pharmacology mind maps

About the Book

This book is prepared to facilitate the studying Pharmacology for students of any medical field

(Pharmacy , Medicine , Dentistry, Nursing, etc.)

As Pharmacology contain too many drugs that are hard to be memorized even if you are

planning to take a Pharmacology exam or you are studying pharmacology for any purpose , This

book will facilitate your mission .

This book is only about 40 pages that make Pharmacology study easy as drinking a cup of

water .

Pharmacology Mind maps

By Raafat Gergis

1st

Edition ,

All Right are reserved for the Author

Copyright© 2016 Raafat Gergis

https://www.facebook.com/raafat.Issaq

Navigate to Contents

Drugs for Bronchial Asthma Drugs for cough Drugs for Peptic ulcer GIT drugs Sedatives and hypnotics General Anesthesia Local Anesthesia Opioid analgesics Anti-Psychotic Drugs Anti-Depressants Drugs ANTI-EPILEPTIC DRUGS ANTI-MIGRINE DRUG

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

Drugs for Asthma

Anti-inflammatory

(glucorticosteroids) Anti-leukotrienes Mast cell stabilizers

β2-adrenergic

agonist Methylxanthines Anti-muscarinic Beclomethasone

LT synthesis inhibitor

LT receptor antagonist

Sodium Cromoglycate

Salbutamole Theophylline Ipratropium Hydrocortisone Zileuton Montelukast

Terbutaline Aminophylline Prednisolone Mucosal inflammation

Mucosal edema

Salmaterol Broncho-

constriction

Role of Leukotrines

in asthma

Mucus

secretion

•Contraction of airway smooth muscle.

•leadiŶg to acute dyspnea & airway obstruction.

•Mucus hypersecretion.

•leadiŶg to mucus pulgging.

Uses of bronchodilator

•Airway inflamation.

•leadiŶg to bronchodema. for acute bronchospasm

during acute phase of

asthma attack

for quick

reduce airway constriction

Bronchodilators

Clin

ical

feat

ure

s o

f b

ron

chia

l as

thm

a.

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

Bronchodilaters

DRUG PHARMACOKINETIC ACTION USES SIDE EFFECT

Β2-

ad

ren

ergi

Salbutamole Fast onest.

Short duration. Given inhaler or Nebulizer. Less side effect.

Given orally, S.C, IV or IM.

Large dose. More side effect.

Bind to β-receptor & stimulate adenylcyclase.

Leading to cAMP. Bronchodilatation.

Used for acute attack. Tremor. Vascular headache. Terbutaline

Salmaterol Slow onest. Long duration.

Used for long term therapy.

Met

hyl

xan

thin

es

Theophylline Has narrow theraputic index.

Given orally. Cause GI irritant.

Inhibit PDEI. Leading to cAMP.

Ca++ influx Bronchodilatation

1) CNS stimulation. 2) Cardiac muscle stimulation. 3) Diuresis. 4) S.M. relaxtion of bronchial & uterus. 5) Periphral & cornory vasodilatation. 6) Cerebralvasoconstriction.

GIT: nausea, vomiting . CNS: stimulation insomnia, irritabillity & headach.

CVS: BP, arrhythmia. Kidney: diuresis. Aminophylline Water mixture of Theophylline + Ethylenediamine.

Given orally, rectally (suppositories) or injection.

Anti- musc

rinic

Ipratropium It is poorly absobed from the GIT.

So,it given by inhalation.

Slower onest & longer duration than salbutamol.

Blocking M receptor in bronchial smooth muscle.

Bronchodilatation

Dry mouth.

Anti-inflammatory(Glucorticosteroid)


Beclomethasone Given by inhalation, orally or IV. 1) Reduce mucosal edema.

2) Sensitize β2-agonist. 3) Reduce inflammatory cell activation

If taken by inhalation, Dysphonia (hoarseness). Oral candidiasis (fungal infection).

Hydrocortisone

Prednisolone

Anti-Leukotrienes


Zileuton 1) Inhibit lipoxygenase enzyme. 2) Reduce conversion of AA to LT.

So, it is … Broncodilater. Anti-inflammatory.

To prevent asthma caused by Aspirin. NASID.

Montelukast 1) Blocking LT receptors. 2) Inhibit bronchoconstriction caused by LT

To prevent asthma caused by NASID & Exercise.

Mast Cell Stabilizers


Na Cromoglycate Given by inhalation. Reduce the mediators that release

from mast cell in response to allergen

that cause bronchoconstriction.

Prophylaxis aginst asthma

attack. Cough.

Wheeze. Ketotifen Given orally.

|

Productive Cough

It clears the excess secretions

& inhaled foreign matters. Expectorants are used.

Non-Productive Cough

Dry cough has no useful function. Anti-tussives are used.

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

Common causes of Cough:

• 1) Acute Respiratory Infection. • Upper respiratory infection.

• Pneumonia.

• Bronchitis

• 2) Chronic Respiratory Infection. • TB.

• Postnasal drip.

• 3) Airway Diseases. • Asthma.

• COPD.

• 4) Irritants. • Cigarettes smoking.

• Inhaled foreign bodies.

• 5) Drug Induced. • Inhaled drugs (aerosols).

• ACE-inhibitors (anti-hypertensive).

Anti-tussive

Locally antitussive

Mucoactive

Agents

• They should be used for dry cough. • because it suppress cough reflex, it should not be used in

the presence of bronchial secretions.

• It reduces the sensitivity of periphral cough receptors to it's

activators which include irritants & autacoids (Bradykinine).

• They clear airway from mucus secretion by:

• ability to expectorate sputum.

• mucus hyper secretion.

|


Centrally &

DRUDS FOR COUGH

Anti-tussives Drugs

Mucoactive

Agents

Centrally Peripherally Expectorants Mucolytics

Opioid

Dervatives Anti-histamins Above Larynx Below Larynx

Hyperosmolar

saline Na citrate Classic

mucolytic

Diphenhydram

ine Lozenge

steam with or without (menthol & benzoin

tincture)

K citrate Na

NAS bicarbonate

Pholcodeine Syrup Nebulized

Lignocaine

Ammonium

Cloride Na Iodide

Peptide

mucolytic

Dextrome- thorphan Nebulized

Benzocaine

K Iodide Guaifenesin Dornasealpha

Noscapine Creosote Guaicolate others

Periphrally Bromhexine

Benzonatate Ambroxol

Mucoregulatory

Anti- cholinergic

Macrolide

Antibiotics

Anti-

inflammatory

Ipratropium

Atropine

Azithromycin Indomethacin Corticosteroids

Codeine

|


Anti-Tussives (cough suppressent)

DRUGS PHARMACOKINETIC ACTION & ITS MECHANISM USES SIDE EFFECT

Act

ing

Cen

tarl

ly

Op

ioid

Der

vati

ve

Codeine They suppress cough reflex by Derict inhibition of Cough Center in the

medulla.

Nausea.

Dizziness.

Urenary retention. Constipation.(vi)

Pholcode

Dextromethorphan

Noscapine

An

ti-

His

tam

ine

Diphenhydramine It depresses CNS including Cough Center. Sedation.

Drowsiness.

Dizziness.

Act

ing

Per

iph

rally

Ab

ove

Lary

nx Lozenges They are demulcents. They form gelatious coat that protects the

inflammed skin Used for cough of Sore throat. Pharyngitis.

Syrup(honey)

Bel

ow

Lary

nx

Steam Without tooking, it taken by

inhalation .

Taken with or

without (menthol & benzoin

tincture)

Promote secretion of dilute mucus, To protect inflammed mucosa

NebulizedLigocaine 1) Local anesthesia. 2) Blooking mucosal cough receptors.

During fiber optic bronchoscopy. intractable cough in bronchial carcinoma.

Nebulized

Benzocaine

Acting both

Centrally &Periphrally

Benzonatate Chemichally, it is related to

tetracaine (local ansthesia). 1) In lungs, acting on

Stretch & cough receptors. 2) Act on CNS

Mucoactive Agents (Expectorants) o They volume or hydration of airway secretion. o They improve expectoration of respiratory mucus secretion.


Exp

ecto

ran

ts

Hyperosmolar Saline (10 ml of 6% saline).

Inhaled by ultrasonic nebulisation. Used in fibross & bronchiectasis.

Na citrate 1) Stimulate secretion of low viscosity watery

mucus & sissolve it.

To make it thinner less sticky.

2) elasticity of bronchi.

To easily expectorate the mucus.

Used in early dry stage of acute bronchitis. K citrate

Na bicarbonate

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

2)has mucolytic action. Chronic respiratory disease.

Chronic asthma.

K Iodide Guaifenesin 1)respiratorysecretion.

2)adhesiveness & surface tension of viscid sputum

Creosote 1)sputum. 2)has mild antiseptic & deodrant action.

Lung absess.

Chronic bronchitis.

Bronchiectasis.

Guaicolate


|

Muocoactive Agentgs (Mucolytic) o They viscosity & of elasticity airway secretion & mucociliary & cough clearance.


Cla

ssic

Mu

coly

tic

N-acetulcysteine (NAC) Taken orally or by inhalation. It is a precursor of intracellular cysteine & glutathione.

1) Hydrolyse disulfid bond of mucin.

So, mucus loss it’s viscosity & elasticity.

2) Act as antioxidant.

So, it prevent pulmonary injury in patient

with COPD or lung cancer.

In condition associated with viscous mucus

secretion: Chronic bronchitis, emphysema,

brochiectasis & cystic fibrosis. (ARD): bronchitis, pneumonia & asthma. Post-operative & post-traumatic

pulmonary complications. Care of tracheostomy.

Act as antidote for paracetamol overdose.

Bronchospasm. Prevent by

β2-agonist.

Disagreeable odor. Sulfur odor &

taste.

GI irritation.

Nausea.

Vomiting.

Stomatitis.

Pep

tide

Muc

olyt

ic Dornase alpha Taken by nebulisation. For cystic fibrosis. Allergicreaction.

Pharyngitis.

Laryngitis.

Voice alteration.

Oth

ers

Bromhexine It is an expectorant & mucolytic

drug.

Taken orally, parentral or by

inhalation.

1) Liquefy mucus.

By viscosity of bronchial secretion.

2) Enhance expectoration.

By the rate of microciliary.

Acute bronchitis.

Chronic bronchitits.

COPD.

Rhinorrhea.

Lacrimation.

Gastric irritant. Avoid with

antacid. Ambroxol Taken orally.

has less GI irritant.

Mucoactive Agents (Mucoregulatory Agents)

o They airway mucus hyper secretion which caused by goblet cells & submucosal gland.


An

ti-i

nfla

mm

ato

ry

Indomethacine inflammation which leading to mucus hyper secretion.

Panbronchiolits

Corticosteroid

Ant

icho

liner

gic

Ipratropium mucus volume that secreted in chronic

bronchitis.

Atropine mucus hypersecrtion. used pre-anesthetically for endotracheal intubation.

Mac

rolid

e

anti

biot

ics

Azithromycin Taken orally for long term

administion.

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

DRUGS FOR PEPTIC ULCER

Drugs Affecting HCL

Mucosal Protictive Agents

Drugs erdicate

H. Pylori

Antacids H2 Blocker Sucralfate Misoprostol

Colloidal Bismuth

compounds Triple Therapy

Quadruple Therapy

AL(OH)3 Cimetidine

Bismuth

Subsalycilate

Omeprazole OR

Lansoprazole (PPI)

Omeprazole OR

Lansoprazole (PPI)

Mg(OH)2 Ranitidine Bismuth

Sobcitrate Clarithromycin

Bismuth

Subsalycilate

Famotidine Amoxycillin OR

Metronidazole

Metronidazole

Proton Pump

Inhibitors Anti-muscarinic Tetracycline

Omeprazole

Lansoprazole

Pirenzepine

• It is caused by imbalance between:

• Protective Factors • (Mucus & Bicharbonate).

• Dameging Factors • (HCL & pepsin).

• So, it is caused by either DF or PF. Pep

tic

Ulc

er

(GU

& D

U)


Drugs Affecting Gastric (HCL) Acid

DRUGS PHARMACOKINETIC ACTION USES SIDE EFFECT A

nta

cid

AL(OH)3 Weak bases (-OH).

Taken 30 min in empty stomach.

Taken 2 hrs after meal.

Relieve heart burn immediatly.

If it take with other drugs, It form insoluble com;ex that adsorb on

GIT wall not absorb.

So, it take 2 hrs after or before other druds

1) Neutralize

already

secreted acid. 2) Inhibit

formation of pepsin

Slowly Usedfor symptomatic

relife of dyspepsia Constipation.

In renal failure,

Aluminum toxicity Encephalopathy

MG(OH)2 Fast Diarrhoea

Combination Fast &

sustained Constipation + Diarrhoea = nothing

Ad

dit

ives

Simethicone They are added to antacid either it combined or no.

surface tension

So, reduce buble

formation.

Anti-flatulent.

To prevent reflux.

Alginates Form a layer of foam on the

top of gastric content. Reduce reflux

H2

antagonist (blokers)

Extremly

save drugs

Potency T1/2 Duration

(hrs) Inhibition of

Cyto-450 Cyto-450 is an enzyme that metabolizes drugs.

H2 antagonist cross placenta & are

also secreted in breast milk.

Cimetidine 1 1.5 – 2.3

6 1 Not used by elderly

male because it is anti- androgenic

Gynecomastia.

Galactorrhea.

Inhibition of Cyto-450 So, conc. of Theophyline &

Warfine.

Ranitidine 5 -10 1– 2.4 8 0.1

Famotidine 32 2.5 - 4 12 0

PP

I

Omeprazole Average T1/2= 1.5 hrs.

Need acidic media, So Taken 1 hr befor meal. DoŶ’t take with other acid suppressing

agent.

Irreversible inhibitors for H+/K+ATPase

Lansoprazole

An

ti-

mu

scar

inic

Pirenzepine Inhibit gastric acid by blocking M3

receptor Used in refractory

cases that is not responding to other drugs.

Used in nocturnal pain.


Muocosal protective Agents

DRUGS PHARMACOKINETIC ACTION USES SIDE EFFECT Sucralfate It is salt of ( socrose + AL(OH)3 ).

Taken 1 hr befor meal.

Work in acidic pH Not used with antacid or H2 antagonist.

1) In acidic pH, it become

viscous gell & protect ulcer. 2) Stimulate PG production.

Misoprostol It is a PGE1 analogue 1) Gastric acid inhibition. 2) Stimulate secretion of

mucus & bicarbonate. 3) Enhance mucusal blood

flow.

Used with NSAID to

prevent peptic ulcer Diarrhoea

Abdominal pain.

Abortion?

Bismuth subsalicylate 1) Coat the ulcer 2) stimulate secretion of

mucus & bicarbonate. 3) PG synthesis.

Stain stools & tongue with black

color.

Cause bismuth toxicity with long

used.

Bismuth sobcitrate

Drugs erdicate Helicobacter pylori

DRUGS PHARMACOKINETIC ACTION USES SIDE EFFECT

Trip

le T

her

apy

Omeprazole

Or

Lansoprazole (PPI)

It is combination of ONE acid suppressant + 2

antibiotics.

Given for 14 days. Then, followed by PPI for 4 - 6 wks.

Clarithromycin

Amoxycillin

or Metronidazole

Qu

adru

ple

Th

erap

y

Omeprazole

Or Lansoprazole (PPI)

It is combination of ONE acid suppressant + 3

antibiotics.

Given when triple therapy fails.

Bismuth Subsalicylate

Metronidazole

Tetracycline

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

Laxative

• It help easy evacuation of the bowel contents during defecation.

• Usually self-prescribed for the relief of constipation

Constipation

• It is best prevented with:

• high fiber diet.

• adequate fluid intake.

• regular exercise.

Management of dehydration

• For mild to moderate dehydration:

• ORS (oral rehydrate salt)

• NaCl, KCl, Na HCO3

• glucose & water • For sever dehydration:

• IV fluids

• 5% dextrose & normal saline.

• KCl &/or Na HCO3, when hypokalemia &/or acidosis


GI Drugs

Laxative Anti-Diarrhoeal

Drugs

Bulk Formation Faecal Softners Simulant

Laxative

Osmotic Laxative

Balance

Polyethylene glycol

(Bowl Cleaning Solution)

Opioid Anti-

muscarinics

Methyl-cellulose Liquid paraffin Bisacodyl Mg hydroxide Polyethylene

glycol

Diphenoxylate Dicyclomine

Glycerin

suppository Senna Mg sulphate

Na sulphate

Loperamide Hyoscine-N-

butyl bromiae

Ispagula husk Na sulphate

Na chloride

5-HT3 antagonists

Adsorbents

Na citrate

Na bicarbonate alosetron Kaolin Pectin Colloidal

Bismuth

Lactulose

K chloride

Al silicate

H2O

Mg silicate

Bran


Laxatives

DRUGS PHARMACOKINETIC ACTION USES SIDE EFFECT Bulk Formation Methyl-cellulose 1) Absorb water.

2) the bulk of stool.

3) Stimulate peristalsis.

Constipation

Diverticular disease.

Colostomy.

Hemorrhoids & fissure.

Irritable bowl syndrome.

Intestinal obstruction Prevented by taking

sufficient H2O. Bran

Ispagulahusk

Faecal Softner

Liquidparaffin Given oraly. 1) Lower surface tension. 2) Make stool soft.

Constipation (can be used in

pregnant ladies)

To avoid straining at stool in

myocardial infarction.

Aspiration pneumonia

Leakage of stool.

Deficiency of Vit. A, D, E & K. with long term use.

Glycein suppository It is inserted via anal canal. 1) Makes stool soft. 2) Help evacuation.

Stimulant laxative

Bisacodyl Given oraly or suppository. The onset of action 6-8 hrs.

The effect is repeated due to entero- hepatic re-circulation.

1) Stimulate intestinal motility. 2) Na & water absorption.

Constipation. Preparation for radiology.

Avoid in intestinal obstruction &

pregnancy

Diarrhoea.

Loss of fluid & electrolyte.

Senna Osmotic

Laxative

Mg hydroxide Its action take 1-3 hrs. 1) Hold water due to osmotic pressure. 2) Distend the bowl. 3) Prompt evacuation.

Constipation.

Preparation for radiology.

Expulsion of worms.

Avoid in pregnancy Avoid Na-salts in CVS, liver & renal diseas.

Diarrhoea.

Loss of fluid & electrolyte. Mg sulphate

Na sulphate

Na citrate

Lactulose Non-absorbablesugar 1) Reduces pH due to conversion of NH3

to NH4. 2) absorption of ammonia.

Constipation.

Control of encephaopathy in liver cirrhosis.

Flatus.

& abd cramps. When it is l

metabolize By bacteria

in GIT.

Balanced

polyethyle

ne glycol

Contains:

Polyethylene glycol It is a bowl cleaning solution. It is isotonic to intestinal contents.

It retaines H2O & electrolytes in the

lumen of GIT.

& take faecal matter out along with it .

Bowl cleaning to prepare for: Surgery. Colonic endoscopy. Radiology.

Na sulphate

Na chloride

Na bicarbonate

K chloride

H2O


Anti- Diarrheals

DRUGS PHARMACOKINETIC ACTION USES SIDE EFFECT Opioid Diphenoxylate Usually given in combination with

atropine. It gonize opioid receptors (e.g. μ R). So, it.

1) peristalsis movement. 2) constrict sphincters.

Most their effects are on GIT.

Minimal sedation. Minimal dependence.

Loperamide Anti-muscarinic Dicyclomin They competitively blocking M3

receptors in GIT. So, theǇ… 1) peristalsis movement. 2) constrict sphincters.

NOT used with elderly patients

that have glaucoma

NOT used with male patients that have prostatic hypertrophy.

Dry mouth.

Constipation.

Tachycardia.

Palpitation.

IOP.

Urineretention.

Hyoscine-N-butyl bromide

5-HT3

antagonists Alosetrone It is well absorbed from GIT.

Has short T1/2. Has long acting.

Competitively block 5-HT3 R. so, it…

o ↓ GI ŵotility

Control of sever.

in irritable bowl syndrome which is

more common in women.

Constipation. Ischemic colitis.

Adsorbents Kaolin Al sikicate Adsorb microorganisms & toxins.

Absorb water. Constipation.

absorption of many

drugs. Colloidal bismuth gives

black color to tongue &

stool.

Mg silicate

Pectin It is indigestible carbohydrate from

apple

Colloidal bismuth


GI Drugs

Drugs for IBD

Anti-Emetics

Drugs Prokinetic

Gluco-

corticoids

Immuno-

suppresive

Cytotoxic

agents

Cytokine Inhibitors

Azo- compounds

5-ASA

Mesalamine

D2 R antagonists

Metoclopr- amide

Domperi- done

Anti- histamine

Cyclizine

Meclozine

D2 R antagonists

Metoclopram ide

Domperidone

5- HT4 R agonist

Metoclopram id

Prednisone Azathioprine Infliximab Sulfasalazine

Droperidol Diphenhydr-

amine

Prednisolon Methotraxate Olsalazine Phenothiazines Anti-

muscarinics

budesonide Balsalazide Promethazine Hyoscine

Hydrocortisone

5-HT3 antagonists

Marijuana derivatives

Ondansetron Dronabinol

Nabilone

Steroids

Dexamethne


Treatment of Inflammatory Bowel Disease DRUGS PHARMACOKINETIC ACTION USES SIDE EFFECT

5-A

SA

Azo

-co

mpo

und

Sulfasalazine 5-ASA + sulfapyridine.

Azo-bond broken in

GIT(colon) by azo- reductase that secreted

by bacteria

1) 5-ASA iŶhiďits…… Cyclo-oxygenase enzymes. Lipo-oxygenaseenzymes.

2) anti-inflammatory action.

1st line drugs for treatment of mild to moderate Ulcerative colitis. ChroŶ’s disease

in colon or rectum.

GIT: Nausea, vomiting.

Hematological: BM suppression. Megaloblastic anemia. Renal:Crystal urea & Renal

stones.

Hypersensitivity: Skin rash. Angiodema.

General: Headache, malaise, arthralgia & myalgia.

Olsalazine 2 molecules of 5-ASA. Diarrhoea.

Balsalazide 5-ASA & amino-benzoyl alanine.

Mes

ala

min

e

Mesalamine Enteric coated form of 5-ASA.

It available as enema &

suppository.

1st line drugs for treatment of mild to moderate Ulcerative colitis. ChroŶ’s disease

in colon, rectum or small intestine.

Renal damage.

Imm

uno-

supp

resi

ve d

rug

s

Gluco- corticoid

Prednisone They given oraly. • Anti-inflammatory & immune suppressant action. So, it…..

1) phospholipae A & C.

2) synthesis of PGs & leukotrienes synth

of cytokines (TNF- , IL-1), chemokine (IL-8.)

3) Destroy lymphoid cells & some T-cells

For acute & sever ulcerative

colitis & ChroŶ’s disease. Hypertension

Hyperglycemia.

peptic ulcer.

Infection.s

Renal suppression. Prevented by terminate

the treatment with

tapering doses.

Prednisolone

Budesonid

Hydrocortisone Given IV injection.

Cytotoxic Azathioprine Purine analog. 1) DNA synthesis. 2) Damage lymphoid & T- cells.

Alternate or additional therapy for Refractory ulcerative

colitis. ChroŶ’s disease.

Nausea.

Vomiting.

BM depression.

Infections.

Infertility.

Methotraxate 1) Inhibitor of dihydrofolate reductase. 2) DNA synthesis. 3) Damage lymphoid & T- cells.

Cytokine

inhibitor Infliximab Enteric coated form of

5-ASA.

It available as enema &

suppository.

1) Anti- TNF(pro-inflammatory cytokine) 2) release of cytokines from inflammatory cells

Alternate or additional therapy for Refractory ulcerative

colitis. ChroŶ’s disease.

Infections

Infusion reaction.

Feve.

Chills.

Urticaria.

Chest pain.

Dyspnoea.


Anti-emitic

DRUGS PHARMACOKINETIC ACTION USES SIDE EFFECT D2 receptor antagonists

Metoclopramide 1) Inhibit D2 receptors in CTZ. 2) Control vomiting . 3) Have prokinetic effect.

Extrapyramidal reaction.

Diarrrhoea.

Domperidone DoŶ’t crossBBB.

Droperidol 1) Inhibit D2 receptors in CTZ. 2) Control vomiting .

Sedation.

Extrapyramidal reaction.

QT-interval & cause

ventriculartachycardia.

Anti-histamines Cyclizine Inhibit H1 & M3 receptors iŶ…

CTZ. Vomiting center.

Sedation.

Anti-muscarinic side effects:

dryness of mouth. Tachycardia. Constipation.

Meclozine

Diphenhydramine Phenothiazines Promethazine Inhibit D2,H1 & M3 receptors iŶ…


5-HT3 receptor antagonists

Ondansetron Inhibit 5-HT3 receptors iŶ…


in sever vomiting e.g. in cancer chemotherapy.

Marijuana

derivatives Dronabinol Inhibit vomiting center by stimulation of

cannabinoid ( CB1 ) receptors.

Euphoria.

Mood disturbances. Nabilone Steroids Dexamethasone • to supplement the effect of other

drugs in sever vomiting.

Prokinetic

DRUGS PHARMACOKINETIC ACTION USES SIDE EFFECT D2 receptors

antagonists & 5-HT4 receptors

agonists

Metoclopramide 1) Blocking D2 receptors in GIT. cholinergic activity in upper GI (pro-

kinetic). 2) Blocking D2 receptors in CTZ.

control vomiting (anti-emetic) 3) Activates 5-HT4 receptors.

. Extrapyramidal reaction

Tremors. Dyskinesia.

Gynecomastia.

Irregularmenstrual.

↑ prolaĐtiŶ seĐretioŶ.

Diarrhoea

Domperidone DoŶ’t crossBBB. 1) Blocking D2 receptors in GIT.

cholinergic activity in upper GI (prokinetic).

2) Blocking D2 receptors in CTZ.

Control vomiting (anti-emetic).

Diarrhoea

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

SEDATIVE & HYPNOTIC DRUGS

BNZ Barbiturates 5-HT R

Agonists

β-adrenergic R

blockers Other Z-Hypnotics

Intermediat

acting Short acting Long acting

Intermediat

acting Buspirone Propranolol

Anti- Clonidine histamines

Chloral

Hydrate Zaleplon

Chlordiazepox

ide Alphazolam Oxazepam Phenobarbital Secobarbital

Diphenhydra

mine Zolpidem

Diazepam Lorazepam Triazolam Short acting Ultra-short

acting

Clonazepam Hexobarbital Thiopental

coma

DEATH

anesthesia

hypnosis

sedation

Long acting

• drugs that produce

Sedatives calm & relaxation.

• used for anxiety.

• drugs that put user

Hypnotics in sleep.

• used for insomnia.

both of them depress CNS but Hypnotic more


Benzodiazepines (BNZ) DRUG PHARMACOKINETIC ACTION USES SIDE EFFECT

Long

act

ing

(1-3

da

ys)

Chlordiazepoxide Absorption Orally / I.M. / I.V.

Distribution

Pass BBB & placenta.

Secreted into breast milk.

Metabolism

It is done by hebatic microsomal system.

Themetabolites: o Active.

o Have longer T1/2. o Cause hangover effect.

The T1/2 depend on the metabolism not excretion.

Excretion

It is done by kidney.

It safe on over dose if it taken alone.

It is the most widely used sedative because: High Ti. Low risk of dependence. Acute overdose or toxicity is treated

by: FLUMAZENILE.

Mechanism of action BNZ hyperpolarizes the membrane of the post-synaptic neurons by:

Binding to GBC binding site. affinity of the R to GABA.

Cl+ permeability. Hyperpolarize the

membrane. Inhibition of the neurons.

Action 1) Reduction of anxiety. 2) Sedation which encourage sleep by:

latency. non-REM. REM.

3) Reduction of muscle tone &

coordination. 4) Anti-convulsant. 5) Prolonged sleep with over dose.

6) Tolerance. It is pharmacodynamic (

the sensitivity of the

receptors). Develop after chronic use

(1-2 wks).

1) Sedativepreoperatively. 2) Epilepsy in emergency. 3) Treatment of muscle plasticity in cerebral

palsy & tetanus

Drowsiness.

Confusion.

Amnesia.

Impairment of motor coordination.

Dependence & addiction.

Psychological dependence.

Stop administration cause:

Craving.

Physical dependence.

Stop administration cause

withdrawalsymptoms:

Insomnia.

Anxiety.

Autonomic over activity. HR & BP. Tremors. Diaphoresis.

Muscle cramps.

Confusion.

Seizures.

Irritability.

Ataxia.

Diazepam

Clonazepam

Inte

rmed

iate

act

ing

(10

-20

hrs

)

Alphazolam 1) Sleep disorder, insomnia. 2) Control alcohol withdrawal symptoms. 3) Treatment of muscle plasticity in cerebral

palsy & tetanus

Lorazepam 1) Short term relief of sever anxiety. 2) Sleep disorder, insomnia. 3) Control alcohol withdrawal symptoms. 4) Treatment of muscle plasticity in cerebral

palsy & tetanus

Sho

rt a

ctin

g

(3-8

hrs

)

Oxazepam 1) Sleep disorder, insomnia. 2) Control alcohol withdrawal symptoms. 3) Treatment of muscle plasticity in cerebral

palsy & tetanus.

Triazolam

Anxiety Fear-induced situation. It has:

CNS symptoms: Insomnia.

Anorexia. Muscle tension.

Peripheral symptoms:

Sweating. Tremors. Palpitation.

Uses of BNZ 1) Short term relief of sever anxiety.

2) Sedativepreoperatively. 3) Sleep disorder, insomnia. 4) Epilepsy in emergency. 5) Control alcohol withdrawal symptoms. 6) Treatment of muscle plasticity in cerebral

palsy & tetanus.


Barbiturates ( acids) DRUG PHARMACOKINETIC ACTION USES SIDE EFFECT

Ult

ra-S

hort

act

ing

Thiopental Absorption Orally / I.M. / I.V.

Distribution

To all body Metabolism

It is done by hebatic microsomal system.

This system cause drug-drug iteractoin.

Excretion

It is done by kidney.

It is pH dependence.

Alkalization of urine with NaHCO3 enhance

barbiturates renal execrerion. So, used for treatment of

overdose.

Depression of the neural activity by : Enhancement of

GABAergicpathway. Blocking excitatory NT.

NOT used as sedative or hypnotic drugs but they are only used for:

1) I.V. anesthesia. 2) Epilepsy. 3) Hyperbilirubinemia.

Death in high dose due to:

CVS depression. Respiratory depression

Dependence.

Drug-druginteraction.

Paradoxical excitement of children.

Prolonged hangover. Porphyria.

Tolerance

It is pharmacodynamic(enzyme

induction).

Sho

rt

act

ing Hexobarbital

NOT used as sedative or hypnotic drugs but they are only used for:

1) Epilepsy. 2) Hyperbilirubinemia.

Inte

rmed

ia

te a

ctin

g

Secobarbital

Lon g

acti

Phenobarbital

5-HT Receptors Agonists

Buspirone Mixed agonist- antagonist.

Minimal risk of dependence.

Anxiolytic action ( 1-3 wks).

Little sedation. Little impairment of coordination.

Minimal risk of dependence.

NO hypnotic , NO euphoria.

Generalizedanxiety. Nervousness.

Dizziness.

Headache. Nausea & vomiting.

β-adrenergic Blockers

Propranolol non-selective β-blocker. peripheral symptoms of anxiety Sweating, Tremors &

Palpitation.

Reduce performance anxiety such: Public speech or Interview.

1) Anxiety. 2) Social phobia. 3) NOT for (asthma, COPD, diabetes)

Other sedative & hypnotic

An

it-H

Diphenhydramine Anti-histamine. Has anit-cholinergic action. 1) Insomnia. 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. Acute anxiety.

2) Panic attack of anxiety.


Z-hypnotic

DRUG PHARMACOKINETIC ACTION USES SIDE EFFECT Zaleplon Selective for α1 subunite of BNZ receptor

comlex.

Depression of the neural activity by

enhancement of GABAergic pathway. 1) Less risk of tolerance. 2) Less risk of amnesia.

3) Minimal rebound: Insomnia. Anxiety. Hagover effect.

The acton is antagonized by

Flumazenil that impact sleep stage.

Zolpidem

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

Ketamine

Etomidate

anesthesia

•loss of

sensation

anesthetic drug

•drugs that produce loss of sensation

GA •produĐe loss of

all sensation with loss of consciousness



Intr

aven

ous

Thiopental It is a barbiturate drug.

Fast onset.

because lipid solubility & cross BBB.

Ultra-short acting. due to fast redistributed to tissues out

side the brain.

Slowlymetabolized.

Narrow margin of the safety.

Induction of GA.

NOT used in asthmatic patients.

Respiratory depression. Bronchospasm.

CVS BP. Cardiac Output

porphyries

Etomidate moremetabolized. Cause low risk of CV &R depression.

Induction of GA.

Involuntarymovement.

adrenocortical response

to stress.

Post-operative nausea &

vomiting.

Midazolam It is a BNZ drugs. Ultra-short acting.

To accelerate the recovery from anesthisea, Use Flumazenil.

The action make little changes in

BP. Ventilation.

Basal anesthesia. Anxiety.

Anesthesia for patient with:

myocardial diseases.

hypovalemicshock.

Amnesia.

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 +

Droperidol). Bronchoscopy. Cystoscopy.

Inha

lati

ona

l

Ga

s

Nitrous Oxide Administration Mixed with water. Taken by inhalation.

Distribution It is well distributed & determines

Speed of duration. Speed of recovery.

Metabolism

It is the major responsible for side effect.

Ex: Methoxyflurane Fluoride + Oxalate (nephrotoxic).

Ex: Halothane Bromide + Triflouroacetate

(hepatotoxic).

Elimination Clearance is mainly by lung.

It determines the duration & recovery.

Low potency (MAC=100).

It is combined with other inhalation A.

Rapid induction & recovery.

It has analgesic property.

It has low lipid solubility in brain.

With prolonged use Leucopenia. Megalobalstic anemia.

Vo

lati

le li

qu

ids

Halothane

Most widely used.

High potency (MAC=0.7). It has weak analgesic property.

All the volatile liquid anesthesia: myocardium contractility. Bradycardia.

o It leads to cardiac

dysrhythmia. o Treated by Atropine.

Hypotension. Uterine relaxation &

bleeding.

Cardiacdysrhythmia.

Liver toxicity.

Enflurane

Isoflurane

Faster induction & recovery.

Has muscle realaxing property.

Heart suergery.

sevoflurane Rapid induction & recovery. Induction of A in children.

Suitable for heart surgery. Because it has minimal effect on CVS.

Methoxyflurane Nephrotoxicity.



GA

I.V. They have narrow Ti.

So, the dose must be calculated accurately.

Mechanism of action

They depress the activity of the

neurons in the brain. By activate inhibitory

pathway (GABA & Glycine).

Site of action:

Reticular formation. Hippocampus. Cortex.

Action

Depression of all CNS function.

On CVS:. o myocardium contractility.

On RS: all GA (excepte N2O)

o respiration. o arterial Pco2. o ventilation in response to

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.

Respiratory depression.

Bradycardia.

Liver toxicity.

Kidney toxicity.

Cough.

Salivation.

Vomiting.

Inhalation They have narrow Ti.

So, the dose must be calculated accurately.

The dose is measured by MAC value.

MAC: o It is the concentration of anesthetic that

result in immobility in 50% of patients

exposed to a painful stimulus.

o It measure: Dose. Potency.

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-

proamide Produce anti-emetic effect

Prevent aspiration 5 Use of other drugs

Anesthetic factors (criteria of ideal anesthetic) Because no GA has all these criteria, We use

combination A

2 Induction of GA

1 Rapidly & smooth induction I.V. GA loss of all sensation & loss consciousness

2 Fast recovery 3 Maintenance of GA & muscle relaxant 3 Has muscle relaxing property Inhal. GA maintain anesthesia 4 Wide margin of safety Tubocuraine muscle relaxant

5 Minimum side effects 4 Recovery ( by terminate inhaler A)

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

LOCAL ANESHESIA

weak Potency & short Duration moderate Potency & intermediate

Duration

Lidocaine (Xylocaine) Tetracaine

Procaine Chloroprocaine

Mepivacaine

Prilocaine

Bupivacaine

Etidocaine

Ropivacaine

high Potency & long Duration

•produĐe local loss

LA of sensation

without loss of consciousness

•ProĐaiŶe •ChloroproĐaiŶe

•Tetracaine

•BeŶzoĐaiŶe

•BeŶoǆiŶate

•LidoĐaiŶe (Xylocaine)

Amide •MepivaĐaiŶe •BupivaĐaiŶe •EtidoĐaiŶe

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


Wea

k P

ote

ncy

&

sho

rt d

urat

ion

Procaine

.

Administration Local injection.

Local application ( solution, powder or cream)

Absorption

NOT desirable because: It duration. It systemic side effects.

Metabolism

Easter, fastly metabolized by tissues &

plasma esterase. Into PABA (cause allergy).

Short duration. Amides, slowly metabolized by liver microsomal enzymes.

Longer duration.

Mechanism of action

LA block nerve conduction (initiation & propagation of AP) by:

Binding to Na+ channels &

prevent Na+ permeability.

Action

LA are lipid soluble / weak base. At pH= 7.4,

o they are UNIONIZED molecule. o They pass lipid membrane.

When reach the cytoplasm, o They become (ionized +

unionized). o The IONIZED molecules:

Bind to Na+ channels.

Block Na+ influx. Prevent AP.

The action are susceptible for (small diameter / unmylinated) fibers more

than (large diameter / mylinated) fibers.

1) Surface anesthesia:

o on Skin (wound & ulcer) o on MM (mouth or nose). o in Ophthalmology (corneal A). o powder, solution creams or ointment

are used. 2) Infiltration anesthesia.

o as in (wound suturing, cyst removal). 3) Individual nerve block anesthesia.

o as in Dental anesthesia. 4) Spinal Epidural anesthesia.

o as in surgery of (LL, abd, pelvis, rectum).

5) Treatment of cardiac dysrhythmia.

Usuallyminimum, because:

o Applied locally. o Combinewd with

vasoconstrictors.

1)Hypotension. 2)Bradicardia. 3)CNS:

Tinnitus. Lightheadness. Headache. Convulsion.

4)Allergy (in ester type).

Side effects occur due to:

o High dose. o Injected into BV.

They are potent & have

long duration.

Chloroprocaine

Mod

era

te P

ote

ncy

& In

term

edia

te

dura

tion

Lidocaine

(Xylocaine)

Mepivacaine

Prilocaine

Hig

h P

ote

ncy

&

lon

g d

ura

tio

n

Tetracaine 1) Infiltration anesthesia. o as in (wound suturing, cyst removal).

2) Individual nerve block anesthesia. o as in Dental anesthesia.

3) Spinal Epidural anesthesia. o as in surgery of (LL, abd, pelvis,

rectum). 4) Treatment of cardiac dysrhythmia.

Bupivacaine

Etidocaine

Ropivacaine

Benoxinate It is ester LA. In ophthalmology for corneal A because : NO mydriasis. NO corneal injury.

Benzocaine Used as powder or cream.

Because it is insoluble, it produces less

systemic toxicity.

Surface anesthesia on Skin (wound & ulcer)

INFLUENCINGFACTORS

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/

inflammation pH action / ionized /effect

Vaso- dilation absorb / side effect/

duration

5 Type of solution Alkali Less painful / fast onset / non-ionized / action / effect

6 +vasoconstrictors duration/ absorb /side effect

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

Diphenoxylate

Loperamide

Noscapine

Fentanyl

• Mu

Classes of Opioid Rs •Kappa

•Delta

place of Opioid R

•CNS

•Periphral tiissues

partial Agonist (mixed agonist-antagonist)

•agonist if it is combined with pure agonist.

•antagonist if it is combined

with antagonist.


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). Urinaryretention.

Distribution Analgesic for labor pain. Allergy:

They are well distributed. Add with inhaler GA to produce analgesia. Itching.

It is lipid soluble. Moderate analgesic for chronic pain (cancer) Tr

c Bronchospasm. s an ealrigidity(back t

n Codeine 4 Resp. sensitivity of RC to CO2

s i g 5 Nausea stimulation of CTZ Vomiting o e hydrocodeine 6 Miosis agonize R on III c.n. A r Antitussive u P They cross BBB & placenta. Cough suppression. 7 depress the CC pain)

Moderate analgesic for chronic pain (cancer 8 BP & VD Depress VMC

Pholocodeine Metabolim

Cough suppression On CVS. ( in large iv dose) By microsomal system Dextropropoxyphen The metabolites are active.

BP depress VMC VD

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) Treatment of diarrhea.

3) Respiratory diseases. effect with repeated administration

(asthma & COPD) 4) Mangment of dyspnea. 1 Analgesic Rapid tolerance 5) Analgesic with GA 4) Acute abdomen pain.

a. Add with inhaler GA Interfere with proper 2 Resp. Slow tolerance

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. 6) Liver diseases Addcation. Hypotension 3) Repeated I.V. Deficient metabolism Physical D Sudden withdrawal lead to Hypothermia Naloxone Psycho. D withdrawalsyndrome


DRUG PHARMACOKINETIC USES ACTION SIDE EFFECT

Par

tia

l Ag

onis

ts

Pentazocine Agonist on Kappa R.

Partial agonist on Mu R.

Cause weak RC.

Milddependency. Mildwithdrawal manifestations.

Analgesia. Dysphoria.

Psychomimetic effect.

Anxiety. Nightmares. Hallucination.

Withdrawal manifest. with morphine addict.

Buprenorphine Maintainance drug for opioid dependent patient.

Psychomimetic effect. Anxiety. Nightmares. Hallucination.

Withdrawal manifest.

with morphine addict

Nalorphine

Pur

e

Ant

ago

nis

t

Naloxone Acute opiod poisoing Reverse sever respiratory depression.

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

Group 1 Group 2 Group 3 Flupenthixol Haloperidol Quetiapine

Chlorpromazine Pericyazine Fluphenazine Zuclopenthixol Pimozide Olanzapine

Trifluperazine Sulpiride Clozapine

Aripiprazole

•+ve symptoms

•-ve symptoms

•delusioŶs

•halluĐiŶatioŶs •disorgaŶized

speech

•ĐatatoŶia

•agitatioŶ

•SoĐial/oĐĐupatioŶal dysfunction

•laĐk of self care Sc

hiz

op

hre

nia

has

Po

siti

ve s

ymp

tom

s o

f Sc

hiz

op

hre

nia

Neg

ativ

e sy

mp

tom

s o

f Sc

hiz

op

hre

nia

•SĐhizophreŶia

•BraiŶ damage

Psychoses are: •MaŶia

•ToǆiĐ delirium

•Agitated depression

Schizophrenic

patients

•ŵaŶifest disorders of

•perĐeptioŶ

•thiŶkiŶg

•speeĐh

•eŵotioŶ

•phǇsiĐalactivity

Antipsychotic drugs are called

•NeuroleptiĐs •due tp neurological effects e.g.

Parkinsonism

•MiŶor tranquilizersas

•du to Đalŵ oƌ tƌaŶƋuilizeຄ psychotic symptoms without loss of consciousness


Typical Anti-Psychotics DRUG PHARMACOKINETIC ACTION USES SIDE EFFECT

Ph

eno

thia

zin

es G1 Chlorpromazine Taken Orally. Mainly antagonize D2 receptors.

Some of them may also antagonize 5-HT2

receptors

More effective in the control of positive

symptoms

Cause more extrapyramidal side effects

• Dopamine hypothesis for schizophrenia:

• Increased dopamine

receptor density in

mesolimbic-frontolarea

in schizophrenics • Most antipsychotic drugs

block Dopamine D2

receptors in brain • Successful treatment of

schizophrenia reduces

homo-vanilic acid (HVA), a metabolite of dopamine in CSF

• Drugs that increase

dopamine activity like

levodopa, cocaine, apomorphine &

amphetasmines

aggravate schizophrenia

or produce psychosis • There is possible

involvement of other neurotransmitters also

likeglutamate, serotonin, histamine, etc e.g. Glutamate receptor

(NMDA-receptor) antagonist (phencyclidine) can produce

schizophrenia like state & atypical anti-

psychotics also inhibit 5-HT2 & D4

receptors

ANS Anti-muscarinic

blurred vision, IOP. dry mouth,HR, confusion. constipation, urine retention

α – blocking ejaculation & impotence. HR & orthostatic BP.

CNS D R blocker

Parkinsonism. Akathesia. Dystonia

Super sensitivity of D R Tradive dyskinesia.

Sedation. Toxic confusional state. Neuroleptic malignant

syndrome.

Endocrine(due to DR block &

prolactin)

Female Amnorrhra & galactorrhea.

Male Gynecomastia & impotence.

Weight gain (appetite).

Hyperglycemia.

Cholestatic jaundice. Cataract.

Risk of teratogenecity.

G2 Pericyazine

G3 Fluphenazine Given I.M. Inj. /3-4 wks

Trifluperazine Taken Orally.

Thio

xan

thin

es

Flupenthixol Given I.M. Inj. /3-4 wks

Zuclopenthixol Taken Orally.

oth

ers

Haloperidol Given I.M. Inj. /3-4 wks

Pimozide Taken Orally.

Sulpiride

DRUGS sedation anti-muscarinic

side effects extra-pyramidal

side effects PATHO-PHYSIOLOGY OF SCHIZOPHRENIA

G1 Marked Moderate Moderate dopamine receptor density in mesolimbic-frontol area in schizophrenics. dopamine activity by drugs (like levodopa, cocaine, apomorphine & amphetasmines) that aggravate schizophrenia or produce psychosis.

NT (like glutamate, serotonin, histamine) that agonist 5-HT & D receptors.

G2 Moderate Marked Less G3 Less Less Marked Thioxa.

others Successful treatment of schizophrenia reduces homo-vanilic acid (HVA) in CSF.


M

ore

eff

ecti

ve in

th

e co

ntr

ol

of n

egat

ive

sym

pto

ms

Atypical Anti-Psychotics


Risperidone Given I.M. Inj. /3-4 wks Block both D2 & 5-HT2 receptors. Relive both + &- symptoms.

Relatively low affinity for dopaminereceptors

Also or receptors

Quetiapine They metabolized by P-450 in the liver.

Drug interactions occur with enzyme inducers & inhibitors.

Olanzapine

Schizophrenia (1st line

drug)

Anti-muscarinic & prolactin related se

Less extra-pyramidal se.

Weight gain.

May cause: Anxiety. Insomnia. Dizziness.

BP

Anti-muscarinic & prolactin related se

Less extra-pyramidal se.

Weight gain.

May cause: Drowsiness. Headache.

Hyperglycemia (by olanzapine)

Clozapine Resistant Schizophrenia (2nd line drug)

Aripiprazole partial agonist at D2 receptors. Antagonist at 5-HT2 receptors.

Agranulocytosis (1st 3 m). So, monitor WBC count:

before start. every 2 wk for 6 m

α – blocking

orthostatic BP. 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 1st

The bioavailability is good pass effect.

R Action

via Adenyl- cyclase

cAMP SITE OF D2 RECEPTORS EFFECT

Some are taken I.M inj. D1 Gs Activated Mesolimbic-Mesocortical anti-psychotic

Drug interactions D5

Distribution activity of anti-Parkinsonism drugs pathway

High lipid solubility. that are DA agonists (levodopa,

Taken 1-2/d due to long T1/2. amantadine, bromocriptine),

D2 Gi Inhibited Nigro-Striatalpathway Extra-pyramidal D3

due to blocking of D2R Potentiate sedative effects of benzodiazepines &

antihistamines

D4 Tubero-Infundibular pathway

Medullary-Periventricular pathway

↑ prolactin secretion

Galactorrhea appetite

May interact with liver CTZ Anti-emetic

anta

gon

ize

D2,

D4

& 5

-HT 2

rece

pto

rs

l

ess

extr

a-p

yram

idal

&

pro

lact

in re

late

d s

ide

effe

cts

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

s

de End

oge

no

us

(mel

anoc

hol

ic)

e

ANTI-DEPRESSANT

DRUGS

ARI MAOI

Tricyclic Heterocyclic SNARI SSRI Selective

NERI

Tranylcypromine

Amitriptyline Amoxapine Venlafaxine Fluoxetine Imipramine Selegiline

Nortriptyline Maprotiline Fluvoxamine Atomoxetine Moclobemide

Imipramine

Clomipramine

• griefe

• illness

Trazodone

Bupropion

•biochemical disorder (genatically)

•iŶaďilitǇ to no cope with is minor life

• bipolar

affective disorder

Citalopram

Sertraline

MAOI cause

selective MAO-B I

Serotonin

syndrom has

depression

• action of Tyramine

(sympathomimetics)

• Serotonin syndrom with SSRI

• does not cause tyramine related reactions

• hyperthermia.

• muscle rigidity.

• myoclonus.

• CVS & Resp. failure.

•due to depletion of amine stores in CNS

pr events

Rea

ctiv

e (s

eco

nd

ary)

dep

ress

ion

Man

ic-d

epre

ssio

n

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

Sex disturbances.

Amine Re-uptake Inhibitors (ARI)

DRUG PHARMACOKINETIC MECHANISM OF ACTION USES SIDE EFFECT

Tric

yclic

anti

-dep

rees

ant

Amitriptyline Caution in glaucoma & BPH due to anti-muscarinic side effect.

Caution in driving & skill full word due to sedation

re-uptake of NE & 5-HT. also concentration in synapse.

Depression.

Anxiety disorders.

Chronic pain.

Enuresis.

Anti-muscarinic blurred vision, dry mouth. HR, confusion. constipation, urine retention.

α – blocking ejaculation & orthostatic BP

sedation.

Seizure.

Weight gain.

Sex disturbances.

Nortriptyline

Imipramine

Clomipramine

Het

ero

cycl

ic

anti

-dep

rees

ant Amoxapine re-uptake of NE & 5-HT. D2 receptors.

So, it acts as anti-psychotic

Depression.

Anxiety disorders

Parkinsonism.

Akathesia.

prolactin.

moderate

sedation &

anti- muscarinic

Maprotiline re-uptake of NE & 5-HT Seizures. Arrhythmias

Trazodone Induce sleep.

Bupropion re-uptake of NE, 5-HT & DA.

Seizures.

Aggravate psychosis.

5-H

T &

N-a

d R

I

(SN

AR

I)

Venlafaxine Low dose acts as SSRI. High dose acts as TSAs

re-uptake of 5-HT (& NE but less). Depression.

Anxiety disorders.

Chronic pain

Low dose

o Sedative & anti-muscarinic. High dose

o Sedative & anti-muscarinic. o Nausea. o BP o Sex distrabunces.

SSR

I

Fluoxetine re-uptake of 5-HT (more selective). obsessive & compulsive D

Bulimia

dep

ress

ion

anxi

ety

Transient nausea.

Libido. (initial)

Sex dysfunction. (maintenance

therapy)

Fluvoxamine obsessive & compulsive D

Citalopram Sertraline

S NERI Imipramine re-uptake of NE (more selective). Attention deficit hyperkinetic

disorder.

Atomoxetine

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.

duration of action of NE, 5-HT & DA.

also concentration.

Headache.

Drowsiness.

Weight gain.

Postural PB.

Selegiline Inhibit MAO- B.

o MAO-A metabolizes NE , 5-HT & Tyramine.

o MAO-B metabolizes DA more than others.

P H R M A C O L O G Y - NOTE 14 - Treatment of Epilepsy

Tiagabine

ANTI-EPILEPTIC DRUGS

Partial seizures &

gneralized tonic-clonic Generalized seizures Others

Old Drugs Newer Drugs Ethosuximide Phensuximide Acetazolamide Benzodiazepines

Phenytoin Lamotrigine Trimethadone Oxazolidinediones Diazepam

Carbamazepine Gabapentine Lorazepam

Valporate Topiramate Clonazepam

Barbiturates Vigabatrine

Levetriacetam

Nitrazepam

Clorazepate Dipotassium

Felbamate Clobazam

Zonisamide

•siŵple;ĐoŶsĐiousŶessͿ

•Đoŵpleǆ(unconsciousness)

•PS secondarily generalized

•GeŶeralized tonic-clonic (grand mal) •AďseŶĐe (petit mal)

•ToŶiĐ , Atonic , Clonic & Myoclonic seizures

•IŶfaŶtile spasm

PAR

TIA

L SE

IZU

RES

GEN

ERA

LISE

D

SEIZ

UR

ES

Involvement of • motor area (convulsion) • hypothalamus (autonomic discharge)

• reticular formation (unconsciousness)

• Repeated seizure activity leads to neurodegeneration due to excitotoxicity

Focal Seizures

•reŵaiŶslocalized

Generalized Seizures

•priŵarǇ (involve all cortical neurons)

•seĐoŶdarǇ (spread afterward)

TREATMENT •inhibitory NT. •excitatory Nt

•alter the permability of membrane to ions (Na, K or Ca)


Partial seizures & generalized tonic-clonic


Old

Dru

gs

Phenytoin It is metabolized in the liver. plasma conc. <10 mg/L .

1st order kinetics.

plasma conc. = 10-20 mg/L . zero order kinetics.

The metabolism is inhibited by:

o Na valporate. o Cimetidine. o Isoniazide. o Chloramphenicol. o Co-trimoxazole.

It is a inducer of HME.

So, it enhances metabolism of:

Carbamazepine

Warfarin,Steroids.

TCA & OC

Block or alter Na-voltage channels.

At high concentration:

Inhibit release of NE & 5-TH. Inhibit MAO activity. Promote uptake of

Dopamine

1) Partial seizures 2) Generalized tonic-clonic seizures. 3) Status epilepticus. 4) Trigeminal neuralgia (2nd choice). 5) Cardiacarrhythmia.

DOSE DEPENDENT

Acute effect

Nystagmus.

Diplopia. Ataxia. Lethargy. Sedation.

Chronic effect:

Gingival hyperplasia, Hirsutism , Acne Nausea ,vomiting ,epigastric pain, anorexia. Megaloblastic anemia.

Mild peripheral neuropathy Osteomalacia. Hemorrhagic diseases of new born.

Fetal Hydantoin syndrome. HYPERSENSITIVITY

Agranulocytosis with fever, rash , SLE & fetal hepatic

necrosis.

Carbamazepine

Block Na-voltage channels.

Act pre-synaptically:

to synaptic

transmission.

Inhibit uptake & release of NE.

1) Partial seizures 2) Generalized tonic-clonic seizures

3) Trigeminalneuralgia. 4) Mania. 5) Diabetes Insipidus (DI).

DOSE DEPENDENT

CNS: Diplopia, Ataxia ,drowsiness, unsteadiness.

GIT: Vomiting , Diarrhoea. H2O retention & hyponatremia.

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 to GABA conc.

Block Na-voltage channels.

1) Partial seizures. 2) Generalized seizures:

a.tonic-clonic.

b.absence. c. myoclonic.

3) Bipolar disorder(mania). 4) Migrineprophylaxis.

DOSE DEPENDENT

Nausea, vomiting, abdominal pain.

Weight gain, ↑ appetite.

hair loss, fine tremor. IDIOSYNATRICREACTION

Hepatotoxicity.

Thrombocytopenia.

Pancreatitis. TERATOGENECITY

Spina bifida,Cardiovascular abnormality.

Orofacial & digital abnormalities.

Bar

bit

ura

tes Penobarbital It is well tolerated, with single dose Enahancement of GABAergic 1) Partial seizures Drowsiness , lethargy , depression

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

Metabarbital o Porphyria (acute attack may occur)

Primidone is used in treatment of Essential Tremor resistant to

Reduction of Glutamate action. Block Na & Ca(L,N) channels.

3) Status epilepticus.

4) Febrile convulsion

Memory loss, irritability & mental confusion.

Teratogenic & hemorrhagic disease of new born.

Megaloblastic anemia & osteomalacia. Primidone

PROPRANOLOL. Tolerated with single dose.


Partial seizures& generalized tonic-clonic;cont…Ϳ

DRUG PHARMACOKINETIC MECHANISM OF ACTION USES SIDE EFFECT N

ewer

Dru

gs

Lamotrigine Block Na-voltage channels, to stabilize pre-synaptic

neuronal membranes.

reduces the release of excitatory

amino acids (Glutamate & Aspertate)

adjunctive therapy for refractory: o Partial seizures. o 1o & 2o generalized tonic-clonic

seizures.

Dizziness, nausea & headache.

Diplopia.

Somnolence.

Skin rash. Flu like symptoms.

Gabapentine It is an analogue of GABA . It crosses blood brain barrier.

GABA synthesis & release.

block L type Ca channels. Agonize GABABreceptor.

1) Resistant partial seizures. 2) Resistant generalized tonic-clonic. 3) Bipolar disorders. 4) Migraine and neuropathic pain.

Somnolence.

Dizziness & headache.

Ataxia & tremors.

Vigabatrine GABA conc. by irreversible inhibition of

GABA aminotransferase.

1) Partial seizures.

2) 2o generalized

seizures.

NOT responsible by

other drugs

AT TOXIC DOSE Dizziness, drowsiness.

Weight gain.

Agitation, confusion & psychosis. LONG USE

Irreversible Visual field defects.

3)Infantile spasms.

Topiramate NOT used during PREGNANCY . Enahancement of GABAergic pathway.

Block Na-voltage channels. Block or antagonize Glutamate

receptors (weak).

adjunctive therapy for refractory: o Partial seizures. o Generalizedtonic-clonic

seizures.

Somnolence, fatigue & Dizziness. Nervousness & confusion.

Acute myopia ,glaucoma & urolithiasis.

Teratogenic abnormalities.

Tiagabine Treatment by discontinuous doses

prevent : Excessive confusion. Somnolence. Ataxia.

prolongs the inhibitory action of synaptically released GABA.

adjunctive therapy for partial seizures.

Nervousness, confusion. Difficulty in concentration & depression.

Tremor & ataxia.

somnolence & dizziness.

Zonisamide Block Na channels.

Block Ca-voltage channels.

1) Partial seizures. 2) Generalised tonic-clonic seizures. 3)Infantile spasms & myoclonas.

Drowsiness.

cognitiveimpairment.

Serious skin rashes.

Levetriacetam At brain-specific binding site, it affects: GABA receptors (sensitivity)

Ca-voltage channels (block).

K-channels.

adjunctive therapy for partial seizures

with or without generalization.

Asthenia.

Dizziness.

Drowsiness.

Felbamate block NMDA receptor via GLYCINE

binding site.

Refractory partial & generalized

seizures(3rd line).

resistant seizures as in Lennox- Gastaur syndrome.

Insomnia.

Dizziness. Ataxia.

Aplastic anemia.

Sever hepatitis.

LENNOX-GASTAURE SYNDROM It consiste of:

multiple seizure types.

mentalretardation.

refractoriness to anti-seizure drugs.


Generalized tonic-clonic


Ethosuximide Therapeutic levels & Dosage– 60-100

mg/ml achieved with 750-1500mg/day. It depresses the cerebral MR.

The clearance is reduced by Valporic

Acid.

Inhibits: T type Ca-channels in thalamas. Na/K ATPase. GABA aminotransferase enzymes

It depresses the cerebral MR.

Absence seizures GIT: Pain, nausea & vomiting.

CNS: Headache, dizziness, euphoria

Blood: Eosinophilia. Pancytopenia (Thrombocytopenia, leucopenia)

Transient lethargy or fatigue.

Skin rash.

Steven Johnson syndrome.

SLE.

Trimethadone NOT used during pregnancy.

Act actively against Pentyleneterazole

that induce seizures.

Petit mal epilepsy ( drug of choice). Sedation.

HEMERALOPIA(reversible impaired visual adaptation)

Others


Ben

zod

iaze

pin

es

Diazepam used I.V. or rectally They act as anti-epileptic by: GABAergic activity.

CLORAZEPATE DIPOTASSIUM---Used as an.

are common adverse effects.

CLOBAZAM— ADVERSE effects of Benzodiazepins ------

.

Generalized tonic-clonic (grand-mal).

Status epilacticus

Sedation.

Tolerance.

paradoxicalhyperactivity(in

children).

Ataxia, hypotonia , dysarthria.

Salivation.

↑respiratorǇ secretions.

WITHDRAWAL SYMPTOMS Exacerbation of seizures if the drug is stopped suddenly.

Lorazepam longer acting than diazepam. More effective in status epilepticus.

Clonazepam Absence (petit mal) siezures.

Myoclonicseizures.

infantile spasms.

Nitrazepam Less potent than Clonazepam.

Clorazepate

Dipotassium adjunct to treatment of complex

partial seizures. Drowsiness.

Lethargy.

Clobazam Commonly not used due to quick & high

tolerance less sedative.

High TOLERANCE

Acetazolamide It is a carbonic anhydrase inhibitor Exerts its anti- seizure activity by: Mild acidosis in the brain.

Epilepsy during menses (as it discontinuously administrated, NO

rolerance)

Tolerance (quick develop).

Sulthium It is a carbonic anhydrase inhibitor TYPE DRUG OF CHOICE ALTERNATIVE DRUG

GEN

ERA

LIZE

DSE

IZU

RES

ALT

ERN

ATI

VE

DR

UG

Lam

otr

igin

e

Lam

otr

igin

e

Ph

eno

bar

bit

on

Ph

enyt

oin

Clo

naz

epam

Ph

eno

bar

bit

o

Lam

otr

igin

e

Top

iram

ate

Clo

naz

epam

Eth

osu

xim

ide

Vig

abat

rin

e

Clo

baz

am

Gab

apen

tin

e

Felb

amat

e

Top

iram

ate

Tiag

abin

e

SIM

PLE

SEIZ

URE

s

Simple partial Phenytoin Gabapentine Complex partial Phenobarbitone Felbamate

Partial with secondarily

generalised valporate Topiramate

Lamotrigine Tiagabine Phenytoin Gabapentine

DR

UG

OF

CH

OIC

E

Clo

naz

epam

Eth

osu

xim

ide

Val

po

rate

Val

po

rate

Val

po

rate

Clo

naz

epam

Car

bam

azep

i

Ph

eno

bar

bit

on

Ph

enyt

oin

Pri

mid

on

e

Val

po

rate

Lam

otr

igin

e

Type Absence Atonic Myoclonic Grand mal/tonic/clonic

P H R M A C O L O G Y - NOTE 15 – Anit-migraine Drugs

ANTI-MIGRINE DRUGS

Acute Attack Prophylaxis

Mild to Moderate

Moderat to

Sever Specific drug

β adrenergic blockers

Ca channel

blockers

5-HT2

antagonist

5HT2 antagonist /partialagonist

NSAIDs Anti- emetics prokinetic Diclofenac 5-HT Agonist P Agonest for α-

Adrenceptors & 5- HT R

Propranolol Flunarizine Pizotifen Methysergide Amitryptyline

Aspirin Diphenhydr-

amine

Metocloper-

amide Sumatripan Ergotamine Metoprolol Nicardipine

Cyprohepata-

dine Imipramine

Paracetamol Promethazine Domperidone Almotriptan Nadolol Nifedipine Sertraline

Ibuprofen Naratriptan Atenolol Nimodipine Fluoxetine

Indomethacin Pizatriptan Timolol Verapamil Clonidine

Naproxene Zolmitriptan Valporate

Opioids

Other


Acute attack of Migraine


Aspirin Given orally. Analgesic. acute migraine attack.

Paracetamol

Ibuprofen

Indomethacin

Naproxene

they must be given early to be absorbed

before there is vomiting.

Opioids Given parentrally (I.V. or I.M.). Refractory cases of

acute attack of migraine(rarly)

Diphenhydramine Prevent vomiting.

Efficient use of analgesic &

antiemetic is sufficient for the

majority of ACUTE ATTACKS

Promethazine

Metocloperamide Given by I.V. injection. They promote gastric emptying, So, enhances absorption of

With very severe

vomiting.

Domperidone Given as rectal suppositories for vomiting can be tried

analgesics.

Diclofenac

Sumatripan Given by oral route or S.C. injection.

Fast absorbtion.

Bioavailabilty by s.c. route is 96%

Dose not cross BBB. Plasma t1/2 is 2 hours.

Almotriptan they are congeners of Sumatriptan.

stimulate 5-HT1 R on pre- synaptic endings of V cn. inhibit releasing of

vasodilators .

selectively stimulates

5HT1B/1D R in cranial BV, constrict them.

acute severe migraine

attack(1st line).

NOT used with IHD. unstable angina. previous MI

Malaise ,fatigue.

Sedation.

Dizziness, vertigo, nausea & vomiting. feeling of chest pressure, tightness & pain.

CARDIAC ARRHYTHMIA & myocardial infarction. due to coronary artery spasm.

Less side effects.

Naratriptan

Pizatriptan

Zolmitriptan

improved pharmacokinetic

better Bioavailability.

better and longer duration.

Reduce cardiac side effects.

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). o Parentral route (inhaler).

rectal route is preferred ???.

caffeine facilitates absorption of ergot alkaloid.

It metabolized in the liver. t ½ is 2 hrs

DOSE. o Tablet (1mg + Caffeine 100mg).

o 1-2 tab. at onset ,then 1 tab/ 30min. o NO > 6 mg/attack & NO >10 mg/wk.

For severe attack, it ginen may be IM/IV injct.

Dihydroergotamine oFor intractable migraine.

oGiven by IV inj.(0.5-1mg)

endings of V cn. inhibit releasing of

vasodilators .

NOT used with disease

of:

Coronary BV. Peripheral BV.

Peripheral ischaemia.

Peripheral GANGRENE with overdose. Precipitate angina pectoris.

Fetal damage.

Spec

ific

dru

g f

or a

cute

att

ake

Mo

dera

t to

Sev

er

atta

ck

Mild

to

Mod

erat

e at

tack

NSA

IDs

P A

go

ne

st

for α

-Adr

ence

ptor

s &

5-H

T R

pr

okin

etic

A

nti-

em

etic

s 5-

HT

Ago

nis

t

+ ef

fect

s on

CN

S


Prophylaxis drugs for Migrine.

DRUG PHARMACOKINETIC ACTION USES SIDE EFFECT β

ad

ren

erg

ic b

lock

ers

Propranolol • PROPRANOLOL– (effect , also prevent migraine ).

the d-isomer part of structure lacks β

blocking action; Alter the permeability of the

membrane.

They are effective and widely used. Fatigue. Broncho-constriction.

Metoprolol Nadolol

Atenolol

Timolol

Ca

ch

an

nel

blo

cker

s Flunarizine Block Ca channel. effective in the preventive treatment of Migraine

Nicardipine

Nifedipine

Nimodipine

Verapamil

5-H

T 2

an

tag

on

ist Pizotifen antagonize5-HT2 receptors.

Atropine like action.

They are RARELY used Weight gain.

Anti-cholinergic side effects.

Cyprohepatadine Antagonize 5-HT2 R & H 1 R.

Block Ca channels

Sedation.

weight gain.

5HT 2

an

tag

on

ist

/pa

rtia

l ag

oni

st Methysergide effective in about 60% patients. It is 5HT2 antagonist /partial agonist Serious Toxicities like;

o RETROPERITONEAL obstruction to the Ureters.

o Subendocardial, Pericardial or Pleural fibrosis. Nausea, vomiting & diarrhoea.

Oth

er

Amitryptyline effective for the PROPHYLAXIS of migraine in some patients.

Imipramine

Sertraline

Fluoxetine

Clonidine

Valporate

pharmacology mind maps

Documents