pharmacology lecture
TRANSCRIPT
Introduction to Nursing Pharmacology
A. Introduction to Drugs
- The human body works through a complicated series of chemical reactions and processes.
- Drugs are chemicals that are introduce into the body to cause some sort of change.
Drugs will undergo process with in the body which involve breaking and eliminating the drugs, in turn affect the body’s complex series of chemical reactions.
- Understanding how drugs act on the body to cause changes and applying that knowledge in the clinical setting are important aspects of nursing practice.
- The nurse is in a unique position regarding drug therapy because nursing responsibilities include the following:
Administering drugs Assessing drug effects Intervening to make the drug regimen more tolerable Providing patient teaching about drugs and drug regimen.
Monitoring the overall patient care plan to prevent medication error
- Knowing how drugs works make these tasks easier to handle, thus enhancing drug therapy.
B. History
o Early drug – plants, animals & mineralso 2700 BC – earliest recorded drug use found in
Middle East & Chinao 1550 BC – Egyptians created Ebers Medical Papyrus
Castor oil – laxative
Opium – pain
Moldy bread – wounds & bruises
Galen (131-201 AD) Roman physician; initiated common use of prescriptions
1240 AD – introduction of apothecary (pharmacy) system (Arab doctors)
1st set of drug standards & measurements (grains, drams, minims), currently being phased out
15th century – apothecary shops owned by barber, surgeons, physicians, independent merchants
18th century – small pox vaccine (by Eward Jenner, British Doctor)
Digitalis from foxglove plant for strengthening & slowing of heartbeat Vitamin C from fruits
19th century – morphine & codeine extract from opium
Introduction of atropine & iodine
Amyl nitrite used to relieve anginal pain
Discovery of anesthetics (ether, nitrous oxide)
Early 20th century – aspirin from salicylic acid- Introduction of Phenobarbital, insulin, sulforamides
Mid-20th century
1940 – Discovery antibiotics (penicilline, tetracycline,streptomycin), antihistamines, cortisone
1950 – Discovery antipsychotic drug, antihypertensives, oral contraceptives, polio vaccine
C. Pharmacology
- Is the study of the biological effects of chemicals
- It is the scientific study of the origin, nature, chemistry, effects and uses of drugs.
- In clinical practice, health care providers focus on how chemicals act on living organisms.
Subdivisions of Pharmacology
1. Pharmacodynamics – study of the biochemical & physiological effects of drugs & mechanisms of action
o what the drug does to the body2. Pharmacokinetics – deals with the absorption, distribution,
biotransformation & excretion of drugs
what the body does to the drug deals with beneficial effects of the drugs (medicines) source of drugs
ex: penicillin from penicillium (fungi)
3. Pharmacotherapeutics – study of drugs used in the diagnosis, prevention, suppression, & treatment of diseases
4. Pharmacognonsy – study of drugs in their original unaltered state; origin of drugs
5. Toxicology – study of biologic toxins: study of poison & its effects deals with deleterious effects of physical & chemical agents (including drugs) in human
Nurses deal with Pharmacotherapeutics, or Clinical Pharmacology, the branch of pharmacology that uses drugs to treat, prevent, and diagnose diseases.
Clinical Pharmacology
- Addresses two key concerns
The drug’s effects on the body The body’s response to the drug
- Because drug can have many effects the nurse must know which ones may occur when a particular drug is administered.
Effects of the Drug
1. Therapeutic Effect
- The primary effect intended, that is the reason the drug is prescribed.
- Also called desired effect.
2. Side Effect
- The effect of the drug that is not intended.
- Also called secondary effect.
3. Drug Allergy
- The immunologic reaction to the drug.
4. Anaphylactic Reaction
- A severe allergic reaction which usually occurs immediately following administration of the drug.
5. Drug Tolerance
- A decreased physiologic response to the repeated administration of a drug or chemically related substance. Excessive increase in the dosage is required in order to maintain the desired therapeutic effect.
6. Drug Interaction - Effects of one drug are modified by the prior or concurrent
administration of another drug, thereby increases or decreases the pharmacological action.
Drug Antagonism – the conjoint effects of two drugs is less than the drugs acting separately.
Summation – The combined effect of two drugs produces a result that equals the sum of the individual effect of each agent.
Synergism – The combined effects of drugs is greater than the sum of each individual agent acting independently.
Potentiation – The concurrent administration of two drugs in which one increases the effect of the other drug.
Therapeutic Effects of Drugs
1. Palliative
- Relieves the symptoms of a disease but not affect the disease itself.
- Ex. Analgesic for pain
2. Curative
- Treats the disease condition
- Ex. Antibiotic for infection
3. Supportive
- Sustains body functions until other treatment of the body’s response can take over.
- Ex Mannitol to reduce/ICP in a client for surgery due to brain tumor.
4. Substitutive
- Replaces body fluids or substances.
- Ex. insulin injection for diabetes mellitus
5. Chemotherapeutic
- Destroys malignant cells
- Ex. Cyclophophamide for cancer of the prostate gland.
6. Restorative
- Returns the body to health.
D. Drug Nomenclature
1. CHEMICAL NAME – atomic/molecular structure of drug
Ex. acetylsalicylic acid
2. GENERIC NAME/NON-PROPERTY NAME – original designation given to the drug when the drug company applies for approval patents
universally accepted & not capitalized; before drug becomes official, used in all countries
protected by law; not capitalized ex. aspirin
3. TRADE/BRAND/PROPRIETY NAME – name given by the drug company that developed it
followed by the symbol R or TM, 1st letter is capitalized ex. Aspilet
E. Sources of Drugs
1. Plants – roots, bark, sap, leaves, flowers, seeds of medicinal plants
digitalis (use as a heart stimulant) from wildflower, purple foxglove, dried leaves of plant
active principles of plants o alkaloids – alkaline in reaction, bitter in taste,
powerful in physiologic activityo atropine & scopolamineo morphine sulfate, cocaine, quinine, nicotine, caffeineo procaineo glycosides – digitaliso resin – soluble in alcohol; example – colonic irritant
found in laxative cascarao gums – used in bulk-type laxatives: some used in
certain skin preparations for their soothing reliefo oils – castor oil, oil of wintergreen
2. Animal Products – from organs, organ secretion or organ cells
o Used to replace human chemical not produces because of disease or genetic problems
o Thyroid drugs & growth hormones preparations – from animal thyroid & hypothalamus tissue (many of these preparations are now created synthetically – safer & purer)
o Insulin – from pancreas of animals (hog, cattle, sheep): thru genetic engineering – cld produce human insulin by altering E. coli bacteria making it a better product without impurities that come with animal products
3. Inorganic Compounds – from free elements, both metallic & non-metallic usually in form of acids bases, salts found in food
Dilute HCI – control/prevent indigestion Calcium, aluminum, fluoride, iron, gold, potassium more potent, more stable, less toxic steroids – arthritis & other diseases sulfonamides/chemotherapeutic agents – kill microorganism
slow their growth meperidine HCI (Demerol)
4. Synthetic Sources – many drugs developed synthetically after chemical in plants, animals, or environment have been screened for signs of therapeutic activity
4.1 Genetic engineering – alter bacteria to produce chemicals that are therapeutic and effective.
Reordering of genetic information enables scientists to develop bacteria that produce insulin for human.
4.2 Chemical alterations – Scientists alter chemical with proven therapeutic effectiveness to make it better.
Sometimes a small change in a chemical’s structure can make that chemical more useful as a drug, more potent, more stable, less toxic.
F. Drug Classification
1. By Actiono Ant- infective – antiseptics, disinfectants, sterilantso Antimicrobials, metabolic, diagnostic materials,
vitamins & minerals
o Vaccine & serums, antifungals, antihistamines, antineoplastics, antacids
2. By Body System
CNS – (+)/(-) actions of neural pathways & centers; ex. Phenobarbital
ANS – governs several bodily functions so that drugs that affect ANS will at the same time affect other systems functions; ex. scopolamine
GIT – acts on muscular & glandular tissues; ex. loperamide Respiratory System – act on resp. tract, tissues, cough center,
suppress, relax, liquefy & stimulate depth & rate of respiration; salbutamol
Urinary system – act on kidney & urinary tract; ex. furosomide
Circulatory system – act on heart, blood vessels, blood; ex. Metroprolol
G. Kinds of Drugs
1. Prescription Drugs
- Also known as legend drugs
- Can be dispensed if with prescription order; with specific name of drug & dosage regimen to be used by patient.
2. Non-Prescription Drugs
- Also known as Over – the – Counter Drugs
- can be dispensed without prescription order
- for self-treatment of variety of complaints
- Vitamin supplements, cold/cough remedies, analgesics, antacids, herbal products
Cautions in use of OTC drugs:
Delay in professional diagnosis & treatment of serious/potentially serious condition may occur
Symptoms may be masked making the diagnosis more complicated
Clients’ health care provider/pharmacist should be consulted before OTC preparations are taken
Labels/instructions should be followed carefully Ingredients in OTC drug may interact with prescribed drug Inactive ingredients may result in adverse reactions Potential for overdose Multiple medication users are at risk as more medications
are added to therapy regimen Interactions of medications are potentially dangerous
3. Investigational drug
- new drugs undergoing clinical trails
4. Illicit/street drug
- used/distributed illegally for non-medical purposes to alter mood of feeling
Drugs and the Body (Pharmacodynamics)
Pharmacodynamics- The study of the drug mechanisms that produce biochemical or physiologic changes in the body.- What happens to the body in response to the drug.- Interactions between chemical components of living systems & foreign chemicals including drugs that enter these systems.
Drug Actions:a. To replace or act as substitutes for missing chemicals.b. To increase or stimulate certain cellular activities.c. To depress or slow cellular activities.d. To interfere with the functioning of foreign cells, such as invading microorganisms or neoplasm.
Theories of Drug ActionsA. Drug Receptors Interactiono Receptor sites – location on a cell surface where certain molecules such as enzymes, hormones, drugs attach to interact with cell component.o Receptor sites react with certain chemicals to cause an effect within the cell.
o “lock and key theory”o Drug action may be:
1. Agonist• Drugs interact directly with receptor sites to cause the same activity that natural chemicals would cause at that site.• Ex. Insulin
2. Antagonist• A drug has an affinity for a receptor but displays little or no intrinsic activity.
A. Competitive antagonisto Competes with the agonist for receptor sitesB. Non-competitive antagonisto Binds to receptor sites and blocks the effects of the agonist
B. Drug Enzyme Interactionso Interferes with enzyme systems that act as catalyst from various chemical reactions.o Enzyme systems: Cascade effect; one enzyme activating another, causing cellular reaction. If single step in one of enzyme system is blocked, normal cell function is disruptedo Ex. ACE inhibitors, inhibiting the release of angiotensin converting enzyme in the lungs, preventing the conversion of Angiotensin I to Angiotensin II which is a powerful vasocontrictor, preventing an increase in blood pressure.
C. Selective Toxicityo All chemotherapeutic agent would act only on 1 enzyme system needed for life of a pathogen or neoplastic cell & will nor affect healthy cells.o Ex. Penicillin
Classifications of Drug Action (in terms of speed of action)a. Rapido few seconds to minutes.o intravenous, sub-lingual, inhalationb. Intermediateo 1-2 hours after administrationo intramuscular, subcutaneousc. Delayed/Slowedo Several hours after administrationo oral and rectal
Parameters of Drug ActionParameters – notable characteristicsa. Onset of actiono Latent period, interval between time the drug is administered and 1st sign of its effect.b. Duration of actiono Period from onset until drug effect is no longer seen.o Length of time the drug exerts pharmacologic effect.c. Peak of actiono drug reaches its highest blood / plasma concentrationd. Termination of actiono point from onset at which drug effect is no longer seen
Drugs and the Body (Pharmacokinetics)
Drugs and the BodyI. Pharmacokinetics- The term kinetics refers to movement.- Pharmacokinetics deals with a drugs actions as it moves through the body- What happens to the drug when it enters the body.- Involves the study of the following:o Absorptiono Distributiono Metabolism/Biotransformationo Excretion
A. Absorption
- In order to reach reactive tissues, a drug must first make its way into the circulation.- Absorption refers to what happens to a drug from the time it is introduced to the body until it reaches the circulating fluids.- Drugs can be absorbed from many different areas in the body:o GITo Mucous membraneso Through the skino Through the lungs
o Through the muscleo Through subcutaneous tissues
A. Cell Absorption- Drugs can be absorbed into cells through various processes
1. Passive Absorption (diffusion)o Movement of drug particles from an area of higher concentration to an area lower concentration.o No energy required: occurs when smaller molecules diffuse across membraneo Stops when drug concentration on both sides of the membrane is equalo Major process through which drugs are absorbed into the bodyo Oral drugs use passive transport
2. Active Absorptiono Movement of drugs particles from an area of low concentration to an area of high concentration.o Energy is requiredo Used to absorb electrolytes (Ex. sodium, potassium)
3. Pinocytosiso Cells engulf the drug to carry it across the membrane.o Transport fat-soluble vitamins (vitamin A,D,E,K)
B. Factors Affecting Drug Absorption:1. Blood Flow2. Pain3. Stress4. Foods (High fat and solid foods)
5. Exercise6. Solubility7. Nature of the absorbing surface8. pH9. Concentration10. Dosage form
c. Oral Administration of Drug
B. Distribution
- Process by which drug becomes available to body fluids & tissues- The ways a drug is transported from the site of absorption to the site of action (transportation)- Happens in the circulation (circulatory system)
A. Factors Affecting Distribution1. Size of the organ2. Blood flows drug is quickly distributed to organs with large supply of blood (heart, liver, kidneys) distribution to other internal organs, skin, fat, muscle is slower3. Solubility Lipid-soluble or non-lipid-soluble Lipid-soluble drugs can cross the blood-brain barrier & enter the brain4. Protein binding
B. Protein Binding- as drug travels through the body, it comes in contract with proteins (albumin)
- the drug can remain free or bind to protein- Portion of drug bound to protein is inactive, no therapeutic affect
1. Free/unbound portion (+) pharmacologic response
2. Highly protein bound drug 89% of drug is bound to protein diazepam, piroxicam, valproic acid
3. Moderately high protein bound drugs 61-89% bound protein Erythromycin, phenytoin
4. Moderately protein bound drugs 30-60% bound to protein aspirin, lidocaine, pindolol, theophyline
5. Low protein-bound drugs 30% bound to protein amikacin, amoxicillin
C. Metabolism/Biotransformation
- Also called detoxification.- Refers to the body’s ability to change a drug from its dosage form
to a more water soluble form that can be excreted- A sequence of chemical events that change a drug to a less active form after it enters the body- Permits the body to inactivate a potent drug before it accumulates & produces toxic effects- Drugs can be metabolized several ways:o Most drugs metabolized into inactive metabolites (products of metabolism), which are then excretedo Other drugs converted to active metabolites – capable of exerting their own pharmacologic action May undergo further metabolism or may be excreted from body unchanged Pro-drugs – some drugs administered as inactive drugs which don’t become active until they’re metabolized
A. Sites of Metabolism1. Liver Through the drug metabolizing enzymes (microsomal enzymes, non-microsomal enzymes) 1st pass effect/hepatic 1st pass – some drugs do not directly go into circulation but pass thru intestinal lumen to liver via portal vein2. Plasma3. Kidneys4. Membranes
B. Factors Affecting Drug Metabolism1. Diseases Liver cirrhosis and heart failure2. Genetics People metabolize drugs rapidly, other more slowly.3. Environment Smoking and stressful environment
4. Age Infants have immature livers that reduce the rate of metabolism. Elderly patients experience a decline in liver size, blood flow and enzyme production that also slows metabolism5. Nutrition Liver enzymes involved in metabolism rely on adequate amounts of amino acids, lipids, vitamins and carbohydrates.6. Insufficient amounts of major body hormones Decrease amounts of insulin and adrenal corticosteroids can reduce metabolism of drugs in the liver.
D. Excretion
- Removal of drug from the body- Is the process by which drugs are eliminated from the body- Drug is changed into inactive form & excreted by the body
A. Sites of Excretion1. Kidney Free/unbound/water soluble drugs are filtered in kidneys Protein bound drug cannot be filtered in kidney2. Lungs, exocrine (sweat, salivary, mammary) glands, skin, intestinal tract
B. Factors Affecting Excretion1. Urine pH Normal urine pH is 4 – 5.8 Acidic urine promotes elimination of weak base drugs• Ex. Cranberry juice decreases urine pH Alkaline urine promotes elimination of weak acid drugs• Ex. Nabicarbonate increases urine pH, use to eliminate as excess aspirin in the system due to overdose
2. Glomerular Filtration Rate The amount of glomerular filtrate in the glomerulus• Glomerular Filtration• Passive Reabsorption• Active Secretion Nephron Glomerulus Proximal Tubule Bladder When there is a decrease in glomerular filtration rate drug excretion are slowed/impaired. Can result to drug accumulation
3. Half-life Time it takes for one half of drug concentration to be eliminated. Short half-life• 4-8 hrs: given several times a day (ex. penicillin G) Long half-life• More than 12 hrs: given 2x or 1x a day (ex. digoxin)
Medications and Calculations
A. Systems of Measurements
- There are 3 systems of measurements
1. Metric system
o Was developed in the late 18th century
o The internationally accepted system of measure
2. Apothecary system
o Was replaced by the metric system
o Dates back to the middle ages and had been used in
England since the 17thcentury.
3. Household system
o Commonly used in community and home settings.
Metric System
- The metric system is a decimal system based on the
power of 10.
- The basic units of measure are:
gram (g, gm, G, Gm) for weight;
liter (l, L) for volume; and
meter (m, M) for length.
Apothecary System
- Common system used by most practitioner s before the
universal acceptance of the International Metric System
- Now all pharmaceuticals are manufactured using the metric
system, and the apothecary system is no longer included on any drug
labels.
- All medication should be prescribed and calculated using
metric measures, but occasionally the use of the fluid ounce and
grains is found. For those rare circumstances, nurses should have a
general understanding of the apothecary system.
- The apothecary system uses Roman numerals instead of
Arabic numbers to express the quantity. The Roman numeral is
placed after the symbol or abbreviation for the unit of measure.
A. Ex. gr x stands for 10 grains.
- In the apothecary system:
the unit of weight is the grain (gr)
the units of fluid volume are the ounce (fluidounce), the
dram (fluidram), and the minim (min).
Household System
- Uses household containers such as spoons, cups and glasses
as measuring devices.
- Not as accurate as metric system because of the lack of
standardization.
B. Methods for Calculation
- The four general methods for the calculation of drug dose are
the (1) basic formula, (2) ration and proportion, (3) fractional
equation, (4) and dimensional analysis. These methods are used to
calculate oral and injectable drug doses.
- For drugs that require individualized dosing, calculation by
body weight (BW) or by body surface area (BSA) may be necessary.
- Before calculating drug doses, all units of measure must be
converted to a single system.
Interpreting Oral and Injectable drug Labels
- Pharmaceutical companies usually label their drugs with the
brand name of the drug in large letters and the generic name in
smaller letters.
- The dose per tablet, capsule, or liquid (for oral and injectable
doses) is printed on the drug label.
1. Method 1: Basic Formula (BF)
- The basic formula is easy to recall and is most frequently used
in calculating drug dosages.
D x V = A
H
- D = desired dose (drug dose ordered by the health care
provider)
H = on hand dose (drug dose on label of container)
V = vehicle (drug form in which the drug comes (tablet, capsule,
liquid)
A = the amount calculated to be given to the client
2. Method 2: Ratio and Proportion
- The ratio and proportion method is the oldest method
currently used in the calculation of drug dosages.
H : V :: D : x
- D = desired dose (drug dose ordered by the health care
provider)
H = on hand dose (drug dose on label of container)
V = vehicle (drug form in which the drug comes (tablet, capsule,
liquid)
x = the amount calculated to be given to the client
3. Method 3: Fractional Equation
- The fractional equation method is similar to ratio and
proportion except it is written as a fraction.
H = D
V x
- H = dosage on hand
V = vehicle
D = desired dosage
X = unknown
- Cross – multiply and solve for x
4. Method 4: Dimensional Analysis
- Dimensional analysis is a calculation method known as units
and conversions. The advantage of DA is that it decreases a number
of steps required to calculate a drug dosage. It is set up as one
equation.
Identify the unit/form (tablet, capsule, ml) of the drug to
be calculated. If the drug comes in tablet, then tablet =
(equal sign)
The known dose and unit/form from the drug label
follows the equal sign.
Order: amoxicillin 500 mg
On the drug label: 250 mg per 1 capsule
Capsule = 1cap
250 mg
The mg (250 mg) is the denominator and it must match
the next numerator, which is 500 mg (desired dose or
order). The NEXT denominator would be 1 or blank.
Capsule = 1cap X 500 mg =
250 mg 1
Cancel out the mg, 250 and 500. What remains is the capsule
and 2. Answer is 2 capsules
5. Method 5: Body Weight
- The body weight method of calculation allows for the
individualization of the drug dose and involves the following three
steps:
I. Convert pounds to kilograms if necessary (lb / 2.2 = kg)
II. Determine drug dose per BW by multiplying as follows:
Drug dose x body weight = clients dose per day
III.Follow the basic formula, ratio and proportion, fractional
equation, or dimensional analysis method to calculate the
drug dosage.
6. Method 6 : Body surface area (BSA)
- The body surface area (BSA) method is considered the most
accurate way to calculate the drug dose for infants, children, older
adults, andclients who are on antineoplastic agents or whose BW is
low. The BSA, in square meters, is determined by where the person’s
height and weight intersect the nomogram scale. To calculate the
drug dosage the BSA method, multiply the drug dose ordered by
number of square meters.
100 mg x 1.8 m2 (BSA) = 180 mg/day
Other computation:
1. Clark's Rule for Infants or Children:Clark’s rule is based upon the weight of the child. To determine the proper dosage for children, divide child’s weight in pounds by 150 to get the correct fraction of adult dose. Example: For a 50 pound child give 50/150 (or 1/3) of the adult dose. Therefore, if the adult dose is 30 drops taken 3 times per day, the child’s dose will be 10 drops taken 3 times per day (not 30 drops taken 1 time per day!)
(Weight in pounds x (Adult dose)
150
2. Fried's Rule for Infants and Children up to 1 to 2 Years:
(Age in Months) x (Adult Dose)
150
3. Young's Rule for Children from 1 year to 12 Years:Young’s rule is based upon the age of the child, regardless of its weight. It is a “rule of the thumb” method for calculating the dose of medicine to be administered to a child. The child’s age divided by age plus 12 represents the fraction of the adult dose suitable for the child.
(Age in Years) x (Adult Dose)
Age + 12
Antibiotics
Antibiotics
- Are chemicals that inhibit a specific bacteria
- Used to treat a wide variety of systemic and topical infections.
- Antibacterial
Antibiotics are made in three ways:
1. By living microorganisms2. By synthetic manufacture3. Through genetic engineering
Major classes:
1. Aminoglycosides2. Cephalosporins3. Fluoroquinolones4. Lincosamides5. Macrolides6. Monobactams7. Penicillins8. Sulfonamides9. Tetracyclines
Bacteria
- one-celled organisms visible only through a microscope. Bacteria live all around us and within us. The air is filled with bacteria, and they have even entered outer space in spacecraft. Bacteria live in the deepest parts of the ocean and deep within Earth. They are in the soil, in our food, and on plants and animals. Even our bodies are home to many different kinds of bacteria. Our lives are closely intertwined with theirs, and the health of our planet depends very much on their activities.
- Bacteria can invade the body the human body through many routes, ex. Respiratory, gastrointestinal and skin.
- The human immune response is activated when bacteria invade. Many of the sign s and symptoms of an infection are related to the immune response as the body tries to rid itself of the foreign cells. Ex. Fever, lethargy, classic sign s of inflammation (redness, swelling, heat and pain)
- To determine which antibiotic will effectively treat a specific infection, the causative agent must be identified. Culture and sensitivity testing is performed.
Types of Bacteria
1. Gram-positive Bacteria – are those whose cell wall retains a stain, known as Gram – stain. They are
commonly associated with infection of the respiratory tract. Ex Streptococcus pneumonia.
2. Gram-negative Bacteria – are those whose cell walls loose a stain. Frequently related with infections of the genitourinary or GI tract. Ex. Escherichia coli.
3. Aerobic bacteria – depends on oxygen for survival.4. Anaerobic bacteria – does not depend on oxygen.
1. Aminoglycosides
- Aminoglycosides are bactericidal. They’re effective against:
Gram-negative bacilli Some aerobic gram-positive bacteria
Aminoglycosides currently in use include:
1. Amikacin sulfate2. Gentamicin sulfate3. Kanamycin sulfate4. Neomycin sulfate5. Streptomycin sulfate6. Tobramycin
Pharmacokinetics
- Because aminoglycosides are absorbed poorly from the GI tract, they’re usually given parenterally. After IV or IM administration, absorption is rapid and complete.
- Aminoglycosides are distributed widely in extracellular fluid. They readily cross the placental barrier but don’t cross the blood brain barrier.
- Aminoglcosides aren’t metabolized. They’re excreted primarily by the kidney’s.
Pharmacodynamics
- Bactericidal
- Binds to the bacteria’s 30S subunit in the ribosome inhibiting protein synthesis.
Pharmacotherapeutics
Infections caused by gram-neagtive bacilli Nosocomial infections such as peritonitis and
pneumonia UTI CNS infections
Adverse Reactions
Peripheral nerve toxicity Ototoxicity Renal toxicity
Oral administration causes:
Nausea Vomiting Diarrhea
1. Cephalosporins
- The cephalosporins were first introduce in the 1960’s. These drugs are similar to the penicllins in structure and in activity. Over time, four generations of cephalosporins have been introduced, each group with its own spectrum of activity.
1. First Generation Cephalosporins
Effective against gram-positive bacteria Also effective against some gram-negative bacteria
such as Proteus mirabilis, E. Coli, and Klebsiella pneumoniae
Some of the First Generation Cephalosporins
Cefadroxil Cefazolin sodium Cephalexin hydrochloride
Cephradine
1. Second Generation Cephalosporins
Effective against gram-positive bacteria Haemophilus influenza, Enterobacter aerogenes and
Neisseria species
Some of the Second Generation Cephalosporins
Cefaclor Cefrozil Ceftibuten Cefoxitin Cefuroxime axetil Cefuroxime Sodium
1. Third Generation Cephalosporins
Effective against gram negative bacilli, as Serratia marcescens
Some of the Third Generation Cephalosporins
Cefdinir Cefoperazone sodium Cefotaxime sodium Cefpodoxine proxetil Ceftazidine
Ceftizoxime sodium Ceftriaxone sodium
1. Fourth Generation cephalosporins
Effective against cephalosporins resistant-staphylococci and P. Aeruginosa
Some of the Fourth Generation Cephalosporins
Cefditoren pivoxil Cefepine hydrochloride
Pharmacokinetics
- Administered parenterally, because they aren’t absorbed from the GI tract.
Pharmacodynamics
- Inhibit cell-wall synthesis by binding to the bacterial Penicillin Binding Protein enzy,es located on the cell membrane.
Adverse Reactions:
Confusion Seizures Nausea and vomiting Diarrhea
1. Penicillin
- Penicillin remain one of the most important and useful antibacterial drugs.
- Discovered by Sir Alexander Flemming in the 1920’s
- The Penicillin can be divided into four groups:
1. Natural Penicillin
Penicillin G benzathine Penicillin G potassium Penicillin G procaine Penicillin G sodium Penicillin V potassium
1. Penicillinase Resistant Penicillin
Dicloxacillin sodium Nafacillin sodium Oxacillin sodium
1. Aminopenicillins
Ampicillin
1. Extended Spectrum Penicillin
Amoxicillin
Pharmacokinetics
- After oral administration, penicillin are absorbed mainly in the duodenum and upper jejunum of the small intestine.
Factors affecting absorption of penicillin
Types of penicillin used pH of the patients stomach and intestine presence of food in the GI tract (penicillin should be
given on an empty stomach, 1 hour before meals or 2 hours after meal).
Pharmacodynamics
- Bactericidal
- Binds to an enzyme outside the bacterial cell wall known as penicillin-binding proteins which is involved in cell wall synthesis and cell division. Interference with these processes inhibits cell wall synthesis, causing rapid destruction of the cell.
Pharmacotherapeutics
- No other class of antibacterial drugs provides as wide spectrum of antimicrobial activity as the penicillin
Gram-positive Gram-negative Anaerobic organisms
Adverse Reactions
Hypersensitivity reactions are the major reactions to penicillin
Anaphylactic reactions Skin rashes Tongue inflammation Nausea and Vomiting Diarrhea
1. Fluoroquinilones
- Structurally similar synthetic antibacterial drugs. They;re primarily administered to treat UTIs, upperrespiratory tract infections, pneumonia and gonorrhoea
Examples of fluoroquinilones:
Cifrofloxacin Gemifloxacin Levofloxacin Moxifloxacin Norfloxacin Ofloxacin
Pharmacokinetics
- After oral administration, fluoroquinilones are absorbed well. They aren’t highly protein bound, minimally metabolized in the liver, and are excreted primarily in the urine
Pharmacodynamics
- Bacteriostatic
- Fluoroquinilones interrupt DNA synthesis during bacterial replication by inhibiting DNA gyrase, an essential enzyme of replicating DNA. As a result, the bacteria can’t reproduce.
Pharmacotherapeutics
- Fluorquinolones can be used to treat a wide variety of UTIs.
Ciprofloxacin is used to treat lower respiratory tract infections, infectious diarrhea and skin, bone and joint infection.
Gemifloxacin is used to treat bronchitis, community acquired pneumonia, UTIs, and gynaecologic infections.
Levofloxacin is indicated for treatment of lower respiratory tract infections, skin infections and UTIs.
Moxifloxacin is used to treat bacterial sinusitis and mild to moderate community acquired pneumonia.
Norfloxacin is used to treat UTIs and prostatitis Ofloxacin is used to treat selected sexually transmitted
diseases, lower respiratory tract infection, skin infections and prostatitis
Adverse Reactions
- Fluoriquinilones are well tolerated by most patients, but some adverse effects may occur, including:
Dizziness Nausea and vomiting Diarrhea Abdominal pain
1. Tetracycline
- Tetracyclines are broad-spectrum antibacterial drugs.
- They may be classified as:
Intermediate-acting compounds, such as demeclocycline hydrochloride
Long-acting compounds, such as doxycycline hyclate and minocycline hydrochloride
Pharmacokinetics
- Tetracyclines are absorbed from the duodenum when taken orally.
- They’re distributed widely into the body tsiisues and fluids and concentrated bile.
- Tetracyclines are excreted primarily by the kidneys. Doxycyclline is also excreted in feces. Minocycline undergoes enterhepatic recirculation.
Pharmacodynamics
- All tetracyclines are primarily bacteriostatic, meaning they inhibit the growth or multiplication of bacteria. They penetrate the bacterial cell by an energy-dependent process. Within the cell, they bind primarily to a subunit of the ribosome, inhibiting the protein synthesis required for maintaining the bacterial cell.
- The long acting compounds doxycycline and minocycline provide more action against various organisms than other tetracyclines
Pharmacotherapeutics
- Tetracyclines provide a broad spectrum of activity, which means they cover a wide range of organisms, including:
Gram-positive and gram-negative aerobic and anaerobic bacteria
Spirochetes Mycoplasmas Rickettsiae Chlamydiae Some protozoa Rocky Mountain spotted fever Q fever Lyme disease
1. Macrolides
- Macrolides are used to treat a number of common infections. They include erythromycin and its derivatives, such as:
Erythromycin estolate Erythromycin ethylsuccinate Erythromycin glucepate Erythromycin lactobionate Erythromycin stearate
Other macrolides include:
Azithromycin Clarithromycin Dirithromycin
Pharmacokinetics
- Because erythromycin is acid sensitive, it must be buffered or have an enteric coating to prevent destruction by gastric acid. Erythromycin is absorbed in the duodenum. It’s distributed to most tissues and body fluids except, in most cases, cerebrospinal fluid. However, as a class, macrolides can enter the CSF when menenges are inflamed.
- Erythromycin is metabolized by the liver and excreted in bile in high concentrations; small amounts are excreted in urine. It also crosses the placental barrier and is secreted in breast milk.
Pharmacodynamics
- Macrolides inhibit RNA-dependent protein synthesis by acting on a small portion of the ribosome.
Pharmacotherapeutics
- Erythromycin has a range of therapeutic uses:
It provides a broad spectrum of antimicrobial activity against gram-positive and gram-negative bacteria, including Mycobacterium, Treponema, Mycoplasma, and Chlamydia.
It’s effective against pneumococci and group A streptococci.
Staphylococcis aureus is sensitive to erythromycin; however, resistant strains may appear during therapy.
It’s drug of choice for treating Mycoplasma pneumonia infections as well as pneumonia caused by Legionella pneumophila.
Adverse Reactions
Although macrolides produces few adverse effects, they may produce:
o Epigastric distresso Nausea and vomitingo Diarrheao Rasheso Fevero Eosinophilia (an increase in the number of
eosinophils, a type of WBC)o Anaphylaxis
Drugs Affecting the Cardiovascular System
Drugs Affecting the Cardiovascular System
1. I. Introduction to the Cardiovascular system
- Circulatory System, or cardiovascular system, in humans, the combines the function of the 3 major components of the body.
1. Heart2. Blood Vessels3. Blood
1. A. Functions of the Cardiovascular System
1. transport oxygen and nutrients to organs and tissues throughout the body
2. carry away waste products.3. increases the flow of blood to meet increased
energy demands during exercise4. regulates body temperature5. when foreign substances or organisms invade
the body, the circulatory system swiftly conveys disease-fighting elements of the immune system, such as white blood cells and antibodies, to regions under attack
6. in the case of injury or bleeding, the circulatory system sends clotting cells and proteins to the affected site, which quickly stop bleeding and promote healing.
The Heart
The human heart is a hollow, pear-shaped organ about the size of a fist.
The heart is made of muscle that rhythmically contracts, or beats, pumping blood throughout the body.
Structure of the Heart
1. a. Chambers of the Heart
The heart has four chambers. The upper two are the right and left atria. The lower two are the right and left ventricles. The atria are the receiving chambers of the heart, receiving blood flowing back to the heart. The ventricles are the chambers of the heart that pump the blood out of the heart.
1. b. The Heart Valves
o The valves of the heart are located within the chambers of the heart and are critical to the proper flow of blood through the heart.
o Tricuspid Valve - between the right atrium and right ventricle
o Pulmonary Valve - between the right ventricle and the pulmonary artery
o Mitral Valve - between the left atrium and left ventricle
o Aortic Valve - between the left ventricle and the aorta
1. Septum – divides the heart to left and right
4. Layers of the Heart
o Pericardium (Outer layer)o Myocardium (Muscular layer)o Endocardium (Inner layer)
1. e. Coronary Arteries
o The heart is nourished not by the blood passing through its chambers but by a specialized network of blood vessels.
o Known as the coronary arteries, these blood vessels encircle the heart like a crown, supplying the cardiac muscle with blood.
The Cardiac Cycle
¡ Although the right and left halves of the heart are separate, they both contract in unison, producing a single heartbeat.
¡ The sequence of events from the beginning of one heartbeat to the beginning of the next is called the cardiac cycle.
¡ The cardiac cycle is a two step process which includes:
¡ Diastole – resting period when the veins carry blood back to the heart
¡ Systole – contraction period when the heart pumps blood out to the arteries for distribution to the body
¡ Deoxygenated blood is carried by the veins to the right side of the heart, which directs the blood to lungs where it takes on oxygen.
¡ Oxygenated blood form the lungs circulate circulates to the left side of the heart to be pumped out to every cell in the body through the arteries
Conduction System of the Heart
¡ Each cycle of cardiac contraction and relaxation is controlled by impulses that arise spontaneously in certain pacemakers cells.
¡ These continuous, rhythmic contractions are controlled by the heart itself; the brain does not stimulate the heart to beat.
¡ Impulses:
Sinoatrial node Atrial bundles Atrioventricular node Bundle of His Bundle branches Purkinje fibers
The Blood Vessels
- any of the veins, arteries, and capillaries that transport blood through the body.
1. Arteries
o Carries oxygen rich blood away from the Heart for distribution in the body.
o The Aorta is the largest artery 2. Veins
o Carries oxygen poor blood towards the Heart and into the lungs for reoxygenation.
o The Vena Cava is the largest vein 3. Capillaries
o Known as the “Distribution Pipes”
The Blood
- vital fluid found in humans that provides important nourishment to all body organs and tissues and carries away waste materials.
The Composition of the Blood
1. The Plasma (Fluid) makes up 55% of the blood volume.
o Blood Plasma :Blood Plasma 97% Watero Other 3% -Antibodies and Proteinso Nutrients and Wastes
2. The Solids (Cells) make up 45% of the blood volume. o Red Blood Cells -Carry oxygen, Contain
Hemoglobino White Blood Cells -Attack bacteria & other
invaderso Platelets -Control the blood clotting process
Drugs Affecting Blood Pressure
- The cardiovascular system is a closed of blood vessels that is responsible for delivering oxygenated blood to the tissue and removing waste products from the tissue.
- The blood in this system flows from areas of higher pressure to areas of lower pressure.
- The maintenance of this pressure system is controlled by specific areas of the brain and various hormones.
- Helping the patient to maintain the blood pressure within normal limits is the goal when drug therapy is instituted.
Blood Pressure-pressure of circulating blood against the walls of the arteries
Blood Pressure Control
- The pressure in the cardiovascular system is determined by three elements:
Heart Rate Stroke volume – or the amount of blood that is pumped
out of the ventricle with each heartbeat (primarily determined by the volume of blood in the system).
Total peripheral resistance – or the resistance of the muscular arteries to the blood being pumped through.
Baroreceptors
- As the blood leaves the left ventricle through the aorta, it influences specialized cells in the arch of the aorta called baroreceptors.
- Baroreceptors – pressure receptors located in different arteries in the body.
- Detects pressure within the arteries and sends a stimulus in the medulla, in area called the cardiovascular center (vasomotor center)
- If the pressure is high, the medulla stimulates vasodilation and a decrease in cardiac rate and output causing the pressure in the system to drop.
- If the pressure is low, the medulla directly stimulates an increase in cardiac rate and output and vasoconstriction.
- The medulla mediates these effects through the autonomic nervous system.
Renin-Angiotensin System
- Another compensatory system is activated when the blood pressure within the kidney falls.
- Because the kidneys require a constant perfusion to function properly, they have a compensatory mechanism to help
- This mechanism is known as the Renin-Angiotensin System.
RENIN-ANGIOTENSIN SYSTEM
Hypertension
¡ When a person’s blood pressure is above normal limits for a sustained period
¡ 90% of people with hypertension have what is called Essential Hypertension
Hypertension with no known cause
¡ The underlying danger of hypertension is the prolonged force on the vessels of the vascular system.
Untreated hypertension increases a person’s risk for the following:
¡ Coronary artery disease
¡ Cardiac death
¡ Stroke
¡ Renal failure
¡ Loss vision
Hypotension
¡ When a person’s blood pressure is below normal limits for a sustained period.
¡ If the blood pressure becomes too low, the vital centers in the brain as well as the rest of the tissues of the body may not receive enough oxygenated blood to continue functioning.
¡ Hypotension can progress to shock
Waste products accumulate Cells die from lack of oxygen
Hypotensive state can occur in the following situations:
¡ When the heart muscle is damaged and unable to pump effectively.
¡ With severe blood loss, when volume drops dramatically.
¡ When there is extreme stress in the body’s levels of norepinephrine are depleted, leaving the body unable to respond to stimuli to raise blood pressure.
Antihypertensive Agents
¡ Because an underlying cause of hypertension is usually unknown, altering the body’s regulatory mechanisms is the best treatment currently available.
¡ Treatment for hypertension does not cure the disease but is aimed at maintaining the blood pressure within normal limits to prevent the damage that hypertension can cause.
Diuretics
¡ Diuretics are drugs that increase the excretion of sodium and water from the kidney.
¡ These drugs are often the first agents tried in mild hypertension; they affect blood volume levels and blood volume.
¡ Diuretics increase urination and can disturb electrolyte and acid-base balances they are usually tolerated well by most patients.
Symphatetic Nervous System Blockers
¡ Drugs that block the effects of the sympathetic nervous system are useful in blocking many of the compensatory effects of the sympathetic nervous system.
Betablockers – blocks vasoconstriction, decreased heart rate, decreased cardiac muscle contraction, increase blood flow in the kidneys, decrease renin release.
Alpha-adrenergic blockers – inhibit the post synaptic alpha 1-adrenergic receptors, decreasing synaphatethic tone in the vascularate and causing vasodilation, which leads to a lowering of blood pressure.
Angiotensin – Converting Enzyme Inhibitor
¡ The ACE inhibotors block the conversion of angiotesin I to angitensin II in the lungs.
¡ ACE inhibitors prevent ACE from converting angitensin I to angiotensin II.
¡ Angiotensin II is a powerful vasocontrictor and a stimulator of aldosterone release.
¡ These drugs are indicated for the treatment of hypertension.
Pharmakokinetics
¡ Well absorbed
¡ Widely distributed
¡ Metabolized in the liver
¡ Excreted through the urine
¡ Cross the placenta and joins the breast milk
Not indicated during pregnancy and lactation
Adverse effects
¡ Tachycardia
¡ Chest pain
¡ Angina
¡ CHF
¡ Cardiac arrhythmias
¡ GI irritation
¡ Ulcers
¡ Constipation
¡ Renal insufficiency
¡ Renal failure
¡ Liver injury
¡ Protenuria
¡ Rash
¡ Alopecia
¡ Dermatitis
¡ Photosensitivity
Common ACE inhibitors
¡ Benazepril
¡ Captopril
¡ Enalapril
¡ Fosinopril
¡ Lisinopril
¡ Moexipril
¡ Perindopril
¡ Quinapril
¡ Ramipril
¡ Trandolapril
Calcium Channel Blockers
- Inhibit the movement of calcium ions across the membranes of myocardial and arterial muscle cells, altering the action potential and blocking muscle cell contraction.
- This effect depresses myocardial contractility, slows cardiac impulse formation in the conductive tissues, and relaxes and dilates arteries, causing a fall in blood pressure and decrease in venous return.
Pharmacokinetics
- Well absorbed
- Metabolized in the liver
- Excreted in the urine
- Cross placenta and enters breast milk
Can cause fetal toxicity Not indicated for pregnant and lactating women
Adverse Effect
- Dizziness
- Lightheadedness
- Headache
- Fatigue
- Nausea
- Hepatic injury
- Hypotension
- Bradycardia
- Peripheral edema
- Heart block
- Skin flushing
- Rash
Common Calcium Channel Blockers
- Amlodipine
- Diltiazem
- Felodipine
- Isradipine
- Nicardipine
- Nifedipine
- Nisoldi
Drugs Acting on the Immune System
Drugs Acting on the Immune System
1. Introduction to the Immune Response And Inflammation
- The body has many defense systems in place to keep it intact and to protect from EXTERNAL STRESSORS. These stressors can include:
Bacteria Viruses Other foreign pathogens Trauma Exposure to extremes of environmental conditions
- The same defense systems that protect the body also help to repair it after cellular trauma or damage.
- Understanding the basic mechanisms involved in these defense systems helps to explain the actions of drugs that affect the immune system and inflammation.
Body Defenses
- The body’s defenses include:
Barrier defenses Cellular defenses Inflammatory response Immune response
1. Barrier Defenses
- Certain anatomical barriers exist to prevent the entry of foreign pathogens and to serve as important lines of defense in protecting the body.
Skin o The skin is the first line of defenseo The skin acts as a physical barrier to protect the
internal tissues and organs of the body. The acid pH of skin secretions inhibits
bacterial growth. Glands in the skin secrete chemicals that
destroy or repel many pathogens. Ex. Sebum contains chemicals that are toxic to bacteria.
The skin sloughs off daily, making it difficult for any pathogen to colonize on the skin.
An array of normal flora bacteria lives on the skin and destroys many disease causing pathogens.
o Mucous membrane Mucous membranes line the areas of the
body that are exposed to external influences but do not have the benefit of skin protection.
Respiratory tract The mucous membrane is
lined with tiny, hair-like processes called cilia. The cilia sweep any captured pathogens or foreign materials upward toward the mouth, either to be
swallowed or to cause irritation to the area and be removed by a cough or a sneeze.
Gastrointestinal tract The mucous
membrane serves as a protective coating, preventing erosion of GI cells by the acidic environment of the stomach, the digestive enzymes of the small intestines, and the waste products that accumulate in the large intestine.
The stomach mucosa secretes hydrochloric acid and protein digesting enzymes. Both kill pathogens.
The mucous membrane also secretes mucus that serves as a lubricant throughout the GI
tract to facilitate movement of the food bolus and of waste products.
1. Cellular Defenses
- Any foreign pathogen that manages to get past the barrier defenses will encounter the human immune system, or mononuclear phagocyte system (MPS) composed of:
Thymus gland Lymphatic tissue Leukocytes Lymphocytes chemical mediators
1. Leukocyte
White blood cells Two types of WBC
o Lymphocytes- key components of the immune system and consist of T cells, B cells and natural killer cells
o Myelocytes- different cell types those are important in both the basic inflammatory response and the immune response. Myelocytes include neuthrophils, basophils, eosinophils and monocytes or macrophages.
1. Neuthrophils
Polymorphonuclear lukocytes that are capable of diapedesis and phagocytosis.
o Diapedesis- moving outside of the bloodstream.o Phagocytosis-engulfing and digesting foreign
materialo When the body is injured or invaded by a
pathogen, neuthrophils are rapidly produced and moved to the site of the insult to attack the foreign material.
o Able to identify nonself-cells by use of MHC.
1. Basophils
Myelocytic leukocytes that are not capable of phagocytosis.
Full of chemical substances that are important for intiating and maitaining an immune or inflammatory response. Ex histamine and heparin
1. Eosinophils
Circulating myelocytic leukocytes. Often found at the site of allergic reaction and
responsible for removing proteins and active componets of the immune reaction from the site of an allergic response.
1. Monocytes
Monuclear phagocytes also called macrophages Mature leukocytes that are capable of phagocytizing an
antigen. o Antigen- an substance capable of exciting our
immunne system and provoking an immune response. As far as our immune system is concern, they are foreign intruders in the body
o A major role of macrophages is to engulf foreign particles and present fragments of these antigens, like signal flags, on their own surfaces, where theyczn be recognized by immunocompetent T cells.
1. Mast cells
Fixed basophils that do not circulate Can be found in the respiratory and GI tracts and in the
skin.
1. The Inflammatory Response
The inflammatory response is the local reaction of the body to invasion or injury.
Any insult to the body that injures cells or tissues sets into action a sereis of events and chemicals reactions.
Cell injuries causes the activation of a chemical in the plasma called factor XII or Hageman Factor.
o Hageman Factor-responsible for activating the Kinin System:
Clottting cascade- which starts blood clotting
+ Hageman factor activates kallikrein, a
bustance found in the local tissues. Kallikrein causes the precursor
substance kininogen to be converted to bradykinin.
Bradykinin Causes local vasodilation to
bring more blood to the injured area
Allow white blood cells to ecape into the tissues. Increase permeability.
Stimulates nerve ending to cause pain,which alerts the body to the injury.
Bradykinin also causes the release of arachidonic acid from the cell memebrane.
Arachidonic acid causes the release of autochoids. Autochoids act like local hormes release from the cell and cause an eefect in the immediate area:
Protaglandins- augments the inflamatory reaction and stimulates nerve ending which causes pain.
Leukotrines- causes vasodilation and increased capillary
permeability. Leukotrines has a property called chemotaxis, which is the ability to attarct neuthrophils and to stimulate them and other macrophages in the area to be very aggressive.
Thromboxanes- cause local vasoconstriction and facilitates aggregation and blood coagulation.
Injury to the cell membrane causes the release of Histamine.
Histamine causes vasodilation, which bring more blood and blood components to the area. Histamine also increases the permeability of the capillary, making it easier for neuthrphils and blood chemicals to leave the blood sream and enter the injured area.
1. The Immune Response
- More specific invasion can stimulate a more specific response through the immune system.
- A major component of the immune response are the lymphocytes
2 major types of lymphocytes:
1. T cells
T cells are programmed in the thymus gland It provides to what is called a cell mediated immunity Cell mediated immunity is an immune response that
does not involve antibodies but rather involves the activation of macrophages and antigen specific cytotoxic T cells, and the release of various cytokines in response to an antigen.
T cells develop into at least 3 different cell types
1. Effector or cytotoxic T cells
Are found throughout the body Aggressive against non-self cells Releases cytokines, or chemicals that can either directly
destroy a foreighn cell or mark it for aggressive destruction.
Attacks body’s own cells that have been invaded by a virus, neoplastic cancer, or transplant foreign cells.
1. Helper T cells
Stimulates other lymphocytes to be more aggressive and responsive.
1. Suppresor T cells
Responds to the rising levels of chemicals associated w/ an immune response to suppress or slow reaction.
- The balance of the helper and suppresor T cells allow for rapid response to body injury or invasion. And slowing allows the body to conserve energy and the component of the immune and inflammatory reaction.
1. B cells
Are programmed to identifay specific protein, or antigens. They provide what is called humoral immunity.
Humoral immunity is the aspect of immunity that is mediated by secreted antibodies.
Antibodies also known as immunoglobulins, are used by the immune system to identify and neutralize foreign objects or microorganms.
When B cells reacts w/ its specific antigen, it changes to become a plasma cell.
Plasma cells produce antibodies, w/c circulate in the body and react w/ this specific antigen when it is encounterd.
Reaction between an antigen ang antibodies will form a Ag-Ab complex will cause an activation of complement.
Complement is a biochemical cascade of the innate immune system that helps clear pathogens fron an organism.
Anti-inflammatory Agents
- The inflammatory response is designed to protect the body from and pathogens. It employs a variety of potent chemical mediators to produce reactions that helps to destroy pathogens and promote healing.
- As the body reacts to these chemicals, it produces some signs and symptoms of disease:
Swelling Pain Redness Heat/fever
- Anti iiflammatory agenys generally block or alter the chemical reactions associated with the inflammatory response to stop one or more of the signs and symptoms of inflammation.
Several diffrent types of drugs are used as anti-inflammatory agents:
1. Corticosteroids- are used sytemically to block the inflammatory and immune systems. Blocking these
important protective processes may produce many adverse effects, including decreased resistance to infection and neoplasm.
2. Antihistamines- are use to block the release of histamine in the initiation of the inflammatory response.
3. Salicylates- are popular anti-inflammatory agebts, not only because of their ability to block the inflammatory response but also because of their antipyretic and analgesic properties. They are generally available without prescription and are relatively nontoxic when used as directed.
4. Nonsteroidal anti-inflammatory drugs (NSAIDS)- are some of the most widely used drugs. They provide strong anti-inflammatory and analgesic effects yet do not have the adverse effects that are associated with the corticosteroids.
5. Acetaminophen- also is widely used agent. It has antipyretic and analgesic properties but does not have the anti-inflammatory effects of salicylates or the NSAIDs.
- Because many anti-inflammatory drugs are available over the counter, there is the potential for abuse and overdosing.
- Patients may take these drugs and block the signs and symptoms of a present illness, thus potentially causing the misdiagnosis of a problem.
- Patients also may combine these drugs and unknowingly induce toxicity.
SALICYLATES
- Are some of the oldest anti-inflammatory drugs used.
- Ancient peoples extract salicylates from willow bark and poplar trees, used to treat fever, pain and inflammation.
- Nowadays synthetic salicylates are commonly used.
- Synthetic salicylates includes the following drugs:
Aspirin- one of the most widely used drugs for treating inflammatory conditions, it is available OTC.
Balsalazide- a new type of anti-inflammatory drug that is delivered intact to the colon, where it delivers a local anti-inflammatory effect for patients with ulcerative colitis.
Choline magnesium trisalicylate- is used to treat mild pain and fevers, as well as arthritis.
Choline salicylate- is used to treat mild pain and fevers, as well as arthritis, it is available only as an OTC.
Mesalanine- is a unique compound that release aspirin in the large intestine for a direct anti-inflammatory effect in ulcerative colitis or other condition involving inflammation of the large intestine.
Olsalazine- is a drug that is converted to mesalamine in the colon and has the same direct anti-inflammatory effects.
Salsalate- is used treat pain, fever, and inflammation.
Sodium thiosalicylate- is used mainly for episodes of acute gout and muscular pain, and to treat rheumatic fever.
Therapeutic Actions
Salicylates inhibit the synthesis of prostaglandin The antipyretic effect of salicylates maybe related to
blocking of a prostaglandin mediator of pyrogen. o Pyrogen are chemicals that can cause an
increase in body temperature and that are released by active WBC, they act at the thermoregulatory of the hypothalamus.
o At low levels , aspirin also affects platelet aggregation by inhibiting the synthesis of thromboxane A2, a potent vasoconstrictor that normally increases platelet aggregation and blood clotting.
o At high levels, aspirin inhibits the synthesis of prostacyclin , a vasodilator that inhibits platelet aggregation.
Indications
Salicylates are indicated for the treatment of:
Mild to moderate pain Fever Numerous inflammatory conditions:
o Rheumatoid arthritiso Ostheoarthritis
Low doses indicated for the prevention of transient ischemic attack
Stroke in adults with a history of emboli Reduce the risk of death and myocardial infarction in
patients with history of MI or unstable angina.
Pharmacokinetics
Salicylates are readily absorbed in the stomach Metabolized in the liver Excreted in the urine Crosses the placenta barrier and enter breast milk Not indicated for use during pregnancy and lactation
because of the potential adverse effect on the neonates
Contraindications
Allergy to salicylates Bleeding abnormalities
Adverse Reactions
Stomach (gastric irritant) o Nauseao Dyspepsia
o Heartburno Epigastric discomfort
Clotting systems o Blood losso Bleeding abnormalities
Salicylism (high levels of salicylates) o Dizzinesso Ringing in the earso Difficulty hearingo Nausea vomitingo Diarrheao Mental confusiono Lassitude
Acute salicylate toxicity (occurs at doses of 20-40g in adults, 4 g in children)
o Hyperpnea (increase depth in breathing)o Tachypneao Hemorrhageo Excitemento Confusiono Pulmonary edemao Convulsionso Tetany (spasms due to decrease calcium)o Metabolic acidosiso Fevero Comao Cardiovascular collapseo Renal failureo Respiratory collapse
NONSTEROIDAL ANTI-INFLAMMATORY DRUGS
The NSAIDs are a drug class that has become one of the most commonly used types. This group of drugs includes the following agents:
Propionic Acid
1. Fenopropen- is used to treat pain and manage arthritis.2. Flurbipropen- is used for the long-term management of
arthritis and as atopical preparations for managig pain after eye surgery.
3. Ibufrofen- is used as an OTC pain medication and for long-term management of arthritis pain and dysmenorrhea; it is the most widely used of the NSAIDs.
4. Ketoprofen- is available for short-term management of pain and as atopical agent to relieve ocular itching caused by seasonal rhinitis.
5. Naproxen- is available for OTC pain relief and to treat arthritis and dysmenorrhea.
6. Oxaprozin- is very successfully used to manage arthritis.
Acetic Acids
1. Diclofenac- is used to treat acute and long term pain associated with inflammatory conditions.
2. Etodolac- is widely used for arthris pain.
3. Indomethacin- is available in oral, topical, and rectal preparations for the relief of moderate to severe pain associated with inflammatory conditions and in intravenous form to promote closure of the patent ductus arteriosus in premature infants.
4. Ketorolac- is used for short-term management of pain and topically to relieve ocular itching.
5. Nabumetone- is used treat acute and chronic arthritis pain.
6. Sulindac- is used for long-and short term treatment of the signs and symptoms of various inflammatory conditions.
7. Tolmetin- is used to treat acute attacks of rheumatoid arthritis and juvenile arthritis.
Fenamates
1. Mefenamic acid- is used only for short-term tratment of pain.
2. Piroxicam- is used to treat acute and chronic arthritis.3. Diflunisal- is used for moderate pain and for the
treatment of arthritis
Oxicam Derivative
1. Meloxicam- is used for the relief of juvenile arthritis, osteoarthritis, and rheumatoid arthristis.
Cyclooxygenase-2 Inhibitor
1. Celcoxib- is used for the acute and long term treatment of arthritis, particularly in patients who cannot tolerte the GI effects of other NSAIDs.
Therapeutic Actions
The anti-inflammatory, analgesic and antipyretic effects of NSAIDs are largely related to the inhibition of prostaglandin.
The NSAIDs block 2 enzymes: o Cyclooxygenase-1 (COX-1)- involves in many
body functions including: Blood clotting Protecting the stomach lining Maintaining sodium and water balance COX-1 turns arachidonic acid into
prostaglandins as needed in a variety of tissues.
Cyclooxygenase-2 (COX-2) Is active at sites of trauma or
injury when more prostaglandins are needed, but it does not seem to be involved in the other tissue function, unlike COX-2.
The adverse effects associated with most NSAIDs are related to blocking of both of these enzymes and changes in the functions that they influence:
Changes in bleeding time GI effects Water retention
Indications
The NSAIDs are indicated for relief of the signs and symptoms of rheumatoid arthritis and osteoarthritis, for relief of mild to moderate pain, for treatment of primary dysmenorrhea, and for fever reduction.
Pharmacokinetics
Rapidly absorbed from the GI tract Metabolized in the liver Excreted in the urine NSAIDs cross the placenta and cross into breast milk Not recommended during pregnancy and lactation
because of the potential adverse effects on the fetus or neonate.
Contraindications
Allergy to any NSAIDs or salicylates.
Celecoxib is also contraindicated in the presence of allergy to sulphonamides.
Cardiovascular dysfunction Hypertension Peptic ulcer or known GI bleeding Renal or hepatic dysfunction
Adverse Effects
Nausea Dyspepsia GI pain Constipation Diarrhea Flatulence Potential for GI bleeding Headache Dizziness Fatigue Bleeding Platelet inhibition Bone marrow depression Rash and mouth sores Anaphylactic shock in cases of severe hypersensitivity.