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1
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.
3
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
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
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
6
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
Pharmacology of critical and
intensive care medicine
7
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
Pharmacology of critical and
intensive care medicine
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
Pharmacology of critical and
intensive care medicine
8
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
Pharmacology of critical and
intensive care medicine
9
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
Pharmacology of critical and
intensive care medicine
10
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.
Pharmacology of critical and
intensive care medicine
11
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)
Pharmacology of critical and
intensive care medicine
12
Preparations:
1. Diltazem: Delaytiazem
2. Nifedipine: Adalat
3. Amlodipine:Norvasc
4. Verapamil: Isoptin
Sodium Nitoprusside
Pharmacology of critical and
intensive care medicine
13
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
Pharmacology of critical and
intensive care medicine
14
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
Pharmacology of critical and
intensive care medicine
15
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.
Pharmacology of critical and
intensive care medicine
16
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
Pharmacology of critical and
intensive care medicine
17
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
Pharmacology of critical and
intensive care medicine
18
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.
Pharmacology of critical and
intensive care medicine
19
Ezetimibe
Mechanism: inhibit cholesterol absorption
Indications: Hypercholesterolemia
Adverse reactions:
Fatigue
Abdominal pain and diarrhea
Pharyngitis and sinusitis • arthralgia • back pain • cough.
Pharmacology of critical and
intensive care medicine
20
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
Pharmacology of critical and
intensive care medicine
21
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
Pharmacology of critical and
intensive care medicine
22
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
Pharmacology of critical and
intensive care medicine
23
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
Pharmacology of critical and
intensive care medicine
24
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
Pharmacology of critical and
intensive care medicine
25
Epinephrine
Mechanism of action:
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
Pharmacology of critical and
intensive care medicine
26
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
Pharmacology of critical and
intensive care medicine
27
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
Pharmacology of critical and
intensive care medicine
28
Norepinephrine
Mechanism of action:
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
Pharmacology of critical and
intensive care medicine
29
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
Pharmacology of critical and
intensive care medicine
30
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
Nursing considerations:
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
Pharmacology of critical and
intensive care medicine
31
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
Pharmacology of critical and
intensive care medicine
32
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
Pharmacology of critical and
intensive care medicine
33
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
Pharmacology of critical and
intensive care medicine
34
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.
Pharmacology of critical and
intensive care medicine
35
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
Pharmacology of critical and
intensive care medicine
36
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
Pharmacology of critical and
intensive care medicine
37
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.
Pharmacology of critical and
intensive care medicine
38
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
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Side effects:
1. Cardiac: may precipitate cardiac arrest.
2. CNS: dizziness & convulsion
N.B: oral lidocaine preparation is available (mexilitine)
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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
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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
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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
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Selective Beta 2 adrenergic receptor agonist
(Salbutamol)
Mechanism of action:
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
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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
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Theophylline (Aminophylline)
Mechanism of action:
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)
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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
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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)
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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
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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.
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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.
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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
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Oral anticoagulant
Warfarin
Mechanism of action:
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.
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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
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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.
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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.
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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
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Nursing considerations:
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.
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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.
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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)
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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
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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
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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.
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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.
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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)
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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.
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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.
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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
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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.
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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.
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Morphine Given IV - IM - SC - epidurally - orally (extensive 1st pass
metabolism)
Pharmacological actions:
Chapter 11
Opioid analgesics
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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
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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)
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N.B. Antidote for morphine: naloxone
Biliary spasm :contraindication: biliary colic)
itching
bronchospasm : (contraindication: asthma)
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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.
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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.
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Antihistamines (H1 receptors blockers)
Preparations
1st generation: Chlorpheneramine – Diphenhydramine
2nd generation: Loratidine – Fexofenadine
Mechanism of action:
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
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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)
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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.
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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.
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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
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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).
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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.
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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
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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.
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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.
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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.
Pharmacotherapeutics
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.
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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.
Pharmacotherapeutics
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.
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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).
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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.
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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
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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.
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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.
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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.
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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
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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
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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.
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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
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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.
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-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.
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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.
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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
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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.
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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.
Pharmacotherapeutics
Potassium replacement therapy corrects hypokalemia.
Hypokalemia is a common occurrence in:
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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.
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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
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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.
Pharmacotherapeutics
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.
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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
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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
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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
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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.
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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.
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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.
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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
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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.
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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