او بصورة‬،‫ إما بصورة التهرب من المجتمع وعدم المخالطة‬،‫ عدم القدرة على التفاعل مع المجتمع‬-
.‫مواجهات عنيفة مع المجتمع‬
Causes of psychosis: -
1. Hereditary, as it presents in family.
2. Head injury, called organic psychosis.
3. Biochemical disturbances. "increasing in the dopamine rate"
i.e. any drug that increase the dopamine, help the happening of S.E.
types of psychosis patients according to the symptoms: -
A) patient with +ve symptoms psychosis: - Delusion, hallucination and
abnormal reaction.
‫ لكن بالرغم من أفكاره المضطربة إﻻ انه قادر‬،‫الذي ﻻ يزال يخالط المجتمع وفقا ً ﻷفكاره وماهية أفكاره‬
👇‫ سيدخل في المرحلة التالية‬،‫ إذا لم يتعالج المريض‬.‫على ان يكون عضو فعال في المجتمع‬
B) Patient with -ve symptoms: -
o Withdrawal from society.
o Inability to perform any tasks in life.
o Inability to be pleasant. ‫ﻻيستطيع ان يكون مسرور‬
o Flattening of emotion. (‫ ﻻ ضحك وﻻ بكاء )خارج نطاق التغطية‬،‫مشاعر سطحية‬
o ‫ ويعيش في غرفة مغلقة ومظلمة بأفكاره واوهامه ﻻ‬،‫عندما يكون في عزلة عن المجتمع‬
.‫يستطيع حتى ان يخالط اسرته‬
o But in both cases, they are " schizophrenia" or psychosis.
C) Cognitive symptoms:- ‫ على حسب وضع المريض‬،‫هذه المرحلة تفاوتية‬
 Inability to memorize.
 Loss ability of attention.
Anti-psychotic drug classified into two groups according to types of receptor
discussed later.
Typical anti-psychotic drugs Atypical anti-psychotic drugs
Pharmacology books Said that typical Pharmacology books said that atypical
anti-psychotic drugs are best choice to anti-psychotic drugs are used for -ve
use for +ve symptoms psychosis. symptoms psychosis.
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Note
Nowadays, Atypical anti-psychotic drugs are 1st line treatment, because their S.E are
less than typical anti-psychotic S.E.
Even patient is +ve or -ve symptoms, atypical group is used for the treatment.
Doctors back to use the typical group if the patient is resistant to the atypical drugs or
has chronic disease. Like (D.M or CVS DISEASE)
MOA: - Pharmacological action of the typical anti-psychotic drugs: -

A- D2 receptor antagonist.
Block D2 receptor leading to : -
1. Anti-psychotic effect.
2. Anti-emetic effect. (for drug induced nausea and vomiting)Because D2
receptor present in the chemoreceptor trigger zone.
3. Depression .
4. Hyperprolactinemia, because blocking the D2 receptor.
Its symptoms are: -
- Galactorrhea.
- Gynecomastia.
- Infertility.
5. EPS " extra pyramidal like side effect.(Parkinsonism).
Why we say EPS, not Parkinson?
Because EPS is drug induce (S.E.), while Parkinson starts as disease itself.
 Its symptoms: -
- Tremors - Rigidity. - Dyskinesia or bradykinesia
- Slow movement - Depression - Dystonia.
- EPS is treated by anticholinergic drug e.g. Procyclidine (the antidote)
Note
Drugs studied before that can cause EPS." metoclopramide and alpha methyl
dopa"
Alpha-methyl dopa is the drug of choice for hypertension during pregnancy.
B- 5HT2 antagonist "all subtypes of 5HT2 " cause: -

Sedation, increase the appetite, increase the body weight.
C- Anticholinergic effect: - " atropine like side effect" (occur with chronic using).
D- α blocking effect causing the following S.E: - postural hypotension and
increase the heart rate(tachycardia).
E- H1 blocking effect: - cause sedation, and can be used for treatment of allergy.
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F- Hypothermic effect: - it means decreasing the normal body temperature.
Note:
- Anti-pyretic decrease the abnormal high temperature to the normal, but
hypothermic means decrease the normal body temperature to low abnormal
temperature
- Causes of hypothermic effect
1. Vasodilatation which lead to heat loss.
2. Decrease of heat production.
All the uses of this group are: -
1. Anti-psychosis.
2. Anti-emetic.
3. Anti-allergic, just for one of the examples, and the other effects are concerned
as side effect.
4. Hiccup.
 Typical anti-psychotic drugs are three groups: -
a. Phenothiazines group: - "orally&parenteral" the most commonly used

E.g.
Chlorpromazine - Promethazine
1- Chlorpromazine: - used for psychosis and nausea and vomiting which
induced by cancer or radiation treatment.
2- Promethazine: - anti H1 receptor. ((sedation))
This drug was safe in pregnancy, but has alpha blocking effect, and cause
hypotension for the first dose just. So, promethazine replaced by meclizine.
Nowadays, promethazine is used just for allergy.
Phenothiazines are:
o High sedative effect.
o High anticholinergic effect.
o High alpha 1 blocking effect.
So, their side effects are more than their benefits, but they have low EPS effect.
Side Effects:-
- Atropine like side effect.
- Postural hypotension.
- Reflexe tachycardia.
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b. Butyrophenones group:
E.g.
1- Haloperidol:
Parenteral (I.M depot injection) that means they has
long dura on of ac on. "One injec on for month or 21
2- Droperidol:
Clinical use:
1) Acute psychosis, which its symptoms is anxiety, ،‫ممكن ينفعل بصورة عدائية‬
So, in this case It's managed by injection, not by orally.
2) Droperidol used with general anesthetics in the neuroleptic anesthesia.
 Characteristics of this group:
- High EPS effect, its block effect on D2 is the strongest effect, and that
lead to EPS.
‫ والذي‬،‫ لكن ما يهتموا بها وأيضا ً ما تخوفش‬،‫ غير هذا‬D2 blocking ‫ باقي اعراض أخرى للـ‬-
‫ )ذُكرت في المحاضرة‬Parkinson ‫ او اعراض الـ‬EPS ‫يخافوا من ظهور اعراضه هو الـ‬
.(‫اﻷولى‬
- Low sedative effect.
- Low alpha 1 blocking effect, so lead to long duration of action.
- Low anti-cholinergic effect.
c. Thioxanthene group: -
* It's similar to phenothiazine but this group is more toxic.
E.g.
1- Clopenthixol "clopentixol" "orally & parenteral) .‫متوفر عندنا ويستخدم بكثرة‬
‫من الوسط‬H‫بعض الكتب ممكن تحذف حرف الـ‬
2- Flupenthixol "flupentixol" " parenteral "
Clinical use and characters:
- Both are used in acute situations " acute psychosis"
- IM injection.
- Long duration of action.
 Atypical anti-psychotic drugs: -
- It's called atypical because its chemical compounds don’t have similar structure.
- Every group has different structure and when structure differentiate, the
chemical character will be different in each drug.
- Atypical group is differing in that atypical is working on serotonin more than
dopamine, and that’s make this group: -
1. Atypical drugs are the first line treatment of +ve & -ve psychosis.
2. It's 5HT2 antagonist more than D2 antagonist.
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E.g.
- Risperidone. - Clonazepine - Olanzepine.
1) Risperidone: -
MOA: -
MOA In pharma books MOA In medicine books
- 5HT2A antagonist. The same effect on both 5HT2A and
- Week D2 antagonist D2. (Antagonist)
Clinical use: -
- First line treatment for psychosis.
Decrease anxiety and decrease psychiatric symptoms
Side effect: -
- Weak EPS.
- Sedation.
- Increase appetite.
- Weight gain.
- Increase the resistant to insulin, which lead to hyperglycemia.
So, if patient has chronic disease like D.M. or CVS diseases, the first line
treatment is typical anti-psychotic.
2) Clonazepine and Olanzapine: -
MOA: -
MOA In pharma books MOA In medicine books
- 5HT2A antagonist more than D2 The same antagonist effect on both
antagonist. 5HT2A and D2.
EPS ‫ الـ‬S.E. ‫لذلك ما حنذكرش في الـ‬
……………………………………………………………………………
‫ يعني لو كان عند المريض أفكار انتحارية‬Decrease the suicide tendency, 
‫ وإذا ما عنده أفكار انتحارية العﻼج اﻷفضل‬clonazepine ‫يجيبوا له‬
.risperidone
 The most effective anti-psychotic drugs.
 Risperidone is the first line treatment even clonazepine &
olanzapine are more effective. Why??
 Because of the idiopathic side effect "agranulocyte"
 Used as 1st line in patient who has sucide tendency. MCQ
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Side effects of Atypical anti-psychotic : -

 S.E as result of MOA: -
- Sedation.
- Increase the appetite and weight gain.
 And its specific side effect is: -
- Hyperglycemia. So C.I in D.M.
 Its idiopathic side effect " side effect NOT related to the MOA":
- Agranulocyte >>>> (decrease in granular leukocyte.)
The antipsychotic using is long term treatment,
.‫ وقد تكون ستة اشهر او احيانا ً يأخذ سنة‬،‫يعني المريض ما يشفى من شهر او شهرين‬
‫ يشترط فيها دائما ً قبل المعالجة فحص كريات‬clonazepine ‫لذلك المريض الذي تبدأ الخطة العﻼجية بالـ‬
(.‫ أسبوع )تقريبا ً اﻷربعة أشهر اﻷولى من فترة العﻼج‬١٨ ‫الدم البيضاء مرة كل أسبوع ولفترة‬
‫ مرات‬٤ ‫ ثم بعد ذلك يبدأ يعمل الفحص‬،‫ أسبوع‬١٢ ‫وبعدين يبدأ يعمل الفحص مرتين في اﻷسبوع ولفترة‬
.‫اسبوعيا ً الى ان تنتهي المعالجة‬
.‫ بيشترطوا انه يعمل الفحص مرة في اﻷسبوع‬،‫وعند انتهاء المعالجة وإيقاف الدواء‬
So because of the agranulocyte, risperidone is the first line treatment.
Also, Doctors back to use phenothiazines when patient became resistant to
the atypical drugs: -
- If low granular leukocyte, not to use the clonazepine, and also risperidone
will not be given to the patient, because patient will not respond to the drug
and that because ‫ﻷن حالة المريض متدهورة‬
Note
- In Acute cases, use the injection is the best choice, other cases use oral drugs.
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Anesthesia
Introduction: -
Def. controlled temporary loss of sensation of awareness are induced for medical
purpose..‫حالة مسيطر عليها من فقدان اﻹحساس‬
Anesthesia is always associated with analgesic effect.
Anesthesia means getting to the result "analgesic" by stopping of sensation. (Sensation
is depending on the nerve impulse.) So Anesthesia is working on stopping the nerve
impulse.
Classification of Anesthesia: -
1) General Anesthetic:
Analgesic effect with loss of consciousness.
2) Local Anesthesia:
loss of sensation of pain "analgesic" without loss the consciousness.
 Note:-
- If general anesthesia is given in overdose, it will lead to death.
- If local anesthesia given in overdose, it will lead to toxicity.
Firstly; Local Anesthesia: -
MOA: -
- Na+ channel blocker.
i.e. stopping the action potential and stop spreading of impulses in the
nerves.
Clinical use: -
1) Minor operations. -Surface anesthetic.
2) Dental clinic. -Burns. Always mixed with antibiotic, to prevent the infection
- Anal fissure to decrease pain sensation in the anal area.
3) Infiltration:
when the dentist needs to work on one tooth. Injected above the tooth
exactly.
4) Filed block:
inject the anesthetic near to the trunk" nervous network" in the mandible
that anaesthetize the jaw.
5) Spinal anesthesia: in the spinal cord between the 3rd and 4th lumber
vertebrae that used when need an operation in the lower half of the body
"pelvis and lower limbs."
6) IV injection, in case of ventricular arrhythmia.
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Chemical classification of Local Anesthesia: -

Ester local anesthesia Amid local anesthesia
-Contains: -Contains:
Alcohol + carboxylic acid. Amine + carboxylic acid.
-the bond that formed is called Ester And the bond is called Amide bond.
bond. -to breakdown down this bond, it needs
-the ester bond is: - hepatic metabolism, and it is: -
1- Easily hydrolyzed by esterase a. difficult to be hydrolyzed.
enzyme. b. Long duration of action.
2- short duration of action?? Why?
Because esterase enzyme is present in
the blood. It is breakdown when it
reaches the blood.
Ester local anesthesia:
E.g.: -
1. Cocaine. 2. Procaine. 3. Benzocaine. 4. Tetracaine.
1. Cocaine: - "drug of abuse"
- Drug of abuse means stopped to be used in medical, why??
Because it is highly addiction.
- The only one of local anesthesia that can be given as I.V injection, so it
is the most one to cause addiction.
- The only one cause tachycardia " increase HR" and hypertension.
2. Procaine: -
- Short duration of action.
- Vasoconstrictor, so increase the B.P. and cause hypertension.
- Because of its short duration, it does not give any benefits as local
anesthesia, but it gives a benefit when used in combination with
penicillin G, So:-
1- As VC. ➡ It prolongs the action of penicillin.
2- As local anesthesia, it decrease the pain sensation during the
injecting, because penicillin G injection is painful.
- Notes: -
- Penicillin G duration is 6 hours and it’s the only one used parenteral, so it is
compatible to use 4 times/day. But the combination make penicillin duration is
12_hours.
- It doesn’t need to add anesthetic to the combination.
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- This combination is called procaine-penicillin. Used 2 times/day.

3. Benzocaine: -
Clinical use: -
4. Tetracaine: -
- Surface anesthetic or corneal anesthetic.
‫ هم اطباء العيون يحتاجوه لعملية القرنية او في منطقة العين‬Ester L.A. ‫أكثر من يستخدم ال‬
.‫ ﻷن قُصر المفعول مناسب جدا ً لهذه العمليات‬،benzocaine & tetracaine ‫يحتاجوا استخدام ال‬
- Tetracaine has the longest duration of action of ester local anesthesia.
Amide local anesthesia: -

E.g.: -
2- Lidocaine. other names (lignocaine, xylocaine)
3- Bupivacaine. 3- Mepivacaine.
1. Lidocaine: - other names (lignocaine, xylocaine)

- The most commonly used.
- Its duration is 2 hours.
.‫ ﻷنه موجود على شكل بخاخات‬surface ‫ اغلب ما يكون‬-
Note: -
- Any rote of administration that doesn't reach the blood is topical "surface"، and the
systemic is occurred when it's given parenteral injection.
2. Bupivacaine: -
- Longer duration of action than lidocaine. «‫الذي يميز هذا الدواء‬
- ‫اغلب ما يستخدم في العمليات الكبرى‬
- More cardio-toxicity than lidocaine. i.e side effects of bupivacaine on
CVS are more than lidocaine side effects.
- Pharmaceutical preparation for all amid local anesthesia is gel,
parenteral, or .‫بخاخ‬
- Prefered as spinal anesthesia.
3. Mepivacaine: -
- The same characteristics of lidocaine.
- Faster than lidocaine in onset of action.
Notes: -
- Onset of action means when the action of drug start appearing.
- Duration of action means the whole time of action of the drug.
- Amide L. A. are used more than Ester L. A.
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Side effect of Local anesthesia: - (mainly with Amid local anesthesia)

1. Paresthesia "appear strongly with using Amid local anesthesia.
‫ ﻻ تشرب؟؟ ليش؟؟‬،‫ يقول لك ﻻ تأكل‬،‫لذلك دائما ً عند الخروج من عند طبيب اﻻسنان‬
.‫ لكل اﻻعصاب متخدر وتحس الفك ثقيل وكمان كبير في الحجم‬sensation ‫ﻷنه الـ‬
Duration of paresthesia is the same as drug duration.
 Lidocaine containing Adrenaline:
Adrenaline is a vasoconstrictor that cause three things: -
i. Prolonged the duration of action. .‫ممكن يتجاوز الساعتين‬
ii. Decrease the bleeding.
iii. Prevent (the hypotension that caused by using Lidocaine) by
causing hypertension.
And hypotension with hypertension lead to normal blood pressure.
Preventing the systemic S.E of lidocaine by preventing it from escaping to the blood
2. Hypotension,
"if this S. E occurred, give the patient Adrenaline as best choice."
The first systemic side effect appeared is hypotension.
3. Bradycardia,
"if this S. E. occurred, give the patient Atropine as best choice."
4. Convulsion, "when dentists have a patient with epilepsy, they warning him to
take his drug of epilepsy before coming to them, because lidocaine make the
seizures appear strongly. If this S. E occurred, diazepam is the the best to use,
because it's Skeletal muscle relaxant.
5. Metabolic acidosis, Why?? Because of the main components of either ester or
amid is carboxylic acid.
- Amid carboxylic amid.
- Ester carboxylic alcohol.
And because of breaking down of the local anesthetic " especially if taken by a
large dose, acidosis appears in the blood. This S. E. is treated by NaHco3.
6. Methemoglobinemia,
Because of lidocaine oxidases the Fe 2 to Fe 3 and this molecule can't carry the
oxygen.
- Its symptoms are: -
. Cellular hypoxia.
. Cyanosis.
Treating the methemoglobinemia by methylene blue or Vit. C/ ascorbic acid.
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Q. The local anesthetic makes losing the sensation of pain, What is the order of
losing the pain?
 Order of losing pain starts by losing the severe pain.
Sever pain mild pain temperature pressure touch
motor function.
pressure ‫ فبيكتفوا لعند الـ‬touch‫وعادة ً ما يوصلش اﻻطباء في التخدير الموضعي الى مرحلة الـ‬
.‫وبس‬
Secondly, General Anesthesia: -

Def. control temporary loss of sensation with loss of conscious which induced
for medical purposes.
 Stages that patient get in under effect of the general anesthesia:
- Analgesia: First step that patient go on under analgesic effect.
- Exciation for second.
- General anesthesia ‫وتتمثل في ال مراحل التالية‬: -
Muscle relaxation: It differ by the differentiation of the drug that used.
(some drug has weak and some are potent.)
Amnesia: patient didn't remember any thing happened at the time of
surgery.
- Surgical anesthesia: How doctors know that the patient enters this step?
Patients will loss of the response to light test on the eye.
No movement of the eye (no responding), and can't talk because the
movement change from voluntary to involuntary.
- Medullary paralysis, If the dosage increased.

Medullary paralysis is dangerous level that affect the medulla and lead to
respiratory arrest and heart arrest. So, the level that doctor achieved is the
surgical anesthesia.
Note:
- All the anesthetic drugs that used in surgical anesthesia are combination of
multi-drugs? Because any combination is more effective and less side effect.
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 Classification of general anesthesia according to the rout of administration: -

I.V general anesthesia Inhaled general anesthesia
 Efficacy of this group:-  Efficacy of this group:-
- Rapid onset: means the patients - Slow induction (if compered with
get anesthetized fast within the IVGA,) but in fact it has fast
seconds,(maximum 30 sec.) induction.
- Rapid induction: the onset when - Its onset is from 15-30 min.
the action start. If compered with IVGA, it's too
- Short duration: the maximum slow.
duration of action is (45 min. this - Slow recovery which means it has
duration just for one type of IV long duration of action.
general anesthesia.  Used for maintenance of the
- Rapid recovery: end of the anesthetic action.
duration of action is fast. ‫ ﻻنهم افيش عملية تستمر‬،‫يحافظ على التخدير‬
 Used for induction of anesthesia, ‫ الدقيقة يادوب‬٣٠‫ ال‬،‫ دقيقة‬١٥ ‫دقيقة او‬٣٠
.‫يعني إحداث التخدير‬ ‫ لذلك ﻻزم يكون هناك فترة‬.‫يجهزوا المريض فيها‬
.‫على اﻷقل من ساعة الى ساعتين‬
IV general anesthesia: - Just the most commonly used
Ex.: -
- Thiopentone. - Propofol. - Ketamine. - Short acting BDZ.(Midazolam)
Thiopentone and Propofol have the same MOA → GABA agonist.
Note about GABA:-
- GABA is the inhibitory neurotransmitter in the CNS, and has receptor on the
CNS called GABA receptor.
- Stimulation these receptors will lead to inhibition in the CNS.
i.e. lead to (sedation, muscle relaxation, respiratory depression, and
cardiovascular depression.) everything in CNS inhibited.
- The receptors have dependence effect (has physical dependence)
- The action of GABA depends on Cl+ channels. When these channels stimulated,
they lead to open the channel and a lot of Cl+ enters leading to
hyperpolarization.
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1- Thiopentone: -
- Is one of the Barbiturate family, and this family are: -
A) More toxic group, but they are more effective.
B) High incidence of dependence.
C) Duration: - is short, the maximum is 15 min. and the onset is 30 seconds.
Side effect: -
- Lead to severe respiratory and CVS depression. - Dependence
2- Propofol: -
- Is less toxic than thiopentone.
- The most commonly used of IV general anesthesia.
- Has anti-emetic effect. (Because during stages of anesthesia, there is induction
of the vomiting.) But under using this drug, it prevents or stope the emetic
effect.
- Duration is 30 min, but they don't use it alone in general anesthetic.
Note: -
- All the drugs of general anesthesia have induction of emetic effect except Propofol.
3- Ketamine: - called (Dissociative anesthetic)

- Called dissociative anesthesia because the patient dissociate from the
environment around him.
‫ قاموا بالحد من استخدام هذا الدواء ﻷن المريض بعد العملية‬.‫ويبدأ يدخل المريض في عالم من الخيال‬
.Diazepam ‫ وما يخرج منها إﻻ بعد إعطائه‬،‫يدخل في هلوسه مزعجة‬
Used IV. So, rapid onset 30 second.
Duration: 45 min.
Suitable for children.
MOA: -
- Inhibition the glutamic acid, (the excitatory neurotransmitter in the CNS.
Note: -
 The excitatory neurotransmitter of CNS are glutamate and aspartate.
And the affective part of them is the glycine.
Side effect: -
A) Increase the blood pressure and increase the heart rate. ( tachycardia).
The only one of IVGA that lead to hypertension and tachycardia.
B) Post. Operative hallucination.
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Contraindication: -
C) In CVS disease.
A patient with hypertension, angina, arrhythmia, and heart failure,
‫ ضروري يكون المريض عنده اقل شي‬،‫ وما يجيش واحد مرض هكذا لوحده‬،‫ﻻن امراض القلب متداخلة‬
.CVS diseases ‫نوعين من ال‬
4- Short acting Benzodiazepine (BDZ): -

(ex. Midazolam)
- Duration: - 3-4hours. And onset 30 seconds.
- Not commonly used, but it still one of the General Anesthetic that can be used,
but with other anesthetic drugs not alone.
- Used pre and during anesthesia.
- Not used for induction for anesthesia.
‫ يعتبر كدواء مساعد في عملية التخدير‬-
MOA: -
GABA agonist that leading to:
- Respiratory and CVS depression and dependence.
- Skeletal muscle relaxation.
 Notes: -
 All the BDZ are hypnotic, but the short acting BDZ are the only used
in anesthesia.
 It can be used in insomnia.
 If the anesthesia done by multi-drugs, it will be safer and more
effective by the synergistic effect.
 And when anesthesia done by one drug, it will be riskier, because here
more side effect are present, and patient may enters in coma and
medullary paralysis.
Ex. If the doctors need to do an operation for long time, they use
propofol and midazolam.
 Midazolam gives hypnotic effect and enhance the propofol action.
 Most cases that have medullary paralysis are cases of caesarean,
because they depend on one anesthetic drug and patient may not
anesthetized and doctors will increase the dosage of anesthetic drug
and that will lead to medullary paralysis.
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MOA of inhaled G.A. is inhibit the CNS by acting as the
Inhaled general anesthesia: - GABA neurotransmitter, but not on the GABA receptor
Gas volatile liquid

 Ex. N2O = Nitrous oxide. - Means that liquid changes to gas
- Should be combined with O2 as (30 under high pressure.
"N2O": 70 "O2")
That's why it causes incomplete
anesthesia
- May lead to Hypoxia
- Skeletal muscle relaxation "laughing
gas"
It's called laughing because it relaxes all Note: -
the muscles of the face. All the dentistry All the general anesthesia IV or
knows this drug, and they are the most inhaled lead to respiratory depression
who use it. and that means it's S.E in all G.A
- No effect on uterus, so commonly used
drugs, except ketamine
in obstetric and clinical dentist.
- Strong sedative, analgesic and amnesic
drug.
 Volatile liquid: - ( chemically Halogenated compounds.)
- Halogenated compound means it has in its chemical structure ( fluorides,
chlorides, and bromides ) in high concentration, and that explain the hepatotoxicity
and nephrotoxicity.
E.g.: -
1. Halothane. 2. Methoxyflurane. 3. Enflurane.
1. Halothane: - (most commonly used)
- This drug has all the halogens in its structure in high concentration, and that
make the suitable environment for hepatic failure.
- The strongest drug to cause hepatotoxicity, ‫وذلك ﻻنه اكثر مركب مجمع فيه‬
.‫الهالوجينات‬
and they call the case autoimmune hepatotoxicity because
.‫بحيث انه يلخبط الجهاز المناعي ويخليه يهاجم الكبد بواسطة آلية مجهولة‬
- Weak skeletal muscle relaxant.
- Affect uterus, so contraindicated in pregnancy and obstetrics.
- Safe in asthmatic patients, because it causes bronchodilatation.
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2. Methoxyflurane: -
- Potent\strong skeletal muscle relaxant.
- Respiratory irritation. “dry cough”
- No effect on uterus, → so used in obstetrics.
- Nephrotoxic. Affect the filtration rate and the tubule. Because it's excreted by
kidney. ‫وهذا العرض نادر حدوثه إﻻ مع اﻻشخاص المريضة من قبل‬
Note: -
o drugs that used in obstetric are Methoxyflurane and Nitrous oxide (N2O).
3. Enflurane, Isoflurone - (uterus relaxation)
- Skeletal muscle relaxation.
- Respiratory irritation. “dry cough”
- Affect Uterus.
- Nephrotoxic.
- Contraindicated in epilepsy, because rate of seizure increases with using this
drug. (Drug-Drug interaction).
In this case the patient of epilepsy anesthetized by Halothane.
Note: -
o All general anesthesia lead respiratory and CVS depression (↓BP and ↓HR) with
one exception the Ketamine that ↑ BP. And ↑ HR.
o Halothane cause autoimmune hepatitis.
o Methoxyflurane cause Nephrotoxicity.
o Isoflurane, Enflurane increase the seizures.
o N2O cause hypoxia with megaloblastic anemia, but in chronic use or exposure “in
medical staff”.
Preparation of patient for surgery:
- Do all the lab tests and X-ray, and examine all the vital signs.
- Fasting and sometimes if the surgery in GIT they give the patient Laxative.
- Preanesthetic medication: -
 They are three medication, the first two are the most common used and the
last one in some cases is not used.
1. Antianxiety: -Ex. Diazepam, and that because
Diazepam has long duration. And given to patient before surgery by one day.
2. Atropine: -
- Given (1-2) hours before operation → to decrease mucous and saliva
secretion.
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- If the operation need longer time than Atropine action the replace the
atropine by hyoscine.
- Hyoscine also has a characteristic better than atropine that is hyoscine is
sedative more than atropine.
3. Skeletal muscle relaxant: -
- E.g. Succinylcholine “most common” and Dantrolene
→ because it's specialized acting on nicotinic receptor that present in
skeletal muscle.
- Dantrolene more effect in muscle spasm.
- This drug used just with patient severe from seizures “ epileptic patient”.
- Antibiotic use after operation Not before but in Yemen used before
because sterilization is not correct.
 Antibiotics used after operation like Cephalosporines, monobactum, Carbapenm
and in abdominal surgery we add Aminoglucosides “gentamycin, amikacine”
because most infection in hospitals are by psudomonas. So we use these anibiotics.
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Anti-Epileptic Drugs
Definition of epilepsy: -
Neurological disorder that patient characterized by sudden recurrent episodes of
sensory disturbance, loss of consciousness and convulsion which are result from
abnormal electrical activity in brain.
Types of epilepsy: -
1. Focal: - (partial seizure)
- defect on one side (hemisphere) of the brain ‫خلل في احد شقي الدماغ‬
- If the defect occurs on the right side, the symptoms will appear on the left
side of the body, and VICE VERSA. ‫ﻻ يشمل الدماغ بالكامل‬
- It's known by the partial seizure.
- Subtypes of it: -
Simple and complex.
- There is no difference in the treatment but there is a difference in the
symptoms.
- General symptoms of both subtypes: -
a) Muscle jerk (Twitching). .‫في العضﻼت‬Tremors ‫زي ال‬
b) Convulsions to a certain part of the body.
c) Simple Complex
No loss of consciousness loss of consciousness
DOC in this case is Carbamazepine___ _______
______ 2nd line is Lamotrigene___ ____________
2. Non-focal: - (Generalized Seizure.)

Defect in the electrical charges throughout the brain.
.‫الخلل حاصل في كل شحنات الدماغ بشكل عام‬
The Generalized Seizure subdivided to :
1. Grand mal = tonic clonic seizure
 Firstly increased tonicity (rigidity) then severe convulsions within
seconds. And progress to status epilepticus.
 Occurs in adults.
 The most common type.
 Loss of consciousness.
 Convulsions.
_______DOC is Na+ valproic acid (sodium valproate)_______
2nd line is Carbamazepine or Lamotrigene__ _______
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2. Myoclonic seizure: - Myo = muscle

 Occurs in the skeletal muscle, especially that of the upper limb.
 Muscle twitching without loss of consciousness.
 Age: - from 10-18 years old.
 Symptoms usually occur early in the morning.
 Considered as genetic disorder.
_______DOC is Na+ valproic acid (sodium valproate)_______
___ 2nd line is Clonazepine _______
 Myoclonic seizure can be easily misdiagnosed as partial seizures.
The mistake in diagnosis appears to us once we begin treatment,
because the myoclonic seizures are treated by Valproic acid but if
Carbamazepine is used instead… there will be a huge
deterioration in the patient health, symptoms will increase → there
will be loss of consciousness and more severe convulsions.
3. Petit mal: -
 Absence of seizure.
 Occur more commonly in girls more than boys (2:1) at age (3-10 years)
 no convulsion.
 The patient come with staring ‫( متّنح او محدق‬loss of consciousness)
‫ بعد ما يفوق المريض من هذه الفصله ويسألوه وهو ما يعرف بشيء ﻻ قبلها وﻻ بعدها‬،‫يفصل لمدة ثواني‬
‫ مع انها ﻻ تتجاوز نصف دقيقة )قصيرة( لكن مشكلة هذه الحالة انها تتكرر‬loss of conscious ‫فيعتبروها هنا‬
.‫ مرة في اليوم الواحد‬١٥ ‫كثيرا ً قد تصل الى‬
 High recurrence rate.
 Good prognosis→ is completely cured.
 90-95% of the time if treated in childhood, there will be a complete
escape of symptoms as soon as they hit puberty.
 But any disturbance in treatment during childhood will decrease the
prognosis.
 The epilepsy with the best prognosis is petit mal.
_______DOC in Young is Ethosuximide _______
___2nd line in young child & DOC in Adult is Na+ valproic acid____
 Pharmacology of 1st line treatment: -

1. Epilepsy is treated as a chronic disease. So → rout of administration is →Orally.
2. Target of drug use: - (decreasing frequency and duration of seizures)
- Producing longer interval between seizures.
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E.g. from 1 min. between seizures,

to 3 min. between seizures.
- Then we try to have the seizure disappear completely. (patient is free of
epileptic symptoms). This depends on: -
A) Patient's response to the treatment. ‫استجابة المريض‬
B) Obligation of the patient to the drugs and treatment course.
.‫التزام المريض بالدواء والدفعات العﻼجية‬
1) Carbamazepine: -
MOA: -
- Central Na+ channel blocker.
Inhibits the propagation of electrical charges in the brain.
Uses: -
- DOC for partial seizure.
- Neurological pain. (trigeminal neuralgia)
- DOC in epileptic pregnant female.
- Due to its NO or Low teratogenic effect. → but before the treatment, the patient
MUST take folic acid to decrease the chance of teratogenicity.
- 2nd line treatment for grandmal seizures.
Notes: -
In general, the drug may cause the same effect, but in order for it to help in
treatment, it must have the exact specificity needed.
E.g. we can't use Lidocaine to treat epilepsy, because: -
o It doesn't cross the BBB.
o Lidocaine has different uses → used topically. If it was used
systemically, it would have caused bradycardia → death.
Side effects: -
1. Water intoxication. ←‫اهم نقطة ﻻزم نعرفها وانها تميز هذا الدواء عن غيره هو‬
‫ أي انه زادت كمية الماء في الدم وهذا سوف يؤدي الى‬-
Hyponatremia.
Any drug causes hyponatremia will cause water intoxication. Due to an ↑ in
ADH.
2. Metabolic inducer →↓efficacy of other drugs; e.g.: -
- Active drug as warfarin → ↓efficacy.
- Prodrugs as clopidogrel → ↑toxicity.
Metabolic inducer means → ‫ تقل فعاليته مع أي دواء‬active drug ‫أي دواء‬
toxicity‫ وممكن يصل للـ‬active ‫ اﻻنزيمات النشطة ستحفز تحويلة الى‬prodrug ‫وأي‬
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3. Ataxia = .‫ أي انه ﻻ يستطيع المشي في خط مستقيم‬،‫الترنح‬

Inability to coordinate muscle movement.
4. Sedation.
5. Osteoporosis "in long term of use → more with elderly.
Carbamazepine→↑degradation of vit. D to inactive form, may progress to
secondary hyperparathyroidism.
2) Valproic acid : - "orally" always gives as salt Na valproate,, Now gives as
acid. .‫وليس كحمض‬Sodium valproate ‫الدواء محضر بالصورة الملحية‬
MOA: -
- Na+ and Ca+2 channels blocker.
- And some books added another MOA (inhibition of GABA transaminase)
‫ لذلك عند تثبيطه سوف‬GABA neurotransmitter ‫وهذا هو اﻻنزيم المسؤول عن تكسير ال‬
.‫ هذه اﻵلية غير مذكورة في كتب الفارما‬.‫ في الجسم‬GABA‫تزداد كمية ال‬
Clinical Uses: -
- DOC in All types of generalized seizure. with one exception (when the
patient is child and the type is petit mal, the child treated by ethosuximide.
- But adults petit mal are treated by valproic acid.
Side effects: -
1. Hepatotoxicity, ‫اكثر واهم عرض جانبي هو هذا‬
.‫ ﻻزم عمل فحص ﻹنزيمات الكبد‬،‫لذلك قبل البدء بالمعالجة واثناء المعالجة‬Liver function test
2. Sedation
3. GIT disturbances. (vomiting, nausea, diarrhea)
4. Teratogenic. (spina bifida), so it's contraindicated in pregnancy.
.ً‫ وإذا عاش يكون مشلول أو متخلف عقليا‬،‫وهذا الطفل ﻻيعيش‬
carbamazepine + folic acid ‫المفروض قبل التخطيط للحمل تأخذ‬
5. Alopecia.
3) Ethosuximide: - "orally"
MOA: -
- Central Ca+2 channel blocker. "inhibits propagation of electrical charges in
the brain"
Clinical Uses : -
- Only in Petit mal. "absence seizures" in young age. "1st line of treatment"
Side effects: -
1. The main S.E is GIT disturbances (nausea, vomiting, diarrhea, and
Abdominal cramps.
most → 2. Loss of appetite, and weight loss. .‫وﻷنه في اﻷطفال لذلك بيراقبوا الوزن بشكل دقيق‬
important S.E 3. Sedation. .‫حالة خمول شديدة في الطفل‬
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 Pharmacology of 2nd line treatment: - Or The Adjuvant therapy: -

2nd line treatment, as a replacement of the 1st line by another drug.
Adjuvant,→ (synergistic effect ←‫ عندما اشتي احافظ على العﻼج بس يحتاج‬-)
1) Lamotrigine: -"orally"
- The most important one as adjuvant and 2nd line.
Clinical Uses : -
- All types of epilepsy, generalized and partial.
MOA : -
- Na+ and Ca+2 channel blocker.
Side effects : -
1. The main side effect is Hypersensitivity and Skin rash.
2. GIT disturbances.
3. Sedation.
2) Clonazepam: - (one of Benzodiazepine)

MOA : -
- GABA agonist,
Epilepsy‫ لذلك استخدم في ال‬skeletal muscle relaxant ‫ استخدم هنا ﻻن لديه خاصية قوية في ال‬-
Clinical Uses : -
- Generalized seizure.
Side effects : -
1. Respiratory depression.
2. CVS depression.
3. Dependence.
3) Vigabatrin: -"orally"
Clinical Uses : -
- Used in generalized seizure. (adjuvant therapy)
MOA : -
- Inhibits the GABA transaminase, which leads to increase the GABA
neurotransmitter.
Side effects : -
- Sedation (in all drugs that cause increasing in GABA.)
- Retinal damage → irreversible visual loos ←‫هذا العرض الجانبي الذي يميز هذا الدواء‬
‫ وعندما تبدأ اﻻعراض‬retinal ‫عند بدء استخدام العﻼج واثناء اﻻستخدام ايضا ً نعمل فحص لل‬
irreversible visual damage .‫بالظهور على العين نوقف العﻼج ﻷنها قد تسبب‬
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4) Topiramate: -
MOA : -
- CAI.(carbonic anhydrase inhibiter.) PCT.in kidney, eye and brain ‫موجود في ال‬
"The same as acetazolamide and dorzolamide" - Dorzolamide → glaucoma
- Na+ and Ca+2 channel blocker. - Acetazolamide → for motion
Clinical Uses : - sickness, glaucoma and
- In Generalized seizure. "adjuvant therapy" ↑↑ICP with mannitol.
Side effects : -
- Sedation and dizziness.
- GIT disturbances, weight loss.
- Renal stones. ←‫الذي يميزه‬
- Hyperthermia.
5) Gabapentin: -
MOA : -
- Analogue of GABA. GABA ‫يعني مشابه او نظير لل‬
Clinical Uses : -
- Used for neuropathic pain.
- Diabetic neuropathy.
- NOT USED in epilepsy.
‫ ولكن بعد ذلك اكتشفوا انه ﻻ يُظهر أي نتيجة إﻻ عند‬،‫ اول ما اكتشف هذا العﻼج كان يستخدم للصرع‬-
.‫ أفضل‬neuropathic pain ‫ ووجدوا ان استخدامه لل‬،‫استخدامه بجرعات عالية‬
Side effects : -
- Sedation.
- Dizziness/ Drowsiness.
- Headache.
- GIT disturbances.
6) Pregabalin: - (was used in epilepsy →(not anymore))

The same as gabapentin, but the different is in the MOA.
Excreted unchanged via kidney 90% →dose adjustment (renal failure)
MOA : -
1- Inhibits the excitatory neurotransmitters release.
2- Inhibits Ca++ channel.
Clinical Uses : -
- Neuropathic pain.
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Side effects : -
1- Sedation.
2- Dizziness / Drowsiness.
3- Headache.
4- GIT disturbances.
7) Phenytoin: -
MOA: -
- Na+ channel blocker.
Clinical use: -
- 2nd line treatment of status epilepticus by I.V injection.
Side effects of phenytoin : -
- Sedation.
- Low therapeutic index. "degree of safety"
‫ فالمريض لو‬،‫ عندما يكون الفارق ما بين الجرعة السامة والجرعة العﻼجية منخفض‬،‫الدليل العﻼجي‬
.toxicity ‫يأخذ نص او ربع حبة زيادة سوف يحصل له‬
- Ataxia, ‫الترنح‬
- Nystagmus. .‫الرأرأة او الحركة الﻼإرادية لجفون العين او إنسان العين‬
- Teratogenic. (cleft lip, and ‫) تغير تصبغ اﻻظافر‬
- Gingival hyperplasia."by ↑ing expression of platelet derived growth factor
PDGF"
- Metabolic inducer.
- Blurred vision.
- Osteoporosis. "in long term of use"
- Hypopigmentation of nail.
- Hirsutism.
Important NOTES: -
1. Drugs used for epilepsy in Pregnant women and Lactating women: -
↓DOC ↓DOC
ST
DOC is →→→→ 1 line Carbamazepine Lamotrigine
nd
2 line Lamotrigine Doesn't have secreting in milk.
- Before decide getting pregnant, the epileptic women should be administrated
5 mg of folic acid with carbamazepine.
‫ مع‬teratogenicity ‫ وذلك عشان يضمنوا انه ما تحصل‬،‫تبدأ بشرب الفوليك اسيد من قبل الحمل‬
folic acid ‫ ومن بعد ذلك تواصل استخدام ال‬،‫ اثناء الحمل‬carbamazepine ‫استخدام الـ‬
.carbamazepine ‫وال‬
- Teratogenicity in the first 3 months is anatomical defect.
- Teratogenicity in the second 3 months is functional defect.
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and the anatomical defect is more dangerous than the functional defect.
- What is the cause of the functional teratogenicity ?
o ACBI.
2. Anti-epileptic ‫متى يتوقف المريض عن ادوية الـ‬
To stop antiepileptic drugs: -
- Patient should be free of symptoms for two years.
- Then start gradual decrease of the dosage over 2-3 moths.
‫ يجب على المريض إعادة استخدام الدواء مرة‬،‫ اشهر‬٣-٢ ‫ إذا ظهرت اﻻعراض خﻼل هذه‬-
.‫أخرى‬
gradual decrease‫ ﻻبد من اﻹيقاف بـ‬،‫ ﻻنوقفها فجأة‬CNS ‫ كل ادوية الـ‬/‫ مﻼحظة‬-
3. In acute epilepsy (Status epilepticus) -
- Called Status epilepticus →→ Symptoms persists for complication of grand
mal.
‫ او اﻻعراض ﻷكثر من‬convulsion ‫ عندما تستمر ال‬status epilepticus ‫ نسمي هذه الحالة‬-
‫ الدقيقة هذه كافية لتقليل الكسجين عن‬٢٠‫ ﻻن ال‬emergency ‫ هنا الحالة تتحول الى‬،‫ دقيقة‬٣٠-٢٠
.brain damage ‫الدماغ فيحدث‬
 Before treatment: -
- 1st step is checking ABC ( airway, breathing, and circulation.)
- Remember DEFG (don't ever forget glucose).
 Treatment: - (anti-convulsion drugs)

 Medication;
o 1st line is BDZ. E.g. Lorazepam. (intermediate acting) effect on
80% of patients.
‫ مالم ننتقل للخطوة‬.‫ إن تحسن المريض تمام‬،‫ دقائق‬١٠ ‫الخطوة العﻼجية اﻷولى الفارق الزمني فيها‬
(Long acting) .Diazepam ‫العﻼجية الثانية والتي هي‬
- If symptoms still persists for 10 min. give the patient diazepam.
- Then if symptoms still persists for 10 min. →start 2nd line treatment.
o 2nd line treatment: -
- Phenytoin or Fosphenytoin (phenytoin prodrug for 10 min).
(IV Or IM parenteral)
Prodrug means it will change to active form in the body.
- :‫ بـ‬phenytoin ‫ عن ال‬Fosphenytoin ‫ يتميز ال‬-
1- Preferred more.
2- More effect.
3- Less toxic.
4- can be injected 3X faster than phenytoin.
- Phenobarbitone→ is NEVER used anymore.
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o If the 2nd line treatment doesn't effect and symptoms still persist for 10 min.
we should use the 3rd line treatment: -
- The patient has to get into the intensive care and start illegal drugs of IV.
General anesthesia, like Propofol.
Other NOTES: -
- In the chronic epilepsy, the old books said phenytoin is the 1st line for all types
of epilepsy, but because its side effect the stop using it and the new books
replace the phenytoin by carbamazepine.
- And the carbamazepine can be replaced by valproic acid and vice versa.
The new protocol of treatment of neuropathy :-
1\ duloxetine.
2\ tricyclic anti-depression.
3\ pregabalin.
4\ gabapentin.
Opioid Analgesics
Analgesics means drug relieve pain and divided to opioid analgesic and non-opioid
analgesics. The opioid analgesic are working on the CNS.
One of characters of opioid is inducing dependence and addiction.
Non-opioid analgesic are not working on CNS and they don't lead to addiction or
dependence.
It classified chemically to steroidal analgesic (explained in hormones), and non-
steroidal that works on the mediators that present in blood, like (prostaglandin)
 Opioid Analgesics: -
Def: -
Drugs relieve pain or decrease sensation of pain but may induce addiction.
Classification: -
Classified according to sources: -
 Natural= Opiates (from  Synthetic = Opioid.

plants) - Low induction of addiction,
- Induction of addiction is high. and we can do withdrawal fast.
- High analgesic effect. - High analgesic effect.
- More active on CNS - More selective on organs
E.g. GIT
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 Firstly: - Natural= Opiates(from plants)

MOA: -
- Stimulate the opioid receptors: -
The opioid receptors are three: -
1) μ = Mu.
2) δ = delta. Analgesic effect
3) κ = kappa.
Also other actions of Kappa is dependance, Euphoria, dysphoria, and
miosis effect.
Notes: -
 μ is the most spread and responsible for most of the pharmacological action.
Pharmacological action of μ (Mu): -

 Analgesic effect.
 Induction dependence and then it change to addiction.
 Miosis. ‫تضييق حدقة العين‬
 Decrease the intestinal motility, so will lead to constipation.
 Bronchoconstriction.
 Release of histamine, allergy. (not hypersensitivity).
 Contraction of smooth muscle of (Uterus, Renal system, and biliary system)
 Euphoria.
 Suppress coughing center in the CNS.
 Stimulation of chemoreceptor trigger zone. → (lead to nausea and vomiting)
 On the Heart → stimulation of μ in the heart lead to vagal stimulation →
then lead to → decrease blood pressure, and decrease heart rate
(Bradycardia).
 Sedative
Notes: -
- There's no vasodilatation with bradycardia except when the drug affect the
CNS.
- Vasodilatation is usually associated with tachycardia.
- Also releasing histamine enhance the vasodilatation leading to hypotension,
also release of histamine will lead to bronchoconstriction and allergy.
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E.g. of Natural (opiate) drugs: -

1. Morphine. 2. Codeine. 3. Heroin.
1) Morphine: -
- Natural drug.
- Highly analgesic effect.
- High induction of addiction.(strong)
- Availible for patient use only in the hospital for severe pain and
emergency
 Rout of administration: -
o Orally → has low bioavailability ≈ (25%).
،ً‫ ووصوله الى الدم ضعيف جدا‬GIT ‫أي ان امتصاصه من الـ‬
first pass metabolism ‫وهذا بسبب الـ‬
o Parenteral → the preferred rout of administration.
 Used in: -
 Post operative analgesia.
 Severe pain → E.g. (cancer, MI, fractures)
.‫وخصوصا ً الذي عندهم كسور في العمود الفقري‬
2) Codeine: -
- Bioavailability (60%)
- Analgesic effect = 1 7 Morphine, so it is weak analgesic.
‫ لكن المريض‬dependence addiction ‫ يعني سوف يقل نسبة الـ‬analgesic ‫ ما دام نقص الـ‬-
. addiction ‫ ممكن يتحول الى‬therapeutic dose ‫ يعني اعلى من الـ‬،high dose ‫آخذ‬
.addiction‫ ﻻن الصافي كان يؤخذ لهدف الـ‬،‫ في السابق منفصل كمشروب‬codeine ‫ كان الـ‬-
‫مل سوف يصل‬٥٠ ‫مل ولكن لو أخذ‬١٠ ‫مل واﻻستخدام هو‬٥٠٠ ‫ﻷنه مثﻼً القارورة تحتوي‬
.morphine ‫ كمفعوله في الـ‬،addiction ‫مفعول ال‬
‫ حتظهر عليه‬high dose‫ عشان لو أخذه بـ‬sympathomimetic‫ اﻻن اصبح مخلوط مع الـ‬-
.‫ بسرعة‬toxocity‫الـ‬
 MOA: -
- Inhibits/depresses cough center in the CNS
 Clinical Uses : -
- Antitussive. Which means it used for dry cough.
Notes: -
- Any drug used to inhibit the cough center in CNS is called antitussive.
3) Heroin: - “Drug of Abuse”
- Induces addiction 20 times more than morphine.
- Strong analgesic.
.addict ‫ إذا عيتحول المريض الى‬analgesic‫ لكن ايش الفائدة من ال‬-
.ً‫ُمنع من اﻻستخدام نهائيا‬ -
.synthetic ‫ في الكتب المصرية يعتبروه‬-
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Notes:-
- Stimulation of Mu receptor in uterus by opioid causes:-
o In Early months of pregnancy, it cause abortion.
o In Late months of pregnancy, it cause embryo-toxic reaction. “reach to
fetus and lead to CVS and respiratory depression”
- Any drug used to inhibit the cough center in CNS is called antitussive.
 Secondly: - Synthetic = Opioids
- Pethidine. - Methadone. - Fentanyl. - Tramadol.
- Dextromethorphan. - Diphenoxylate. - Loperamide
1) Pethidine = Meperidine
- Synthetic, acts on Mu (μ), but it's more selective on the analgesic effect more
than induction of addiction.
- Post-operative analgesic, "Parenteral"
2) Methadone "orally"
- For Mild to Moderate pain
- For treatment of addiction, gradual replacement of the addicted drug.
How??
If the patient may take 100mg of morphine or heroin, they have to
decrease it to ≈ 95mg and add methadone by 5mg, then after week or
two weeks they decrease the morphine to 90mg and increase the
methadone until decrease the morphine up to 0 and the methadone
usage become 100mg.
 Why the patient can't stop the addicted drug?
Because it cause withdrawal symptoms.
 But the methadone doesn't cause withdrawal symptoms, because it
has long duration of action (long T half) and the second dose coms
while the methadone action still effect.
.‫ بيحطوها للمريض بين العصير ويشربها بدون ما يحس وعاده بيكونوا المراض في المستشفى‬
3) Fentanyl (Rapid onset and short durationofaction): -
o Used IV injection with general anesthesia in cases of Neuroleptic
anesthetic (analgesia)
Analgesia means if there a neuro surgery the patient should take analgesia
and usually the analgesia that used is Fentanyl.
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4) Tramadol: -
- Orally: (Most common in medical use)
- Parentally:
o Induces weak opioid analgesic (Its much weaker on opioid receptors
in comparison with other synthetic analgesics)
o Inhibits reuptake of Serotonin and Noradrenaline.
o NOW It's mainly used as a post-operative analgesic.
o Although this is a weak opioid analgesic, but that doesn’t prevent it
from causing dependence; but won't reach the level of addiction and
stopping it doesn't need another drug to replace it.
o If any another pain presents, other analgesics doesn't effect because
the patient get-used with using tramadol. But this drug doesn't need
replacement treatment.
o Withdrawal from this drug doesn’t occur.
5) Dextromethorphan
o Anti-tussive (used to replace Codeine)
o Selective mainly on cough center.
o Very weak analgesic effect.
6) Diphenoxylate
7) Loperamide
- 6 and 7 selective on GIT (used as anti-diarrheal drug)
- Loperamide is the most commonly used.
And in diarrhea if the patient has (irritable bowel disease or diabetic patient).
- Most commonly used to treat non-infectious diarrhea.
 Side effects : -
1. Hypotension & ↓BP. Due to V.D Types of Anaphylactic shock: -
2. Tachycardia & ↑HR.
3. Bronchoconstriction. 1. Anaphylactic shock
4. Miosis. IgE + Mast cells → releasing
5. Urine retention. Histamine.
6. Constipation.
7. Biliary colic. 2. Anaphylactoid shock
8. Nausea and vomiting. Drugs + Mast cells →releasing
9. Anaphylactoid shock. Without Histamine.
production of IgE.
10. Euphoria then dysphoria (anxiety – insomnia).
11. Sedation.
12. Dependence + addiction.
@medical_subjects_summary ٤٠ t.me/medical_subjects_summary
Notes:
- Tolerande occurs often with synthetic drugs before dependance occurs and
doesn't lead to addiction like in the medical aspect dextromethorphen
- the patient responds to ٥mg of dextramethrphen, if the patient develops a
cough again he will need ١٠mg tolerance and if the drug isn't changed it will
lead to dependance
- if the patient develops tolerance from a certain drugs (antitenssive) changing
the drug is the best option
There are Opioid agonists and antagonists

Opioid antagonists are the antidotes to treat toxicity caused by overdose of opioid
agonists.
Opioid receptor antagonist: -  Another drug used to prevent relapse is

1. Naloxone (Parenteral): - Clonidine
- Antidote for morphine over dose.  Which is alpha 2 agonist, and
stimulator of imidazole receptor that
Not just an antidote for morphine;
present in the GABA receptor that
but for all opioid analgesics. cause sedation and prevent dependence.
- Diagnosis of addiction.  also used to treat of drug withdrawal
(hospitalized) syndrome
2. Naltrexone (Orally): -
- Used to prevent relapse.
Relapse means: the return to addiction. So, this drug would be used for the
rest of the patient life.
 For treatment of addiction:
1. Replace Morphine with Methadone gradually
2. Then Replace Methadone by Diazepam.
3. Replace Diazepam with SSRI anti-depressants
4. SSRI (start replacement after 2 weeks from beginning with antidepressants
SSRI).
- Begin by using SSRI and Diazepam for 2 weeks then after 2 weeks, begin to
decrease Diazepam gradually (NOT AT ONCE) and this should be done
throughout 1-3 months.
- Then continue on the Anti-depressants for another 2 weeks until the patient
is stable.
5. Patients should use either Naltrexone (if addicted to opioid) or
Clonidine (if addicted to another drug) to prevent relapse, ‫وبيستخدموهم مدى الحياة‬
@medical_subjects_summary ٤١ t.me/medical_subjects_summary
Notes:-
- all opioid agonists are contraindicated in pregnant and lactating women
(embryotoxic)
- opioid agonist is contraindicated in renal and hepatic failure patients and
asthmatic and CVS patient
SEDATIVE – HYPNOTICS "Anti-anxiety drugs =

"anxiolytics"
‫المنومات‬
Def. drugs treatment anxiety and to induce hypnosis (sleeping.) reducing insomnia
 Classified according to mechanism of action: -
1. Sedating anti-H1 : -
E.g.
- Diphenhydramine. Also used for motion sickness.
The strongest two.
- Promethazine. Also used for morning sickness.
- Chlorpheniramine.
- Meclizine. etc…
Characteristic: -
- Sedation. “ sedation is not considered as S.E because these drugs used for
sedation.
- Blocks cough center (Anti-tussive).
- Anti- cholinergic (Atropine-like side effects).
- α1 blocker (Hypotension and reflex tachycardia).
Promethazine is the most potent α1 blocker. ‫لذلك اصبح استخدامه الطبي نادر‬
hypotension and reflex tachycardia ‫ﻻنه من الجرعة اﻻولى يؤدي الى‬
Clinical use: -
- Used only in Children and teenagers, NOT THE ELDERLY who has
insomina.
2. Non-Selective β blockers: -
E.g.: -
- Propranolol as (anti-anxiety).
Because it treats the symptoms of anxiety which are (Tachycardia –
Hyperventilation) by stabilizing the Heart rate and Respiratory rate.
@medical_subjects_summary ٤٢ t.me/medical_subjects_summary
Side effects: -
- Cold extremities
- Hypoglycemia
- Bradycardia.
Clinical Use: -
- Migraine (prophylactic)
- (Thyrotoxicosis)
- treats symptoms of anxiety (tachycardia – hyperventilation)
3. Selective 5HT1A agonists: -
E.g.: -
- Buspirone
o Used "Orally " (anti-anxiety).
o Used in combination with Mebeverine (which is a direct skeletal
muscle relaxant) to treat Irritable bowel Syndrome (IBS)
o Mebeverine may be used alone to treat GIT colic
o The advantage that Mebeverine has over anti-cholinergic drugs is that
it doesn’t cause atropine-like side effects.
Drugs used to treat IBS????
1. Librax.
2. Colona.
Side effects: -
- Atropine-like side effects
4. GABA receptor agonist: -
- This drug has the ability to bind to GABA receptors causing increased influx
of Cl- by opening Cl- channels which will cause hyperpolarization leading to
the inhibition of the CNS leading to the following effects: -
3- Sedation.
4- Hypnosis.
5- Antianxiety.
6- Skeletal muscle relaxant.
7- Dependence.
8- Respiratory and CVS depression.
Note: -
- Barbiturate is GABA agonist.
- Increases duration of Cl- channels remaining open. So, they are more toxic, and
therfore less commonly used
@medical_subjects_summary ٤٣ t.me/medical_subjects_summary
 Benzodiazepine: -
 Classified according to duration of action:
a) Short acting BDZ (duration = 4hrs.)
E.g. : -
1. Midazolam.
- Duration Of Action: Maximum 4 hrs.
Clinical use : -
- Used pre- (before) and during anesthesia
b) Intermediating acting (12 hrs – 24 hrs)
- Used 1 – 2 times daily
E.g. : - (O/P)
1. Lorazepam (used more frequently)
١and ٢ are(used in acute epilepsy)
2. Oxazepam = Duration of action: 12 hrs
3. Alprazolamine
4. Clonazepam
- Duration of action 24hrs
3.+ 4. Are (used in chronic epilepsy).
In a nutshell,
c) Long acting BDZ (25 – 36 hrs) (other
medical references 48 hrs) - Short acting BDZ are
used for Anesthesia
- Mostly used for medical treatment.
- they have long duration of action - Intermediate acting
BDZ are used for
because they metabolized to
Epilepsy
active metabolite
E.g. : - - Long acting BDZ are
1. Diazepam and flurazepam used for Insomnia
and Skeletal muscle
2. Clorazepate relaxant.
3. Chlordiazepoxide
Clinical use:
- Insomnia
- Anxiety
- Status epilepticus (Skeletal muscle relaxant)
- Pre anesthetic medication
- Chlordiazepoxide + Clinidium = Librax → Irritable Bowel
Disease (IBD)
@medical_subjects_summary ٤٤ t.me/medical_subjects_summary
Side Effects of Benzodiazepine :

1. Sedation
2. Dependence
3. Respiratory and CVS depression
4. Rebound insomnia and anxiety (if the drug is stopped suddenly)
o Notes: -
o Rebound insomnia and anxiety then lead to agitation and
severe tantrums
o If a patient withdrawal from any drug that treats insomnia
(causes sedation), the patient will have rebound insomnia on
the first night, and if the drug causes dependence it will
cause heavier insomnia (1 -2 days)
and heavy addiction. Rebound insomnia is
less severe than usual
o Overdose of drugs that are used to
insomnia and only
treat insomnia may cause respiratory occurs for a short
and CVS depression (like with GABA period of time
agonists).
5. BDZ1 agonist (act only as a sedative hypnotic):
 Part of GABA receptors act selectively as a sedative and hypnotic
Clinical Use:
- ONLY in insomnia.
 Less toxic than BDZ (GABA agonists in general)
 Won't cause Respiratory or CVS depression, Not even dependence on
sudden withdrawal.
E.g. : -
1. Zolpidem "orally"
Drugs that cause addiction have
2. Zaleplon “orally” Central and peripheral effects
- Rapid onset: 30 min Whereas drugs that cause dependence
- Short duration: 4 hrs have central effect only
Side effects:
- Early morning headache that gradually disappers
- Rebound insomnia.
@medical_subjects_summary ٤٥ t.me/medical_subjects_summary
6. Melatonin derivatives (MT1 and MT2 receptor agonist): -

- Melatonin is a hormone secreted from the pineal gland
- OTC (Over the Counter Drug)
- These can be administered without a prescription.
E.g. : -
1. Ramelton "Orally"
- Rapid onset (30 min)
- Duration of action: - 7 hours
CU:
- Insomnia.
- Induces sleep.
SE:
- Early morning headaches
- Rebound insomnia (Less occurrence)
7. Barbiturate: -
E.g. : -
Thiopentone "IV" Clinical Use as general anesthesia.
Phenobarbitone “orally” Clinical use: Insomnia, anxiety and epilepsy.
Side effect:
- Severe CVS & respiratory depression
- Dependence.
These side effect are more severe than Benzodiazepine.
Notes: -
- This group is more toxic than Benzodiazepine, because they open chloride
channels of GABA for longer duration. And there is difficulty in its dose
adjustment, so they are rarely used nowadays.
- Occasionally, low dose of phenobarbitone is used to reduce the insomnia in a
combination with theophylline “Xanthine derivatives bronchodilator, one of
its S.E is Insomnia” .‫حاليا ً كليهما لم يعد يستخدما بكثرة‬
Antidote of Benzodiazepine overdose is GABA receptor antagonist “ flumazenil” (IV

injection)
@medical_subjects_summary ٤٦ t.me/medical_subjects_summary
Parkinson's Disease
 Parkinson's disease: motor neurogenic disease caused by degeneration of
dopaminergic receptors in the Substantia Nigra leading to an imbalance between
ACH and dopamine.
(↑↑ACH and ↓↓Dopamine)
 Appears in elder patients (over 65)
 Occurs more in males more than females
 Characterized by 3 main classical symptoms: -
1.Dyskinesia, difficulty of initiation of movement.
2.Tremors, especially in the fingers.
3.Rigidity.
 Other symptoms:
- (Depression - Bradycardia - Hypotension - drooling of saliva"‫ المريض "بيتلل‬-
Mask face – Insomnia – Dementia)
 Treatment depends on correction of the defect.
 Decrease in Dopamine causes:
o Causes "depression" in the beginning and on long term may cause
"dementia" ↓dopamine ↑Ach. (it has strong effect.)
Note: -
Parkinsonism: drug induced "extrapyramidal" like effect
As a side effect to certain drugs:
E.g. Anti-D2 antipsychotic – Metclopromide – Methyl-dopa.
 Drugs of Parkinson's: -
 Firstly: Drugs of Parkinson’s disease (increase dopamine "Dopamine
Precursor")
- Why do we give the precursor of Dopamine and not Dopamine itself ???
Dopamine can't be used to treat Parkinson's because it's not lipid soluble
(polar); it can't pass the BBB.
Consequently, it'll only work peripherally.
Parkinson’s → treated by ↑dopamine.
Parkinsonism → treated by ↓acetylcholine.
@medical_subjects_summary ٤٧ t.me/medical_subjects_summary
E.g: -
1. L-dopa (Levodopa)
- can cross the BBB and forms dopamine under the effect of a
decarboxylase enzyme.
- But decarboxylase is also partly present in the blood which leads to
synthesis of dopamine peripherally, in order to ensure that it passes
through the blood without forming dopamine we add Carbidopa to
L-dopa, this combination is called Sinemet.
- Sinemet is preferred to be used in patients more than 65years old,
or if the main problem is a motor problem.
2. Carbidopa:
- inhibits decarboxylase.
 Main therapy :
- L-dopa (Dopamine) + Carbidopa → Sinemet (Used orally once daily)
(1st line treatment in: -
a) IF patient > 65 years
Efficacy of this drugs decreases after 2 years of use. So, the symptoms
may reappear.
b) If the main complain is muscle rigidity (difficulty of movement).
 Secondly: Selective D2 agonists
E.g: -
1. Ropinirole "always preferred"
Central effect more than
2. Apomorphine peripheral.
Used for disturbances in the CNS.
3. Bromocriptine
4. Pergolide
5. Cabergoline Used for hormonal disturbances e.g.
Hyperprolactinemia
Clinical use: -
- Selective D2 agonists are the main and adjuvant therapy:
 1st line treatment if patient is less than 65 years
 2nd or 3rd line treatment if the efficacy of other drugs has
decreased or the symptoms haven’t disappeared yet
Note: -
- 1st treatment if patient is over than 65 years is (Dopamine Precursors)
@medical_subjects_summary ٤٨ t.me/medical_subjects_summary
 Thirdly: MAO-B inhibitor (Mono Amino Oxide-beta)

- Responsible for destroying dopamine and acetylcholine.
- Response of the drug is measured by the improvement of movement.
E.g.: -
1. Siligiline "O"
Clinical use: -
- 2nd line treatment if PTS never respond
 Fourthly: COMT inhibitor (Catechol O Methyl Transferase)
- Degrades dopamine
E.g. : -
1. Entacapone "O"
Clinical use: -
- 3rd line treatment: Stalevo = L-dopa + Carbidopa + Entacapone
Stalevo: increases efficacy of Sinemet
Using of the 1st line treatment (Sinemet), and if there is NO improvement add a 2nd
line treatment (MAO inhibitors) if they both don’t work then remove one of them an
replace with Entacapone.
 Fifthly: Increase dopamine release and decrease dopamine reuptake
E.g: -
1. Amantadine "orally"
Clinical use: -
- 2nd line of adjuvant therapy.
 Side effects of Dopamine drugs: -
1. Nausea and vomiting (treated with Domperidone).
2. Anxiety.
3. Psychosis.
4. Tachycardia.
5. Hypertension or Hypotension depending on the dose
6. If patient has hypertension → Midodrine.
7. Involuntary movement of lips.
8. Insomnia.
9. Dementia.
 Treatment of dementia with:
1. Rivastigmine
2. Donepezil
3. Galantamine
 They Work centrally inhibiting ACH esterase.
@medical_subjects_summary ٤٩ t.me/medical_subjects_summary
 Drugs of Parkinsonism: -
 (decrease Acetylcholine "Anticholinergic drugs"): -
E.g: -
1. Benztropine
2. Trihexyphenidyl
3. Procyclidine→ dopamine-antagonist antidote.
4. Orphanidrine oral, topical, parenteral preparation. (used for
muscle rigidity) not favored in Parkinson's.
5. Glycopyrrolate → given when there is drooling of saliva.
Side effect: -
o All these drugs have atropine-like side effects
( mydriasis - dry mouth - dry skin – constipation - urinary retention -
tachycardia)
Clinical use: -
o Used if patient suffering from drooling of saliva
o Not used in patients over 65 (because anti-cholinergic drugs may
accelerate occurrence of dementia)
o DOC for EPS (Extra Pyramidal Side effects - Parkinsonism)
Begin with Procyclidine, then continue with Trihexyphenidyl or
Benztropine.
Note:
- Addition to the Side effect of SSRI: -
1. HYPOnatremia, especially if used in the elderly.
- If patients more than 65years old and complain from motor pain,
the treatment is Sinemet.(1st line).
- If patient less than 65 years old or laek motor problems,
The treatment is D2 agonist.
- Drooling saliva → Glycopyrrolate.
- Hypotension→ midodrine (selective α1)
@medical_subjects_summary ٥٠ t.me/medical_subjects_summary

Lectures of CNS Pharmachology Last Edition - 1

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‫]عنوان المستند[‬

‫]العنوان الفرعي للمستند[‬

1. SSRI Selective Serotonin Reuptake Inhibitor.

2. SSNRI Selective Serotonin Norepinephrine Reuptake Inhibitor.

3. SRI Serotonin Antagonist of Reuptake Inhibitor.

4. MAO inhibitor Mono-Amino-Oxidase Inhibitor.

5. TCA Tricyclic Anti-Depressant.

- SSRI Selective Serotonin Reuptake Inhibitor.

Clinical use of SSRI: -

5. Gambling disorder: - ‫عند ترجمتها تكون )القمر القهري( فماذا تعني؟‬

In case of suicidal tendency, follow up should be (at least) weekly.

2. SSNRI Selective Serotonin Norepinephrine Reuptake Inhibitor.

Side effect of SSNRI: -

3. SRI Serotonin Antagonist Of Reuptake Inhibitor. (Adjuvant Therapy)

4. Non selective irreversible MAO inhibitor

Side effect of MAO inhibitor: -

5. TCA Tricyclic Anti-Depressant.

MOA of TCA inhibitor: -

E.g. of TCA inhibitor: -

- i and ii are the 3rd and 4th line of treatment of depressant.

E.g. of Atypical anti-depressant: -

Clinical use of mirtazapine: -

MOA: - Pharmacological action of the typical anti-psychotic drugs: -

B- 5HT2 antagonist "all subtypes of 5HT2 " cause: -

F- Hypothermic effect: - it means decreasing the normal body temperature.

a. Phenothiazines group: - "orally&parenteral" the most commonly used

Side effects of Atypical anti-psychotic : -

Chemical classification of Local Anesthesia: -

- This combination is called procaine-penicillin. Used 2 times/day.

Amide local anesthesia: -

1. Lidocaine: - other names (lignocaine, xylocaine)

Side effect of Local anesthesia: - (mainly with Amid local anesthesia)

Secondly, General Anesthesia: -

- Medullary paralysis, If the dosage increased.

 Classification of general anesthesia according to the rout of administration: -

IV general anesthesia: - Just the most commonly used

3- Ketamine: - called (Dissociative anesthetic)

4- Short acting Benzodiazepine (BDZ): -

Gas volatile liquid

2. Non-focal: - (Generalized Seizure.)

2. Myoclonic seizure: - Myo = muscle

 Pharmacology of 1st line treatment: -

E.g. from 1 min. between seizures,

3. Ataxia = .‫ أي انه ﻻ يستطيع المشي في خط مستقيم‬،‫الترنح‬

 Pharmacology of 2nd line treatment: - Or The Adjuvant therapy: -

2) Clonazepam: - (one of Benzodiazepine)

6) Pregabalin: - (was used in epilepsy →(not anymore))

 Treatment: - (anti-convulsion drugs)

 Natural= Opiates (from  Synthetic = Opioid.

 Firstly: - Natural= Opiates(from plants)

Pharmacological action of μ (Mu): -

E.g. of Natural (opiate) drugs: -

There are Opioid agonists and antagonists

Opioid receptor antagonist: -  Another drug used to prevent relapse is

SEDATIVE – HYPNOTICS "Anti-anxiety drugs =

Side Effects of Benzodiazepine :

6. Melatonin derivatives (MT1 and MT2 receptor agonist): -

Antidote of Benzodiazepine overdose is GABA receptor antagonist “ flumazenil” (IV

 Thirdly: MAO-B inhibitor (Mono Amino Oxide-beta)

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