pharmacology of emergency and critical care...pharmacology of critical and intensive care medicine 7...

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Pharmacology of Emergency

and Critical Care

Dr: Doaa Ibrahim Mohamed

Lecturer of pharmacology

Faculty of medicine

Ain Shams University

Second Year

2018/2019

2

Acknowledgments

This two-year curriculum was developed through a participatory and collaborative approach between the Academic faculty staff affiliated to Egyptian Universities as Alexandria University, Ain Shams University, Cairo University , Mansoura University, Al-Azhar University, Tanta University, Beni Souef University , Port Said University, Suez Canal University and MTI University and the Ministry of Health and Population(General Directorate of Technical Health Education (THE). The design of this course draws on rich discussions through workshops. The outcome of the workshop was course specification with Indented learning outcomes and the course contents, which served as a guide to the initial design.

We would like to thank Prof.Sabah Al- Sharkawi the General Coordinator of General Directorate of Technical Health Education, Dr. Azza Dosoky the Head of Central Administration of HR Development, Dr. Seada Farghly the General Director of THE and all share persons working at General Administration of the THE for their time and critical feedback during the development of this course.

Special thanks to the Minister of Health and Population Dr. Hala Zayed and Former Minister of Health Prof. Ahmed Emad Edin Rady for their decision to recognize and professionalize health education by issuing a decree to develop and strengthen the technical health education curriculum for pre-service training within the technical health institutes.

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جىصيف مقشس دساسً

تيانات المقشس -1

المقشس :اسم الشمض الكىدي :

Pharmacology of emergency and critical

care

طىاسئالحشجه و الشعايه الادويه

الفشقة /المسحىي :

Grade 2

الحخصص :

سعايه حشجه وطىاسئ

ساعه 2 عذد الىحذات الذساسية : نظشي

هذف المقشس: -2

Understanding the pharmacology of the commonly used drugs

emergency and critical care unit, including action, adverse

effects, drug interactions and drug dose adjustment in critically

ill patients.

المسحهذف من جذسيس المقشس : -3

Students of technical health institute-anesthesia technician

ا. المعلىمات

والمفاهيم :

Knowledge &Understanding

By the end of the course the student should be able to:

Identify the action of the most common drugs used in

critical and intensive care unit.

Describe the possible adverse effects of the most

common drugs used in critical and intensive care unit

Discuss the possible drug interaction between the most

common drugs used in critical and intensive care unit

Identify dose adjustment in critically ill patients

Identify the precautions needed during administration of

the most common drugs used in critical and intensive

care unit

المهارات -ب

: الذهنية

Calculate the appropriate dosing of drugs according to

the different characteristics of patients

Evaluate the different agents used in endocrinal

emergencies

Evaluate the different agents used in cardiovascular

emergences

Compare the pharmacotherapies of acid base disorders

المهارات المهنية -ج

الخاصة بالمقزر:

Report the different drug adverse reactions and

toxicities.

Preparing intravenous drugs.

Preparing intravenous therapy administration

equipment

https://en.wikipedia.org/wiki/Intravenous

https://en.wikipedia.org/wiki/Intravenous_therapy

4

Establish peripheral intravenous access.

Monitoring and maintaining patient's vital signs

Collection and analysis of patient's blood samples.

Acquiring and administering transfusion fluids and

equipment.

المهاسات -د

العامة :

Communicate effectively with other health care

professional to maximize patient benefits and minimize

the risk of errors

Understand the importance of continuing medical

education

Communicate with the patients.

Call for help when needed.

Communicate with operating room and critical care unit

staff.

مححىي المقشس: -4

Vasopressors

Vasodilators

Inotropes

Bronchodilators

Antiarrhythmic drugs

Antihistamines

Corticosteroids

Antibiotics & Antifungal

Antiemetic's

Acid suppressant

IV. Fluids

Anticoagulants& Thrombolytic Drugs and hemostatic

Potassium

Calcium

Magnesium

Analgesics

Insulin

Hypolipidemic drugs

Acid base disorders pharmacotherapies

NSAIDs

Opioid analgesics

أسااية الحعليم والحعلم -5

1. Lectures

2. Active learning-discussion

أسالية الحعليم والحعلم -6

للطالب روي القذسات المحذودة

(Premedical examination: should be fit for admission)

In case of accidental disability after admission :

Intervention of a Specialist according to the situation

https://en.wikipedia.org/wiki/Vital_signs

https://en.wikipedia.org/wiki/Blood

5

جقىيم الطالب : -7

األسالية المسحخذمة -أ

Quiz

Midterm

Final exam

الحىقيث -ب

Class work:

Quiz I (5th week)

Midterm (7th week)

Final exam

Written exam (15th week) Class work:

جىصيع الذسجات -ج9

Quiz : 5 mark

Midterm: 15 marks

Attendance 5 marks

Final written exam 80 marks.

Total percentage 100 mark

قائمة الكحة الذساسية والمشاجع : -8

مزكشات -أ

Pharmacology of critical and

intensive care medicine

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Course Description ..................................................................... i

Course overview ......................................................................... ii

Chapter 1: Drug therapy of ischemic heart disease ................................. 8

Chapter 2: Drug therapy of hypertension ............................................ 20

Chapter 3: Drug therapy of shock ..................................................... 23

Chapter 4: Drug therapy of heart failure ………………………………………………………….32

Chapter 5: Drug therapy of arrhythmias …………………………………………………………..38

Chapter 6: Drug therapy of bronchial asthma ....................................... 42

Chapter 7: Drug therapy of thrombosis…………………………………………………………..…48

Chapter 8: Drug therapy of vomiting and peptic ulcers………………………………………56

Chapter 9: Drug therapy of diabetic ketoacidosis and hepatic coma…………………62

Chapter 10: Non-steroidal anti-inflammatory drugs…………………………………………65

Chapter 11: Opioid analgesic………………………………………………………………………………71

Chapter 12: Antihistamines and corticosteroids…………………………………………………77.

Chapter 13: Antibiotics – antifungal ……………………………………………………………………84

Chapter 14: Intravenous fluids …………………………………………………………………………96

Chapter 15: Magnesium – Potassium – Calcium ………………………………………………102

Chapter 16: Acid base disturbance pharmacotherapy………………………………………109

حقىق النشز والتأليف لىسارة الصحة والسكان ويحذر بيعه

Contents



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This course will focus on Understanding the pharmacology of the commonly

used drugs in critical and intensive care unit, including action, adverse

effects, drug interactions and drug dose adjustment in critically ill patients.

The students will also gain practical experience by applying the knowledge

gained during the first academic year to better understand their audience and

create more effective health messages and programming.

Core Knowledge

By the end of this course, students should be able to:

Identify the action of the most common drugs used in critical and intensive care unit.

Describe the possible adverse effects of the most common drugs used in critical and intensive care unit

Discuss the possible drug interaction between the most common drugs used in critical and intensive care unit

Identify dose adjustment in critically ill patients Identify the precautions needed during administration of the most common

drugs used in critical and intensive care unit.

Core Skills

By the end of this course, students should be able to:

Report the different drug adverse reactions and toxicities. Preparing intravenous drugs. Preparing intravenous therapy administration equipment Establish peripheral intravenous access. Monitoring and maintaining patient's vital signs Collection and analysis of patient's blood samples. Acquiring and administering transfusion fluids and equipment.

Course Description

i

https://en.wikipedia.org/wiki/Intravenous

https://en.wikipedia.org/wiki/Intravenous_therapy

https://en.wikipedia.org/wiki/Vital_signs

https://en.wikipedia.org/wiki/Blood



8

Course Overview

Methods of Teaching/Training

with Number of Total Hours

per Topic

ID

Topics

Inte

racti

ve

Lectu

re

Fie

ld W

ork

Cla

ss

Ass

ignm

ents

Rese

arc

h

Lab

1 Drug therapy of ischemic heart

disease

1

2 Drug therapy of hypertension

1

3 Drug therapy of shock

2

4 Drug therapy of heart failure

1

5 Drug therapy of arrhythmia 1

6 Drug therapy of bronchial asthma 2

7 Drug therapy of thrombosis 2

8 Drug therapy of vomiting and peptic ulcers 2

9 Drug therapy of diabetic ketoacidosis and

hepatic coma

2

10 Non-steroidal anti-inflammatory drugs

(NSAIDs)

2

11 Opioid analgesics 2

12 Antihistamines and corticosteroids 2

13 Antibiotics and antifungal 2

14 Intravenous fluids

2

15 Potassium – Calcium – Magnesium

Acid base disturbance pharmacotherapy

2

TOTAL HOURS (26)

26



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Angina: imbalance between myocardial oxygen supply and oxygen demand

due to coronary atherosclerosis

Myocardial infarction: sudden occlusion of one other atherosclerotic

coronaries

Drug therapy of angina:

1. Life style modifications: stop smoking , treatment of obesity ,↓fat in diet

,control diabetes & hypertension

2. Antiplatelet (aspirin , clopedogril)

3. Hypolipedemic agents: (Statins)

4. ACE Inhibitors (Captopril)

5. Acute Attack: Nitroglycerine & Isosorbid Dinitrate

6. Maintenance Therapy In Chronic Angina:

a. Beta Blockers: 1st Choice

b. Isosorbid mononitrate: Long Acting Nitrates

7. Calcium channel blockers: If beta blockers are contraindicated

8. In Myocardial Infarction (MI) Add:

a. Iv Heparin Or Sc LMW Heparin

b. Revascularization And Angioplasty

Chapter 1

Drug therapy of ischemic heart disease



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Nitrates

Mechanism of action

1. Direct relaxation of blood vessels and smooth muscles

vasodilatationdecrease O2 requirements.

2. Relaxation of smooth muscles of coronary arteries coronary

vasodilatation increase blood supply to the myocardium.

3. Relaxation of arteries and veins decrease blood pressure decrease

workload in the heart.

Indications:

1. Angina pectoris.

2. Acute pulmonary edema

3. Congestive heart failure –myocardial infarction

4. Hypertensive emergency

5. Biliary colic

Side effects:

1. Throbbing headache and flushing: due to arterial vasodilation

2. Postural hypotension ,dizziness, syncope: due to venodilation



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3. Reflex tachycardia ( due to hypotension )worse angina (decrease by Beta

Blockers)

4. Sudden stop withdrawal angina

5. Tolerance :due to depletion of SH group & compensatory increase in

sympathetic vasoconstriction

Precautions:

1. Drug stored in tightly closed container

2. Patient should sit while taking drug and to lie down if syncope occur

3. Remove sl tablet on relief

4. Allow nitrate free interval 8hours/day to avoid tolerance

5. Avoid sudden stoppage to avoid rebound angina

6. Take sublingual tablets 5-15 minutes prior to any situation likely to cause

anginal pain

7. If anginal pain is not relieved on 3 consecutive tablet on 5min interval

consider myocardial infarction

Preparations:

Nitroglycerine: sublingual in acute attack

Isosorbide dinitrate: Isordil

Isosorbide mononitrate given for patients with liver impairments.



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Calcium channel blockers

Mechanism of Action:

1. Decrease myocardial contractility.

2. Decrease heart rate

3. Vasodilatationdecrease peripheral resistance- dilate coronaries

4. Relaxation of bronchial –intestinal –uterine smooth muscle

Uses:

1. Angina

2. Hypertension ( decrease peripheral resistance due to vasodilation)

3. PVD (peripheral vascular disease)

4. PSVT (paroxysmal supra ventricular tachycardia): protect ventricle from

high rate coming from atrium

Side effects:

1. Reflex tachycardia worse angina (especially with nifidipine & amlodipine

vasoselective)

2. Hypotension & headache & flushing

3. Dizziness, tinnitus, ankle edema

4. Bradycardia ( verapamil & diltiazemcardioselective)



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Preparations:

1. Diltazem: Delaytiazem

2. Nifedipine: Adalat

3. Amlodipine:Norvasc

4. Verapamil: Isoptin

Sodium Nitoprusside



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Beta blockers

Action:

Blocking of βeta 1 receptorsdecrease heart rate, myocardial contractility

and cardiac output, blood pressure.

Blocking of βeta 2 receptors bronchospasm and vasoconstriction.

These drugs could be selective (working on one receptor such as β1

selective drugs (Atenolol) or it could be nonselective (such as Propranolol)

Uses:

Hypertension

Angina pectoris.

Heart failure.

Cardiac arrhythmias.

Myocardial infarction.

Prophylaxis of migraine & esophageal varices

Thyrotoxic crisis.

Glaucoma.

Tremors



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Side effects and Contraindications:

Bradycardia, heart block

Heart failure & hypotension

Bronchospasm (contraindicated in bronchial asthma)

Hyperglycemia & increase triglycerides

Cold extremities (contraindicated in peripheral vascular disease, vasospatic angina)

Hyperkalemia (take care in renal impairment and diabetes mellitus )

Sudden withdrawal angina

Prolong insulin induced hypoglycemia

Sexual dysfunction



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Preparations

Propranolol: Inderal

Others, Esmolol- carvidolol– bisoprolol -nebivolol –metoprolol

Treating overdose:

Inducing vomiting, gastric lavage.

Artificial respiration.

Give atropine sulfate 0.6 mg (up to 3 mg) and glucagon for the

treatment of bradycardia.

Intravenous fluids

Adrenaline or dopamine to increase blood pressure.



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Angiotensin converting enzyme inhibitors

(Captopril) Mechanism of Action:

VD of arteries and veins decrease blood pressure & decrease peripheral

resistance.

Decrease aldosterone secretion increase Na & water loss & increase

serum potassium level.

Decrease NE centrally decrease blood pressure without reflex

tachycardia

Indications:

1. Hypertension.

2. Congestive heart failure.

3. Acute myocardial infarction

4. Diabetic nephropathy



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Side effects:

Mild side effects

1. Chronic dry cough 2. Angioedema 3. 1st dose hypotension 4. Hyperkalemia 5. Hypersensitivity 6. GIT upset : taste disturbance

Antiplatelet

Aspirin: Prophylaxis for transient ischemic attacks (TIA) Clopidogrel (Plavix): Thrombotic stroke prophylaxis Side effect of Clopidogrel : Purpura, dizziness, rash, epitaxsis

Severe side effects

1. Renal impairment if taken with:

2. Hypovolemia 3. bilateral renal artery

stenosis 4. Bone marrow depression 5. Teratogenic & fetotoxic



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Oral hypolipidemic drugs

Statins

Mechanism of action: interfere with cholesterol synthesis.

These drugs include atorvastatin, fluvastatin, lovastatin, pravastatin,

rosuvastatin, and simvastatin.

Indications:

Primary hypercholesterolemia

Hyperlipidemia

Reduce the risk of coronary artery disease and to prevent myocardial

infarction or stroke in patients with high cholesterol levels.

Drug interactions:

Statin with fibrate increases the risk of myopathy

Lovastatin, rosuvastatin and simvastatin may increase the risk of bleeding

when administered with warfarin.

Adverse reactions:

Increase liver enzymes

Myalgia is the most common musculoskeletal effect

Nausea, vomiting, diarrhea, abdominal pain, flatulence, and constipation.



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Ezetimibe

Mechanism: inhibit cholesterol absorption

Indications: Hypercholesterolemia

Adverse reactions:

Fatigue

Abdominal pain and diarrhea

Pharyngitis and sinusitis • arthralgia • back pain • cough.



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Definition of hypertension : is an abnormal sustained rise in arterial blood

pressure above optimal level 120/80

Drugs used to treat hypertension:

a. Thiazide

b. Calcium channel blockers

c. ACEIs

d. Beta blockers

Drugs used to treat hypertensive encephalopathy

a. Sodium nitroprusside

b. Loop diuretics

Sodium Nitroprusside

Mechanism of action:

Arteriolar and venular vasodilation

Uses:

hypertensive emergency

Sever acute heart failure with high blood pressure

Side effects:

Sever hypotension

Cyanide toxicity in liver dysfunction

Thiocyanate toxicity in renal dysfunction

Chapter 2

Drug therapy of hypertension



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Precautions:

Given slowly IV infusion

Should be freshly prepared and covered with opaque foil

Monitor BP (avoid drop in BP <95/70)

avoid prolonged administration in liver & kidney dysfunction

Loop diuretic (Furosemide): Lasix

Action:

1. It inhibits the reabsorption of sodium and chloride& increase the excretion of

potassium in the distal tubule.

2. ↑prostaglandines release in nephronvasodilation↑GFRdiuresis

Uses:

1. Emergency (rapid-potent-iv):

a. Hypertensive encephalopathy

b. Acute pulmonary edema

2. Edema of liver cirrhosis & congestive heart failure

3. Acute renal failure

4. Hypercalcemia

5. hyperkalemia

Side effects:

1. Hypovolemia hypotension & thrombosis

2. Hypokalemia and alkalosis

3. Hypocalcaemia

4. Hypomagnesmia & hyperurecemia

5. Hypersensitivity reaction

6. Ototoxicity- GIT upset



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Refractoriness to loop diuretics (decrease response to loop

diuretics):

a. Defective intestinal absorption in congestive heart failure give diuretics IVI

b. Defective plasma protein binding in hypoalbuminemic states (liver cirrhosis-

nephrotic syndrome) mix the diuretics with albumin prior to infusion

c. Defective excretion of diuretics in renal impairment increase dose 5 folds

d. Increase activity of distal and convoluted tubules add spironolactone

Precautions:

1. Monitor for signs of excess diuresis (hypotension, tachycardia, poor skin

turgor, and excessive thirst).

2. Monitor blood pressure, heart rate, and intake and output.

3. Monitor serum electrolyte levels.

Thiazide diuretic

Like loop diuretic but less potent

Used in treatment of hypertension

Decrease calcium excretion & preferred in treatment of hypertension in

old age as it protect against osteoporosis.

Side effects like loop diuretics



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Definition: Shock occurs when the circulation of arterial blood is

inadequate to meet the tissue metabolic needs

Types of shock:

1. Hypovolemic shock

2. Cardiogenic shock

3. Septic – Anaphylactic- Neurogenic Shock

Management of different types of shock:

Hypovolemic shock:

a. Rapid volume repletion: 1-2 liters of isotonic saline

b. If hemorrhagic shock : red blood cells transfusion

c. If lactic acidosis occurs give IV bicarbonate

Septic shock:

a. Maintain patent airways

b. Intravenous fluids

c. Vasopressors : norepinephrine

d. Inotropic drugs: (dopamine – dobutamine)

e. Empiric antibiotic therapy till culture and sensitivity

f. Corticosteroids

Chapter 3

Drug therapy of shock



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Cardiogenic shock:

a. Maintain patent airways

b. Aspirin + heparin

c. Inotropes (dopamine – dobutamine)

d. Vasopressors (epinephrine – norepinephrine)

e. Fibrinolytics (if MI)

f. Antiplatelet

Anaphylactic shock:

a. Epinephrine

b. Maintain patent airways

c. Antihistamines

d. Corticosteroids

e. IV normal saline



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Epinephrine


1. Stimulates alpha and beta-receptors, thereby increasing heart rate and

myocardial contractility.

2. It increases systemic vascular resistance by constriction of arterioles,

thereby increasing systolic blood pressure

3. It relaxes bronchial smooth muscle (Bronchodilation).

4. Reduces swelling of the face, lips, and throat.

Indications:

1. Local Anesthesia 2. Anaphylactic shock 3. Cardiac Arrest 4. Asthma 5. Arrests bleeding 6. Open Angle

glaucoma



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Side effects

When you receive emergency medical care after injecting epinephrine, tell the

doctor or nurse if you experience any of the following side effects:

Necrosis at Injection Site

Irregular heartbeat

Headache

Preparations

SC or IM injection in mild anaphylactic shock (1/1000).

IV in severe anaphylactic shock or cardiac arrest.

Intracardiac for cardiac resuscitation 0.5 mg diluted to 10 ml with

normal saline may be administered I.V. or intracradiac to restore

myocardial contractility.

Epinephrine inhalation in asthma (1/100).

1% solution for ophthalmic use.

Nursing considerations:

Never administer 1: 100 solution IV. Use 1: 1000 mg sol. For I.V. use.

Administer infusion by electronic infusion device for safety & accuracy.

Closely monitor patients receiving I.V. epinephrine infusion.

Note the client for signs of shock “loss of consciousness, clammy, cold skin, cyanosis…. etc.).

Briskly massage site of S.C. or I.M. injection to hasten the action of the drug. Do not inject epinephrine into the buttocks or any other part of your body.

The medicine can be injected through clothing if needed in an



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emergency.

Monitoring:

Heart rate and blood pressure continuously (ie arterial line).

Watch urine output.

Observe IV site for infiltration. Infusion rate > 0.3mcg/kg/min.

Monitor cardiac output and consider cardiac ECG



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Norepinephrine


Acts on alpha 1&2 (α1&2) – beta 1 (β1) receptors:

α effect marked vasoconstriction marked increase in blood pressure

or gangrene.

β1 effect positive inotropic (increase heart contraction) &

chronotropic effect (increase heart rate) but ,

Marked increase BP → reflex vagal bradycardia masks its direct effect.

clinical uses :Septic shock, carcinogenic shock (BP<70mmHg)

Dose:

Norepinephrine is typically given as a continuous IV infusion in a hospital or emergency setting.

The starting dose is weight-based, and then the doctor will increase the dose to the desired response.

Administration

Add prescribed amount to 10% dextrose or 0.9% sodium chloride to make a total of 50ml solution.

Continuous IV infusion via a central line only! Ensure patient is not hypovolaemic.

Storage

Drug is stable but best prepared every 24hrs unless protected from light

Norepinephrine Warnings

Monitor blood pressure, breathing, and other vital signs while receiving



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this medication.

You should tell your healthcare provider if you experience any irritation,

pain, coldness, or other discomfort where the drug is injected.

Norepinephrine can damage the skin around the injection site if it leaks

out of the vein.

Before taking norepinephrine, you should tell your doctor if you have:

Diabetes

Heart disease

High blood pressure

Varicose veins

Circulation issues

Overactive thyroid

https://www.everydayhealth.com/type-2-diabetes/guide/

https://www.everydayhealth.com/high-blood-pressure/guide/

https://www.everydayhealth.com/thyroid/guide/



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Dopamine

Mechanism of action

Low dose stimulate dopamine 1 receptors increase renal blood

flow

Intermediate dose βeta1 receptors stimulation resulting in

increasing myocardial contraction, cardiac output.

High dose alpha (α1) receptors stimulationvasoconstriction of blood

vessels up to necrosis

Indications:

Acute heart failure with renal impairment

Iv infusion 2ug-20ug/kg/min gradually

Side effects:

Hypertension

Arrhythmia

Necrosis at site of injection in case of extravasation


Drug must be diluted before use and administer through a central line or a big vein.

Do not add dopamine to NaHCO3 or other alkaline I.V. solutions since the drug is inactivated in alkaline solution.

Administer only by IV infusion neither (Not IV bolus nor IM)

Check I.V. site for extravasation. Available for hospital use only



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Dobutamine

Mechanism of action

It’s a selective beta 1 receptor agonist

Increase cardiac contractility and heart rate

Uses:

In treatment of acute heart failure with normal kidney function

Cardiogenic shock

Monitoring:

Breathing, blood pressure, oxygen levels, and other vital signs should be

watched closely while you are receiving dobutamine.

Adverse effect:

Tachycardia & arrhythmia & angina pain



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Definition: condition in which the heart is unable to pump an adequate

supply of blood for the metabolic needs of the body.

Drug therapy of chronic congestive heart failure:

1. Drugs decrease preload: Loop Diuretics – ACEIs- Nitrates

2. Drugs decrease after load: ACEIs

3. Drugs increase contractility: Digoxin

4. Drugs decrease mortality : Beta blockers (carvedilol , bisoprolol,

metorolol )– Spironolactone

Drug therapy of acute heart failure:

1. Drugs decrease preload: Loop diuretics – Nitrates- Sodium

nitroprusside

2. Drugs decrease after load: Sodium nitroprusside

3. Drugs increase contractility: Dopamine- Dobutamine

Chapter 4

Drug therapy of heart failure



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Digoxin Action:

It increases the force of myocardial contractions (positive inotropic).

It increases the contractility of the heart muscle by minimizing the

movement of Na+ and K+ ions and increasing the release of Ca+ ions in

the myocardial cells.

It decreases the heart rate due to increase in parasympathetic nervous

system and decrease in the sympathetic tone.

Primarily excreted through the kidneys.

Results:

Increase cardiac output decrease cardiac size.

Decrease sympathetic activityincrease heart rate & renin

Diuretic effect decrease edema.

Increase intracardiac Na & Ca level arrhythmia

inhibit SAN decrease heart rate

inhibit AVN conduction

CNS stimulation



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Pharmacokinetics:

Absorption: 1/3 dose inactivated by bacterial flora

Distribution: 2/3 dose is free unbound top

Elimination: 2/3 dose eliminated renal & rest in liver, stool long t1/2=36

Dose: digitalization dose = 0.4 – 0.6 mg followed by 0.05 – 0.35 mg once or

twice daily.

Low TI (therapeutic plasma level =0.5-1.5ng/ml) close to toxic level (>2ng/ml)

Uses:

1. Congestive heart failure

2. Congestive heart failure +Atrial fibrillation (AF)

3. Atrial fibrillation (AF) & paroxysmal supra ventricular tachycardia

(PSVT): protect ventricle

Contraindications:

1. Acute myocardial infarction: increase risk of arrhythmia

2. Partial heart block: convert it to complete heart block

3. Ventricular tachycardia: convert it to ventricular fibrillation

4. Given with caution for elderly and people who have kidney failure.



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Drug interaction with digoxin

A. Pharmacokinetic Interaction

1. Metoclopramide decrease absorption

2. Anticholinergic increase absorption

3. Antacid decrease absorption

4. Erythromycinkill bacterial flora↑absorption

5. Antiarrhythmic drugs (verapamil-amiodarone) ↓excretion & displace it

from tissue binding sitesincrease plasma level of digoxin

B. Pharmacodynamics Interaction

1. Drugs increase digoxin tachyarrhythmia:

a. Diuretics: Hypokalemia

b. Hypercalcemia :Thiazide

c. Sympathomimetic

2. Drugs increase digoxin Bradyarrhythmia:

a. Beta blockers (BB)

b. Calcium channel blockers (CCBs)

3. Liver and kidney dysfunction increase level of digoxin

Digoxin toxicity

Symptoms:

1. GIT: Anorexia ,Nausea, Vomiting ,Diarrhea (early ) 2. CVS: cardiac arrhythmias (tachy or bradyarrythmias) 3. CNS: hallucination ,confusion- yellow & green vision 4. Gynecomastia



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Treatment of digitalis toxicity:

1. Stop digitalis and K losing diuretics

2. KCL if serum K is low (<3.5 mmol/L)

3. Lidocaine or phenytoin for ventricular arrhythmias

4. Atropine : in bradycardia and heart block

5. Digibind (fab fragment):help its excretion through kidney (in fatal toxicity)

6. Plasmapharesis: in renal dysfunction when Digibind are contraindicated



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Spironolactone

Action:

Is a mild diuretic it increase secretion of sodium and water & conservation

of potassium.

It is also aldosterone antagonist.

It has slight antihypertensive effect.

Uses:

1. Edema of hyperaldosteronism (congestive heart failure -liver cirrhosis-

nephrotic syndrome)

2. Hypokalemia & hypomagnesaemia Magnesium

Side effects:

1. Hyperkalemia & Magnesium

2. Gynecomastia

Precautions:

1. Monitor electrocardiogram for arrhythmias.

2. Monitor serum potassium levels.



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Drug therapy of atrial fibrillation:

1. Amiodarone

2. Beta blockers

3. Verapamil

4. Digoxin

5. Anticoagulant (warfarin)

Drug therapy for PSVT:

1. Adenosine

2. Verapamil

3. Beta-blockers

Drug therapy for ventricular arrhythmia

1. Amiodarone

2. Lidocaine

Lidocaine Indications:

1. Acute ventricular arrhythmias as which follow myocardial infarction or

cardiac surgeries.

2. Local anesthetic

3. Digitalis induced arrhythmia

Dosage:

Iv bolus then maintenance dose by iv infusion (has very short half-

life)

Not effective orally due to extensive 1st pass metabolism

Chapter 5

Drug therapy of Arrhythmia



39

Side effects:

1. Cardiac: may precipitate cardiac arrest.

2. CNS: dizziness & convulsion

N.B: oral lidocaine preparation is available (mexilitine)



40

Amiodarone Indications:

Life-threatening arrhythmias resistant to other antiarrhythmic

Kinetics:

long half-life 35-103 day

start with loading dose followed by maintenance dose oral or IV

delayed onset:1-3 weeks

displace digoxin from binding sits increase its toxicity

Side effects:

1. Cardiac : bradycardia & heart block

2. Thyroid dysfunction

3. Pulmonary fibrosis

4. Eye: corneal opacities

5. Increase liver enzymes

6. Photosensitivity

Precautions:

Amiodarone increases the risk of digoxin toxicity in patients also taking digoxin.

Monitor blood pressure, heart rate, and rhythm for changes.

Monitor for signs of pulmonary toxicity (dyspnea, nonproductive cough, and pleuritic chest pain).

Liver &thyroid function every 6months-chest x ray every 3 month



41

Adenosine

Uses:

Paroxysmal supra ventricular tachycardia

Dosage:

Rapid IV bolus repeated after 2 min

Adenosine must be administered over 1 to 2 seconds, followed by

a 20 ml Flush of normal saline solution.

Record rhythm strip during administration

Side effects:

Chest pain & dyspnea

Headache & flushing

Bradycardia & heart block



42

Definition of bronchial asthma:

Chronic inflammatory disease of the airways most commonly allergic

characterized by reversible bronchial obstruction with bronchial hyper

responsiveness.

Drug therapy of bronchial asthma:

1. Beta 2 agonist: salbutamol

2. Anticholinergic : ipratropium

3. Theophylline

Drug therapy of acute attack of bronchial asthma

1. Salbutamol by inhalation & iv

2. Corticosteroidsoral prednisone (7days) & iv methyl prednisolone

3. Ipratropium by inhalation alone or with salbutamol

4. Aminophylline : slowly iv infusion

5. Volatile anesthetics

6. Artificial respiration

7. Antibiotics for infection

Chapter 6

Drug therapy of bronchial asthma



43

Selective Beta 2 adrenergic receptor agonist

(Salbutamol)


Stimulate β 2 receptors in bronchi and uterine smooth muscle.

Preparations:

Salbutamol – terbutaline (short acting Beta 2 agonist) (oral,

inhalation , injection)

Salmeterol (long acting Beta 2 agonist) used in combination with

corticosteroids (inhaler only)

Uses:

Bronchial asthma (Ventolin)

Premature labor (Ritodrine)

Side effects:

Anxiety

Tremors

Tachycardia

Tolerance

Hypokalemia

Hyperglycemia

Hypoxemia



44

Anticholinergic bronchodilators

Ipratropium (short acting) & Tiotropium (long acting) cholinergic

receptors blockers

Atropine substitute useful in treatment of bronchial asthma and is

taken by inhalation

Has less systemic side effects than atropine

Effective in COPD and patient taking beta blockers

Tolerance is common with Ipratropium

Side effects and precautions:

Given cautiously in patient with benign prostatic hyperplasia

Worsening symptoms of narrow-angle glaucoma

Other side effects :Dry mouth – Cough -Dizziness

https://www.medicinenet.com/benign_prostatic_hyperplasia/article.htm

https://www.medicinenet.com/glaucoma/article.htm

https://www.medicinenet.com/dry_mouth/article.htm

https://www.medicinenet.com/dizziness_dizzy/article.htm



45

Theophylline (Aminophylline)


Bronchodilator

Anti-inflammatory

Action:

CNS: insomnia- convulsion- respiratory stimulant

CVS: increase heart rate & myocardial contraction

Blood vessels vasodilatation decrease blood pressure

Kidney: weak diuretic effect

GIT: increase HCL secretion - relax intestine- tocolytic

Uses:

Bronchial asthma as a second line drug

COPD (chronic obstructive airway disease)

Route of administration:

Oral – injection- rectal

Side effects & precautions:

1. Anorexia –Nausea –Vomiting & proctitis (rectal)

Precautions: oral preparation taken with meal –avoids oral

preparations in peptic ulcer- avoid suppositories

2. Insomnia &headache & convulsion

Precautions: add pyridoxine (vitamin B6)



46

3. Hypotension & arrhythmia& cardiac arrest

Precautions: intravenous should be very slowly to avoid cardiac arrest

4. Low therapeutic & saturable kinetics& increase risk of drug

interactions

Precaution: monitor plasma level & adjust dose in certain

patients

Factors affecting theophylline plasma level requiring dose

adjustment

Decrease dose in:

extreme of age

liver & heart failure

with enzyme inhibitors drugs : erythromycin-ciprofloxacin-oral

contraceptive pills

Increase dose in:

children

heavy smoker

with enzyme inducer drugs : rifampicin- phenytoin



47

Corticosteroids in bronchial asthma

Mechanism:

Anti-inflammatory – potentiate the effect of Beta 2 agonist

Preparations:

inhalation (beclomethazone- fluticasone)

Oral (prednisolone)

Parenteral (hydrocortisone)

Side effects:

Oropharyngeal candidiasis

Horsiness of voice

Eye: cataract- glaucoma

Bone: osteoporosis – growth retardation

CVS: hypertension –edema

Endocrine: Diabetes - Cushing syndrome

How to avoid these side effects:

Patient should gargle and spit after inhalation

Use by inhalation decrease systemic side effects

Avoid sudden withdrawal

Drugs contraindicated in Bronchial Asthma:

Beta-blockers

Cholinomimetics (Neostigmine)

Histamine librators (Morphine)

NSAIDs (aspirin)



48

Definition: Drugs used to dissolve thrombus

Parenteral anticoagulant

Heparin Pharmacological Action:

Combines with antithrombin (natural anticoagulant factor)

forming heparin antithrombin complex which accelerates the

inhibitory effect of antithrombin on activated clotting factors.

Pharmacokinetics

Immediate onset of action after intravenous injection and short

duration (4-6 h).

80 % hepatic metabolism in liver, 20 % excreted renally,

unchanged.

Does not cross placenta & is not secreted in milk (high molecular

weight) can be used during lactation or pregnancy

Routes of Administration & Doses

IV bolus (5,000 IU), followed by IV infusion (1,000 IU/h); guided

by aPTT).

Chapter 7

Drug therapy of Thrombosis



49

SC: 5,000 IU (low dose of heparin) for prophylaxis, 2 hours

preoperative and every 12 hours postoperative for 5-7 days.

N.B. Heparin should not be given by IMI as hematoma can occur.

Control of Therapy

aPTT (activated partial thromboplastin time) should be kept as close

as possible to twice normal value (normal value 30-35 seconds).

Platelet count every 2-3 days

Adverse Effects

1. Hemorrhage treated by protamine sulfate (antidote).

2. Hair loss (alopecia).

3. Hematoma if given by IMI.

4. Hypersensitivity.

5. Osteoporosis

6. Thrombocytopenia (regular platelet count is required)

Treatment: replace heparin by fondaparinux.



50

Low-Molecular-Weight Heparins (LMWHs)

(Clexane)

They are given subcutaneously.

Advantages of LMWHs

1. Equal efficacy to heparin.

2. Greater bioavailability from subcutaneous sites.

3. Long half-life given subcutaneously once or twice/day.

4. Less thrombocytopenia & osteoporosis.

5. Less risk of bleeding.

Precautions:

Never administer I.M.

Don’t massage the site after subcutaneous

injection.

Rotate injection sites, keeping a record of sites used.

Monitor platelet count and for signs of bleeding.

Check I.V. infusions regularly for under dosing and overdosing.

Protamine sulfate (Protam)

Highly basic with low molecular weight carrying

electropositive charge.

Neutralizes heparin (each 1 mg neutralizes ≈ 100 IU heparin).

Partially antagonizes LMWHs but does not antagonize

fondaparinux.

Has a slight anticoagulant effect avoid overdose.



51

Fondaparinux

Synthetic pentasacharide molecule, derivative of heparin.

Binds to antithrombin with high specificity efficient inactivation

of factor Xa.

Long duration of action given once daily subcutaneous.

Low risk of heparin - induced thrombocytopenia.

Used in venous thromboembolism & heparin - induced

thrombocytopenia.

Bleeding is its major side effect: not antagonized by protamine

sulfate.

Requires less monitoring than heparin (due to predictable

pharmacokinetics).

Treatment of heparin induced thrombocytopenia:

1. Stop heparin

2. Heparin Replaced by Fondaparinux



52

Oral anticoagulant

Warfarin


Inhibition of vitamin K activationinhibition of clotting factors

(II, VII, IX, X) synthesis

Pharmacokinetics

Well absorbed after oral administration.

More than 99 % bound to plasma proteins.

Metabolized by liver & excreted by kidney.

Delayed onset with long duration of action (up to 6 days).

Crosses placenta.

Safe during lactation.

Dosage of Warfarin

Loading dose: 5- 10 mg/day (followed by maintenance dose).

Maintenance dose: 5-7 mg/day (according to INR).

Control of Therapy

PT (Prothrombin Time): Should be kept as close as possible to

twice normal value (12 s).

INR: Should be kept at 2-3.

Antidotes

Fresh frozen plasma.

Vitamin K1.



53

Adverse Effects

1. Hemorrhage.

2. Skin necrosis (especially in patients with protein C deficiency).

3. Teratogenic (avoid in pregnancy).

Disadvantages

Delayed onset (2-3 days are required for depletion of already

formed coagulation factors)requires overlapping therapy

with heparin

Narrow therapeutic index

Requires routine monitoring of coagulation.

Drug interactions.

Drug Interactions with Warfarin requiring Dose Adjustment:

Effect is↑ by Effect is ↓ by:

1. Enzyme Inhibitors

Amiodarone

Erythromycin

Chloramphenicol

Ciprofloxacin

1. Enzyme Inducers:

Rifampin

Carbamazepine

2. Paraffin Oil Interferes with vitamin K absorption

2. Vitamin K ↑Coagulation

factors

3. Broad-Spectrum Antibiotics Interfere with synthesis of vitamin K

3. Oral contraceptives increase Coagulation factors



54

4. Aspirin – Sulfonamides: Displace warfarin from Plasma proteins.

4. Cholestyramine :Interferes with absorption of oral anticoagulants

5. Aspirin :Antiplatelet effect

6. Anabolic Steroids Quinidine decrease Coagulation factors

Contraindications of Anticoagulants

o Hemophilia.

o Head injuries.

o Intracranial hemorrhage.

o Severe hypertension.

o Threatened abortion.

o Active peptic ulcer.

o Active TB

o Allergy

Protocol for anticoagulation

Heparin (initially), followed by concomitant administration of

oral anticoagulants for 2-3 days before stopping heparin

(guided by INR).

New oral anticoagulant: Rivaroxiban - Dabigatran

More rapid onset and offset.

No monitoring is required

Less drug interactions.



55

Thrombolytic

Old generation: Streptokinase – Urokinase

New generation: Alteplase – Reteplase

Uses:

Acute myocardial Infarction

Acute ischemic stroke

Pulmonary embolus

Catheter occlusion

Arterial thrombosis

Adverse effect:

Bleeding

Allergic reaction (streptokinase-urokinase)

Antidote: Aminocaproic acid – Tranexamic acid

Precautions

Monitor aPTT, PT, INR, HB, during and after administration.

Monitor vital signs frequently during and immediately after

administration. Monitor for signs of bleeding.

Monitor puncture sites for bleeding

Do not use a tourniquet when obtaining blood specimens.



56

Antiemetic drugs

Nausea & vomiting can be caused by a variety of conditions such as

infections, drugs, motion, organic disease or psychological factors.

The underlying cause of the symptoms must be elicited before emesis

is corrected.

The act of vomiting is complex.

The vomiting center in the medulla responds to stimulation from many

peripheral areas as well as stimuli from CNS itself, the CTZ in the

medulla, the vestibular apparatus of the ear & the cerebral cortex.

The selection of antiemetic depends on the cause of the symptom as

well as on the manner in which the vomiting is triggered.

Chapter 8

Drug therapy of vomiting and peptic ulcers



57


Take a complete history, if it is unusual occurrence or if it is a

recurring phenomenon.

Assess for other untoward symptoms as increased intracranial

pressure or intestinal obstruction (antiemetic may mask signs of

underlying pathology)

Caution the patient that drug tends to cause drowsiness &

dizziness, advice him\her to avoid hazardous tasks.

Metoclopramide Mechanism of Action:

It is dopamine receptor antagonist acts both centrally & peripherally:

Centrally due to inhibition of CTZ.

Peripherally it stimulate the motility of the upper GIT. It

relaxes the pyloric sphincter & increases the peristalsis of the

duodenum resulting in accelerated gastric emptying &

intestinal transit.

Indications:

GERD (gastroesophageal reflux disease)

pre and postanasthetic

All types of vomiting except motion sickness.

Facilitate diagnostic procedure e.g. barium meal.



58

Side effects:

Diarrhea

Extrapyramidal side effect

N.B. Domperidone: more effective with less central adverse effects

Ondansetron Uses: Prevention and treatment of:

Postoperative nausea and vomiting

Cancer chemotherapy induced nausea and vomiting

Side effects:

Diarrhea

Liver function test abnormalities

pruritus, headache, tachycardia, myalgia, anorexia, fatigue

Precautions:

Monitor cardiac rhythm.

They're contraindicated in patients with prolonged QT intervals

Monitor liver function.

Correct hypokalemia and hypomagnesemia before administering.



59

Drug therapy of peptic ulcers

H2 Receptors blockers

Proton pump inhibitors (PPIs)

H2 Receptors blockers

Members: Ranitidine – Famotidine

Mechanism of Actions:

Reversible competitive antagonists of H2 receptors on parietal cells.

Potent inhibition of nocturnal or fasting but less inhibition of

daytime (meal-stimulated) acid secretion.

Adverse Effects of H2 Blockers

Headache, diarrhea or constipation.

Tolerance, rebound hyperacidity & recurrence (upregulation of H2 receptors).

Hypotension & bradycardia if given rapidly IV in intensive care

Ranitidine (contraindicated in liver dysfunction)

Famotidine (preferred in liver dysfunction)



60

Proton pump inhibitors

Members: Omeprazole - Lansoprazole- Pantoprazole – Rabeprazole

Mechanism of Action

PPIs are the most effective acid suppressants since they act on the

final step of HCl secretion

They are prodrugs, inhibit basal & meal stimulated acid secretion

(98%, 1-2 h after 1st dose).

Pharmacokinetics

Food decrease bioavailability by 50% (so taken on empty stomach).

These drugs ideally should be given about 30 minutes before meals.

Long duration (action starts in 1 hour & lasts for 1 day).

Metabolized in the liver.

Adverse effects

GIT: abdominal pain, nausea, vomiting, diarrhea or constipation.

CNS: headache, dizziness, somnolence.

Hypochlorhydria → increase risk of infection (e.g. hospital acquired

pneumonia & H. pylori).

Vitamin B12 deficiency (long term use)

Enzyme inhibition with clopedogril



61



62

1. Fluid replacement (1st and most important line of ttt):

Isotonic saline (3-5 L) then 1/2 tonic saline if serum Na ↑

Add 5% glucose if blood glucose ↓to 250mg/dl to avoid cerebral

edema

2. insulin therapy

regular insulin by iv infusion dose : low dose 0.15ug/kg/h

↓Iv dose by half when blood glucose falls to 250mg/dl

once patient is stable ,switch to sc insulin 4 times/day

3. potassium replacement

initial: acidosishyperkalemiano need for K

during insulin therapy (K insulin) :

a. if K normal :give 20 mmol/l

b. if K is low : give 40 mmol/l

4. Bicarbonate administration

mild acidosis: is spontaneously corrected by insulin

sever acidosis (PH< 7.1): give NaHCO3 IV till correction of PH.

Avoid alkalosis (PH> 7.2) add KCL prophylactic

5. Treatment of underlying cause: infection by antibiotics

Chapter 9

Drug therapy of diabetic ketoacidosis

(DKA) and hepatic coma



63

Insulin

Patients with type 1 diabetes require an external source of insulin

to control blood glucose levels. Insulin may also be given to patients

with type 2 diabetes. Types of insulin include:

Rapid-acting lispro

Short-acting regular

Intermediate-acting: NPH

Long-acting: Ultralente.

Indications:

Type 1 diabetes

Uncontrolled type 2 diabetes.

Type 2 diabetes in case of infection and surgery

Type 2 diabetes during pregnancy or lactation

DKA (diabetic ketoacidosis)

Hyperkalemia

Adverse reactions:

Hypoglycemia

Hypersensitivity reactions

Lipodystrophy (disturbance in fat deposition)

Insulin resistance.



64

Drug therapy of hepatic coma

1. Treatment of precipitating factors: infection, GIT bleeding,

hypokalemia or hypoglycemia.

2. H2 receptors antagonists (ranitidine): decrease acidity, gastric

erosions and bleeding.

3. Drugs decreasing portal pressure: ↓ bleeding of esophageal varices:

Octreotide - vasopressin (plus nitrates) - beta Blockers

4. Decrease ammonia by:

Decrease dietary protein.

Evacuant enema with lactulose.

Lactulose (mainstay of therapy):

Precautions:

After administration through a nasogastric (NG) tube, flush

tube with water.

For administration by retention enema, instruct the patient

to retain drug for 30 to 60 minutes.

Be aware that neomycin and other antibiotics may

decrease effectiveness.

Monitor the patient’s serum ammonia levels while receiving

the drug.

Titrate the dose to 2 to 3 soft stools per day.

Neomycin (kills bacterial flora, which form ammonia from proteins).

Stimulation of ammonia metabolism:

Ornithine-aspartate and Sodium benzoate: increase

ammonia removal by hepatocytes via stimulation of

glutamine synthesis.



65

NSAIDs inhibition of prostaglandens (PGs) production alleviates most of

the pathologic effects associated with inflammation, but it also

interferes with the physiologic role of these molecules

Consequently, long-term therapy with nonspecific NSAIDs is frequently

limited by their adverse effects, particularly those caused by erosion

of gastric mucosal protection

Pharmacodynamic Effects of NSAIDs

Analgesic: refers to the relief of pain; produce a mild degree of

analgesia which is much less than the analgesia produced by opioid

analgesics such as morphine

Anti-inflammatory : these drugs are used to treat inflammatory

diseases and injuries, and with larger doses - rheumatoid disorders

Antipyretic : reduce fever; lower elevated body temperature by their

action on the hypothalamus; normal body temperature is not reduced

Anti-platelet: inhibit platelet aggregation, prolong bleeding time;

have anticoagulant effects.

Chapter 10

Non-steroidal Anti-Inflammatory Drugs

(NSAIDs)



66

Nonsteroidal anti-inflammatory drugs (NSAIDs) includes:

1. Acetylsalicylic acid (aspirin)- selective NSAIDs .

2. Non selective NSAIDs (ibuprofen, naproxen, diclofenac, piroxicam,

indomethacin).

3. Paracetamol is an analgesic-antipyretic with NO anti-inflammatory

action.

Aspirin Action:

Irreversibly inhibits cyclooxygenase enzymes (COX-1, COX-2)

inhibits the formation of PG & TXA2.

Uses:

1. Prophylactic as Antiplatelet for transient ischemic attacks,

unstable angina, acute myocardial infarction

2. Anti-inflammatory: rheumatic fever& other inflammatory joint

disease

3. Analgesic & Antipyretic (intermediate dose 325mg)

Dose-Dependent Effects of aspirin:

Low: < 300mg: blocks platelet aggregation

Intermediate: 300-2400mg/day: antipyretic and analgesic effects

High: 4000-8000mg/day: anti-inflammatory effects.



67

Adverse Effects:

A. Effects Common to all NSAIDs (particularly in the elderly)

1. GIT: gastritis & ulceration with ↑ risk of bleeding, reduced by co-

administration of misoprostol or omeprazole.

2. Nephrotoxicity (less frequent with aspirin)

3. In renal insufficiency or in hypovolemic patient vasodilator

PGs by NSAIDs renal blood flow resulting in:

a. Salt & water retention (edema), increase blood pressure.

b. Hyperkalemia.

c. Acute renal insufficiency

4. Hypersensitivity reactions: Skin rash, rhinitis, asthma

5. Bleeding tendency Antiplatelet effect. Displacement of warfarin from plasma proteins

potentiating its effect.

B. Effects Specific to Aspirin

1. Hypoprothrombinemia: bleeding risk (> 5 g/d competes with vit. K).

2. Hyperuricemia (low-dose aspirin in gout)

3. Reye’s syndrome: encephalopathy and liver damage in patients with fever due to viral infection (# as antipyretic in viral infections).

4. Chronic toxicity (salicylism) dizziness, tinnitus, nausea & vomiting.



68

Indomethacin

Strong anti-inflammatory.

Due to serious adverse effects its use is limited to:

1. Acute gouty arthritis.

2. Rheumatoid arthritis.

3. Postoperative pain.

4. Patent ductus arteriosus (inhibits PG synthesis closing the ductus).

Adverse Effects

1. Adverse effects common with other NSAIDs (see before).

2. CNS: dizziness, confusion, ataxia, severe headache (cerebral VD).

3. Aplastic anemia.

Selective COX-2 Drugs

Celecoxib

COX-2 is also up-regulated in the CNS and plays an essential role in

the mediation of pain and the febrile response

Use: strong anti-inflammatory drugs with low GIT side effects

Side effects

Increased risk of cardiovascular events

Nephrotoxicity

Hypersensitivity reactions



69

Analgesic: compared with Opioids

NSAIDs Opioids

Effects Inhibit PGs and TXA 2 synthesis by inhibiting COX

Stimulate opioid receptors

Clinical usage Headache, toothache，

neuralgia, arthralgia

Various pain including severe pain

Side effects GIT reactions, no addiction

Addiction

Anti-inflammatory: compared with glucocorticoid

NSAIDs Glucocorticoid

Effects Inhibit PGs and TXA 2 synthesis by inhibiting COX

Various effects including inhibition of PLA 2

Clinical usage Rheumatic, rheumatoid, trauma

Various inflammation

Side effects GIT reactions Various side effects, such as metabolism disturbance, damage of defense etc.



70

Paracetamol

It is an analgesic antipyretic with NO anti-inflammatory action.

It is preferred to aspirin in:

1. Patients allergic to aspirin.

2. Peptic ulcer (no GIT disturbances).

3. Gout (aspirin may cause hyperuricemia).

4. Viral infections in children (to avoid Reye’s syndrome with aspirin).

5. Bleeding disorders (does not affect platelet function).

Kinetics

Paracetamol is conjugated in the liver to inactive metabolites & only

5% is converted by CYP450 to a hepatotoxic metabolite which

deactivated by conjugation with glutathione.

In toxic doses saturation of conjugating enzymes results in ↑ conversion

of the drug to the toxic metabolite beyond the capacity of liver to

conjugate it with glutathione hepatotoxicity.

Adverse Effects & Toxicity

1. Minimal adverse effects - well tolerated.

2. Paracetamol hepatotoxicity (in toxic doses>4gm nausea and

vomiting, followed in 24-48 h by liver damage)

Treatment: acetylcysteine (mucomyst) (orally or IV) or methionine

(orally) can prevent liver damage if given early.

Intravenous paracetamol

1. Analgesic: in mild to moderate postoperative pain safe ( opioid

dose).

2. Antipyretic: in acute fever of infectious origin requiring IV therapy.



71

Morphine Given IV - IM - SC - epidurally - orally (extensive 1st pass

metabolism)

Pharmacological actions:

Chapter 11

Opioid analgesics



72

Uses:

1. Analgesic in:

Acute trauma.

Chronic visceral pain

Postoperative pain

Cancer pain

Myocardial infarction

2. In anesthesia: Preanaesthesia & cardiovascular surgery

3. Acute pulmonary edema in acute heart failure following myocardial

infarction:

decrease preload & after load

decrease Respiratory distress

decrease Anxiety

4. Antitussive : Replaced by Codeine , Dextromethorphan (less

addictive)

5. Antidiarrheal: Loperamide, Diphenoxylate (less addictive, more

widely used)

Adverse effects and contraindications:

Masks pain: (contraindication: acute undiagnosed abdomen)

Sedation – Narcosis

Drug dependence



73

Hypotension

Nausea –vomiting- sever constipation

Respiratory depression & asphyxia neonatorum

Increase Intracranial tension: (contraindication: head injury)

Delayed labor (contraindicated in pregnancy)

Miosis

Urine Retention:(contraindication: enlarged prostate)



74

N.B. Antidote for morphine: naloxone

Biliary spasm :contraindication: biliary colic)

itching

bronchospasm : (contraindication: asthma)



75

Pethidine Use:

In acute moderate & severe pain e.g, trauma, postoperative pain,

biliary colic or labor pain.

Route : IM- oral

Pethidine differs from morphine in:

Less constipating

Less respiratory depressant in neonates

Does not delay labor g preferred during labor (decrease risk of asphyxia neonatorum).

Atropine-like action: dry mouth, blurred vision

increase risk of convulsions

Fentanyl

More potent than morphine with rapid onset & shorter action

(preferred in anesthesia).

High anesthetic doses→ chest wall rigidity↓ thoracic compliance

ventilation.

Uses (IV– epidural- spinal - transdermal patch – patient controlled

infusion)

1. Analgesic in severe pain e.g. perioperative & cancer pain.

2. In anesthesia (for its analgesic & sedative effects):

Preanesthetic medication.



76

IV anesthetic in cardiovascular surgery (safer).

Conscious sedation

Tramadol

Analgesic acting by inhibiting uptake of serotonin and noradrenaline

partially antagonized by naloxone

Less constipation, respiratory depression & addiction than

morphine.

↑ Risk of convulsions.

Uses (oral, IM, IV)

Analgesic in postoperative & chronic moderate pain - neuropathic

pain.



77

Antihistamines (H1 receptors blockers)

Preparations

1st generation: Chlorpheneramine – Diphenhydramine

2nd generation: Loratidine – Fexofenadine


The effect of histamines may be reversed either by drugs that block

histamine receptors (antihistamine) or by drugs that have effects

opposite to those of histamine e.g. epinephrine.

Antihistamines used for the treatment of allergic conditions are

referred to as H1-receptor blockers while those used for treatment

of gastrointestinal disorders as peptic ulcer are referred as H2-

receptor blockers.

They don’t prevent the release of histamine, they prevent or

reduce increased permeability edema & itching & bronchospasm.

H1-blockers manifest varying degrees of CNS depression,

anticholinergic & antiemetic effect.

Chapter 12

Antihistamines – Corticosteroids



78

2nd generation has long duration of action and less sedating effect

(less cross blood brain barrier)

Uses:

Treatment of seasonal allergic rhinitis, allergic conjunctivitis.

Treatment of urticarial transfusion reactions.

Treatment of topic dermatitis.

Sneezing & rhinorrhea due to common cold.

Prophylaxis & treatment of motion sickness “nausea & vomiting”.

Night – time sleep aid

Contraindications:

Hypersensitivity.

Glaucoma

Prostatic hypertrophy

CNS depression.

Side effects:

Sedation - deep sleep - Dizziness

dry mouth

urinary retention

Paradoxical excitation (especially in children & elderly)



79

Nursing Considerations:

Inject I.M. preparations deep into muscles.

Note if the patient has glaucoma

Note signs of CNS depression.

If the drug is being used for motion sickness, it should be taken 30

minutes before transporting.

The patient should not drive a car or operate other machinery work.

Corticosteroids Mechanism of action:

1. CHO metabolism:

Deposition of glucose as glycogen in the liver & conversion of

glycogen to glucose when needed. (Gluconeogenesis).

2. Protein metabolism:

The stimulation of protein loss from many organs.

3. Fat metabolism:

The deposition of fatty tissue in facial, abdominal & shoulder regions.

4. Water & electrolyte balance:

Alteration of glomerular filtration rate, increase sodium &

fluid retention, also affect the excretion of potassium,

calcium & phosphorus.



80

5. Have anti-inflammatory effect:

They decrease prostaglandin synthesis.

6. The immunosuppressant effect:

They decrease number of T-lymphocyte, monocytes, and

eosinophils.

7. Anti-stress effects e.g. trauma & sever illness.

According to their chemical structure, they fall into 2 classes.

Glucocorticoids e.g. cortisone & hydrocortisone: regulate the

metabolism of CHO, protein & fat.

Mineralocorticoids e.g. hydrocortisone: increase reabsorption of

Na+ (+water) & excretion of potassium & hydrogen.

Uses:

Therapy with glucocorticoids is not curative & many situations should be

considered as adjunctive rather than primary therapy:-:

Replacement therapy: adrenal insufficiency (Addison’s disease).

Rheumatic disorders: rheumatoid arthritis & osteoarthritis.

Collagen diseases: systemic lupus erythematosus, rheumatic

cardiac.

Allergic diseases: drug hypersensitivity, urticarial transfusion

reaction.

Respiratory diseases: bronchial asthma, rhinitis.



81

Ocular diseases: allergic & inflammatory conjunctivitis, keratitis.

Dermatological diseases: psoriasis, contact dermatitis, urticaria.

Nervous system: Myasthenia gravis.

Diseases of the GIT: ulcerative colitis.

Malignancies: leukemia, lymphoma- Nephrotic syndrome.

Hematologic diseases: hemolytic anemia, thrombocytopenic

purpura.

Miscellaneous: septic shock, liver cirrhosis, stimulation of surfactant

production, prevention of organ rejection.

Contraindications:

If infection is suspected (it Masks signs & symptoms).

Peptic ulcer.

Cushing’s syndrome.

Congestive heart failure.

Hypertension.

Hyperlipidemia.

Side effects:

Edema, hypertension and CHF

Diabetes mellitus

Metabolic Alkalosis

Hypokalemia



82

muscle wasting , weakness

osteoporosis

peptic ulcer

hirsutism, amenorrhea

Depression.

Redistribution of body fats: thin extremities and fat trunk, moon-

like face, buffalo hump.

Steroid withdrawal syndrome may lead to: anorexia, nausea,

vomiting, weight loss, headache, myalgia & hypotension.

Nursing Considerations:

Administer oral forms with food to minimize ulcerogenic effect.

For chronic use, give the smallest dose possible.

Gradual withdrawal if used more than 2 weeks

Document blood pressure, Pulse, temperature, monitor body

weight (signs of Na+ & H2O retention).

Periodic serum electrolytes, blood sugar monitoring.

Report signs & symptoms of side effects (Cushing-like syndrome).

Discuss with female patient about the potentials of menstrual

difficulties.

Instruct the patient to take diet high in protein & potassium.

Instruct the patient to avoid falls & accidents (osteoporosis

causes pathological fracture).



83

Remind the patient to carry a card identifying the drug being

used.

Advice the patient to delay any vaccination while taking these

medications (weakened immunity).

Explain the need to maintain general hygiene & cleanliness to

prevent infection.



84

Antibiotics

Antibacterial drugs, also known as antibiotics (drugs that inhibit the

growth of bacteria), are used mainly to treat systemic (involving the

whole body rather than a localized area) bacterial infections.

The antibacterial include:

Aminoglycosides

Penicillins

Cephalosporins

Macrolides

Vancomycin

Carbapenems & Monobactams

Fluoroquinolones

Sulfonamides

Nitrofurantoin (nitrofuran).

Aminoglycosides Preparations:

Amikacin sulfate - gentamicin sulfate - neomycin sulfate - tobramycin

sulfate.

Pharmacokinetics

Aminoglycosides are absorbed poorly from the GI tract.

They are usually given parenterally.

Chapter 13

Antibiotics – Antifungal



85

Distribution

Aminoglycosides are distributed widely in extracellular fluid.

They readily cross the placental barrier, but don’t cross the blood

brain barrier.

Metabolism and excretion

Aminoglycosides aren’t metabolized. They’re excreted primarily

unchanged by the kidneys.

Pharmacodynamics

Aminoglycosides act as bactericidal drugs

Pharmacotherapeutics

Infections caused by gram-negative bacilli

Serious nosocomial (hospital-acquired) infections, such as gram-

negative bacteremia, peritonitis and pneumonia in critically ill

patients.

Urinary tract infections (UTIs)

Infections of the central nervous system (CNS) and the eye (treated

with local instillation).

N.B.

Aminoglycosides are used in combination with penicillins to treat

gram-positive organisms, such as staphylococcal or enterococcal

Aminoglycosides are inactive against anaerobic bacteria.



86

Adverse Effects

1. Nephrotoxicity

2. Ototoxicity

3. Neuromuscular paralysis (inhibits Acetylcholine release)

4. Allergy

Pencillins

Penicillins remain one of the most important and useful

antibacterial, despite the availability of numerous others.

Pharmacokinetics

After oral administration, penicillins are absorbed mainly in

the duodenum and the upper jejunum of the small intestine.

Most penicillins should be given on an empty stomach (1 hour

before or 2 hours after a meal) to enhance absorption.

Penicillins that can be given without regard to meals include

amoxicillin, and amoxicillin/clavulanate potassium.

Distribution

Penicillins are distributed widely to most areas of the body,

including the lungs, liver, kidneys, muscle, bone, and

placenta.

High concentrations also appear in urine, making penicillins

useful in treating UTIs.



87

Metabolism and excretion

Penicillins are metabolized to a limited extent in the liver to

inactive metabolites and are excreted 60% unchanged by the

kidneys.

Pharmacodynamics

Penicillins are usually bactericidal in action.


Cover gram-positive, gram-negative, and anaerobic organisms.

Penicillin is given by I.M. injection when oral administration is

inconvenient

Long acting penicillin are relatively insoluble, they must be

administered by the I.M. route.

Adverse Effects (one of the safest antibiotics)

1. Hypersensitivity (most important): Cross-allergy may occur

between beta lactam antibiotics.

2. Diarrhea: ampicillin.

3. Neurotoxicity: seizures if injected intrathecally or with high

blood level.

Cephalosporins First-generation: cefadroxil and cephalexin monohydrate.

Second-generation: cefoxitin and cefuroxime

Third-generation: cefotaxime and ceftriaxone sodium.



88

Fourth-generation: cefepime hydrochloride.

N.B.

Because penicillins and cephalosporins are chemically similar cross

sensitivity occurs in 10% to 15% of patients. This means that

someone who has had a reaction to penicillin is also at risk for a

reaction to cephalosporins.

Pharmacokinetics

Many cephalosporins are administered parenterally and others

are given orally.

Distribution

Cefuroxime (second-generation) and the third-generation

drugs cefotaxime, ceftriaxone cross the blood-brain barrier

after I.V. or I.M. administration.

Excretion

All cephalosporins are excreted primarily unchanged by the

kidneys with the exception of ceftriaxone, which is excreted

in stool via bile.


First-generation : acts primarily against gram-positive organisms,

may be used as alternative therapy in the patient who’s allergic to

penicillin

Second-generation: acts against gram-negative bacteria. Cefoxitin is

the only cephalosporin effective against anaerobes.



89

Third-generation: acts primarily against gram-negative organisms.

Fourth-generation: active against many gram-positive and gram-

negative bacteria.

Adverse effects

1. Hypersensitivity: (cross-allergy with penicillin).

2. Nephrotoxicity especially if used with aminoglycosides.

3. Local irritation g severe pain after IMI and thrombophlebitis after IVI.

4. Hypoprothrombinemia & bleeding with warfarin

Carbapenem and Monobactam

Imipenem Aztreonam

Broadest-spectrum beta lactams: effective against Gram +ve, -ve organisms and anaerobes.

Given IV

Increase cross-allergy with penicillin

Narrow spectrum: effective against aerobic gram -ve organisms (as aminoglycosides).

Given IV & IM

Nephrotoxic Increase risk of convulsion

avoided in meningitis Meropenem & Etrapenem less

adverse effect

No cross-allergy with beta lactams (penicillin).



90

Vancomycin

Mechanism: Bactericidal inhibits cell wall synthesis

Uses: ORSA or MRSA & Serious infections

Given by IV infusion

Adverse effects

1. Fever, chills, rigors and phlebitis.

2. Shock with rapid infusion g red man syndrome (due to histamine release), avoided by slow infusion & pretreatment with antihistamines.

3. Ototoxic.

4. Nephrotoxic.

Macrolides

Members: Erythromycin- Clarithromycin -Azithromycin

Mechanism: inhibition of protein synthesis

Uses

1. Patients with allergy to beta lactam antibiotics (penicillins).

2. Chlamydia infection in pregnancy.



91

Adverse Effects

1. Epigastric pain & GIT upset (increases bowel motility).

2. Cholestatic jaundice: contraindicated in liver disease.

3. Ototoxicity.

4. Thrombophlebitis if injected intravenously.

5. Drug Interactions

a. Enzyme inhibitor: increase level of theophylline, warfarin, carbamazepine (g arrhythmias).

b. Increase digoxin level (inhibits intestinal flora that inactivate digoxin).

Clindamycin

It used specifically against anaerobic infections.

It used in bone infection (good penetration into bone).

Adverse Effects: Pseudomembranous colitis (diarrhea) treated by

metronidazole (flagy) or vancomycin



92

Quinolones

Action: inhibit DNA synthesis

Preparations: ciprofloxacin- ofloxacin - Levofloxacin

Uses of quinolones

1. Typhoid fever & infective diarrhea (ciprofloxacin: 1st choice for

empiric therapy).

2. Urinary tract infections.

3. Gonorrhea.

Adverse Effects and Contraindications (CI)

1. GIT: Nausea, vomiting & diarrhea (most common).

2. CNS: Headache, dizziness, insomnia, convulsions.

3. Hepatotoxicity.

4. Reversible arthropathy (children < 18 years).

Quinolones are contraindicated in pregnancy & lactation.

Not routinely recommended in patients <18 years.

5. Drug interactions

Enzyme inhibitor increase levels of warfarin, theophylline.

Arrhythmias (increase risk with hypokalemia & with drugs that increase QT interval e.g., erythromycin, antiarrhythmic drugs.

Antacids → decrease absorption of quinolones.



93

Sulfonamides

Members: cotrimoxazol (septrin or sutrium )

Mechanism of Action: Inhibit DNA synthesis

Adverse Effects

1. Crystalluria & Nephrotoxicity

2. Hypersensitivity reactions.

3. Kernicterus (Jaundice & CNS affection): Displace bilirubin from plasma protein. Free bilirubin crosses BBB (immature in newly-born) & reaches CNS.

4. Interactions: increase level of oral hypoglycemic & anticoagulants (displacement from plasma proteins).

Metronidazole

Mechanism of action: Inhibit DNA structure & function → cell death.

Uses of metronidazole:

a. Amebiasis & Giardiasis - Urogenital trichomoniasis.

b. Brain abscess, ulcerative gingivitis & dental infections- leg ulcers.

Adverse effects:

1. GIT: metallic taste.



94

2. CNS (serious): dizziness - convulsions

3. Dark urine – dysuria.

4. Neutropenia.

5. Enzyme inhibitor: increase warfarin level.

6. Disulfiram- like reaction with alcohol.

Antifungal

Amphotericin-B

Mechanism of action: fungicidal

Indications: Most important antifungal in deep infections

especially:

Severe life threatening (IV- not absorbed orally).

Meningitis (intrathecal- does not reach CSF after IVI).

Side effects & toxicity:

1. Fever, rigor, vomiting, hypotension & shock after IVI

2. Convulsions if given (intrathecally)

3. Nephrotoxic: decrease level of erythropoietin and induce anemia.

4. Hypokalaemia and cardiac arrhythmias.



95

Azoles

Preparations: Ketoconazole - fluconazole – Itraconazole

Mechanism of action: Inhibition of synthesis of cell membrane by

inhibiting cytochrome P450.

Ketoconazole

1st oral broad spectrum antifungal for:

1. Deep fungal infections

2. Candidal infection.

Avoid its combination with:

1. Antacids or H2 blockers → gastric acidity ketoconazole

absorption.

2. Amphotericin B: ketoconazole → amphotericin effect.

Adverse effects

1. Nausea - vomiting – rash (common).

2. Hepatotoxic (serious).

3. Steroid synthesis which depends on cytochrome P450:

a. Decrease corticosteroids adrenal suppression (used in

Cushing's disease).

b. Decrease Testesterone gynecomastia, impotence (used in

cancer prostate).

c. Decrease Female sex hormones menstrual irregularities,

infertility.

d. Decrease Metabolism of drugs drug interactions: decrease

Level of oral anticoagulants, antiepileptics



96

Intravenous solutions and different blood component

Types of total parenteral nutrition

Type Solution components per liter Uses

Total parenteral nutrition by central venous (CV) catheter or peripherally inserted central catheter

- 1 Liter dextrose 25% - Crystalline amino acids 2.5% to 8.5% - Electrolytes, vitamins, trace elements, and insulin, as ordered - Lipid emulsion 10% to 20% (usually infused as a separate solution)

- Used for long-term (2 weeks or more) feedings - Promotes tissue synthesis, wound healing, and normal metabolic function - Allows bowel rest and healing

Chapter 14

Intravenous Fluids



97

Peripheral parenteral nutrition by peripheral catheter

-Crystalline amino acids 2.5% to 5% -Electrolytes, minerals, vitamins, and trace elements. -Lipid emulsion 10% or 20% -1 L dextrose 10% and amino acids 3.5% infused at the same time -Heparin or hydrocortisone, as ordered

-Used for short-term (2 weeks or less) feedings -Maintains adequate nutritional status in a patient who resumes bowel function and oral feedings after a few days, and one susceptible to infections associated with the CV catheter

Drugs Indications Adverse effects Precautions

-Normal serum albumin 5%-25% -Plasma protein fractions

-Hypovolemic shock Hypoproteinemia

Vascular overload after rapid infusion

hypotension,

nausea, vomiting,

dyspnea, pulmonary edema

chills,fever

-Don’t give more than 250 g in 48 hours. -Watch for hemorrhage or shock if used after Surgery or injury. -Watch for signs of vascular overload (heart failure or pulmonary edema). Don’t use cloudy solutions or those with Sediment.



98

Blood Components

Aminocaproic acid

Excessive bleeding

resulting from hyperfibrinolys

is

Dizziness, malaise, headache,

tinnitis, nausea, cramps, rash

diarrhea,

-Monitor coagulation studies, heart rhythm, and blood pressure -Dilute the solution with sterile water for injection, normal saline solution, dextrose 5% in water, or lactated Ringer’s solution.

Blood component

Indications Nursing considerations

Packed blood Cells (RBCs)

-To restore or maintain oxygen-carrying capacity -To correct anemia and surgical blood loss -To increase RBC mass

-Use a blood administration set to infuse blood within 4 hours. -Administer only with normal saline solution. -Keep in mind that an RBC transfusion is not appropriate for anemias treatable by nutritional or drug therapies.

Platelets

-To treat bleeding caused by decreased circulating platelets or functionally abnormal platelets -To improve platelet count preoperatively in a patient whose count is 50,000/μl or less

-Administer prophylactic pre-transfusion medications, such as antihistamines or antipyretics, to reduce chills, fever, and allergic reactions. -Complete transfusion within 20 minutes or at the fastest rate the patient can tolerate. -Use single-donor platelets if patient must have repeated transfusions because of the risk of allergic reaction to foreign leukocyte antigens that may be present on



99

A look at intravenous solutions

Solution Uses Special considerations

Isotonic Dextrose 5% in

water

-Fluid loss and dehydration -Hypernatremia

-Solution is isotonic initially; becomes hypotonic when dextrose is metabolized. - Don’t use for resuscitation; can cause hyperglycemia. - Use cautiously in renal or cardiac disease; can cause fluid overload. -Doesn’t provide enough daily calories for prolonged use; may cause eventual breakdown of protein.

Isotonic Normal saline

- Shock -Hyponatremia -Blood transfusions -Resuscitation -Fluid challenges -Metabolic alkalosis -Hypercalcemia

-Because this replaces extracellular fluid, use cautiously in patients with heart failure, edema, or hypernatremia; can lead to overload.

leukocytes and platelets. -Keep in mind that platelets should not be used to treat autoimmune thrombocytopenia or thrombocytopenic purpura unless patient has a life-threatening hemorrhage.

Fresh frozen plasma (FFP)

-To correct a coagulation factor deficiency -To replace a specific factor when that factor isn't available To reverse Warfarin -To treat thrombotic thrombocytopenic purpura

-Complete transfusion within 20 minutes or at the fastest rate the patient can tolerate. -Monitor patient for signs and symptoms of hypocalcemia because the citric acid in FFP may bind to calcium.



100

-Fluid replacement in patients with diabetic ketoacidosis (DKA)

Isotonic Lactated

Ringer’s solution

-Dehydration -Burns -Lower GI tract fluid loss -Acute blood loss -Hypovolemia due to third-space shifting

-Electrolyte content is similar to serum but does not contain magnesium. -Contains potassium; do not use in patients with renal failure; can cause hyperkalemia. -Don’t use in liver disease because the patient can’t metabolize lactate; a functional liver converts it to bicarbonate -do not give if patient’s pH is greater than 7.5.

Hypotonic Half-normal

saline

-Water replacement -DKA after initial normal saline solution and before dextrose infusion -Hypertonic dehydration -Sodium and chloride depletion -Gastric fluid loss from nasogastric suctioning or vomiting

-Use cautiously; may cause cardiovascular collapse or increased intracranial pressure. -Don’t use in patients with liver disease, trauma, or burns.

Hypertonic Dextrose 5% in

half normal saline

-DKA after initial treatment with normal saline solution and half-normal saline solution prevents hypoglycemia and

-In DKA, use only when glucose level falls below 250 mg/dl.



101

cerebral edema (occurs when serum osmolatity is reduced too rapidly)

Hypertonic Dextrose 5% in

normal saline

-Hypotonic dehydration -Temporary treatment of circulatory insufficiency and shock if plasma expanders aren’t available -Syndrome of inappropriate antidiuretic hormone (or use 3% sodium chloride) -Addisonian crisis

-Use cautiously in cardiac or renal patients because of danger of heart failure and pulmonary edema.

3% sodium chloride

-Severe dilutional hyponatremia -Severe sodium depletion

-Administer cautiously to prevent pulmonary edema. -Observe infusion site closely for signs of infiltration and tissue damage.

Dextrose 10% in water

-Water replacement -Conditions in which some nutrition with glucose is required

Monitor serum glucose levels.



102

Magnesium

Magnesium is the most abundant cation in intracellular fluid after

potassium.

It’s essential in transmitting nerve impulses to muscle and

activating enzymes necessary for carbohydrate and protein

metabolism.

About 65% of all magnesium is in bone, and 20% is in muscle.

Magnesium stores may be depleted by:

Malabsorption

Chronic diarrhea

Prolonged treatment with diuretics

Prolonged therapy with parenteral fluids not containing

magnesium

Magnesium sulfate is administered I.V.

Pharmacokinetics

I.V. magnesium sulfate acts immediately

I.M. magnesium sulfate acts within 30 minutes

Chapter 15

Magnesium – Potassium - Calcium



103

I.M. injections can be painful

Metabolism and excretion: Magnesium sulfate isn’t

metabolized and is excreted unchanged in urine and stool

Pharmacotherapeutics:

I.V. magnesium sulfate is the drug of choice in

hypomagnesemia.

It’s widely used to treat or prevent preeclamptic and

eclamptic seizure

Treatment of ventricular arrhythmias such as torsades de

pointes.

Adverse reactions: may be life-threatening:

Hypotension

Circulatory collapse

Flushing

Depressed reflexes

Respiratory paralysis

Cardiac arrest.

Antidote for toxicity: IV. Calcium gluconate

Drug interactions:

Magnesium used with digoxin may lead to heart block

Magnesium sulfate with general anesthetics may increase central

nervous system depressant effects.



104

Magnesium sulfate combined with succinylcholine or tubocurarine

potentiates and prolongs the neuromuscular blocking action of

these drugs.

Potassium

Potassium is the major positively charged ion (cation) in

intracellular fluid. Because the body can’t store potassium,

adequate amounts must be ingested daily. If this isn’t possible,

potassium replacement can be accomplished orally or I.V. with

potassium salts.

Pharmacokinetics

Oral potassium is absorbed readily from the GI tract.

Normal serum levels of potassium are maintained by the kidneys,

which excrete most excess potassium intake. The rest is excreted in

stool and sweat.

Pharmacodynamics

Potassium is necessary for proper functioning of all nerve and

muscle cells and for nerve impulse transmission.

It’s also essential for tissue growth and repair and for maintenance

of acid-base balance.


Potassium replacement therapy corrects hypokalemia.

Hypokalemia is a common occurrence in:



105

vomiting, diarrhea, or nasogastric suction

excessive urination

some kidney diseases

cystic fibrosis

burns

insufficient potassium intake

drugs

Drugs induce hypokalemia Drugs induce hyperkalemia

Beta 2 agonist (salbutamol) Digoxin

K- losing diuretics (Lasix) Beta blockers (Inderal)

Insulin Succinylcholine

Corticosteroids NSAIDs

Amphotericin B Spironolactone

Metabolic alkalosis ACE inhibitors (captopril)

Metabolic acidosis

Renal impairment

Drug interactions

Hypokalemia increase the risk of digoxin toxicity.

Potassium should be used cautiously in patients receiving

potassium-sparing diuretics (such as amiloride, spironolactone, and

triamterene) or angiotensin-converting enzyme inhibitors (such as

captopril, enalapril, and lisinopril) to avoid hyperkalemia.



106

Treatment of hypokalemia Treatment of hyperkalemia

1. Use K rich diet 2. Combine K sparing

(spironolactone) + K -losing diuretics (Lasix)

3. Drug holiday for patient taking K -losing diuretics

4. KCL

1. Intravenous calcium 2. Insulin + intravenous glucose 3. Intravenous NaHCO3 4. Lasix 5. Hemodialysis in resistant cases

Adverse reactions:

a. Oral KCL should be given with plenty of water & setting upright:

as it causes nausea, vomiting, abdominal pain, gastric ulceration

b. Intravenous KCL: phlebitis so ,used in large veins

c. Rapid, I.V. administration may cause cardiac arrest. Infusion of

potassium in patients with decreased urine production increases

the risk of hyperkalemia.

Calcium

Calcium is a major cation in extra cellular fluid. Almost all of the

calcium in the body (99%) is stored in bone, where it can be

mobilized, if necessary.

When dietary intake isn’t enough to meet metabolic needs,

calcium stores in bone are reduced.

Chronic insufficient calcium intake can result in bone

demineralization.

Calcium is replaced orally or I.V. with calcium salts, such as:

Calcium carbonate

Calcium gluconate



107

Pharmacokinetics

Oral calcium is absorbed readily from the duodenum and proximal

jejunum. A pH of 5 to 7, parathyroid hormone, and vitamin D all aid

calcium absorption.

Calcium is distributed primarily in bone. Calcium salts are

eliminated unchanged primarily in stool; the remainder is excreted

in urine.

Pharmacodynamics

Extracellular ionized calcium plays an essential role in normal nerve

and muscle excitability.

Calcium is integral to normal functioning of the heart, kidneys, and

lungs, and it affects the blood coagulation rate as well as cell

membrane and capillary permeability.

Calcium is a factor in neurotransmitter and hormone activity, amino

acid metabolism, vitamin B12 absorption, and gastrin secretion.

Calcium plays a major role in normal bone and tooth formation.


Calcium is helpful in treating magnesium intoxication.

Strengthen myocardial tissue after defibrillation.

During childhood and adolescence (increase demand).

The major clinical indication for I.V. calcium is acute hypocalcemia

which necessitates a rapid increase in serum calcium levels, as in

tetany, cardiac arrest, vitamin D deficiency, alkalosis and

hypocalcemic reaction during exchange transfusions.



108

Oral calcium is commonly used to supplement a calcium-deficient

diet and prevent osteoporosis, osteomalacia (softening of bones),

long term glucocorticoid therapy and vitamin D deficiency

Drug interactions

Digoxin may cause cardiac arrhythmias.

Calcium channel blockers may decrease response to it.

Tetracycline lead to its inactivation.

Beta blockers: decrease its effect

Total parenteral nutrition: calcium may react with phosphorus

present in the solution to form insoluble calcium phosphate

granules, which may find their way into pulmonary arterioles,

causing emboli and possibly death.

Adverse reactions to calcium:

Calcium preparations may produce hypercalcemia (elevated serum

calcium levels). Early signs include:

Drowsiness

Lethargy

muscle weakness

headache

constipation

metallic taste

Rapid intravenous infusion of calcium gluconate can induce

cardiac arrhythmias, cardiac arrest, and coma.

N.B.Treatment of hypercalcemia:

intravenous saline infusion

loop diuretics



109

What is acid-base balance?

Your blood needs the right balance of acidic and basic (alkaline)

compounds to function properly. This is called the acid-base

balance. Your kidneys and lungs work to maintain the acid-base

balance.

Even slight variations from the normal range can have significant

effects on your vital organs.

Acid and alkaline levels are measured on a pH scale. An increase in

acidity causes pH levels to fall. An increase in alkaline causes pH

levels to rise.

When the levels of acid in your blood are too high, it’s called

acidosis. When your blood is too alkaline, it is called alkalosis.

Respiratory acidosis and alkalosis are due to a problem with the

lungs. Metabolic acidosis and alkalosis are due to a problem with

the kidneys.

Each of these conditions is caused by an underlying disease or

disorder.

Treatment depends on the cause.

Chapter 15

Acid base disturbance pharmacotherapy



110

Respiratory acidosis

Definition:

When you breathe, your lungs remove excess carbon dioxide from your

body. When they cannot do so, your blood and other fluids become too

acidic.

Symptoms of respiratory acidosis

Symptoms may include: fatigue, shortness of breath, and

confusion.

Causes of respiratory acidosis

There are several different causes of respiratory acidosis including:

chest deformities or injuries

chronic lung and airway diseases

overuse of sedatives

obesity

Types of respiratory acidosis

There are no noticeable symptoms of chronic respiratory

acidosis. This is due to the fact that your blood slowly becomes

acidic and your kidneys adjust to compensate, returning your

blood to a normal pH balance.

Acute respiratory acidosis comes on suddenly, leaving the

kidneys no time to adjust. Those with chronic respiratory acidosis

may experience acute respiratory acidosis due to another illness



111

that causes the condition to worsen.

Diagnosis of respiratory acidosis

A complete physical examination is necessary. Diagnostic testing may

include:

arterial blood gas test

metabolic panel

pulmonary function test

chest X-ray

Treatment of respiratory acidosis

Treatment is targeted to the cause.

Bronchodilator medications may be given to correct some forms of

airway obstruction.

If your blood oxygen level is too low, you may require oxygen.

Noninvasive positive pressure ventilation or a breathing machine

may be necessary.

Treat the underlying cause.

The cause could be from an organ deformity, an infection, or some

type of inflammation.

Antibiotics.

Stop smoking.



112

Complications of respiratory acidosis

Respiratory failure

Organ failure

Shock.

Preventing respiratory acidosis

Maintain a healthy weight

Take sedatives only under strict doctor supervision and never

combine them with alcohol

Do not smoke.

Metabolic acidosis

Definition: Metabolic acidosis occurs either when your body produces

too much acid, or when your kidneys are unable to remove it properly.

Symptoms of metabolic acidosis

Rapid breathing, fatigue, and confusion.

Causes of metabolic acidosis

Diabetic ketoacidosis

Hyperchloremic acidosis is when your body loses too much sodium

bicarbonate, often after severe diarrhea.

https://www.healthline.com/health/type-2-diabetes/ketoacidosis



113

Lactic acidosis is when too much lactic acid builds up. This can be

due to:

prolonged exercise

lack of oxygen

certain medications, including salicylates

low blood sugar, or hypoglycemia

alcohol

seizures

liver failure

cancer

kidney disease

severe dehydration

Diagnosing metabolic acidosis

serum electrolytes

urine pH

arterial blood gases

Treatment of metabolic acidosis

Sodium bicarbonate is prescribed to return the blood to a normal

pH.



114

Complications of metabolic acidosis

Severe cases can lead to shock and can be life threatening

Alkalosis

Definition: Alkalosis is when alkaline levels are too high due to

decreased carbon dioxide or increased bicarbonate.

Symptoms of alkalosis

muscle twitching, hand tremor, muscle spasms

numbness and tingling

nausea

vomiting

lightheadedness

confusion

Causes and types of alkalosis

lack of oxygen

high altitude

fever

lung disease

liver disease

salicylate poisoning



115

When you have alkalosis your carbon dioxide levels are low. This

causes your body to release more bicarbonate to return your blood

pH level back to normal. This is called compensated alkalosis. Your

blood pH levels will test normal, however your kidneys are releasing

more bicarbonate, compensating for the lower levels of carbon

dioxide.

When your blood has too much bicarbonate, it is called metabolic

alkalosis. This can happen from prolonged vomiting. Prolonged

vomiting can also make you lose too much chloride. This is called

hypochloremic alkalosis. Some diuretic medicines can cause you to

lose too much potassium. This is called hypokalemic alkalosis.

Diagnosing alkalosis

Along with a physical exam, diagnostic testing for alkalosis may

include a metabolic panel, blood gas analysis, urinalysis, and urine

pH.

Treatment for alkalosis

Some medications (such as chloride and potassium) can help correct

chemical losses.

Further treatment will depend on the cause. Your physician will

need to monitor your vital signs and create a proper plan to correct

your pH imbalance.



116

Complications of alkalosis

In severe cases, alkalosis can lead to heart arrhythmias or coma.

References

1. Pharmacology department book(2017-2018)

2. Pharmacology Made Incredibly Easy

3. Medical pharmacology at Glance

Book Coordinator ; Mostafa Fathallah

General Directorate of Technical Education for Health

حقىق النشز والتأليف لىسارة الصحة والسكان ويحذر بيعه

https://www.amazon.com/Pharmacology-Made-Incredibly-Easy/dp/1496326326

pharmacology of emergency and critical care...pharmacology of critical and intensive care medicine 7...

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