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‫بسم اهلل انرمحن انرحيم‬

‫انههم صم عهى حممد أل حممد انطيبني انطاهرين‬

KFU – DAMMAM

COLLEGE OF MEDCINE
PHARMACOLOGY – SUMMARY & REVIEW
Dr. Abdulaziz Al-Khawaja

Dr. Mohammed Akram

Dr. N. B. Biswas

Done by: Ahmed Ali Al-Ghareeb

207
 P H R M A C O L O G Y - NOTE 1 - Treatment of Asthma

Drugs for Asthma

Anti-inflammatory
Bronchodilators Anti-leukotrienes Mast cell stabilizers
(glucorticosteroids)

β2-adrenergic LT synthesis LT receptor Sodium

Methylxanthines Anti-muscarinic Beclomethasone
agonist inhibitor antagonist Cromoglycate

Salbutamole Theophylline Ipratropium Hydrocortisone Zileuton Montelukast

Terbutaline Aminophylline Prednisolone Mucosal Mucosal

inflammation edema

Salmaterol Broncho- Mucus

constriction secretion
Role of
Leukotrines
in asthma
Clinical features of bronchial

•Contraction of airway smooth muscle.

•leading to acute dyspnea & airway Uses of bronchodilator
obstruction.
•Mucus hypersecretion.
•leading to mucus pulgging.
•Airway inflamation. for acute during acute for quick
. broncho- phase of reduce airway
asthma.

•leading to bronchodema 2
spasm asthma attack constriction

‫| نســـــأنكم اندعاء‬
P H R M A C O L O G Y - NOTE 1 - Treatment of Asthma

 Bronchodilaters
DRUG PHARMACOKINETIC ACTION USES SIDE EFFECT
Salbutamole  Fast onest.  Given inhaler or Nebulizer.  Bind to β-receptor & stimulate Used for acute attack.  Tremor.
adrenergi
c agonist

Terbutaline  Short duration.  Less side effect. adenylcyclase.  Vascular headache.

 Given orally, S.C, IV or IM.
Β2 -

 Leading to  cAMP.
Salmaterol  Slow onest.  Large dose.  Bronchodilatation. Used for long term therapy.
 Long duration.  More side effect.
Theophylline  Has narrow theraputic index.  Inhibit PDEI.  GIT: nausea, vomiting .
 Given orally.  Leading to  cAMP.  CNS: stimulation insomnia,
++
 Cause GI irritant.  Ca influx irritabillity & headach.
Methylxanthines

 Bronchodilatation  CVS:  BP, arrhythmia.

Aminophylline  Water mixture of Theophylline + Ethylenediamine.
1) CNS stimulation.  Kidney: diuresis.
2) Cardiac muscle stimulation.
 Given orally, rectally (suppositories) or injection.
3) Diuresis.
4) S.M. relaxtion of bronchial & uterus.
5) Periphral & cornory vasodilatation.
6) Cerebral vasoconstriction.
Anti- Ipratropium  It is poorly absobed from the GIT.  Blocking M receptor in bronchial  Dry mouth.
musc  So,it given by inhalation. smooth muscle.
rinic
 Slower onest & longer duration than salbutamol.  Bronchodilatation

 Anti-inflammatory(Glucorticosteroid)
DRUG PHARMACOKINETIC ACTION USES SIDE EFFECT
Beclomethasone  Given by inhalation, orally or IV. 1) Reduce mucosal edema. If taken by inhalation,
2) Sensitize β2-agonist.  Dysphonia (hoarseness).
Hydrocortisone 3) Reduce inflammatory cell activation  Oral candidiasis (fungal
Prednisolone infection).
 Anti-Leukotrienes
DRUG PHARMACOKINETIC ACTION USES SIDE EFFECT
Zileuton  1) Inhibit lipoxygenase enzyme.  To prevent asthma caused by 
2) Reduce conversion of AA to LT.  Aspirin.
 So, it is …  NASID.
 Broncodilater.
 Anti-inflammatory.
Montelukast  1) Blocking LT receptors.  To prevent asthma caused by 
2) Inhibit bronchoconstriction caused by LT  NASID & Exercise.
 Mast Cell Stabilizers
DRUG PHARMACOKINETIC ACTION USES SIDE EFFECT
Na Cromoglycate  Given by inhalation.  Reduce the mediators that release  Prophylaxis aginst asthma  Cough.
from mast cell in response to allergen attack.  Wheeze.
Ketotifen  Given orally.
that cause bronchoconstriction. 3

‫| نســـــأنكم اندعاء‬
 P H R M A C O L O G Y - NOTE 1 - Treatment of Cough
• It clears the excess secretions
& inhaled foreign matters.
Productive Cough
• Expectorants are used.

Common causes of Cough: • Dry cough has no useful

Non-Productive function.
• 1) Acute Respiratory Infection. Cough • Anti-tussives are used.

• Upper respiratory infection.

• Pneumonia.
• Bronchitis
• They should be used for dry cough.
• 2) Chronic Respiratory Infection. • because it suppress cough reflex, it should not be used in
• TB. Anti-tussive the presence of bronchial secretions.
• Postnasal drip.
• 3) Airway Diseases.
• It reduces the sensitivity of periphral cough receptors to it's
• Asthma. Locally anti- activators which include irritants & autacoids (Bradykinine).
• COPD. tussive
• 4) Irritants.
• Cigarettes smoking. • They clear airway from mucus secretion by:
•  ability to expectorate sputum.
• Inhaled foreign bodies. Mucoactive
Agents •  mucus hyper secretion.
• 5) Drug Induced.
• Inhaled drugs (aerosols).
• ACE-inhibitors (anti-hypertensive).
4

|
 P H R M A C O L O G Y - NOTE 1 - Treatment of Cough
DRUDS FOR COUGH

Anti-tussives Mucoactive
Drugs Agents

Centrally Peripherally Expectorants Mucolytics

Opioid Hyperosmolar Classic

Anti-histamins Above Larynx Below Larynx Na citrate mucolytic
Dervatives saline

Diphenhydram steam with or without Na NAS

Codeine Lozenge K citrate
ine (menthol & benzoin bicarbonate
tincture)

Ammonium Peptide
Pholcodeine Syrup Na Iodide mucolytic
Nebulized Cloride
Lignocaine

Dextrome- Dornase alpha

K Iodide Guaifenesin
thorphan Nebulized
Benzocaine

Noscapine Creosote Guaicolate others

Centrally & Bromhexine

Periphrally

Benzonatate Ambroxol

Mucoregulatory

Anti- Macrolide Anti-

cholinergic Antibiotics inflammatory

Ipratropium Azithromycin Indomethacin Corticosteroids

5
Atropine

|
 P H R M A C O L O G Y - NOTE 1 - Treatment of Cough

 Anti-Tussives (cough suppressent)

DRUGS PHARMACOKINETIC ACTION & ITS MECHANISM USES SIDE EFFECT
Codeine  They suppress cough reflex by  Nausea.
 Derict inhibition of Cough Center in the  Dizziness.
Dervative

Pholcode
Opioid
Acting Centarlly

Dextromethorphan medulla.  Urenary retention.

 Constipation.(vi)
Noscapine
Diphenhydramine  It depresses CNS including Cough Center.  Sedation.
Histamine

 Drowsiness.
Anti-

 Dizziness.

Lozenges  They are demulcents.  They form gelatious coat that protects the  Used for cough of
Larynx
Above

Syrup (honey) inflammed skin  Sore throat.

 Pharyngitis.
Acting Periphrally

Steam  Without tooking, Taken with or  Promote secretion of dilute mucus,

it taken by without (menthol  To protect inflammed mucosa
& benzoin
inhalation .
tincture)
Larynx
Below

Nebulized Ligocaine 1) Local anesthesia.  During fiber optic bronchoscopy.

2) Blooking mucosal cough receptors.  intractable cough in bronchial carcinoma.
Nebulized
Benzocaine
Acting both Benzonatate  Chemichally, it is related to 1) In lungs, acting on
Centrally tetracaine (local ansthesia).  Stretch & cough receptors.
&Periphrally 2) Act on CNS
 Mucoactive Agents (Expectorants)
o They  volume or hydration of airway secretion.
o They improve expectoration of respiratory mucus secretion.
DRUGS PHARMACOKINETIC ACTION & ITS MECHANISM USES SIDE EFFECT
Hyperosmolar Saline  (10 ml of 6% saline).  Used in fibross & bronchiectasis.
 Inhaled by ultrasonic nebulisation.
Na citrate 1) Stimulate secretion of low viscosity watery  Used in early dry stage of acute bronchitis.
K citrate mucus & sissolve it.
 To make it thinner less sticky.
Na bicarbonate
2) elasticity of bronchi.
 To easily expectorate the mucus.
Expectorants

Ammonium Cloride  Stimulate secretion of low viscosity watery mucus

 By stimulation of sensory nerve ending in
the stomach.
Na Iodide 1) Stimulate secretion of low viscosity watery mucus  Chronic respiratory disease.
K Iodide 2) has mucolytic action.  Chronic asthma.
Guaifenesin 1) respiratory secretion.
2) adhesiveness & surface tension of viscid sputum
Creosote 1) sputum.  Lung absess.
2) has mild antiseptic & deodrant action.  Chronic bronchitis. 6
Guaicolate  Bronchiectasis.

|
 P H R M A C O L O G Y - NOTE 1 - Treatment of Cough

 Muocoactive Agentgs (Mucolytic)

o They  viscosity & of elasticity airway secretion &  mucociliary & cough clearance.
DRUGS
N-acetulcysteine (NAC)
Classic Mucolytic
PHARMACOKINETIC
 Taken orally or by inhalation.
 It is a precursor of intracellular
cysteine & glutathione.
ACTION & ITS MECHANISM USES SIDE EFFECT
1) Hydrolyse disulfid bond of mucin.  In condition associated with viscous mucus  Bronchospasm.
 So, mucus loss it’s viscosity & elasticity.
secretion:
 Chronic bronchitis, emphysema,
 Prevent by
β2-agonist.
2) Act as antioxidant.
brochiectasis & cystic fibrosis.  Disagreeable odor.
 So, it prevent pulmonary injury in patient

 (ARD): bronchitis, pneumonia & asthma.  Sulfur odor &

with COPD or lung cancer.  Post-operative & post-traumatic taste.
pulmonary complications.  GI irritation.
 Care of tracheostomy.  Nausea.
 Act as antidote for paracetamol overdose.  Vomiting.
 Stomatitis.
Dornase alpha  Taken by nebulisation.  For cystic fibrosis.  Allergic reaction.
Mucolytic

 Pharyngitis.
Peptide

 Laryngitis.
 Voice alteration.
Bromhexine  It is an expectorant & mucolytic 1) Liquefy mucus.  Acute bronchitis.  Rhinorrhea.
drug.
 Taken orally, parentral or by

By viscosity of bronchial secretion.
 Chronic bronchitits.
 COPD.
 Lacrimation.
 Gastric irritant.
2) Enhance expectoration.
inhalation.  Avoid with
Others

Ambroxol  Taken orally. 

By the rate of microciliary. antacid.
 has less GI irritant.
 Mucoactive Agents (Mucoregulatory Agents)
o They  airway mucus hyper secretion which caused by goblet cells & submucosal gland.
DRUGS PHARMACOKINETIC ACTION & ITS MECHANISM USES SIDE EFFECT
Indomethacine  inflammation which leading to mucus hyper  Panbronchiolits
nflammatory

secretion.
Anti-i

Corticosteroid

Ipratropium  mucus volume that secreted in chronic

bronchitis.
Anticholinergic

Atropine  mucus hypersecrtion.  used pre-anesthetically for endotracheal

intubation.

Azithromycin  Taken orally for long term

antibiotics
Macrolide

administion.

|
P H R M A C O L O G Y - NOTE 3 - Treatment of Peptic Ulcer

DRUGS FOR PEPTIC ULCER

Drugs Affecting Mucosal Drugs erdicate

HCL Protictive Agents H. Pylori

Colloidal Bismuth Quadruple

Antacids H2 Blocker Sucralfate Misoprostol Triple Therapy
compounds Therapy

Omeprazole OR Omeprazole OR
Bismuth
AL(OH)3 Cimetidine Lansoprazole Lansoprazole
Subsalycilate
(PPI) (PPI)

Bismuth Bismuth
Mg(OH)2 Ranitidine Clarithromycin
Sobcitrate Subsalycilate

Amoxycillin OR
Famotidine Metronidazole
Metronidazole

Proton Pump
Anti-muscarinic Tetracycline
Inhibitors

Omeprazole Pirenzepine
(GU & DU)
Peptic Ulcer

• It is caused by imbalance between:

• Protective Factors
Lansoprazole • (Mucus & Bicharbonate).
• Dameging Factors 8
• (HCL & pepsin).
• So, it is caused by either  DF or PF.

‫نســـــألكم الدعاء‬
P H R M A C O L O G Y - NOTE 3 - Treatment of Peptic Ulcer
 Drugs Affecting Gastric (HCL) Acid
DRUGS PHARMACOKINETIC ACTION USES SIDE EFFECT
AL(OH)3  Weak bases (-OH). 1) Neutralize Slowly Used for symptomatic  Constipation.
 Taken 30 min in empty stomach. already relife of dyspepsia  In renal failure,
 Taken 2 hrs after meal. secreted acid.  Aluminum toxicity
Antacid

 Relieve heart burn immediatly. 2) Inhibit  Encephalopathy

MG(OH)2  If it take with other drugs, formation of Fast  Diarrhoea
 It form insoluble com;ex that adsorb on pepsin
Combination Fast &  Constipation + Diarrhoea = nothing
GIT wall not absorb. sustained
 So, it take 2 hrs after or before other druds
Simethicone  They are added to antacid either it combined or   surface tension  Anti-flatulent.
Additives

no.  So, reduce buble  To prevent reflux.

formation.
Alginates  Form a layer of foam on the  Reduce reflux
top of gastric content.
H2 Potency T1/2 Duration Inhibition of Cyto-450 is an enzyme that H2 antagonist cross placenta & are
antagonist (hrs) Cyto-450 metabolizes drugs. also secreted in breast milk.
(blokers) Cimetidine 1 1.5 – 6 1 Not used by elderly  Gynecomastia.
2.3 male because it is anti-  Galactorrhea.
Extremly androgenic  Inhibition of Cyto-450
save drugs  So, conc. of Theophyline &
Warfine.
Ranitidine 5 -10 1– 2.4 8 0.1

Famotidine 32 2.5 - 4 12 0
Omeprazole  Average T1/2= 1.5 hrs. Irreversible inhibitors for
+ +
Lansoprazole  Need acidic media, So H /K ATPase
PPI

 Taken 1 hr befor meal.

 Don’t take with other acid suppressing
agent.
Pirenzepine Inhibit gastric acid by blocking M3  Used in refractory
receptor cases that is not
muscarinic

responding to other
Anti-

drugs.
 Used in nocturnal
pain.

‫نســـــألكم الدعاء‬
P H R M A C O L O G Y - NOTE 3 - Treatment of Peptic Ulcer

 Muocosal protective Agents

DRUGS PHARMACOKINETIC ACTION USES SIDE EFFECT
Sucralfate  It is salt of ( socrose + AL(OH)3 ). 1) In acidic pH, it become
 Taken 1 hr befor meal. viscous gell & protect ulcer.
 Work in acidic pH 2) Stimulate PG production.
 Not used with antacid or H 2 antagonist.
Misoprostol It is a PGE1 analogue 1) Gastric acid inhibition. Used with NSAID to  Diarrhoea
2) Stimulate secretion of prevent peptic ulcer  Abdominal pain.
mucus & bicarbonate.  Abortion?
3) Enhance mucusal blood
flow.
Bismuth subsalicylate 1) Coat the ulcer  Stain stools & tongue with black
2) stimulate secretion of color.
Bismuth sobcitrate mucus & bicarbonate.  Cause bismuth toxicity with long
3)  PG synthesis. used.
 Drugs erdicate Helicobacter pylori
DRUGS PHARMACOKINETIC ACTION USES SIDE EFFECT
Omeprazole  It is combination of ONE acid suppressant + 2
Or antibiotics.
Lansoprazole (PPI)  Given for 14 days.
Triple Therapy

Clarithromycin  Then, followed by PPI for 4 - 6 wks.

Amoxycillin
or
Metronidazole
Omeprazole  It is combination of ONE acid suppressant + 3
Or antibiotics.
Lansoprazole (PPI)  Given when triple therapy fails.
Quadruple Therapy

Bismuth Subsalicylate
Metronidazole
Tetracycline

10

‫نســـــألكم الدعاء‬
P H R M A C O L O G Y - NOTE 4 & 5 - GIT Drugs

• It help easy evacuation of the bowel

contents during defecation.
Laxative
• Usually self-prescribed for the relief of
constipation

• It is best prevented with:

• high fiber diet.
Constipation
• adequate fluid intake.
• regular exercise.

• For mild to moderate dehydration:

• ORS (oral rehydrate salt)
• NaCl, KCl, Na HCO3
• glucose & water
Management of dehydration • For sever dehydration:
• IV fluids
• 5% dextrose & normal saline.
• KCl &/or Na HCO3, when
hypokalemia &/or acidosis

11

| ‫ نســـــألكم الدعاء‬...
 P H R M A C O L O G Y - NOTE 4 & 5 - GIT Drugs

GI Drugs

Anti-Diarrhoeal
Laxative
Drugs

Balance
Simulant Osmotic Polyethylene glycol Anti-
Bulk Formation Faecal Softners Opioid
Laxative Laxative muscarinics
(Bowl Cleaning
Solution)

Methyl-cellulose Liquid paraffin Bisacodyl Mg hydroxide Diphenoxylate Dicyclomine

Polyethylene
glycol

Glycerin Hyoscine-N-
Bran Senna Mg sulphate Loperamide
suppository butyl bromiae
Na sulphate

5-HT3
Ispagula husk Na sulphate Adsorbents
antagonists
Na chloride

Colloidal
Na citrate alosetron Kaolin Pectin
Bismuth
Na bicarbonate

Lactulose Al silicate
K chloride

Mg silicate
H2O

12

| ‫ نســـــألكم الدعاء‬...
 P H R M A C O L O G Y - NOTE 4 & 5 - GIT Drugs

 Laxatives
DRUGS PHARMACOKINETIC ACTION USES SIDE EFFECT
Bulk Formation Methyl-cellulose 1) Absorb water.  Constipation  Intestinal obstruction
2)  the bulk of stool.  Diverticular disease.  Prevented by taking
Bran
3) Stimulate peristalsis.  Colostomy. sufficient H2O.
Ispagula husk  Hemorrhoids & fissure.
 Irritable bowl syndrome.
Faecal Liquid paraffin  Given oraly. 1) Lower surface tension.  Constipation (can be used in  Aspiration pneumonia
Softner 2) Make stool soft. pregnant ladies)  Leakage of stool.
 To avoid straining at stool in  Deficiency of Vit. A, D, E & K.
myocardial infarction. with long term use.
Glycein suppository  It is inserted via anal canal. 1) Makes stool soft.
2) Help evacuation.
Stimulant Bisacodyl  Given oraly or suppository. 1) Stimulate intestinal motility.  Constipation.  Diarrhoea.
laxative  The onset of action 6-8 hrs. 2)  Na & water absorption.  Preparation for radiology.  Loss of fluid & electrolyte.
 The effect is repeated due to entero-  Avoid in intestinal obstruction &
hepatic re-circulation. pregnancy
Senna
Osmotic Mg hydroxide  Its action take 1-3 hrs. 1) Hold water due to osmotic pressure.  Constipation.  Diarrhoea.
2) Distend the bowl.  Preparation for radiology.  Loss of fluid & electrolyte.
Laxative Mg sulphate 3) Prompt evacuation.  Expulsion of worms.
Na sulphate  Avoid in pregnancy
Na citrate  Avoid Na-salts in CVS, liver & renal
diseas.
Lactulose  Non-absorbable sugar 1) Reduces pH due to conversion of NH 3  Constipation.  Flatus.
to NH4.  Control of encephaopathy in liver  & abd cramps.
2)  absorption of ammonia. cirrhosis.  When it is l
metabolize By bacteria
in GIT.
Balanced Polyethylene glycol  It is a bowl cleaning solution.  It retaines H2O & electrolytes in the  Bowl cleaning to prepare for:
Na sulphate  It is isotonic to intestinal contents. lumen of GIT.  Surgery.
polyethyle  & take faecal matter out along with it .  Colonic endoscopy.
ne glycol Na chloride  Radiology.

Na bicarbonate
Contains:
K chloride
H2 O

13

| ‫ نســـــألكم الدعاء‬...
 P H R M A C O L O G Y - NOTE 4 & 5 - GIT Drugs

 Anti- Diarrheals
DRUGS PHARMACOKINETIC ACTION USES SIDE EFFECT
Opioid Diphenoxylate  Usually given in combination with It gonize opioid receptors (e.g. μ R). So, it.  Minimal sedation.
atropine. 1) peristalsis movement.  Minimal dependence.
2) constrict sphincters.
Loperamide  Most their effects are on GIT.
Anti-muscarinic Dicyclomin  They competitively blocking M3  NOT used with elderly patients  Dry mouth.
receptors in GIT. So, they… that have glaucoma  Constipation.
1) peristalsis movement.  NOT used with male patients that  Tachycardia.
Hyoscine-N-butyl bromide 2) constrict sphincters. have prostatic hypertrophy.  Palpitation.
  IOP.
 Urine retention.
5-HT3 Alosetrone  It is well absorbed from GIT.  Competitively block 5-HT3 R. so, it…  Control of sever.  Constipation.
antagonists  Has short T1/2. o ↓ GI motility  in irritable bowl syndrome which is  Ischemic colitis.
 Has long acting. more common in women.
Adsorbents Kaolin Al sikicate  Adsorb microorganisms & toxins.  Constipation.
Mg silicate  Absorb water.   absorption of many
Pectin  It is indigestible carbohydrate from drugs.
apple  Colloidal bismuth gives
Colloidal bismuth black color to tongue &
stool.

14

| ‫ نســـــألكم الدعاء‬...
 P H R M A C O L O G Y - NOTE 4 & 5 - GIT Drugs

GI Drugs

Anti-Emetics
Drugs for IBD Prokinetic
Drugs

D2 R Anti- D2 R 5-HT4 R
Immuno- antagonists histamine antagonists agonist
5-ASA
suppresive
Metoclopr- Metoclopram Metoclopram
Cyclizine
amide ide id
Gluco- Cytotoxic Cytokine Azo-
Mesalamine
corticoids agents Inhibitors compounds
Domperi-
Meclozine Domperidone
done

Prednisone Azathioprine Infliximab Sulfasalazine

Diphenhydr-
Droperidol
amine

Prednisolon Methotraxate Olsalazine Anti-

Phenothiazines
muscarinics

Promethazine Hyoscine
budesonide Balsalazide

5-HT3 Marijuana
antagonists derivatives
Hydrocortisone

Ondansetron Dronabinol

Nabilone

Steroids

Dexamethaso
ne
15

| ‫ نســـــألكم الدعاء‬...
P H R M A C O L O G Y - NOTE 4 & 5 - GIT Drugs

 Treatment of Inflammatory Bowel Disease

DRUGS PHARMACOKINETIC ACTION USES SIDE EFFECT
  1 line drugs for treatment of  GIT: Nausea, vomiting.
st
Sulfasalazine 5-ASA + sulfapyridine. 1) 5-ASA inhibits……
 Cyclo-oxygenase enzymes. mild to moderate  Hematological:
 Lipo-oxygenase enzymes.  Ulcerative colitis.  BM suppression.
2) anti-inflammatory action. &  synthesis
 Chron’s  Megaloblastic
diseaseof PGs & leukotrienes Chron’s disease in colon or rectu
anemia.
 in colon or rectum.  Renal:Crystal urea & Renal
Azo-compound

 Azo-bond broken in stones.

GIT(colon) by azo-  Hypersensitivity:
reductase that secreted  Skin rash.
by bacteria  Angiodema.
 General: Headache, malaise,
5-ASA

arthralgia & myalgia.

Olsalazine  2 molecules of 5-ASA.  Diarrhoea.

Balsalazide  5-ASA & amino-benzoyl

alanine.
  1 line drugs for treatment of  Renal damage.
st
Mesalamine Enteric coated form of
Mesalamine

5-ASA. mild to moderate

 It available as enema &  Ulcerative colitis.
suppository.  Chron’s disease
 in colon, rectum or small
intestine.
Gluco- Prednisone  They given oraly. • Anti-inflammatory & immune suppressant action.  For acute & sever ulcerative 
Hypertension
corticoid So, it….. colitis & Chron’s disease. 
Hyperglycemia.
Prednisolone 
peptic ulcer.
1)  phospholipae A & C.
Budesonid 2)  synthesis of PGs & leukotrienes  synth 
Infection.s
of cytokines (TNF-  , IL-1), chemokine 
Renal suppression.
Hydrocortisone  Given IV injection. (IL-8.)  Prevented by terminate
3) Destroy lymphoid cells & some T-cells &  synthesis of PGs & leukotrienes theChron’s
treatment within colon or rectu
disease
Immuno-suppresive drugs

tapering doses.
Cytotoxic Azathioprine  Purine analog. 1) DNA synthesis.  Alternate or additional therapy for  Nausea.
2) Damage lymphoid & T- cells.  Refractory ulcerative  Vomiting.
colitis.  BM depression.
Methotraxate 1) Inhibitor of dihydrofolate reductase.  Chron’s disease.  Infections.
2) DNA synthesis.  Infertility.
3) Damage lymphoid & T- cells.

Cytokine Infliximab  Enteric coated form of 1) Anti- TNF (pro-inflammatory cytokine)  Alternate or additional therapy for  Infections
inhibitor 5-ASA. 2)  release of cytokines from inflammatory cells  Refractory ulcerative  Infusion reaction.
 It available as enema & colitis.  Feve.
suppository.  Chron’s disease.  Chills.
 Urticaria.
 Chest pain.
 Dyspnoea.
16

| ‫ نســـــألكم الدعاء‬...
 P H R M A C O L O G Y - NOTE 4 & 5 - GIT Drugs

 Anti-emitic
DRUGS PHARMACOKINETIC ACTION USES SIDE EFFECT
D2 receptor Metoclopramide 1) Inhibit D2 receptors in CTZ.  Extrapyramidal reaction.
antagonists 2) Control vomiting .  Diarrrhoea.
3) Have prokinetic effect. &  synthesis of PGs & leukotrienes Chron’s disease in colon or rectu
Domperidone  Don’t crossBBB.

Droperidol 1) Inhibit D2 receptors in CTZ.  Sedation.

2) Control vomiting .  Extrapyramidal reaction.
  QT-interval & cause
ventricular tachycardia.
Anti-histamines Cyclizine  Inhibit H1 & M3 receptors in…  Sedation.
Meclozine  CTZ.  Anti-muscarinic side effects:
 Vomiting center.  dryness of mouth.
Diphenhydramine  Tachycardia.
Phenothiazines Promethazine  Inhibit D2,H1 & M3 receptors in…  Constipation.
 CTZ.
 Vomiting center.
5-HT3 receptor Ondansetron  Inhibit 5-HT3 receptors in…  in sever vomiting e.g. in cancer
antagonists  CTZ. chemotherapy.
 Vomiting center.
Marijuana Dronabinol  Inhibit vomiting center by stimulation of  Euphoria.
derivatives
Nabilone cannabinoid ( CB1 ) receptors.  Mood disturbances.
Steroids Dexamethasone • to supplement the effect of other
drugs in sever vomiting.
 Prokinetic
DRUGS PHARMACOKINETIC ACTION USES SIDE EFFECT
D2 receptors Metoclopramide 1) Blocking D2 receptors in GIT. .  Extrapyramidal reaction
antagonists &   cholinergic activity in upper GI (pro-  Tremors.
5-HT4 receptors kinetic).  Dyskinesia.
agonists 2) Blocking D2 receptors in CTZ.  Gynecomastia.
 control vomiting (anti-emetic)  Irregular menstrual.
3) Activates 5-HT4 receptors. 
Chron’s disease in colon or rectu ↑ prolactin secretion.
 Diarrhoea
Domperidone  Don’t crossBBB. 1) Blocking D2 receptors in GIT.  Diarrhoea
  cholinergic activity in upper GI (pro-
kinetic).
2) Blocking D2 receptors in CTZ.
 Control vomiting (anti-emetic).

17

| ‫ نســـــألكم الدعاء‬...
 P H R M A C O L O G Y - NOTE 6 - Sedative & Hypnotic Drugs

SEDATIVE & HYPNOTIC DRUGS

5-HT R β-adrenergic R
BNZ Barbiturates Other Z-Hypnotics
Agonists blockers

Intermediat Intermediat Anti- Chloral

Long acting Short acting Long acting Buspirone Propranolol Clonidine Zaleplon
acting acting histamines Hydrate

Chlordiazepox Diphenhydra
Alphazolam Oxazepam Phenobarbital Secobarbital Zolpidem
ide mine

Ultra-short
Diazepam Lorazepam Triazolam Short acting
acting
• drugs that produce
Clonazepam Hexobarbital Thiopental
Sedatives calm & relaxation.
• used for anxiety.

• drugs that put user

Hypnotics in sleep.
• used for insomnia.
DEATH
coma both of them
anesthesia
depress CNS but
Hypnotic more
hypnosis

sedation
P H R M A C O L O G Y - NOTE 6 - Sedative & Hypnotic Drugs

 Benzodiazepines (BNZ)
DRUG PHARMACOKINETIC ACTION USES SIDE EFFECT
Chlordiazepoxide Absorption Mechanism of action 1) Sedative preoperatively.  Drowsiness.
 Orally / I.M. / I.V.  BNZ hyperpolarizes the membrane of 2) Epilepsy in emergency.  Confusion.
Long acting
(1-3 days)

Diazepam the post-synaptic neurons by: 3) Treatment of muscle plasticity in cerebral  Amnesia.
Distribution  Binding to GBC binding site. palsy & tetanus  Impairment of motor
Clonazepam  Pass BBB & placenta.   affinity of the R to GABA. coordination.
+
 Secreted into breast milk.   Cl permeability.  Dependence & addiction.
 Hyperpolarize the
Alphazolam membrane. 1) Sleep disorder, insomnia.
Metabolism
 Inhibition of the neurons. 2) Control alcohol withdrawal symptoms.
 It is done by hebatic microsomal system.
3) Treatment of muscle plasticity in cerebral
 The metabolites: Psychological dependence.
Action palsy & tetanus
o Active.  Stop administration cause:
Intermediate acting

o Have longer T1/2. 1) Reduction of anxiety.  Craving.

(10-20 hrs)

o Cause hangover effect. 2) Sedation which encourage sleep by:

Lorazepam  The T1/2 depend on the metabolism not   latency. 1) Short term relief of sever anxiety. Physical dependence.
excretion.   non-REM. 2) Sleep disorder, insomnia.  Stop administration cause
  REM. 3) Control alcohol withdrawal symptoms. withdrawal symptoms:
Excretion 3) Reduction of muscle tone & 4) Treatment of muscle plasticity in cerebral  Insomnia.
 coordination. palsy & tetanus
It is done by kidney.  Anxiety.
 4) Anti-convulsant.
 Autonomic over activity.
 5) Prolonged sleep with over dose.
It safe on over dose if it taken alone.   HR & BP.
 6) Tolerance.
It is the most widely used sedative because:  Tremors.
Oxazepam  High Ti.  It is pharmacodynamic ( 1) Sleep disorder, insomnia.  Diaphoresis.
 Low risk of dependence. the sensitivity of the 2) Control alcohol withdrawal symptoms.  Muscle cramps.
Short acting

receptors).
(3-8 hrs)

 Acute overdose or toxicity is treated 3) Treatment of muscle plasticity in cerebral  Confusion.

 Develop after chronic use palsy & tetanus.
by:  Seizures.
Triazolam  FLUMAZENILE. (1-2 wks).
 Irritability.
 Ataxia.

Anxiety
 Fear-induced situation. Uses of BNZ
 It has: 1) Short term relief of sever anxiety.
 CNS symptoms: 2) Sedative preoperatively.
 Insomnia. 3) Sleep disorder, insomnia.
 Anorexia. 4) Epilepsy in emergency.
 Muscle tension. 5) Control alcohol withdrawal symptoms.
 Peripheral symptoms: 6) Treatment of muscle plasticity in cerebral
 Sweating. palsy & tetanus.
 Tremors.
 Palpitation.
19

‫| نسألكم الدعاء‬
P H R M A C O L O G Y - NOTE 6 - Sedative & Hypnotic Drugs

 Barbiturates ( acids)
DRUG PHARMACOKINETIC ACTION USES SIDE EFFECT
Thiopental Absorption  Depression of the neural activity by : NOT used as sedative or hypnotic drugs but  Death in high dose due to:
Ultra-Short

 Orally / I.M. / I.V.  Enhancement of they are only used for:  CVS depression.
acting

GABAergic pathway. 1) I.V. anesthesia.  Respiratory depression

Distribution  Blocking excitatory NT. 2) Epilepsy.  Dependence.
 To all body 3) Hyperbilirubinemia.  Drug-drug interaction.
Hexobarbital Metabolism  Paradoxical excitement of
acting
Short

 It is done by hebatic microsomal system. children.

 This system cause drug-drug iteractoin.  Prolonged hangover.
NOT used as sedative or hypnotic drugs but  Porphyria.
Secobarbital Excretion they are only used for:  Tolerance
Intermedia
te acting

 It is done by kidney. 1) Epilepsy.  It is pharmaco-

 It is pH dependence. 2) Hyperbilirubinemia. dynamic (enzyme
 Alkalization of urine with NaHCO3 enhance induction).
barbiturates renal execrerion.
Phenobarbital  So, used for treatment of
acti
Lon

ng
g

overdose.
 5-HT Receptors Agonists
Buspirone  Mixed agonist- antagonist.  Anxiolytic action ( 1-3 wks).  Generalized anxiety.  Nervousness.
 Minimal risk of dependence.  Little sedation.  Dizziness.
 Little impairment of coordination.  Headache.
 Minimal risk of dependence.  Nausea & vomiting.
 NO hypnotic , NO euphoria.
 β-adrenergic Blockers
Propranolol  non-selective β-blocker.   peripheral symptoms of anxiety 1) Anxiety. 
 Sweating, Tremors & 2) Social phobia.
Palpitation. 3) NOT for (asthma, COPD, diabetes)
 Reduce performance anxiety such:
 Public speech or Interview.
 Other sedative & hypnotic
Diphenhydramine  Anti-histamine.  Has anit-cholinergic action. 1) Insomnia. 
Anit-H

2) Anxiety & agitation.

Chloral Hydrate   Used to induce sleep in children 

 to perform certain medical
procedure.
Clonidine  α2 agonist.  1) Control sympathetic overactivity 
associated with:
 Narcotic withdrawal.
20
 Acute anxiety.
2) Panic attack of anxiety.

‫| نسألكم الدعاء‬
P H R M A C O L O G Y - NOTE 6 - Sedative & Hypnotic Drugs
 Z-hypnotic
DRUG PHARMACOKINETIC ACTION USES SIDE EFFECT
Zaleplon  Selective for α1 subunite of BNZ receptor  Depression of the neural activity by
comlex. enhancement of GABAergic pathway.
1) Less risk of tolerance.
2) Less risk of amnesia.
3) Minimal rebound:
Zolpidem  Insomnia.
 Anxiety.
 Hagover effect.

 The acton is antagonized by

Flumazenil
 that impact sleep stage.

21

‫| نسألكم الدعاء‬
P H R M A C O L O G Y - NOTE 7 - General Anesthesia

GENERAL ANESHESIA
DRUGS

I.V. GA Inhalational GA

Thiopental GAS Volatile Liquids

Midazolam Nitrous Oxide Halothane Enflurane Isoflurane Sevoflurane

Fentanyl

•loss of
anesthesia sensation
Ketamine

•drugs that
anesthetic drug produce loss
of sensation
Etomidate
•produce loss of

GA all sensation
with loss of
consciousness

22

‫| نسألكم الدعاء‬
P H R M A C O L O G Y - NOTE 7 - General Anesthesia

DRUG PHARMACOKINETIC ACTION USES SIDE EFFECT

Thiopental  It is a barbiturate drug.  Induction of GA.  Respiratory depression.
 Fast onset.  NOT used in asthmatic patients.  Bronchospasm.
 because lipid solubility & cross BBB.  CVS
 Ultra-short acting.  BP.
 due to fast redistributed to tissues out  Cardiac Output
side the brain.  porphyries
 Slowly metabolized.
 Narrow margin of the safety.
Etomidate  more metabolized.  Induction of GA.  Involuntary movement.
 Cause low risk of CV &R depression.   adrenocortical response
to stress.
Intravenous

 Post-operative nausea &

vomiting.
Midazolam  It is a BNZ drugs.  The action make little changes in  Basal anesthesia.  Amnesia.
 Ultra-short acting.  BP.  Anxiety.
 To accelerate the recovery from anesthisea,  Ventilation.  Anesthesia for patient with:
 Use Flumazenil.  myocardial diseases.
 hypovalemic shock.
Ketamine  Mainly in pediatrics for minor surgery.  Post-operative
 Basal & dissociative anesthesia. hallucination in adult.
 Anesthesia for hypovalemic shock patient.  Amnesia.
 BP &HR
Fentanyl  Analgesic by using (Fentanyl +  Bronchoscopy.
Droperidol).  Cystoscopy.
Nitrous Oxide Administration  Low potency (MAC=100).  With prolonged use
 Mixed with water.  It is combined with other inhalation A.  Leucopenia.
Gas

 Taken by inhalation.  Rapid induction & recovery.  Megalobalstic anemia.

Distribution  It has analgesic property.
 It is well distributed & determines  It has low lipid solubility in brain.
Halothane  Speed of duration.  Most widely used. All the volatile liquid anesthesia:  Hypotension.
 Speed of recovery.  High potency (MAC=0.7).   myocardium contractility.  Uterine relaxation &
Metabolism  It has weak analgesic property.  Bradycardia. bleeding.
Inhalational

o It leads to cardiac  Cardiac dysrhythmia.

 It is the major responsible for side effect.
dysrhythmia.  Liver toxicity.
Volatile liquids

 Ex: Methoxyflurane 
Enflurane o Treated by Atropine.
 Fluoride + Oxalate (nephrotoxic).
 Ex: Halothane 
Isoflurane  Bromide + Triflouroacetate  Faster induction & recovery.  Heart suergery.
(hepatotoxic).  Has muscle realaxing property.
sevoflurane  Rapid induction & recovery.  Induction of A in children.
Elimination
 Clearance is mainly by lung.
 Suitable for heart surgery. 23
 Because it has minimal effect on CVS.
 It determines the duration & recovery.
Methoxyflurane  Nephrotoxicity.

‫| نسألكم الدعاء‬
P H R M A C O L O G Y - NOTE 7 - General Anesthesia

DRUG PHARMACOKINETIC ACTION USES SIDE EFFECT

I.V.  They have narrow Ti. Mechanism of action  Respiratory depression.
 So, the dose must be calculated accurately.  They depress the activity of the  Bradycardia.
neurons in the brain.  Liver toxicity.
 By activate inhibitory  Kidney toxicity.
pathway (GABA & Glycine).  Cough.
 Site of action:  Salivation.
 Reticular formation.  Vomiting.
 Hippocampus.
Inhalation  They have narrow Ti.  Cortex.
 So, the dose must be calculated accurately. Action
 The dose is measured by MAC value.  Depression of all CNS function.
 MAC:  On CVS:.
o It is the concentration of anesthetic that o  myocardium contractility.
GA

result in immobility in 50% of patients  On RS: all GA (excepte N2O)

exposed to a painful stimulus. o  respiration.
o It measure: o  arterial Pco2.
 Dose. o  ventilation in response to
 Potency. hypoxia.
o  mucociliary function.
o Post-operative R infection
with long use.
 Nephrotoxicity.
 On Liver:
o  blood flow
o Hepatotoxicity.
 On uterus:
o Relaxation  bleeding.
INFLUNCING FACTORS FOR THE SELECTION OF GA COURSE OF ANESTHESIA
Patient's factors 1 Anesthetic premedication.
1 Age Diazepam  Produce sedation
 Relief anxiety Reduce GA dose
2 Allergy history Morphine  Produce analgesia
3 Status of organ system (e.g. RSD, CVSD, NSD, Endocrine D, Liver &kidney D) Atropine  Reduce side effect of GA
4 Genetical diseases (e.g. porphyria) Metoclo-  Produce anti-emetic effect
5 Use of other drugs proamide  Prevent aspiration
Anesthetic factors (criteria of ideal anesthetic)  Because no GA has all 2 Induction of GA
1 Rapidly & smooth induction these criteria, I.V. GA  loss of all sensation & loss consciousness
2 Fast recovery  We use 3 Maintenance of GA & muscle relaxant
combination A
3 Has muscle relaxing property Inhal. GA maintain anesthesia
4 Wide margin of safety Tubocuraine muscle relaxant
24
5 Minimum side effects 4 Recovery ( by terminate inhaler A)

‫| نسألكم الدعاء‬
 P H R M A C O L O G Y - NOTE 8 - Local Anesthesia

LOCAL ANESHESIA

moderate Potency & intermediate

weak Potency & short Duration high Potency & long Duration
Duration

Lidocaine (Xylocaine) Tetracaine

Procaine Chloroprocaine
Mepivacaine
Bupivacaine

•produce local loss

LA of sensation
without loss of
consciousness
Prilocaine Etidocaine

•Procaine
•Chloroprocaine

Esters •Tetracaine
•Benzocaine Ropivacaine
•Benoxinate
•Lidocaine
(Xylocaine)

Amide •Mepivacaine
•Bupivacaine
•Etidocaine
25

‫| نسألكم الدعاء‬
P H R M A C O L O G Y - NOTE 8 - Local Anesthesia

DRUG PHARMACOKINETIC ACTION USES SIDE EFFECT

Procaine Administration Mechanism of action 1) Surface anesthesia:  Usually minimum,
Weak Potency &
short duration

 Local injection.  LA block nerve conduction (initiation o on Skin (wound & ulcer) because:
 Local application ( solution, powder & propagation of AP) by: o on MM (mouth or nose). o Applied locally.
+
Chloroprocaine or cream)  Binding to Na channels & o in Ophthalmology (corneal A). o Combinewd with
+
prevent Na permeability. o powder, solution creams or ointment vasoconstrictors.
Absorption are used.
 NOT desirable because: Action 2) Infiltration anesthesia.
Lidocaine  It  duration.  LA are lipid soluble / weak base. o as in (wound suturing, cyst removal). 1) Hypotension.
Moderate Potency

(Xylocaine)
& Intermediate

 It  systemic side effects.  At pH= 7.4, 3) Individual nerve block anesthesia. 2) Bradicardia.
o as in Dental anesthesia.
duration

o they are UNIONIZED molecule. 3) CNS:

Mepivacaine Metabolism o They pass lipid membrane. 4) Spinal Epidural anesthesia.  Tinnitus.
 Easter, fastly metabolized by tissues &  When reach the cytoplasm, o as in surgery of (LL, abd, pelvis,  Lightheadness.
plasma esterase. o They become (ionized + rectum).  Headache.
Prilocaine  Into PABA (cause allergy). unionized). 5) Treatment of cardiac dysrhythmia.  Convulsion.
 Short duration. o The IONIZED molecules: 4) Allergy (in ester type).
Tetracaine + 1) Infiltration anesthesia.
 Amides, slowly metabolized by liver  Bind to Na channels. o as in (wound suturing, cyst removal).
High Potency &

+
 Block Na influx.
long duration

microsomal enzymes. 2) Individual nerve block anesthesia.

Bupivacaine
 Longer duration.  Prevent AP. o as in Dental anesthesia.
.  Side effects occur due to:
Etidocaine 3) Spinal Epidural anesthesia.
 The action are susceptible for (small o as in surgery of (LL, abd, pelvis,
o High dose.
diameter / unmylinated) fibers more o Injected into BV.
Ropivacaine rectum).
than (large diameter / mylinated)  They are potent & have
4) Treatment of cardiac dysrhythmia.
fibers. long duration.
Benoxinate  It is ester LA. In ophthalmology for corneal A because :
 NO mydriasis.
 NO corneal injury.
Benzocaine  Used as powder or cream. Surface anesthesia on Skin (wound & ulcer) 
 Because it is insoluble, it produces less
systemic toxicity.
INFLUENCING FACTORS
IF Advantage Disadvantage
1 Dosage High Fast onset / long duration  side effect
2 Site BV  side effect / Short duration
3 Lipid solubility LS  effect
4 Infection/ pH action / ionized /effect
inflammation Vaso-  absorb /  side effect/
dilation
duration
5 Type of solution Alkali Less painful / fast onset /
 non-ionized /  action / effect
6 + vasoconstrictors duration/ absorb /side effect 26

‫| نسألكم الدعاء‬
P H R M A C O L O G Y - NOTE 9 - Opioid Analgesics (Nacrotic analgesic)

OPIOID ANALGESICS DRUGS

pure Agonist patial Agonist Atagonist

Morphine Nalorphine Pentazocainel Naloxone

Methagone

Codeine

Pholocodeine

Dextropropoxyphene
• Mu
Classes of Opioid Rs •Kappa
•Delta
Diphenoxylate

•CNS
Loperamide
place of Opioid R •Periphral tiissues

Noscapine •agonist if it is combined

partial Agonist with pure agonist.
(mixed agonist-antagonist) •antagonist if it is combined
Fentanyl with antagonist.

27

‫| نسألكم الدعاء‬
P H R M A C O L O G Y - NOTE 9 - Opioid Analgesics (Nacrotic analgesic)

DRUG PHARMACOKINETIC USES ACTION SIDE EFFECT

Morphine Administration  Strong analgesic for chronic pain (cancer). On CNS.  Dysphoria.
 All taken by orally.  MI ACTION MECHNISM  Respiratory depression.
 Sustained release formulation.  Add with inhaler GA to produce analgesia. 1 Analgesia  Nausea & vomiting.
 Morphine is given by I.V.  Manegment for dyspnea. 2 Euphoria  prominent with pain   intra-cranial pressure.
Methadone o 75% of it, become inactive  Strong analgesic for chronic pain (cancer). 3 Dysphoria  Constipation.
Meperidine after absorption  Strong analgesic for chronic pain (cancer). 4 Resp.  sensitivity of RC to CO2  Urinary retention.
 Analgesic for labor pain. 5 Nausea stimulation of CTZ  Allergy:
Distribution
 Add with inhaler GA to produce analgesia. Vomiting  Itching.
 They are well distributed.
Pure Agonists

Codeine  Moderate analgesic for chronic pain (cancer) 6 Miosis agonize R on III c.n.  Bronchospasm.
 It is lipid soluble.
 7 Antitussive depress the CC  Tranceal rigidity(back
 They cross BBB & placenta. Cough suppression.
pain)
hydrocodeine  Moderate analgesic for chronic pain (cancer 8  BP & VD Depress VMC
Metabolism
Pholocodeine  Cough suppression On CVS. ( in large iv dose)
 By microsomal system
Dextropropoxyphen BP depress VMC  VD
 The metabolites are active.
Noscapine  Heroin (diacetylmorphine) Morphine. direct VD effect
Diphenoxylate  Codeine (Methylomorphine)  Morphine.  Treatment of diarrhea. release of histamine  VD
Loperamide  The metabolite are conjugated. On GIT.
Fentanyl  Add with inhaler GA to produce analgesia. 1 Constipa- sphincter tone
Elimination tion s.m. motility
 Mainly by kidney. 2 intra- spasm of bile duct
USES COTRA-INDICATION billary P spasm sphincter of oddi Treatment of addication
1) Analgesic for acute & chronic sever pain. 1) Head injury. On UT. Clonidine.
a. Acute pain (MI , post-operative)  Miosis. 1 spasm of ureters Control withdrawal
b. Chronic pain (cancer)   Resp. 2 Constriction of U sphincter symptom.
c. Labor pain 2) Biliary & renal colic(ex Meperidine) 3 micturation reflex
2) Cough suppression. Tolerance & Dependence. Methadone
3) Respiratory diseases.
3) Treatment of diarrhea. effect with repeated administration
 (asthma & COPD)
4) Mangment of dyspnea. 1 Analgesic Rapid tolerance
5) Analgesic with GA 4) Acute abdomen pain.
 Interfere with proper 2  Resp. Slow tolerance
a. Add with inhaler GA
diagnosis. 3 Miosis NOT develop
Acute MORPHINE poisoning 5) Pregnancy & labor (ex Meperidine) 4 constipation
Manifestation: Treatment  Addict fetus. 5 convulsion
Coma / pin point pupil 1) Artificial respiration.  Neonatal asphyxia. 6 Cross tolerance occur different agonist
Hypoventilation & hypoxia 2) Stomach wash. Addcation.
6) Liver diseases
Hypotension 3) Repeated I.V. Physical D Sudden withdrawal lead to
 Deficient metabolism
Hypothermia Naloxone Psycho. D withdrawal syndrome

28

‫| نسألكم الدعاء‬
P H R M A C O L O G Y - NOTE 9 - Opioid Analgesics (Nacrotic analgesic)

DRUG PHARMACOKINETIC USES ACTION SIDE EFFECT

Pentazocine  Agonist on Kappa R.  Analgesia.  Dysphoria.
 Partial agonist on Mu R.  Psychomimetic effect.
 Cause weak  RC.  Anxiety.
 Mild dependency.  Nightmares.
Partial Agonists

 Mild withdrawal manifestations.  Hallucination.

 Withdrawal manifest.
with morphine addict.
Buprenorphine  Maintainance drug for opioid dependent  Psychomimetic effect.
patient.  Anxiety.
 Nightmares.
Nalorphine  Hallucination.
 Withdrawal manifest.
with morphine addict
Naloxone  Acute opiod poisoing  Reverse sever respiratory depression.
Antagonist
Pure

29

‫| نسألكم الدعاء‬
P H R M A C O L O G Y - NOTE 10 - Anti-Psychotic Drugs
ANTI-PSYCHOTIC DRUGS

Typical Atypical

Phenothiazines Thioxanthines others Risperidone

Flupenthixol Haloperidol Quetiapine

Group 1 Group 2 Group 3

Chlorpromazine Pericyazine Fluphenazine Zuclopenthixol Pimozide Olanzapine

•Schizophrenia
•Brain damage Trifluperazine Sulpiride Clozapine
Psychoses are: •Mania
•Toxic delirium
•Agitated depression
Aripiprazole
•manifest disorders of
•perception
Schizophrenic •thinking
•speech
patients •emotion •+ve •delusions •Social/occupational
•physical activity

Negative symptoms of
symptoms •hallucinations dysfunction

Positive symptoms of
•Neuroleptics •disorganized •lack of self care
•-ve
Schizophrenia has

•due tp neurological effects e.g.

speech
Antipsychotic Parkinsonism symptoms

Schizophrenia
Schizophrenia
•Minor tranquilizersas •catatonia
drugs are called •du to calm or ‘tranquilize’ psychotic
symptoms without loss of
•agitation
consciousness
30

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P H R M A C O L O G Y - NOTE 10 - Anti-Psychotic Drugs

 Typical Anti-Psychotics
DRUG PHARMACOKINETIC ACTION USES SIDE EFFECT
G1 Chlorpromazine  Taken Orally.  Mainly antagonize D2 receptors. • Dopamine hypothesis for  ANS
 Some of them may also antagonize 5-HT2
Phenothiazines

schizophrenia: Anti-muscarinic
G2 Pericyazine receptors • Increased dopamine  blurred vision, IOP.
 More effective in the control of positive receptor density in  dry mouth,HR, confusion.
symptoms mesolimbic-frontol area  constipation, urine retention
G3 Fluphenazine  Given I.M. Inj. /3-4 wks
 Cause more extrapyramidal side effects in schizophrenics α – blocking
• Most antipsychotic drugs  ejaculation & impotence.
Trifluperazine  Taken Orally. block Dopamine D2  HR & orthostatic BP.
receptors in brain  CNS
Flupenthixol  Given I.M. Inj. /3-4 wks • Successful treatment of D R blocker
schizophrenia reduces  Parkinsonism.
Thioxanthines

homo-vanilic acid (HVA),  Akathesia.

a metabolite of  Dystonia
dopamine in CSF
Zuclopenthixol  Taken Orally. Super sensitivity of D R
• Drugs that increase  Tradive dyskinesia.
dopamine activity like  Sedation.
levodopa, cocaine,  Toxic confusional state.
apomorphine &  Neuroleptic malignant
Haloperidol  Given I.M. Inj. /3-4 wks amphetasmines syndrome.
aggravate schizophrenia  Endocrine(due to DR block &
or produce psychosis prolactin)
• There is possible
Pimozide  Taken Orally. Female
involvement of other  Amnorrhra & galactorrhea.
neurotransmitters also Male
others

like glutamate,  Gynecomastia & impotence.

Sulpiride serotonin, histamine, etc
e.g. Glutamate receptor  Weight gain (appetite).
(NMDA-receptor) antagonist  Hyperglycemia.
(phencyclidine) can produce
 Cholestatic jaundice.
schizophrenia like state
 Cataract.
& atypical anti-
 Risk of teratogenecity.
psychotics also inhibit 5-HT2 & D4
receptors

DRUGS sedation anti-muscarinic extra-pyramidal PATHO-PHYSIOLOGY OF SCHIZOPHRENIA

side effects side effects
G1 Marked Moderate Moderate   dopamine receptor density in mesolimbic-frontol area in schizophrenics.
G2 Moderate Marked Less   dopamine activity by drugs (like levodopa, cocaine, apomorphine & amphetasmines) that
G3 Less Less Marked aggravate schizophrenia or produce psychosis. 31
Thioxa.  NT (like glutamate, serotonin, histamine) that agonist 5-HT & D receptors.
others  Successful treatment of schizophrenia reduces homo-vanilic acid (HVA) in CSF.

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P H R M A C O L O G Y - NOTE 10 - Anti-Psychotic Drugs
 Atypical Anti-Psychotics
DRUG PHARMACOKINETIC ACTION USES SIDE EFFECT
 Given I.M. Inj. /3-4 wks  Block both D2 & 5-HT2 receptors.  Schizophrenia (1 line
st

 less extra-pyramidal &

Risperidone Anti-muscarinic & prolactin related se

prolactin related side

 Relive both + &- symptoms. drug) Less extra-pyramidal se.
Weight gain.
 Relatively low affinity for May cause:
dopamine receptors  Anxiety.
 Also or receptors  Insomnia.

effects
 Dizziness.
 BP
Quetiapine  They metabolized by P-450 in the liver.  Anti-muscarinic & prolactin related se

 More effective in the control

 Drug interactions occur with enzyme inducers  Less extra-pyramidal se.
& inhibitors.  Weight gain.
Olanzapine

of negative symptoms
 May cause:
 Drowsiness.
 Headache.
 Hyperglycemia (by olanzapine)
 Resistant Schizophrenia  Agranulocytosis (1 3 m).
st
Clozapine
nd
(2 line drug) So, monitor WBC count:
 before start.
 every 2 wk for 6 m
Aripiprazole  partial agonist at D2 receptors.  α – blocking

& 5-HT2 receptors

 Antagonist at 5-HT2 receptors.  orthostatic BP.

 antagonize D2, D4
 D2 R blocker
 Tradive dyskinesia.
 Neuroleptic malignant
syndrome
 Weight gain.
 Hyperglycemia.
PHARMACOKINETIC ACTION OF DOPAMINE RECEPTORS MECHANISIM OF ACTION of anti-psychotic drugs
Administration Metabolism
 Taken Orally.  It occur in liver & subject to 1
st
R Action Adenyl- cAMP SITE OF D2 RECEPTORS EFFECT
 The bioavailability is good pass effect. via cyclase
 Some are taken I.M inj. D1 Gs Activated  Mesolimbic-Mesocortical anti-psychotic
Drug interactions D5 pathway
Distribution  activity of anti-Parkinsonism drugs
 High lipid solubility. that are DA agonists (levodopa,
D2 Gi Inhibited  Nigro-Striatal pathway Extra-pyramidal
D3
 Taken 1-2/d due to long T1/2. amantadine, bromocriptine),
 due to blocking of D2R D4 Tubero-Infundibular ↑ prolactin secretion
 Potentiate sedative effects of pathway Galactorrhea
benzodiazepines & antihistamines Medullary-Periventricular  appetite
 May interact with liver enzyme pathway
inducers & inhibitors. CTZ Anti-emetic
32

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 P H R M A C O L O G Y - NOTE 11 - Anti-Depressants Drugs

ANTI-DEPRESSANT
DRUGS

ARI MAOI

Selective
Tricyclic Heterocyclic SNARI SSRI Tranylcypromine
NERI

Amitriptyline Amoxapine Venlafaxine Fluoxetine Imipramine Selegiline

Nortriptyline Maprotiline Fluvoxamine Atomoxetine Moclobemide

Imipramine Trazodone Citalopram

•  action of Tyramine
MAOI cause (sympathomimetics)
• Serotonin syndrom with SSRI

Clomipramine Bupropion Sertraline • does not cause

selective MAO-B I tyramine related
reactions
• hyperthermia.
Serotonin • muscle rigidity.
syndrom has • myoclonus.
Endogenous (melanocholic)

• griefe •biochemical • bipolar • CVS & Resp. failure.

disorder
Reactive (secondary)

• illness affective
Manic-depression

(genatically) disorder •due to depletion

•inability to depression of amine stores in
CNS
depression
depression

cope with
minor life 33
events

‫| نسألكم الدعاء‬
P H R M A C O L O G Y - NOTE 11 - Anti-Depressants Drugs

 Amine Re-uptake Inhibitors (ARI)

DRUG PHARMACOKINETIC MECHANISM OF ACTION USES SIDE EFFECT
Amitriptyline  Caution in glaucoma & BPH   re-uptake of NE & 5-HT.  Depression.  Anti-muscarinic
 due to anti-muscarinic side effect.  also  concentration in synapse.  Anxiety disorders.  blurred vision, dry mouth.
anti-depreesant

Nortriptyline  Caution in driving & skill full word  Chronic pain.  HR, confusion.
 due to sedation   constipation, urine retention .
Tricyclic

Enuresis.
Imipramine  α – blocking
 ejaculation & orthostatic BP
 sedation.
Clomipramine
 Seizure.
 Weight gain.
 Sex disturbances.
Amoxapine   re-uptake of NE & 5-HT.  Depression.  Parkinsonism. moderate
anti-depreesant

  D2 receptors.  Anxiety disorders  Akathesia. sedation

Heterocyclic

 So, it acts as anti-psychotic  prolactin. &

Maprotiline   re-uptake of NE & 5-HT  Seizures. anti-
 Arrhythmias muscarinic
Trazodone  Induce sleep.
Bupropion   re-uptake of NE, 5-HT & DA.  Seizures.
  Aggravate psychosis.
Venlafaxine  Low dose  acts as SSRI.   re-uptake of 5-HT (& NE but less).  Depression.  Low dose
5-HT & N-ad RI

 High dose  acts as TSAs  Anxiety disorders. o Sedative & anti-muscarinic.

(SNARI)

 Chronic pain  High dose

o Sedative & anti-muscarinic.
o Nausea.
o  BP
o Sex distrabunces.
Fluoxetine   re-uptake of 5-HT (more selective). obsessive & compulsive D  Transient nausea.

depression
Bulimia  Libido. (initial)

anxiety
SSRI

Fluvoxamine obsessive & compulsive D  Sex dysfunction. (maintenance

Citalopram therapy)
Sertraline
S NERI Imipramine   re-uptake of NE (more selective).  Attention deficit hyperkinetic
Atomoxetine disorder.
 Mono-Amine Oxide Inhibitors (MAOI)
DRUG PHARMACODYNAMIC MECHNISM OF ACTION USES SIDE EFFECT
Tranylcypromine  Inhibits MAO-A & MAO- B.  They  metabolism of amines by MAO.   Headache.
  duration of action of  Drowsiness.
Selegiline  Inhibit MAO- B. NE, 5-HT & DA.  Weight gain. 34
 also  concentration.  Postural PB.
o MAO-A metabolizes NE , 5-HT & Tyramine.  Sex disturbances.
o MAO-B metabolizes DA more than others.

‫| نسألكم الدعاء‬
 P H R M A C O L O G Y - NOTE 14 - Treatment of Epilepsy
ANTI-EPILEPTIC DRUGS

Partial seizures & Generalized seizures Others

gneralized tonic-clonic

Old Drugs Newer Drugs Ethosuximide Phensuximide Acetazolamide Benzodiazepines

Phenytoin Lamotrigine Trimethadone Oxazolidinediones Diazepam

Carbamazepine Gabapentine Lorazepam

• motor area (convulsion)
• hypothalamus (autonomic discharge)
Involvement of • reticular formation (unconsciousness)
Valporate Topiramate • Repeated seizure activity leads to Clonazepam
neurodegeneration due to excitotoxicity

Barbiturates Vigabatrine
Focal Seizures •remains localized
Nitrazepam

Generalized •primary (involve all cortical neurons) Clorazepate

Levetriacetam
Seizures •secondary (spread afterward) Dipotassium

• inhibitory NT.
• excitatory Nt
Felbamate TREATMENT •alter the permability of membrane
Clobazam
to ions (Na, K or Ca)

Zonisamide
Tiagabine
PARTIAL SEIZURES

GENERALISED
SEIZURES
•simple(consciousness) •Generalized tonic-clonic (grand mal)
•complex (unconsciousness) •Absence (petit mal) 35
35
•PS secondarily generalized •Tonic , Atonic , Clonic & Myoclonic
seizures
•Infantile spasm

‫| نسألكم الدعاء‬
P H R M A C O L O G Y - NOTE 14 - Treatment of Epilepsy
 Partial seizures & generalized tonic-clonic
DRUG PHARMACOKINETIC MECHANISM OF ACTION USES SIDE EFFECT
Phenytoin  It is metabolized in the liver.  Block or alter Na-voltage channels. 1) Partial seizures DOSE DEPENDENT
 plasma conc. <10 mg/L .  At high concentration: 2) Generalized tonic-clonic seizures.  Acute effect
st
 1 order kinetics.  Inhibit release of NE & 5-TH. 3) Status epilepticus.  Nystagmus.
 plasma conc. = 10-20 mg/L .  Inhibit MAO activity. 4) Trigeminal neuralgia (2nd choice).  Diplopia.
 zero order kinetics.  Promote uptake of 5) Cardiac arrhythmia.  Ataxia.
 The metabolism is inhibited by: Dopamine  Lethargy.
o Na valporate.  Sedation.
 Chronic effect:
o Cimetidine.
 Gingival hyperplasia, Hirsutism , Acne
o Isoniazide.
 Nausea ,vomiting ,epigastric pain, anorexia.
o Chloramphenicol.
 Megaloblastic anemia.
o Co-trimoxazole.
 Mild peripheral neuropathy
 It is a inducer of HME.  Osteomalacia.
 So, it enhances metabolism of:  Hemorrhagic diseases of new born.
 Carbamazepine  Fetal Hydantoin syndrome.
 Warfarin,Steroids. HYPERSENSITIVITY
 TCA & OC  Agranulocytosis with fever, rash , SLE & fetal hepatic
necrosis.
Carbamazepine  Block Na-voltage channels. 1) Partial seizures DOSE DEPENDENT
 Act pre-synaptically: 2) Generalized tonic-clonic seizures  CNS: Diplopia, Ataxia ,drowsiness, unsteadiness.
 to  synaptic 3) Trigeminal neuralgia.  GIT: Vomiting , Diarrhoea.
transmission. 4) Mania.  H2O retention & hyponatremia.
Old Drugs

 Inhibit uptake & release of NE. 5) Diabetes Insipidus (DI). IDIOSYNACRATIC BLOOD DYSCRASIS
 Aplastic anemia
 Agranulocytosis.
 Leucopenia.
 Hepatic dysfunction.
TERATOGENECITY
 Fetal malformation ( neural tube defects).
 valporate doubles teratogenicity.
Na Valporate  NOT used during PREGNANCY .  Inhibite GABA aminotransferase 1) Partial seizures. DOSE DEPENDENT
 to  GABA conc. 2) Generalized seizures:  Nausea, vomiting, abdominal pain.
 Block Na-voltage channels. a. tonic-clonic.  Weight gain, ↑ appetite.
b. absence.  hair loss, fine tremor.
c. myoclonic. IDIOSYNATRIC REACTION
3) Bipolar disorder(mania).  Hepatotoxicity.
4) Migrine prophylaxis.  Thrombocytopenia.
 Pancreatitis.
TERATOGENECITY
 Spina bifida,Cardiovascular abnormality.
 Orofacial & digital abnormalities.
Penobarbital  It is well tolerated, with single dose  Enahancement of GABAergic 1) Partial seizures  Drowsiness , lethargy , depression
Barbiturates

Mephbarbital  Contraindication. pathway. 2) Generalized tonic-clonic seizures.  Nystagmus, ataxia. 36

36
Metabarbital
o Porphyria (acute attack may occur)  Reduction of Glutamate action. 3) Status epilepticus.  Memory loss, irritability & mental confusion.
 Primidone is used in treatment of  Block Na & Ca(L,N) channels.  Teratogenic & hemorrhagic disease of new born.
Primidone 4) Febrile convulsion
Essential Tremor resistant to  Megaloblastic anemia & osteomalacia.
PROPRANOLOL.  Tolerated with single dose.

‫| نسألكم الدعاء‬
P H R M A C O L O G Y - NOTE 14 - Treatment of Epilepsy
 Partial seizures & generalized tonic-clonic (cont…)
DRUG PHARMACOKINETIC MECHANISM OF ACTION USES SIDE EFFECT
Lamotrigine  Block Na-voltage channels,  adjunctive therapy for refractory:  Dizziness, nausea & headache.
 to stabilize pre-synaptic o Partial seizures.  Diplopia.
o o
neuronal membranes. o 1 & 2 generalized tonic-clonic  Somnolence.
 reduces the release of excitatory seizures.  Skin rash.
amino acids (Glutamate & Aspertate)  Flu like symptoms.
Gabapentine  It is an analogue of GABA .   GABA synthesis & release. 1) Resistant partial seizures.  Somnolence.
 It crosses blood brain barrier.  block L type Ca channels. 2) Resistant generalized tonic-clonic.  Dizziness & headache.
 Agonize GABAB receptor. 3) Bipolar disorders.  Ataxia & tremors.
4) Migraine and neuropathic pain.
Vigabatrine   GABA conc. by 1) Partial seizures. NOT AT TOXIC DOSE
o
 irreversible inhibition of 2) 2 generalized responsible by  Dizziness, drowsiness.
GABA aminotransferase. seizures. other drugs  Weight gain.
3) Infantile spasms.  Agitation, confusion & psychosis.
LONG USE
 Irreversible Visual field defects.
Topiramate  NOT used during PREGNANCY .  Enahancement of GABAergic pathway.  adjunctive therapy for refractory:  Somnolence, fatigue & Dizziness.
Newer Drugs

 Block Na-voltage channels. o Partial seizures.  Nervousness & confusion.

 Block or antagonize Glutamate o Generalized tonic-clonic  Acute myopia ,glaucoma & urolithiasis.
receptors (weak). seizures.  Teratogenic abnormalities.
Tiagabine  Treatment by discontinuous doses  prolongs the inhibitory action of  adjunctive therapy for partial  Nervousness, confusion.
prevent : synaptically released GABA. seizures.  Difficulty in concentration & depression.
 Excessive confusion.  Tremor & ataxia.
 Somnolence.  somnolence & dizziness.
 Ataxia.
Zonisamide   Block Na channels. 1) Partial seizures.  Drowsiness.
 Block Ca-voltage channels. 2) Generalised tonic-clonic seizures.  cognitive impairment.
3) Infantile spasms & myoclonas.  Serious skin rashes.
Levetriacetam   At brain-specific binding site, it affects:  adjunctive therapy for partial  Asthenia.
 GABA receptors ( sensitivity) seizures  Dizziness.
 Ca-voltage channels (block).  with or without  Drowsiness.
 K-channels. generalization.
Felbamate   block NMDA receptor via GLYCINE  Refractory partial & generalized  Insomnia.
rd
binding site. seizures(3 line).  Dizziness.
 resistant seizures as in Lennox-  Ataxia.
Gastaur syndrome.  Aplastic anemia.
 Sever hepatitis.

LENNOX-GASTAURE SYNDROM
It consiste of:
 multiple seizure types.
 mental retardation.
 refractoriness to anti-seizure drugs. 37
37

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P H R M A C O L O G Y - NOTE 14 - Treatment of Epilepsy
 Generalized tonic-clonic
DRUG PHARMACOKINETIC MECHANISM OF ACTION USES SIDE EFFECT
Ethosuximide  Therapeutic levels & Dosage– 60-100  Inhibits:  Absence seizures  GIT:
mg/ml achieved with 750-1500mg/day.  T type Ca-channels in thalamas.  Pain, nausea & vomiting.
 It depresses the cerebral MR.  Na/K ATPase.  CNS:
 The clearance is reduced by Valporic  GABA aminotransferase enzymes  Headache, dizziness, euphoria
Acid.  It depresses the cerebral MR.  Blood:
 Eosinophilia.
 Pancytopenia (Thrombocytopenia, leucopenia)
 Transient lethargy or fatigue.
 Skin rash.
 Steven Johnson syndrome.
 SLE.
Trimethadone  NOT used during pregnancy.  Petit mal epilepsy ( drug of choice).  Sedation.
 Act actively against Pentyleneterazole  HEMERALOPIA(reversible impaired visual
that induce seizures. adaptation)
 Others
DRUG PHARMACOKINETIC MECHANISM OF ACTION USES SIDE EFFECT
Diazepam  used I.V. or rectally  They act as anti-epileptic by:  Generalized tonic-clonic (grand-mal).  Sedation. 
  GABAergic activity.  Status epilacticus  Tolerance.
Lorazepam  longer acting than diazepam.  CLORAZEPATE  More effective in status epilepticus.  paradoxical hyperactivity(in 
Benzodiazepines

DIPOTASSIUM---Used as an. children).

Clonazepam  Absence (petit mal) siezures. 
are common adverse effects.
  Ataxia, hypotonia , dysarthria.
Nitrazepam  Less potent than Clonazepam. Myoclonic seizures. 
 CLOBAZAM—  Salivation.
 infantile spasms.
 ADVERSE effects of  ↑respiratory secretions.
Clorazepate  adjunct to treatment of complex  Drowsiness.
Benzodiazepins ------
Dipotassium partial seizures.  Lethargy.
 . WITHDRAWAL SYMPTOMS
Clobazam  Commonly not used due to quick & high  less sedative.
 Exacerbation of seizures if
tolerance
the drug is stopped suddenly.  High TOLERANCE
Acetazolamide  It is a carbonic anhydrase inhibitor  Exerts its anti- seizure activity by:  Epilepsy during menses (as it  Tolerance (quick develop).
 Mild acidosis in the brain. discontinuously administrated, NO
rolerance)
Sulthium  It is a carbonic anhydrase inhibitor

TYPE DRUG OF CHOICE ALTERNATIVE DRUG

ALTERNATIVE

Lamotrigine

Phenobarbito

Ethosuximide
Phenobarbiton

Gabapentine
Clonazepam
Clonazepam
Simple partial Phenytoin Gabapentine

Lamotrigine
Lamotrigine

Topiramate

Carbamazepi Vigabatrine

Topiramate
Felbamate
DRUG

Phenytoin
GENERALIZED SEIZURES

Clobazam

Tiagabine
Complex partial Phenobarbitone Felbamate
SEIZUREs
SIMPLE

Partial with secondarily valporate Topiramate

generalised Lamotrigine Tiagabine

ne
Phenytoin Gabapentine

Phenobarbiton
Ethosuximide

Clonazepam
Clonazepam

Lamotrigine
DRUG OF
CHOICE

Primidone
ePhenytoin
Valporate

Valporate

Valporate

Valporate
38
38

ne
N ote
Type Absence Atonic Myoclonic Grand mal/tonic/clonic

‫| نسألكم الدعاء‬
 P H R M A C O L O G Y - NOTE 15 – Anit-migraine Drugs
ANTI-MIGRINE DRUGS

Acute Attack Prophylaxis

Mild to Moderat to β adrenergic Ca channel 5-HT2 5HT2 antagonist

Specific drug /partial agonist Other
Moderate Sever blockers blockers antagonist

P Agonest for α-
NSAIDs Anti- emetics prokinetic Diclofenac 5-HT Agonist Adrenceptors & 5- Propranolol Flunarizine Pizotifen Methysergide Amitryptyline
HT R

Diphenhydr- Metocloper- Cyprohepata-

Aspirin Sumatripan Ergotamine Metoprolol Nicardipine Imipramine
amine amide dine

Paracetamol Promethazine Domperidone Almotriptan Nadolol Nifedipine Sertraline

Ibuprofen Naratriptan Atenolol Nimodipine Fluoxetine

Indomethacin Pizatriptan Timolol Verapamil Clonidine

Naproxene Zolmitriptan Valporate

Opioids

39

‫| نسألكم الدعاء‬
P H R M A C O L O G Y - NOTE 15 – Anit-migraine Drugs
 Acute attack of Migraine
DRUG PHARMACOKINETIC ACTION USES SIDE EFFECT
Aspirin  Given orally.  Analgesic.  acute migraine attack.
Mild to Moderate

Paracetamol  they must be given early to be absorbed before

NSAIDs

Ibuprofen there is vomiting.

attack

Indomethacin
Naproxene
Opioids  Given parentrally (I.V. or I.M.).  Refractory cases of
acute attack of
Efficient use of analgesic &
migraine(rarly)
antiemetic is sufficient for the
Diphenhydramine  Prevent vomiting.
Anti- emetics

majority of ACUTE ATTACKS

Moderat to Sever

Promethazine
attack

Metocloperamide  Given by I.V. injection.  They promote gastric emptying,  With very severe
prokinetic

 So, enhances absorption of vomiting.

Domperidone  Given as rectal suppositories for vomiting can analgesics.
be tried
Diclofenac
Sumatripan  Given by oral route or S.C. injection.  stimulate 5-HT1 R on pre-  acute severe migraine  Malaise ,fatigue.
 Fast absorbtion. synaptic endings of V cn. attack(1st line).  Sedation.
 Bioavailabilty by s.c. route is 96%  inhibit releasing of  Dizziness, vertigo, nausea & vomiting.
 Dose not cross BBB. vasodilators .  NOT used with  feeling of chest pressure, tightness & pain.
5-HT Agonist

 Plasma t1/2 is 2 hours.  selectively stimulates  IHD.  CARDIAC ARRHYTHMIA & myocardial infarction.
5HT1B/1D R in cranial BV,  unstable angina.  due to coronary artery spasm.
 constrict them.  previous MI
Almotriptan  they are congeners of Sumatriptan.  Less side effects.
Specific drug for acute attake

+ effects
on CNS
Naratriptan  improved pharmacokinetic  Reduce cardiac side effects.
Pizatriptan  better Bioavailability.
 better and longer duration.
Zolmitriptan
Ergotamine Ergotamine tartrate  stimulate 5-HT1 R on pre-synaptic  Migrine (high specific).  Paresthesiae in hands & feet.
 Given by o Entral route (oral, sublingual, rectal). endings of V cn.  Peripheral ischaemia.
P Agonest for α-Adrenceptors & 5-HT R

o Parentral route (inhaler).  inhibit releasing of  Peripheral GANGRENE with overdose.

 rectal route is preferred ???. vasodilators .  Precipitate angina pectoris.
 caffeine facilitates absorption of ergot alkaloid.  Fetal damage.
 It metabolized in the liver.
 t ½ is 2 hrs  NOT used with disease
 DOSE. of:
o Tablet (1mg + Caffeine 100mg).  Coronary BV.
o 1-2 tab. at onset ,then 1 tab/ 30min.  Peripheral BV.
o NO > 6 mg/attack & NO >10 mg/wk.
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 For severe attack, it ginen may be IM/IV injct.
 Dihydroergotamine o For intractable migraine.
o Given by IV inj.(0.5-1mg)

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P H R M A C O L O G Y - NOTE 15 – Anit-migraine Drugs
 Prophylaxis drugs for Migrine.
DRUG PHARMACOKINETIC ACTION USES SIDE EFFECT
Propranolol • PROPRANOLOL– (effect ,  the d-isomer part of structure lacks β  They are effective and widely used.  Fatigue.
also prevent migraine ). blocking action;  Broncho-constriction.
β adrenergic blockers

 Alter the permeability of the

membrane.
Metoprolol
Nadolol
Atenolol
Timolol
 Block Ca channel. 
Ca channel blockers

Flunarizine effective in the preventive treatment

Nicardipine of Migraine
Nifedipine
Nimodipine
Verapamil
Pizotifen  antagonize5-HT2 receptors.  They are RARELY used  Weight gain.
antagonist

 Atropine like action.  Anti-cholinergic side effects.

5-HT2

Cyprohepatadine  Antagonize 5-HT2 R & H 1 R.  Sedation.

 Block Ca channels  weight gain.
Methysergide  effective in about 60% patients.  It is 5HT2 antagonist /partial agonist  Serious Toxicities like;
5HT2 antagonist
/partial agonist

o RETROPERITONEAL
 obstruction to the Ureters.
o Subendocardial, Pericardial or Pleural fibrosis.
 Nausea, vomiting & diarrhoea.
Amitryptyline  effective for the PROPHYLAXIS of
Imipramine migraine in some patients.
Other

Sertraline
Fluoxetine
Clonidine
Valporate

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