Pharmacology II Outline

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NIP Fall 2010 Pharmacology Review Page 1

Level II

Pharmacology Outline Review Notes

Chapter I Drug Action:

Drugs that are taken by mouth go through three phases

I. Pharmaceutics Phase: A PO drug has to become a solution so that it can pass throughbiological membrane. This process is called dissolution. If a drug is administered

intravenously, intramuscularly or subcutaneously there is no

II. Pharmacokinetic Phase : There are four phases to this processA. AbsorptionB. DistributionC.

Metabolism

D. Excretion or EliminationIII. Pharmacodynamic Phase: Is the study of drug concentration and its effect on

body. Drug response can be primary effect or a secondary physiological effect.

A. Think Onset of action-Is the time it takes the drug to reach minimum effectconcentration

B. Time of Peak effect of the drug -Time that it takes for drug to reach its highest blood orplasma level

C. Duration- The length of time the drug has a pharmacological effect.IV. Agonist: Drugs that produce a responseV. Antagonist: Drugs that inhibit/block a response

VI. Categories : There are fourA. Stimulation/or Depression- either the drug stimulates of depresses a cell or a glands

activity.

B. Replacement- drug replaces an essential body compound like insulinC. Inhibition or killing of Organism- think antibacterial or anti- fungal agentsD. Irritation-here think of laxatives causing intestinal irritation to stimulate peristalsis.

VII. Side Effects / Adverse Reactions and Toxic Effects-A. Side Effects- physiological effects not related to the desired effect of the drug.B. Adverse Reaction- Anaphylaxis They must always be reported & documented.C. Toxic effect/Toxicity- can always be identified by drug plasma levels.


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Chapter 2: Nursing Process and Client Teaching

I. Nursing Process has four phasesA. Assessment/Diagnosis- Data collection involves both Subjective and Objective. Should be

focused on symptoms & organs most likely to be affected by clients drug therapy

1. Subjective- Current Healthy history, client verbalized symptoms, current medications(dosage, route, frequency, & prescribing physician), clients knowledge of their

medications, drug allergies, clients compliance of drug regimen, over the counter

supplements, past medical history, clients environment, and their support system.

2. Objective Gross and fine motor movement, ROM, laboratory results, diagnosticstudies, clients height weight and other physical assessment values temperature, pulse,

blood pressure and respirations.

B. Planning- Setting of the goals for the patient and developing interventions to help patientto accomplish them.

1. Goals should always follow SAME:2. Specific for this patient3. Action oriented4. Measurable ( and in a specific time frame)5. Evaluation- is able to continually be evaluated and revised as necessary.

C. Implementation- this would be our Nursing actionsREMEMBER OUR NURSING RESPONSIBILITY IS TEACHING !

Chapter 20 Central Nervous System Depressants

I. Sedatives/Hypnotics: Often are prescribed for treatment of insomniaRemember that dreams occur during Rapid Eye Movement stage of sleep.

A. They are the mildest form of CNS depressants are our sedative drugs.B. They do not affect the consciousness.

II. Barbiturates 1900s were introduced as a sedative.A. Long acting - PhenobarbitalB. Intermediate Acting- Butabarbital (Butisol)C. Short- Acting Secobarbital ( Seconal) & Pentobarbital (Nembutal) {Prototype}D. Ultra Short Acting- Barbiturate, Thiopental (Na Pentothal)

III. Benzodiazepines minor tranquilizer or anxiolytic. Class IV according to ControlledSubstances Act. They the action of the inhibitory neurotransmitter gamma-aminobutyric

acid (GABA) to the GABA receptors. Neuron excitability is . Also of the

Benzodiazepines except temezepam can cause vivid dreams/nightmares. Should not be

used for longer than 3 to 4 weeks. Remember that it is recommended that with renal or

hepatic dysfunction smaller doses should be used.


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A. Chlordiazepoxide (Librium) class IV. Used also for treatment of alcohol withdrawlsyndrome DTs, anxiety and tension. For anxiety usual PO dose is 5-25mg t.i.d. or

q.i.d. For alcohol withdrawl PO/IM/IV 50-100mg max. 300mg/d

B. Flurazepam (Dalmane) {Prototype}C. Temazepam (Restoril)D. Triazolam ( Halicon)E. Lorazepam (Ativan) {Prototype} used for treatment of mild to moderate

anxiety. PB 85-95%, t 3.5- 21 hr.

F. Diazepam (Valium) used to manage anxiety, muscle spasms status postepilepticus. PO/IM/IV 2-10mg b.i.d.- q.i.d. For Post epilepticus IV 5-10mg q 10-20

min. max. 30mg

IV. Non benzodiazepines Used for short term insomonia (< 10 days duration)a. Zolpidem (Ambien) .Duration is 6-8 hrs. with a short t1/2 of 2 to 2.5 hrs. M

a. Metabolized in the liver to 3 inactive metabolites and excreted in bile, urine, andfeces.

V. Chloral Hydrate- It is used to induce sleep and decrease nocturnal awakenings. Feweroccurrences of hang-over, resp. depression, and tolerance. Effective in older clients. It can

be given to patients with mild hepatic dysfunction, but should be avoided if liver or renal

failure is severe.

VI. Anesthetics - Two classifications1. General Anesthetic depresses the CNS, alleviates pain, and causes loss of

consciousness. One of the first ones used was Nitrous Oxide (laughing gas)

1. Four Stages of Anesthesia-1

ststage is Analgesia (induction stage) (consciousness and goes to loss of

consciousness. Loss of sensation of smell and pain occur.2. 2nd stage is Excitement Or Delirium produces loss of consciousness caused

by depression of the cerebral cortex. Confusion, excitement or delirium occurs.

3. 3rd stage Surgical Surgical procedure is performed during this stage.4. 4th stage Medullary Paralysis Toxic stage of anesthesia Resp. are lost &

circulatory collapse occurs. Must be on Ventilator.

2. Inhalation Anesthetics- used during the 3rd stage, inhalation gases are used. Somelike Nitrous Oxide are absorbed quickly, have rapid action but also eliminated

quickly. Some examples in the 1950s and later are Halothane, Methoxyflurane,

Enflurane ,Isoflurane, Desflurane, and in 1995 Seroflurane.

Inhalation agents are usually combined with a barbiturate, a strong analgesic like

morphine, and a muscle relaxant like pancuronium.

Potential adverse effects are respiratory depression, hypotension, dysrhythmias,&

hepatic dysfunction.


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3. Intravenous Anesthetics May be used for induction with addition of inhalationanesthesia or in an outpatient setting for procedures with an anticipated short

surgical time.

a. Midazolam (Versed) b. Propofol (Diprivan)- this drug supports microbial growth & may risk for

infections. Open vials should be discarded after 6 hours to prevent sepsis.

4. Topical Anesthetics- Available in many different forms. Decrease the sensitivity ofthe nerve endings to the affected/injured area.

5. Local Anesthetics These drugs block pain at the site where the drug isadministered, allowing for consciousness to be maintained. Beneficial in many

minor procedures. Consist of two main groups Esters and Amides.

a. Esters Short Acting - Chloroprocaine (Nesacaine), Procaine HCl (Novacain)which both is effective for (1/2-1hr.).

Long Acting -Tetracaine (Pontocaine), which is effective for (3-10 hr.)

b. Amides Low incident of allergic reactions. Lidocaine Hydrochloride(Xylocaine) has a rapid onset and long duration of action. Labeled as Moderate

acting (1-3 hr.) Another example would be Prilocaine (Citanest).

Long Acting Bupivacaine (Marcaine & Sensorcaine)

6. Spinal Anesthesia use of local anesthetics injected in the subarachnoid space atL3-4. Potential complications could be respiratory distress if anesthetic is injected

or travels to high in the spinal column, headaches due to leak of cerebral spinal

fluid.

a. Spinal Nerve Block local anesthetics is injected into the 2nd layer of thespinal column subarachnoid membrane

b. Epidural Block- local anesthetic is injected into the outer covering of thespinal column the dura mater.

c. Caudal Block- anesthetic is placed near the sacral area. Ad. Saddle Block anesthetic placed near the lower end of the spinal column to

numb the perineal area.


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Chapter 24 Anti-inflammatory Drugs

Inflammation -is our bodys normal protective response to neutralize and destroy harmful

agents at the site of tissue injury.

Infection- is caused by the presence of microorganisms and results in inflammation, but NOT

all inflammations are infections

I. Five Cardinal signs of Inflammation - because cardinals are red!A.Erythema - Redness occurs in the 1st phase of inflammation. Blood

accumulates to the injury site d/t ( kinins, prostaglandins,& histamines)

B.Edema - swelling 2nd phase of inflammation. Plasma leaks into interstitial tissueat injury. Kinins dilate arterioles cap. Permeability.

C. Heat - can be caused by the inflammation at the site d/t blood accumulationand may result from pyrogens

D.Pain- Caused by the chemical mediators that were released by injured tissuesand the tissue swelling

E. Loss of Function Loss of function accurse d/t fluid accumulations and d/tpain which decrease mobility.

b.Chemical Mediator that are released during the Inflammatory process-A. Prostaglandins- have many effects vasodilation, relaxation of smooth muscle,

capillary permeability and sensitization of nerve cells to pain.

B. Cyclooxygenase (COX) - enzyme responsible for converting arachidonic acidinto prostaglandins & their products. 2 forms of the cyclooxgenase

COX-1 - protects the stomach lining and regulates blood platelet, promoting

clotting

COX-2 - triggers the inflammation and pain responses.

c. Anti-Inflammatory Agents Group of drugs that inhibit the synthesis ofprostaglandin they are called prostaglandin inhibitors, but are most commonly

called anti-inflammatory agents. They have potent anti-inflammatory effects that

mimic the corticosteroids they are also known as NSAIDS (Nonsteriodal Anti-

Inflammatory Drugs. Some of the newer NSAIDS block only the COX-2.

A. Acetylsalicylic Acid (Aspirin) was developed in 1899 by Adolph Bayer. It is aprostaglandin inhibitor in the inflammatory process. It is also an Anti

Platelet. Remember that ASA should not be used with other NSAIDS.

{Prototype}. Common symptom of sensitivity to Salicylate is

Tinnitus (ringing in the ears) ,vertigo, bronchospasm. Many foods have

salicylates in them such as wine, prunes, curry, and licorice.

B. Para- Chlorbenzioc Acid- Used to treat Rheumatoid ,Gout and Osteo-Arthritis. Potent prostaglandin inhibitor, 90% protein bound and displaces other

protein bound drugs drug toxicity. Half life is 4-11hrs.


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1. Examples Indomethacin (Indocin) which is very irritating to the stomachand should be taken with food. Sulindac (Clinoril), Tolmetin (Tolectin)

these drugs produce less severe reactions then Indocin and may cause

retention of Na and H2O

C. Phenlacetic Acid Derivatives effects are similar to aspirin, but minimal anti-pyretic properties. Used for same arthritic conditions as para-chlorbenzoic acid

but also for anklosing spondylitis.

1. Examples Diclofenac sodium (Voltaren) and Ketorolac (Toradol). Toradolwas the first injectable NSAID that has high analgesic properties which are

to that of opiods. Intramuscular dose is 30-60mg q 6 hrs.

D. Propionic Acid New group of NSAIDs but are stronger than ASA but have lessGI irritation.

1.

Examples Ibuprofen (Motrin Advil) {Prototype}, Fenoprofen Calcium(Nalfon), Naproxen (Naprosyn), Ketoprofen (Orudis), Flurbiprofen (Ansaid) and

Oxaprozin ( Daypro).

E. Fenarnates and Oxicams are the last two classification of 1st generation ofNSAIDs.

F. Only one true COX2 inhibitor is Celecoxib (Celebrax){Prototype}. Rememberbiggest Cautious use listed was Heart Failure and Bleeding tendencies.

G. Corticosteriods Have a long half life of > 24 hrs. When drugs are D/C the doseshould be tapered over a period of 5-10 days before it is just stopped.

I.Examples Prednsone, Prednisolone and Dexamethazone.H. Disease Modifying Antirheumatic Drugs these therapies include such elements

as Gold {Prototype}, Immunosuppressive Agents, Immunodulators , &

Antimalaries.

I. Antigout Drug - Gout inflammatory condition that affects the joints, tendons, andother tissues. Characterized by a buildup of urates (uric acid salts) uric acid

levels(hypouricemia) d/t kidneys being unable to excrete. Also uric acid my

buildup in the kidneys causing uric acid calculi. When patient are on anti-gout

medication make sure that fluid intake is .Patients should be instructed to avoid

alcohol. They should also take Tylenol for discomfort instead of aspirin d/t

aspirin would the acid levels even more.

1. Examples of anti-gout medications are Uric acid inhibitors likeAllopurinol (Zyloprin) {Prototype}.

2. Uricosurics increase the rate of uric acid excretion by inhibiting itsreabsorption. They are used for the chronic condition not an acute attack.

Potential side effects flushed skin, sore gums, and headache. Also might


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cause a metallic taste. Instruct patients to avoid alcohol and caffeine because

they can uric acid levels.

Examples - Probenecid (Benemid)- this drug may cause gastric irritation and

when this occurs should be taken with food.

Sulfinpyrazone ( Anturane)- is even more potent the Benemid and should

be taken with food or with and antacid to prevent gastric irritation.

Chapter 25 Nonopioid and Opioid Analagesics

I. Pain is defined as an unpleasant sensory and emotional experience related to tissueinjury. The nurse must be knowledgeable and skillful in the assessment and treatment

of pain (it is a subjective type of assessment based on the patients perception of the

level of pain they are experiencing).II. Pain Threshold reflects the level of stimulus needed to create a painful sensation.

III. Analgesics class of drug that reduces the sensation/perception of pain may benonopioids (like NSAIDs) or opioids (like narcotics).

A. Nonopioids- like Aspirin, Acetaminopen (tyenol), ibuprofen (motrin/advil) areused to treat mild pain and are available as OTC. They are especial effective for

dull, throbbing pain of headaches, dysmenorrheal, inflammations, minor

abrasions, and mild arthritic pains.

IV. Types of Pain A. Duration

Acute - ( sudden onset & responds to treatment verses

Chronic - (pain that persists for > 6 months and is difficult to treat or control).

Cancer pain from pressure on the nerves and organs, blockage to blood supply

or metastasis to the bone.

B. Origin 1. Somatic Pain of the skeletal muscle, ligaments, and joints

2. Visceral Pain from smooth muscle and organs.

V. Opioid Analgesic (Opioid Agonists) Most Opioids have an antitussive and anti-diarrheal effects. Demerol does not have antitussive effect. Opioids taken with kava

kava , St. Johns wart , or valerian may sedation.A. Morphine- a derivative from Opium.{Prototype} It affects two type of receptors

1. Primarily affects the receptors (responsible for Analgesia, respiratory

depression, euphoria and sedation) when they are activated.

2. It has a weak activating affect on the k receptors (Analgesia, sedation but no

effect on causing respiratory depression or euphoria).

*** Antidote for Respiratory depression is Naxolone (NARCAN).


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B. Other Opioid derivatives are 1. Meperidine (Demerol) preferred drug to be given during pregnancy because it

does not diminish uterine contractions, and it causes less neonatal respiratory

depression. It also causes less constipation and urinary retention than

morphine. It is metabolized in the liver to an active metabolite therefore

decrease the dose with any patient with

hepatic or renal insufficiency. A major side effect is decrease in blood

pressure.

2. Hydromorphone (Dilaudid) is a semisynthetic Opioid similar to morphine.

The analgesic effect is approx. 6 times more potent than morphine with few

hypnotic effects and less GI distress. It has a faster onset and shorter duration

time than morphine. Use of opioids is contraindicated in patients with head

injuries.

Chapter 28 Antibacterial Agents Penicillins and Cephalosporins

I. Types of Bacteria according to their shape and the use of Gram stainingA. Gram Positive If the bacteria after using Crystal violet or methalyne blue

stain keep a purple stain. Examples: Staphylococcus aureus, Streptococcus

pneumoniae, Group B streptococcus, and Closteridium perfingens.

B. Gram Negative Bacteria- doesnt stain. Examples would be: Neisseriameningitides, Escherichia Coli, Haemophilus Influenzae.

C. Antibacterials/Antimicrobial substances that inhibit bacterial growth or killbacterial and other microorganisms including fungus viruses, protozoa.

D. Antibiotic refers to the chemical produced by one kind of microorganism thatinhibits the growth of or kills another. Remember that antibacterial drugs dont

work alone we use other treatment modalities to assist such as natural body

defenses, surgical procedures to excise infected tissue and dressing changes.

They are either obtained for natural sources or manufactured. Five mechanisms

of action:

1. Inhibition of bacterial cell- wall synthesis2. Alteration of membrane permeability3. Inhibition of protein synthesis4. Inhibition of the synthesis of bacterial ribonucleic acid (RNA) and

Deoxyribonucleic acid (DNA)5. Interference with the metabolism with the cell.

E. Bacteriostatic verses Bactericidal drugs :1. Bacteriostatic drugs - inhibit the growth of bacteria. Example drugs are

tetracycline and sulfonamides

2. Bactericidal drugs - kill the bacteria. Example of drugs Penicillin andcephalosporin.


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F. Adverse Reactions- Superinfections, vaginitis, urticaria, stomatitis and hearingloss.

II. Lincosamides like erythromycin inhibit bacterial protein synthesis and have bothbacteriostatic and bactericidal actions depending upon the dosage of the drug.

A. Examples Clindamycin(Cleocin) widely prescribed d/t active against most

gram-positive organisms like Staphylococcus aureus and other anaerobic

organisms. It is also absorbed better in the GI tract than lincomycin (Lincocin), and

has fewer side effects than lincocin.

B. Side Effects- Both can cause GI irritation, rash.

C. Severe Adverse Colitis and anaphylactic shock.

D. Drug interactions Both are incompatible with aminophyline, phenytoin

(Dilantin), barbiturates and ampicillin.

III. Vancomycin (Vancocin) a glycopeptides bactericidal antibiotic was used widely totreat staphylococcal infections. Vancomycin is also used against drug- resistantStaphylococcus aureus, and in cardiac surgical prophylaxis for patients whom are

allergic to penicillin. It is ineffective for treating enterococci.

A. Pharmokinetics given orally to treat staphylococcal entercolitis & antibiotic

associated pseudomembranous colitis d/t Clostridium difficile. When it is given

orally it is not aborbed systemically & is excreted in the feces. Vancomycin given

IV is effective to treat severe infections d/t MRSA, septicemia, bone, skin and

lower respiratory tract. It must be diluted in 250 ml of D5 W, NS or LR. and

administered at of a rate of 10mg/min, when given IV it is excreted in the urine and

30% is PB. Half life is 6 hrs.

B. Pharmacodynamics inhibits the bacterial cell wall synthesis and is activeagainst several gram-postitive microorganisms.

1. Peak is 30 minutes after the end of the infusion

C. Side Effects Vancomycin may cause nephrotoxicity and ototoxicity. May also

cause chills, dizziness, fever, rashes, N/V , and thrombophelbitis at the injection

site. Redman Syndrome if the IV infusion is given too rapidly which is more a

toxic effect rather than an allergic reaction

D. Adverse Reactions Severe hypotension, tachycardia, generalized tingling,

rarely cardiac arrest, eosinophilia, neutropenia, and Stevens- Johnson syndrome

E. Drug Interactions Dimenhydrinate(Dramamine) if taken with vancomycin may

mask ototoxicity. The risk of nephrotoxicity may be potentiated when taken with

Furosemide, aminoglycosides, amphotericin B, colistin, cisplatin, and cyclosporine.

IV.Ketolides Newer classification of antibiotics structurally related to macrolides.Telithromycin (Ketek) used for adults and those older than 18 to treat acute chronic

bronchitis, acute bacterial sinusitis and community acquired pneumonia. These

disorders are usually caused by Strptococcus pneumonia and Haemophilis influzena.


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A. Pharmacokinetics- Ketek is given orally and is well absorbed from GI tract and

is not affect by food intake. It is excreted in the feces and urine. It is 60-70% PB.

Half life is 10 hrs.

B. Pharmacodynamics Blocks protein synthesis in microorganisms.

1. Peak is 1 hr.

2. Side Effects visual disturbances, stomatitis glossitis, gastritis, N/V, abdominal

distention, flatulence, oral and vaginal candidiasis, constipation, and watery stools.

3. Adverse Reactions Ketek may also lead to an exacerbation of myasthesis

gravis.

4. Drug Interactions if taken concurrently with anti-lipidemics (simvastatin,

lovastatin, atorvastatin), class 1A or class antidysrhythmics. Ketek blood levels are

decreased when taken with rifamin, phenytoin, carbamazepine, phenbarbital,

producing a sub-therapeutic level.

V.Tetracyclines were the first broad-spectrum antibiotics effective against gram-positive and negative bacteria, mycobacteria, rickettsiae, spirochetes, and chlamydiae.Tetracyclines act by inhibiting bacterial protein synthesis and have a bacteriostatic

effect. They are not effective against Staphylococcus aureus(except for the newer

forms of tetracycline),Pseudomonas, or Proteus. Tetracycline in combination with

metronidazole and bismuth subsalicylate is useful in treating Helicobacter

pylori(bacterium in the stomach that can cause peptic ulcer).It can be given orally,

intramuscular, or intravenously. IM is very painful and is seldom used. Newer oral

forms are : Doxycycline {Prototype}, minocycline and methacycline these

preparations should not be taken with aluminum and magnesium antacids, milk

products containing calcium, or iron- containing drugs d/t substances binding with

tetracycline and prevent absorption.Doxycycline & Minocycline- there absorption is improved with food ingestion.

A. Side Effects GI disturbances such as N/V, diarrhea. Photosensitivity may

occur especially when taking Demclocycline(Declomycin).Pregnant women should

not take tetracycline during the 1st trimester d/t possible teratogenic effects. Women

in their last trimester and children older than 8 yrs. should not take tetracycline d/t

irreversibly discoloration of the permanent teeth. Minocycline(Minocin)can

cause damage to the vestibular part of the inner ear which leads to difficulty

maintaining balance.

B. Adverse Reactions Nephrotoxicity results when higher doses of tetracycline

have been given. It can also disrupt microflora in the body and lead to

Superinfection.

C. Drug Interactions Antacids (Maalox and others) and iron-containing drugs can

prevent absorption of tetracycline from the GI tract. Milk and other drugs high in

calcium can do the same, so to avoid decrease absorption of tetracycline while those

drugs they should be taken 2 hrs,apart from the tetracycline.The desired effect of


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oral contraceptives can be lessened when taking with tetracyclines. Administering

tetracycline with an aminoglycoside may increase the risk of nephrotoxicity.

VI. Aminoglycosides They act by inhibiting bacterial protein synthesis. They are usedagainst gram- negative bacteria such as E. coli, Proteus spp , and Pseudomonas.

Streptomycin was the 1st

aminoglycoside available for clinical use to treat

tuberculosis. D/t its ototoxicity it is infrequently used today. It is however the drug

of choice for tularemia & bubonic pneumonic forms of the plague.

Aminoglycosides are used for serious infections. They cannot be absorbed from GI

tract and cannot cross into the cerebrospinal fluid. They do cross the blood brain

barrier in children but not in adults. They are primarly given IV or IM. Neomycin,

or paramomycin are 2 types of aminoglycoside that can be given orally . Neomycin

is given for a pre-op bowel antiseptic and paramomycin is useful for treating

intestinal amebiasis and tapeworm infections. Tobramycin, Amikacin , and

Netilmicin are newer aminoglycoside. Gentamycin(Garamycin) {Prototype} is

currently used to treat Pseudomonas Aeruginosa .A. Pharmacokinetics of Gentamycin has a short half life and the drug can begiven 3-4 times/day. It is primarily excreted unchanged in the urine.

B. Pharmacodynamics- Inhibit bacterial protein synthesis and have a bactericidaleffect.

1. Onset- is rapid or immediate2. Peak is 1 hr3. Duration 6-8 hrs.

C. Side Effects/ Adverse Reactions Ototoxicity and nephrotoxicity.D. Drug Interactions- When aminoglycoside are given with penicillins the desired

effects are greatly decreased. Actions of warfarin can be increased if taken atthe same time as an aminoglycoside.

VII. Fluoroquinolones(Quinolones) - The mechanism of action is to interfere with the

enzyme DNA gyrase, which is needed to synthesize bacterial DNA. Their

antibacterial spectrum includes both gram- positive & negative organisms. They

are bactericidal. The fluoroquinolones that is effective against some gram-

positive organisms such as Haemophilus influenza, Proteus aeruginosa,

Salmonella and Shigella. Effective for treatment of urinary tract infections;

bronchitis; pneumonia; gastroenteritis; and gonorrhea.

A. Examples: Ciprofloxacin (Cipro)and Norfloxacin (Noroxin) are syntheticantibacterials related to nalidixic acid and are broad spectrum on both gram-

positive and negative organisms. Both are indicated for urinary tract infections;

lower respiratory infections; skin; soft tissue; and bone and joint infections. In

the past few years the number of fluoroquinolones has increased. Levofloxacin

(Levaquin) {Prototype} used for community pneumonia, chronic bronchitis,

acute sinusitis.


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B. Pharmacokinetics approximately 70% of Levaquin is absorbed from the GItract. It has a low PB effect. Moderately short half life of 6.5-7.5 hrs. More than

75% is excreted unchanged in the urine.

C. Pharmacodynamics- This drug has a high tissue distribution. If possible shouldbe taken before meals, d/t food slowing down absorption rate. Antiacids also

decrease absorption. Levaquin increases the effect of oral hypoglycemic,

theophylline and caffeine.

1. Onset 30 minutes to 1hr2. Peak 1-2 hrs.3. Duration- is unknown

Chapter 36 Anticancer Drugs- Chemotherapy, Alkylating & Antimetabolites

I. Pharmaceuticals often used to destroy cancer cells and are called by differentnames such as: Anticancer, Cancer Chemotherapeutic agents, Antineoplastic drugsand Cyotoxic therapy. In the 1970s a combination of two antineoplastic drugs was

used together to battle the growth of the cancer cells with increased success.

Chemotherapy may be used as the sole treatment or in conjunction with other

treatment modalities such as radiation, surgery, biological response modifiers. The

most common route of chemotherapy is IV. Some types of cancer can be cured with

chemotherapy such as Hodgkins, Burkitts lymphoma. Wilms tumor, testicular

cancer.

A. A djunctive therapy - when surgery is performed first and then chemotherapy isadministered to eliminate any residual cells that may have remained.

B. Neoadjuvant Chemotherapy - Chemotherapy is given first to reduce the size ofthe tumor then surgery is performed to remove the smaller tumor.

C. Palliative Chemotherapy is used to relieve the symptoms associated withprogressing disease and to improve the quality of life.

D. Chemotherapy Administration administration guided by specific protocols.The length of treatment determined by the type and extent of the malignancy.

E. Multidrug Resistance malignant tumors often develop resistance tochemotherapeutic agents. This can occur for several reasons:

1.Anticancer drugs may not kill all neoplastic cells, and these cells may mutateand become resistant to the chemotherapeutic agent.

2.Some tumor cells have a natural resistance to certain chemotherapy agents.3.Tumor resistance can occur as a result of gene amplification in which a gene

produces many copies of itself.

F.Combination Chemotherapy - Single drug therapy is not usually effective.Combination of chemotherapy drugs are used to achieve tumoricidal effect.

They attack the cancer cells at different phases of the cell cycle.


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1. Side Effects These drugs exert adverse effects on rapidly growing normalcells such as skin, hair blood cells. They also affect the GI tract, mucous

membranes, bone marrow and the reproductive systems.

II. Alkylating Drugs cause cross- linking of DNA strands, abnormal pairing, or

DNA strand breaks. Drugs in this category are effective against many types of

cancer including acute and chronic leukemias, lymphomas multiple myeloma, and

solid tumors of the breast, ovary, uterus, lung, bladder, and stomach.

A.Examples Mustard gas derivatives Cyclophosphamide (Cytoxan)- used to treatHodgkins disease. Vesicant can cause tissue necrosis if it infiltrates into the

tissue. Patients should be well hydrated while taking this drug. Drug

Interactions occur when taking aspirin, allopurinol, Phenobarbital, warfarin,

Thiazides and some psychiatric medications.

B.Ethylenimines Thiotepa (Thiopex),Alkylsulfonates- Busulfan (Myleran)Metal Salts- Cisplatin (Platinol)

C.Side Effects- N/V, hemorrhagic cystitis, alopecia, anemia, leucopenia,thrombocytopenia, bone marrow suppression, 2

ndmalignancy and sterility.

III. Antimetabolites resemble natural metabolites which synthesize, recycle, &

breakdown organic compounds for use by the body. They are used to treat acute

leukemia, breast cancer, head& neck cancer, lung cancer, osteosacroma and non-

Hodgkins lymphoma This group is classified by the substances with which they

interfere;

A. Folic Acid( folate) antagonists- examplesMethotrexate (Rheumatrex, Trexall) numerous drugs interactions occur withMethotrexate (MTX ). Leucovorin is needed to rescue normal cells from the

adverse effects of the drug. Protein bound drugs like aspirin, phenytoin

increase the toxicity of MTX. Clients who are taking penicillins,

cyclooxygenase 2 inhibitors and OTC herbs interact with MTX.

The side effects of antimetabolites include bone marrow suppression (anemia,

leucopenia, thrombocytopenia), stomatitis, N/V, alopecia and hepatic and renal

dysfunction.

B. Pyrimidine antagonist- (Fluorouracil, Adrucil) (5 FU, {Prototype} used forthe treatment of colorectal cancer. Also can treat breast, stomach, liver,

pancreas, and skin cancers. Given IV for solid tumors and topically for

superficial basal cell cancer. IV half life is 10-20 minutes. Small amount is

excreted in urine and 80% is excreted by the lungs as CO2.

C. Purine antagonist- (6-mercaptopurine PurinetholD. Adenosine deaminase inhibitors- (Fludarabine Fludara)


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IV. Antitumor Antibiotics - inhibit protein & RNA synthesis and bind DNA, causingfragmentation. All of these drugs are CCNS except for Bleomycin which has its

major effect on G2. Adverse reactions to antitumor antibiotics include alopecia, N/V,

stomatitis, leucopenia, and thrombocytopenia.

A. Anthracyclines - Doxorubicin (Adriamycin) {Prototype}, Daunorubicin (Cerubidine), Mitomycin ( Mutamycin), Bleomycin (Blenoxane)

B. Doxorubicin ( Adriamycin) {Prototype} lead to the development of manyanalogs Epirubicin (Ellence), Idarubicin (Idamycin). They have severe

cardiotoxic side effects must be given with caution. Maxium lifetime dose

is 550mg/m2 d/t cardiotoxicity.

1. Pharmacokinetics Administered IV and metabolized in the liver to activeand inactive metabolites. The initial phase is 12 minutes, intermediate

phase is 3 to 5 hrs., and final phase is 30 hrs.

2. Pharmacodynamics Prescribed in combination with other anticanceragents for the treatment of breast, ovarian, lung, bladder, lymphomas andleukemias. Has maxium lifetime dose of 550 mg/m2. This dose may be

lowered for patients with pre-existing cardiac conditions or those

whom are using other cardiac toxic medications, are older patients, or

have received chest radiation. Prior to administration cardiac function

must be assessed. Pts may be given Dexrazoxane (Zinecard) to help

prevent cardiac toxicities from occurring. It is a cytoprotective agent.

Remember that Green Tea might enhance the antitumor effect.

Use cautiously with Grape Seed(inhibits effects of Doxorubicin)

Garlic (anti- clotting properties may effectiveness of chemotherapy.

3. Side Effects and Adverse Reactions can cause organ toxicity. Patientsreceiving Bleomycin may develop pneumonitis which progresses to

pulmonary fibrosis. Assessment of CBC, RBC, WBC, and Platelet counts

should be done. Drugs may be with held if RBCs, WBCs or Platelet

counts below predetermined levels.

VI. Mitotic Inhibitors Plant Alkaloids and other compounds derived from naturalproducts that are CCS and block cell division at the M phase of the cell cycle.

A. Vinca Alkaloids Vinblastine (Velban),Vincristine (Oncovin) {Prototype},Vinorelbine ( Navelbine ) are obtained from periwinkle plant.

B. The Docetaxel- ( Taxotere), Paclitaxel (Taxol), were originally procured fromthe needles and bark of the Yew tree which only grows in the Pacific northwest;

d/t the scarcity of the natural resources semi-synthetic form of Paclitaxel was

developed Docetaxel ( Taxotere) .

1. Adverse Reactions include : leucopenia, allergic reactions, N/V , diarrhea,and phlebitis. The plant alkaloids damage peripheral nerve fibers and may

cause reversible and irreversible neurotoxicity (muscle strength, tingling,


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numbness of the fingers and toes (Think Stocking/glove syndrome). May

also cause loss of deep tendon reflexes, joint pain, and bone marrow

depression.

C. Vincristine (Oncovin){Prototype} Used to treat Wilms tumor in children.1. Pharmacokinetics Only given IV. Half life between 5 minutes and 85

hours. Primarily PB. Extensively metabolized by the liver.

2. Pharmacodynamics Used to treat leukemia, Hodgkins disease and non-Hodgkin Lymphoma , neuroblastoma , rhabdomyosarcoma, Ewings

sarcoma, Wilms tumor, multiple myeloma, chronic leukemia, thyroid cancer

and brain tumors.

3. Onset may be in minutes however therapeutic effect may take severaldays.

4. Side Effects and Adverse Reactions Severe drug interactions can occurwith Vincristine such as L- Asparaginase ( Elpar), digoxin ,Phenobarbital

(Sofoton), calcium channel blockers, mitomycin( mutamycin). Some sideeffects are sensory loss, hyperuricemia, severe local reactions with

extravasations. Monitor Bilirubin levels dose may be if level > 1.5mg.

Check bowel function Autonomic Neuropathy ileus.

5. Life threatening - Intestinal necrosis, seizures, coma, and acutebronchospasms.

g. Liposomal Chemotherapy Use of anticancer drugs packaged inside syntheticfat globules called liposomes. Fatty coating helps the drugs stay in the system

longer and the duration of therapeutic effects while decreasing the side effects (

alopecia, N/V, and cardiac toxicity) . Encapsulated forms are :

Doxorubicin (Doxil, Caelyx, Myocet), Daunorubicin (DaunoXome) andVincristine (ONCO- TCS, Marqibo).

I.Hormonal Agents Not considered true chemotherapy. There are several classes:Corticosteroids, hormones, antitestrogen, aromatase inhibitors, gonadrotropin-

release hormone analogues, and anti androgens.

A. Corticosteriods glucocorticoids, anti inflammatory agents that suppress theinflammatory process that occurs as a result of tumor growth. These agents

block the inflammatory receptors on the surface of cells. This blocking action

slows the growth of the tumor cells. Examples :

Prednisone ( Cordrol, Deltasone), Dexamethasone ( Cortastat, Dalalone), and

Hydrocortisone ( Hydrocortone, Solu- Cortef) can help to cerebral edema

caused by malignant brain tumor.

B. Side Effects and Adverse Reactions Fluid retention, potassium loss, risk forinfection, in blood sugar, in fat distribution, and bleeding tendencies.

C. Sex Hormones - Estrogen, Androgen used to slow growth of hormonedependent tumors (prostate & breast cancers).


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1. Estrogen- used as a palliative treatment for men with prostate cancer andwomen with hormonal responsive breast tumors to slow the growth of the

tumor down.

Examples: Diethlstibestrol (DES), EthinylEstradiol (Estinyl), Chlorotrianase

(TACE), and conjugated estrogen Premarin.

2. Progestrins may be used to treat breast, endometrial and renal cancers.There drugs hydroxyprogesterone acetate (Depro- Provera), Megestrol

Acetate ( Megace) , act by shrinking cancer tissures.

3. Side Effects and Adverse Reactions include fluid retention andthromboitic disorders.

4. Androgens given to treat advanced breast cancer in pre-menopausalwomen. Male hormone promotes regression of tumor if taken for prolong

period of time it leads to secondary sexual characteristics like growth of

body hair, lowering of voice, and muscle growth.

5.

Anti Estrogens- such as Tamoxifen (Nolvadex) & Fulvestrant (Faslodex)Are used to treat breast cancer tumors that are estrogen- receptor

positive(ER+). Tamoxifen has shown efficacy in preventing tumor

reoccurrence in both pre- & post menopausal women.

a .Side Effects hot flashes, irregular menses, fatigue, H/A, impotence, and

libdo.

Chapter 41 Cardiac Glycosides, Antianginals, and Antidysrythmics

I.Cardiac Glycosides They are a group of drugs that inhibit the sodium- potassiumpump, resulting in in intracellular Na Ca which causes cardiac muscle fibers

to contract more efficiently. Three effects on the heart muscle are :

1. Positive Inotropic action- ( on mycocardial contraction& stroke volume).2. Negative Chronotropic action- ( the heart rate)3. Negative Dromotrophic action- (conduction of the heart cell)The in myocardial contractility increases cardiac, peripheral and kidney

function by CO, preload, improving blood flow to the periphery and

kidneys, edema, and increasing fluid excretion.

II. Glycosides Used for the Treatment - Atrial Fibrillation and Atrial Flutter with rapid

Ventricular response with rates 200-300 beats/min. REMEMBER DIGOXIN DOESNOT CONVERT A- FIBRILLATION TO NORMAL SINUS RYTHYM

A. Drugs used for Treatment of Heart Failure-First drugs of choice is Inotropic medication like Dopamine and Dobutamin,

Phosphodiaesterase inhibitors like ( Inamrinone, & Milrinone -Primacor),


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Diuretics, Beta blockers, ACE inhibitors, Angiotension Receptor

Blockers(ARBs), Calcium Channel Blockers and Vasodilators.

1. Lab Values to consider to confirm diagnosis of Heart Failure in patientswith other Lung Pathophysiological disorder-

a. ANP- Atrial Natriuretic Hormone Peptide 20- 77 ng/l (An elevation mayconfirm Heart Failure. It is secreted from the atria of the heart and acts as an

antagonist to the renin and aldersterone. It is released during the expansion

to the atrium, produces vasodilation , and glomerular filtration rate.

b. BNP- Brain Natruiretic Peptide- Desired level < 100 pg/l. A positive resultis recorded as > 100 pg/l and aides in diagnosing Heart failure. It is a more

sensitive test than ANP . Today there is an emergency bedside test available

for measuring BNP.

B.

Other drugs used to treat Heart Failure- Digoxin (Lanoxin) {Prototype}-1. Pharmacokinetics - Absorption is 90-100% in the capsule form. The

protein bounding power for Digoxin is low(25%).

t = 30- 45hrs. (remember that because of the longer half life that the

drug accumulation should be monitored very carefully).

Excretion is 70% in the urine and 30 % by liver metabolism.

2. Pharmacodynamics used in treatment of heart failure. They myocardialcontraction and cardiac output and improves circulation through the Atrial

Ventricular node the heart rate .

Therapeutic Serum level 0.5 2.0 ng/ml

3. Digitalis Toxicity Signs & Symptoms Anorexia, diarrhea, N/V, H/A,Bradycardia, PVCs, blurred vision, (white & green halos), confusion, and

Delirium. Digitalis toxicity can lead to first degree hear t block then to 2nd

degree A V block and finally to a third or complete heart block. The antidote

for Digitalis Toxicity is (Ovine, Digibind) this agent binds with digoxin to

form complex molecules that can be excreted in the urine.

4. Herb Interactions Ginseng may falsely digoxin levels.St. Johnss wart- absorption of digoxin.

Psyllium (Metamucil) digoxin absorption

Hawthorn - may the effect of digoxin

Licorice- promotes K+ loss digoxin toxicity.


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III.Other Drugs used to Treat Heart Failure- Vasodilators, Angiotension ConvertingEnzyme Inhibitors, Angiotension II Receptor Antagonist Blockers, Diuretics,

Aldactone, & some Beta Aderenergic Blockers.

I.Vasodilators- venous blood return which decreases cardiac filling, ventricularstretching (pre-load) and O2 demand on the heart. Arteriolar dilators act in 3 ways

1. Reduce cardiac after load which cardiac output.2. Dilate the arterioles of the kidneys which improves renal profusion and fluid loss

3. prefusion to the skeletal muscleII.ACE inhibitors - usually prescribed for Heart failure to dilate venules and arterioles

improving renal blood flow(profusion) and blood fluid volume also moderately

Aldesterone which can K+ levels.

III.Angiotension II Receptor Blockers- Valsartan(Doivan) and Cardesartan(Atacand)

have been approved for Heart Failure for those clients whom cant tolerate ACE

inhibitors.

IV.Diuretics First line of drugs for Heart Failure when you are trying to fluid volume

used with Digoxin or other agents.

1. Spirolactone (Aldactone) K+ sparing , used for moderate to severe HeartFailure. It blocks the production of Aldesterone. (Normally with Heart Failure

the Aldesterone production goes up Na and Water retention K+ and

Magnesium loss ( both electrolytes are need for the hearts contracts.Usually dose is 12.5mg 25 mg/ day.

E. Beta Blockers usually contraindicated for clients with Heart Failure. Reducescontractility .

1. Carvedilol- (Coreg) and Metopropolol( Toprolol)- have been shown toimprove cardiac performance.

F. Nesiritide (Natrecor)- an atrial Natuiretic Peptide hormone that inhibits Anti-Diuretic hormone by Na loss (causes vasodilation, natriuresis, And diuresis.

G. Bi- Dilators combination of Hydralizine (which B/P) and Isosorbide dinatrate (a dilator to relieve heart pain) in 2005 FDA approved it for the treatment of Heart

Failure especially in African Americans(who are 2 times more likely to have Heart

Failure than are Caucasians.


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Chapter 41 Cardiovascular Anti Anginal Drugs cont.

I.Anti Anginal Drugs- Acute Cardiac pain caused by inadequate blood flow to themyocardium due to plaque, occlusion within or spasms of coronary arteries. There are

three types:

A. Stable (Classic) occurs with stress or exertion

B. Unstable (Pre-Infarction) occurs frequently over the course of a day with pro-severity.

C.Variant (Printz Metal or Vasospasic)- occurs during rest often wakes pt. from asleep.

II. Non- Pharmacological Measures- Avoid eating a heavy meals, smoking, extremes

in weather changes, strenuous exercise , emotional upsets, proper nutrition and rest,

moderate exercise.III. Pharmacological Agents- Anti- Anginals work one of 2 ways :

Either it O2 supply or by O2 demand by the myocardium. Three types of

medications are: 1. Nitrates 2. Bate- Blockers 3. Calcium Channel Blockers

A.Nitrates- major systemic effect is they venous tone, which workload of theheart and promotes vasodilatation. Beta Adrenergic & Calcium Channel Blockers

the workload of the heart by O2 demands. Nitrates and Calcium blockers are

helpful in the treatment of Variant Angina because they actively preload and

afterload both of which O2 demand.

1.Sublingual NTG 0.4 mg or 1/150 gr can be repeated every 5 minutes for a totalof 3 doses. Effect last for 10 minutes. Must be protected from light and heat.

2.Isosorbide Dinatrate ( Isordil Sorbtrate)-available sublingual, chewable tablets,immediate release tablets, and sustained released.

3.Nitroglycerine ( Nitrostat, Nitro-Bid, Transderm Nitro Patch, NitrogardSR){Prototype} used to control angina pectoris (angina pain).

a. Pharmacokinetics: Approximately 40-50% GI tract inactivated bythe liver.

SL > 75% absorbed rapidly directly into the internal Jugular Vein Right

Atrium.

Topical Transderm Nitro Patch- slow absorption by the skin acts on the smooth

muscle, blood vessel, causing relaxation & dilatation cardiac preload and after

load( Peripheral vascular resistance) myocardial O2 demand.


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Distribution Protein Bound 60%

Metabolism- t 1 4 minutes

Excreted Liver & in the urine

Pregnancy - C

b. Pharmacodynamics-SL- Onset- 1- 3 minutes, Peak- 4 min. Duration- 20-30 min

Slow Released Onset 20-45 min. Duration- 3-8 hrs.

Ointment - Onset 20 -60 min Peak 1-2 hrs. Duration 6-8hrs.

Patch - Onset 30- 60 min Peak 1-2 hrs. Duration20-24hrs.

I.V. - Onset 1-3 min. Duration 3-5 min.

c. Side Effects nausea, vomiting, H/A, dizziness, syncope, weakness,

flush, confusion, pallor, rash, dry mouth.

d. Adverse Reactions: Hypotension, reflex tachycardia, paradoxical

bradycardia.e. Drug-Lab-Food Interactions - effect with alcohol, beta-blockers,

calcium channel blockers, anti-hypertensives, effects of heparin.

B. Beta Adrenergic Blockers Beta I and Beta II the effects of the Sympathetic

nervous Systems by blocking catecholamines Epinepherine and Norepinepherine

which heart rate and blood pressure. Used as an anti-anginal, anti-dysrhythmic, and

antihypertensive. Patients should be told that they should NOT abruptly stop these

medications.

1. Beta1

- Atenolol ( Tenorium) - PO dose is 25-100 mg/d with max. dose of200mg/day. It can be used with asthmatic patients. Protein bound 5-15%

t = 6-7 hrs.

a) Metoprolol( Lopressor)- Beta1 50-100mg/ B.I.D. High dose can effectBeta2 Bronchoconstriction Protein Bound 12% t = 3-7 hrs.

2. Beta1 and Beta2 - used to treat Angina Pectoris and hypertension

a) Nadolol (Corgard) - PO 40 mg/day Protein B. 28% t = 10-24 hrs.b) Propanolol (Inderal) - PO initial dose 10-20 mg B.I.D. or T.I.D.

Maintenance 20-60 T.I.D. or Q.I.D. if using SR 80-160mg /dayRisk for Bronchospasms Protein B.- 90% t = 3-6 hrs.

C. Calium Channel Blockers - myocardial contractions O2 demand bymyocardial tissue. Relax coronary artery spasms and peripheral arterioles, cardiac

oxygen demand.

1. Amilodipine (Norvasc) PO initial dose 10 mg maintenance dose 2.5-10mg/day


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Preganancy- C Protein B. 95% , t = 30-50 hrs., Angina and Hypertension

1. Diltiazem ( Cardizem) - PO 30-60 mg Q.I.D. SR 60mg every 12 hrs.Used for treatment of Angina Pectoris, its hypotensive effect is not as severe as with

procardia. Kidney function should be monitored, Pregnancy = C Protein B. = 70-

85% t = 3.5- 9 hrs.

2. Nifedipine ( Procardia) - PO 10-30 mg every 6-8 hrs. max. dose = 180 mg/day. It isused for to treat angina pectoris and hypertension. Suppresses contraction of cardiac

and vascular smooth muscle. Increases heart rate and cardiac output. Decreases

blood pressure. Pregnancy = C Protein B. > 99% t = 7-12 hrs.

3. Three of the Calcium Channel Blockers are used for the long term treatment ofAngina Verapamil( Calan), Nifedipine (Procardia), and Diltiazem (Cardizem).

Procardia is the most potent.

4. Side Effects H/A, hypotension ( more common with procardia) and less commonwith Diltiazem.

D.

Antidysrhythmia - A dysrhythmia is any deviation from a normal rate or pattern of aheartbeat.

1. Dysrhythmia- disturbance of a heart rhythm.2. Arrhythmia- absence of a heart rhythm3. Aterial Dysrhythmia- prevents ventricular filling and.4. Arrhythmia- absence of a heart rhythm5. Aterial Dysrhythmia- prevents ventricular filling and cardiac output by 1/36. Ventricular Dysrhythmia- are life threatening because of ineffective filling of the

ventricle resulting in or absence of cardiac output.

7. Cardiac Dysrhythmias commonly occur after a M.I.(myocardial infarct) orhypoxia or hypercapnia (level of CO2 in the blood) , thyroid disease, C.A.D.,Cardiac Surgery, Excessive catecholamines, or electrolyte imbalances.

8. Action Potential-Remember when Na+ and Ca+ enter the mycocardial cells musclecontraction and depolarization occurs.

E. Anti-dysrhythmia drugs- there are four class of anti-arrhythmic drug which effect thedifferent phases of the action potential.

F. Class I: Sodium Chanel Blockers:1A Slow condition which prolongs Repolarization (Atrial and Ventricular such as

PAT- Paroxysmal Atrial Tachycardia and SVT Supra Ventricular

Tachycardia)

1B Slow conduction that shortens Repolarization(Acute Ventricular Dysrhythmias)

1C Prolong condition with little effect on Repolarization (Life threatening

Ventricular dysrhythmias).

G. Class II: Beta Blockers: Reduce Ca+ entry, conduction velocity ,automaticity andrecovery time (refractory period) Used to treat (Atrial flutter & Fibrillation,

tachydysrhythmias and Ventricular and Supraventricular dysryhthmias).


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H. Class III: Drugs that prolong Repolarization: Prolong repolarization duringventricular dysrhythmias, and prolong action potential duration. Used to treat (Life

threatening Atrial & Ventricular dysrhythmias resistant to other drugs).

I. Class IV: Calcium Channel Blockers: Block influx of Ca+, Slow conductionvelocity, myocardial contractility (Negative Inotropic), and refraction in the AV

node. Used to treat (Supraventricular tachdysrhythmias, prevention of Paroxysmal

supraventricular tachycardia PSVT).

J. Examples:1. Na+ Channel Blockers: Class IA

a. Napamide (Norpace) Adult dose PO: 100-200mg every 6 hrs. or if CR is usedthen PO 300mg every 12 hrs.

b. Procainamide (Procanbid or Pronestyl)- Adult PO 250-500mg q 3-4 hrs.,or if SR is used dose is 250mg 1 Gm. q 6 or q 12 hrs.

2. Na+ Class IB :a. Lidocaine (Xylocaine)- USE cautiously with patients who have Liver

Failure or an AV Block. Given I.V. Bolus dose:50-100mg over 2-3min.:

then Continuous infusion at dose 20-50mcg/kg/min.

b. Mexiletine (Mexitil)- Adult dose PO 200-400mg q 8hrs.c. Tocainide (Tonocard)- Adult loading dose is 600mg then 400mg q 8hrs. with

a maximum dose of 2.4 Gm/day.

3. Na+ Class IC :a. Flecainide (Tambor) Adult PO initial dose 50-100mg q 12hrs, then dose

by 50mg q 12hrs every 4 days; Maintenance dose of 150mg q 12hrs. Maximum

dose of 300mg/day.

b. Propafenone (Rythmol) Adult PO dose 150-300mg q 8hrs. Maximum doseis 900mg /day.

4. Class II Beta-Adrenergic Blockers- (more frequently used prescription fordysrhythmias than Na+ channel blockers.

A. Acetbutolol (Sectral)-Beta1 blocker -{Prototype} Adult dose PO 200mgB.I.D.

1. Pharmocokinetics- Well absorbed from the GI tract.Metabolized in Liver to active metabolites- 50-60% is eliminated in bilevia feces. 30-40 is excreted in urine. Pregnancy class is B. Protein

Bound: UK .

Metabolism: t : 3-4 hrs. Metabolites: 8-13 hrs.

2.Pharmocodynamics: Ventricular dysrhythmia: PO: Onset: 1 hr.

3.Peak: 4-6 hrs.

4.Duration: 10 hrs. For treatment of HTN duration = 20-24 hrs.


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5. Therapuetic : to help in treatment of recurrent stable ventriculardsyrhythmias.

6. Side Effects: Dizziness, H/A , B//P, diaphoresis, fatigue, constipation,contraindicated in 2 or 3

rddegree heart blocks, and severe bradycardia,

severe HF, or in cardiogenic shock.

7. Adverse Reactions: Palpitations with abrupt withdrawal . LifeThreatening: agranulocytosis, bronchospasm with high doses.

8. Teach patients that they should avoid alcohol, smoking and caffeine.B. Esmolol (Brevibloc Beta1)- Adult IV dose 500mg/kg over 1 min.

Maintenance dose is 50-100mcg/kg/min. Maximum dose of

200mcg/kg/min.

C. Propanolol ( Inderal Beta1&2 Blockers- Adult dose PO 10-30mg T.I.D. ,IV bolus 0.5-3mg at a rate of 1mg/min. Used for treatment of Ventricular

dysrhythmia, angina, and hypertension.D. Sotalol (Betapace) Beta1&2 Blockers {Prototype} - Adult PO 80 mg B.I.D.

with a Maximum dose of 240mg-320mg/day

1. Pharmocokinetics- Well absorbed from the GI tract.

2. Metabolized in Liver to active metabolites- 50-60% is eliminated in bile

via feces. 30-40 is excreted in urine. Pregnancy class is B.

5. Class III- Drugs that prolong Repolarization-a. Adenosine (Adenocard)-Adult IV initial dose is 6mg rapid bolus

May repeat the dose at 12 mg IV x 2 more doses.

b. Amiodarone (Cordarone) Adult loading dose is 400mg-1600mg/day.Be-aware of the photosensitivity it causes.

c. Bretylium Tosylate (Bretylol)- Adult IM 5-10mg/kg q 6-8hr. or IV 5-10 mg/kgmay repeat in 15-30 min, IV bolus or drip.

d. Sotalol (Betapace)- {Prototype} Adult POdose is same as Class II.6. Calcium Channel Blockers- Contraindicated in 2nd & 3rd degree heart blocks

a. Verapamil (Calan Isoptin)- Adult dose 240-480 mg/day in 3 to 4 divideddoses. IV 5- 10 mg IV push.

b. Diltiazem (Cardizem)- Adult IV 0.25mg/kg IV bolus over 2min. or 5-10mg/hrs in IV infusion.

7. Othera. Phenytoin (Dilantin)-Adult IV 100mg q 5-10 min until dysrhythmia ceases.

Maximum dose 1000mg. Used for digitalis induced dysrhythmia.

b. Digoxin (Lanoxin) -Adult IV loading dose 0.6-1mg/d in 24hrs.


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IV. Diuretics- Two main purposes A). Blood Pressure; & B). Edema

(peripheral/pulmonary). Diuretics work by inhibiting Na+ and H2O re-absorption

from the kidneys in the tubules thus promoting their loss through excretion in the

form of urine.

Renal Tubule Components- Proximal tubules, Loop of Henle descending and

ascending loops, and the collecting tubule. Every 1.5 hrs the total volume of the

bodys extracellular fluid goes through the kidneys glomeruli. Our glomeruli filter

electrolytes, drugs, glucose, and the waste products of protein metabolism. Large

particles such as protein & blood cells are not filtered from the blood & they remain

in the circulation. Na+ and H2O are the largest filtrate substances. Normally 99% of

Na+ is reabsorbed (50-55% is reabsorbed in the proximal tubules, 33-40% in the

Loop of Henle, 5-10% in the distal tubules and effect in causing

Natriuresis (Na+ loss in the urine). An example is Mannitol an osmotic Diuretic.

A.

Five Categories of Diuretics:1. * Thiazide and Thiazide like2. * Loop or high ceiling diuretics3. Osmotic4. Carbonic anhydrase inhibitor5. * Potassium sparing

(* Most frequently prescribed for HTN, edema associated with Heart failure)

6. Combination Diuretics- (Both K+ sparing and K+ wasting) used for the

treatment of HTN

Thiazide- Diuretics used primarily in patients with normal renal functions. If creatinine

clearance is < 3oml/min the effectiveness of thiazide is greatly decreased. Thiazide drugs cause

not only loss of Na+, K+, and magnesium they also cause calcium re-absorption, which may

lead to Hypercalcemia, another consideration that it cause glucose intolerance or possible

Hyperglycemia so it should be used with caution in patients with diabetes mellitus.1st drugs

used are in the Short Acting Chlorothaizide then Hydrochlorathiazide- HydroDIURIL,

HCTZ, Esidex, Oretic, Urozide{Prototype}- PO dose for HTN 12.5-50 mg/d

Edema PO dose: 25- 200mg in divided doses; maintenance dose 25-

100mg/day

Drug -Lab/Food Interactions: Drugs: digitalis toxicity with digitalis andhypokalemia; K+ loss with steroids; antidiabetic effect; thiazide effect

with cholestramine and colestipol.

Lab: serum calcium, glucose, uric acid, serum potassium, sodium &

magnesium.

A. Pharmacokinetics- Readily absorbed from the GI tract1. 65% Protein bound


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2. Metabolism: t = 6-15 hrs.3. Excretion in the urine

B. Pharmacodynamics- PO Onset : 2 hr1. Peak: 3-6 hrs2. Duration: 6- 12 hrs3. Therapeutic Effects: to urine output, to treat: HTN, edema from HF, hepatic

cirrhosis, renal dysfunction. Mode of action to Na+, K+, and H2O excretion and

preload and cardiac output.

4. Side Effects: dizziness, vertigo, weakness, N/V, diarrhea, hyperglycemia,constipation, rash, and photosensitivity.

5. Adverse Reaction: Severe dehydration, hypotension, severe hypokalemia,uremia, aplastic anemia, hemolytic anemia, thrombocytopenia, &

agranulocytosis.

2. Loop (High Ceiling) Diuretics: act in the thick ascending Loop of Henle to inhibit

chloride transport of Na+ into the circulation.They inhibit passive re-absorption of Na+which leads to loss of Na+ , water, K+, Ca+, Mg+ . They can also effect blood sugar

levels and uric acid levels. These groups of drugs are extremely potent causing a

marked electrolyte and water depletion. Less effective as anti hypertensive agents than

the Thiazides. They can renal blood flow up to 40%. Frequently prescribed when pt.s

creatinine clearance is < 30ml/min. & for end stage renal disease. This group of

diuretics cause Ca+ excretion where as the Thiazides inhibit Ca+ loss.

Example: Furosemide (Lasix) {Prototype} Both Lasix and Bumex are

sulfonamide derivatives for patients who are allergic to Sulfa (use Ethancrynic

Acid) Lasix should never be prescribed with another loop diuretic. It should beadministered in the AM when taken orally or administered IV when the clients

condition warrants immediate removal of body fluid.

a. Pharmacokinetics: PO readily absorbed from the GI tract. Adult PO dose 20-80mg in asingle dose/day may increase in 6-8 hrs. 20-40mg; maximum dose 600mg/day.

1.Distribution : Protein bound 95%

2.Metabolism: t = 30-50 min3.Excretion: In urine, some in feces: crosses the placenta. 4.Drug-Lab/Food Interactions : Drug- orthostatichypotension with alcohol; ototoxicity with aminoglycosides; bleeding with anticoagulants; K+ loss with steroids; digitalis toxicity with digoxin and hypokalemia; lithium toxicity;amphotericin B

ototoxicity and nephrotoxicity.

Lab: BUN, blood/urine glucose, serum uric acid, ammonia, potassium, sodium,

calcium, magnesium, & chloride serum levels.

b. Pharmacodynamics:1. Onset: < 60 min. PO IV Onset: 5 min


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2. Peak: 1-4 hrs. PO IV Peak: 20-30 min3. Duration: UK PO IV 2 hrs.

c.

Side Effects: dizziness, electrolyte imbalances, vertigo, cramping, rash, headache,weakness, ECG changes, blurred vision, photosensitivity.

d. Adverse Reactions: Severe dehydration; marked hypotension.e. Life threatening: Renal failure, thrombocytopenia, and agranulocytosis. Transient

deafness. Prolonged use could cause Thiamine deficiency.

f. Aloe K+ level especially when taken with K+ wasting diuretics and licorice can K+

loss.

3. Osmotic Diuretics: osmolality & Na+ re-absorption in proximal tubules and in Loop ofHenle. This group of drugs are used to prevent kidney failure, Intracranial pressure,

Intraocular pressure (glaucoma). Mannitol potent osmotic K+ wasting diuretic frequently used

in Emergency situations. It can also be used with Chemotherapy drugs Crisplatin andCaboplatin to induce diuresis( common side effect of these drugs fluid retention). Diuresis

with Mannitol occurs in 1-3 hrs. for IV route.

a. Side Effects: Fluid and Electrolyte Imbalances, pulmonary edema from rapid fluid shift,N/V, tachycardia, acidosis, crystallization of Mannitol may occur in the vial due to exposure

to lower temperatures. Vial may be warmed to dissolve the crystals. CRYSTALS MUST BE

DISOLVED BEFORE DRUG CAN BE GIVEN IV.

MUST BE GIVEN WITH EXTREME CAUTION in Patients with Heart Disease & Heart

Failure.

4. Carbonic Anhydrase Inhibitors: Acetazolamide, Dichlorphenamide, Ethoxzolamide,Methazolamide block the action of the enzyme carbonic anhydrase (needed to maintain

acid/base). Inhibition of this enzyme causes Na+, K+, HCO3 excretion. These groups of

drugs are used to intraocular pressure in patients with open angle (chronic) glaucoma. Other

uses are for diuresis, treatment of Epilepsy, and treatment of high altitude or acute mountain

sickness.

a. Side Effects: Acetazolamide can cause fluid and electrolyte imbalance, metabolicacidosis, N/V, anorexia, confusion, orthostatic hypotension, hemolytic anemia,& renal

calculi.

5. Potassium Sparing Diuretics: Weaker drugs than the Thiazides and Loop Diuretics( dailyK+ supplements are not used when patients is taking K+ sparing diuretics).Monitor : K+ levels if > 5.3 Meq/L while on these drugs, stop drugs and restrict diet of foods

K+. Area of action is in the collecting ducts and distal tubules to promote Na+ and H2O

excretion and K+ retention.

a. Spironolactone ( Aldactone)- An Aldosterone antagonist. First K+ sparing diuretic.Remember Aldosterone is a mineralocorticoid secreted by Adrenal Cortex. Other

examples are : Amiloride(Midamor), Triamterene(Dyrenium){Prototype},


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Eplerenone(Inspra). They are used in treatment of edema caused by HF or cirrhosis of the

liver.None of the K+ sparing drugs should be taken with ACE inhibitors & Angio II

Recptor Blockers (ARBs) because they also can K+ levels. The commons combinations

of diuretics contain Spironolactone & Hydrochlorothiazide (Aldactazide), Amiloide and

HCTZ( Moduretic), and Triamterene & HCTZ (Dyazide & Maxzide).

b. Side Effects- K+ especially with patient with poor renal function. Urine output shouldbe @ least 600ml/day. GI disturbances like N/V, diarrhea, numbness & tingling of hands

and feet.

6. Triameterene ( Dyrenium)- Adult dose for edema 100mg/day in 2 divided doses p.c., not toexceed300mg/day. Contraindications severe kidney or hepatic disease severe K+.

Use with Caution : In patients with renal ,hepatic dysfunction and those who have diabetes

mellitus.

a. Pharmacokinetics: PO rapidly absorbed from GI tract1. Distribution : 67 % Protein Bound2.

Metabolism: t = 1.5 2.5 hrs

3. Excretion: in urine; mostly as metabolites and bileb. Pharmacodynamics: PO Onset : 2-4 hr

1. Peak: 6-8 hrs2. Duration: 12-16 hrs

c. Drug-Lab/Food Interactions: Drug- Serum K+ level with K+ supplements; effectsof antihypertensive and lithium; Life threatening: Hyperkalemia if given with ACE

inhibitor. Lab- Increase serum K+ level; may BUN, AST, alkaline phosphatase levels;

serum sodium chloride.

d. Side Effects: N/V, diarrhea, rash, dizziness, H/A, weakness, dry mouth, photosensitivity. e. Adverse reactions: - Life threatening severity hyperkalemia, thrombocytopenia,

megaloblastic anemia. Monitor signs and symptoms of K+ - peaked T wave,

Bradycardia, oliguria. Teach patient to avoid exposure to direct sunlight.

Chapter 43 Anti-Hypertensives

I. Hypertension is defined as an increase in systolic B/P > 140 and the diastolic > 90 mmHg.

Essential HTN: affecting 90 % of persons with HTN exact origin of essential HTN is unknown.

A. Contributing Factors- Family Hx of HTN

Hyperlipidemia

African American background-

Diabetes

Obesity

Aging

Stress

Excessive smoking and alcohol


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II.Secondary HTN- it is the other 10% of HTN cases are related to Renal & Endocrine disorders Kindeys regulate the Reni- Angiotension I to Angiotension II-(causes release of Aldosterone

from the Adrenal glands). Baro-receptors in the Aorta and Carotid Sinus and the vasomotor in

center of the medulla assist in regulating B/P.

Catecholamines Norepinepherine released from sympathetic nerve terminals and Epinepherine

released from the Adrenal Medulla B/P through vasoconstriction activity on the blood vessels.

Anti- Diuretic Hormone (produced by hypothalamus by stored and ANP (atrial naturetic peptide

and Brain Naturetic Peptide) released by the posterior pituitary gland.

III. Non- Pharmacologic Control for HTN : If systolic is > 140 anti hypertension drugs aregenerally necessary.

A. Stress reduction techniquesB. ExerciseC. Salt restrictionD. Alcohol ingestionE.

Weight reduction

IV. Most Clients may need two or more Anti - hypertensive drugs to achieve a goal Blood

pressure reading:

1. Six Categories of drugs to treat HTN:1. Diuretics- ** see chapter 412. Sympatholytics-(Beta Adrenergic Blockers)3. Direct- acting Arteriolar Vasodilators-4. Angiotension Convert Enzyme inhibitors-5. Angiotension II receptor Blockers6. Calcium Channel Blockers

2. Beta Adrenergic Blocker : Beta ( 1 & 2) Adrenergic Blockers reduce cardiac output bydiminishing the sympathetic nervous system response to basal sympathetic tone. They

reduce heart rate, contractility, and Renin release. African Americans with HTN do NOT

respond as well to Beta blockers for HTN control so they are given beta blockers combined

with diuretics.

1. Metroprolol (Lopressor, Toprol SR)- Beta1 {Prototype}-PO Adult dose for HTN 50-100mg/d in 1-2 divided doses Maintenance dose is 450mg/day

in divided doses. Elderly- PO 25mg/day Maintenance dose of 25-300mg/day

Myocardial Infarction- PO: 100mg B.I.D. IV: 5mg q 2 min X 3 doses.

Drug- Lab/Food Interactions: Drug- bradycardia with digitalis: Hypotensive effect with

other anti-hypertensive, alcohol, anesthetics.

a. Pharmacokinetics :1. Absorption: PO 95%


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2. Distribution: Protein Bound is 12%

3. Metabolism: t1/2= 3-7 hrs.

4. Excretion : in urine

b. Pharmacodynamics: PO : Onset 15 min IV Onset: ImmediatePeak: 1.5 hrs IV Peak : 20 min

Duration: 10-19 hrs. IV Duration: 5-10 hrs.

c. Side Effects: Fatigue, weakness, dizziness, nausea, vomiting, diarrhea, mentalchanges, nasal stuffiness, impotence, libido, depression.

d. Adverse Reaction: Bradycardia, thrombocytopeniae. Life Threatening: Complete heart block, bronchospasm, and agranulocytosis.

1.

Cardioselective Beta-blockers- are preferred Beta Blockers because they act mainly onthe cardiac Beta1 receptors rather than Beta2 so bronchoconstriction is less likely to occur.

Medications in this group are: Acebutolol ( Sectral), Atenolol ( Tenormin), Betaxolol(

Kerlone), Bisoprolol (Zebeta).

2. Centrally Acting Alpha2- Centrally acting alpha2 agonists the sympathetic responsefrom the brainstem to the peripheral vessels. By stimulating the alpha2 receptors which in

turn sympathetic activity: vagus activity, cardiac output and serum epinephrine,

norepinepherine, & renin release. All actions result in reducing peripheral vascular

resistance and vasodilation. This group of drugs has minimal effect on cardiac output

and kidney perfusion. Beta Blockers are NOT given with centrally acting

sympatholytics, because of bradycardia during therapy and rebound hypertension ondiscontinuing therapy that can occur. Example: Of these types of drugs is Methyldopa

(Aldomet). In higher doses Methyldopa & clonidine can cause water retention therefore

they should be used with a diuretic. Potential side effects: drowsiness, dry mouth,

dizziness, and slow heart rate(bradycardia). Methyldopa should NOT be used in clients

with impaired liver functions & serum liver enzymes should be monitored periodically.

These drugs must not be stopped abruptly d/t rebound hypertensive crisis.

3. Alpha-Adrenergic Blockers: - These drugs block the alpha receptor sites resulting invasodilation B/P. Useful in treat of HTN in patients with Hyperlipidemia. They the

very low density lipoproteins (VLDL) and the low density lipoproteins (LDL) which

cause plaque buildup leads to artherosclerosis, they also build up the good lipoproteins

High density ones (HDL). They are also good for diabetic patients because they do not

effect Glucose metabolism.

4. Examples of Alpha Adrenergic Blockers: Prazosin (Minipres) {Prototype}, Terazosin(Hytrin), Doxazosin( Cardura) are mainly used for HTN but can also be used for treatment

of Benign Prostatic Hypertrophy. Terazosin & Doxazosin have longer half lives so they


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usually are given once/day. They do cause NA+ & water retention therefore a diuretic is

also given concomitantly to fluid accumulation.

More potent medications like Phenoxybenzamine and Tolazoline are used to treat HTN

Crisis & vere HTN resulting from catecholamine secreting tumors of the adrenal medulla

like (phenochromocytomas).

A. Prazosin HCL (Minipres) Alpha Adrenergic Blocker PO Adult dose 1mg B.I.D. orT.I.D. With a maintenance dose of 3-15mg/day. Drug- lab/ Food Interactions:

Hypotension effect with other anti-hypertensives, nitrates and alcohol.

a. Pharmacokinetics : Absorption in G.I. 60%, 5% in circulation1. Distribution: Protein Bond 95%2. Metabolism: 3 Hours3. Excretion: in bile & Feces 10% in urine.4. Mode of Action: Dilation of peripheral blood vessels via blocking Alpha

Adrenergic receptors.2. Pharmacodynamics: P.O. Onset o.5 2 hrs. Peak: 2-4 hrs. Duration: 10 hrs.

a. Adverse Reactions: Orthostatic Hypotension, palpitations, Tachycardia,pancreatitis

b. Side Effects: Drowsiness, H/A, N/V, diarrhea, impotence, vertigo, urinaryfrequency, tinnitus.

c. Drug Interactions:when Alpha Adrenergics Blockers are taken with Anti-inflammatory drugs and nitrates Fluid Retention peripheral edema

Nitrates - Lower B/P as do Alpha-Adrenergic which leads to syncope/fainting.

II. Adrenergic Neuron Blockers are potent antihypertensive drugs that block NorepinepherineRelease from the Sympathetic nerve endings, causing a decrease in B/P, & decrease in

Cardiac output & in peripheral vascular resistance.

A.Reserpine, Guanethidine, Guanadrel (are 3 very potent drugs) that are used to treat severeHTN. Adrenergic Neuron Blockers are the LAST drugs considered for treatment of HTN

because of the orthostatic hypotension.

Reserpine can cause nightmares and suicidal tendencies.

III. Alpha1, Beta1, Adrenergic Blockers : Labetalol( Normodyne) & Carteolol(Cartrol) areexamples of Alpha/Beta blockers. When the Alpha1 receptor sites are blocked it causes

Vasodilation. , which decreases the resistance of the blood flow. The blocking of effect on

the Alpha receptor site is stronger than that on the Beta receptor therefore B/P is lowered

and pulse rate is moderately decreased.

A.Common side Effects: Orthostatic Hypotension, GIdistrubances, nervousness, drymouth, fatigue.

*** Large doses of Labetalol may cause Atrial Ventricular Heart Block. (Property of

Beta blockers that slows Atrial Ventricular conduction which in turn slows heart rate).


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IV. Direct Acting Arteriolar Vasodilators: This group of drugs act by relaxing the smoothmuscle of mainly the arterioles. Vasodilatation leads to blood flow to the Brain and

kidneys, with a decrease in B/P Na and water are retained leading to edema. This is why a

diuretic would be given with these drugs. Examples would be Hydralazine and Minoxidilboth can be used to treat mild to moderate HTN. Also because of the vasodilatation that

these drugs cause Reflex Tachycardia and Renin is released. Beta Blockers are frequently

prescribed with D.A.A. V. to decrease the Heart rate (counter act the Reflex Tachycardia).

A. Nitroprusside & Diazoxide : These are 2 very potent vasodilators used for acuteHTN emergency. Nitroprusside acts on both arterial & venous blood vessels, whereas

Diazoxide acts on only arteries. Common side effects: Hydralazine side effects are

tachycardia, palpitations, edema, nasal congestion, H/A, dizziness, bleeding, and

Lupus like symptoms.

Minoxidil & Diazoxide : Refex Tachycardia, palpitation, restlessness, agitation,

nausea, and confusion.

Diazoxide: hyperglycemia due to its action of inhibiting release of insulin from the

Pancreatic Beta cells.

V. Angiotension Converting Enzyme Inhibitors: They inhibit the formation of Angiotension IIand blocks the release of Aldesterone. When aldesterone is blocked Na and water are not

retained but are excerted. K + is retained. ACE inhibitors cause little change in Cardiac

Output or HR but do peripheral vascular resistance. These drugs can be used in patients

with renin levels. They are primarily used to treat HTN , some are effective in treatment of

Heart Failure. There are 10 drugs in this category:

1.

First one discovered in 1970s is Captopril (Capoten) 7. Moexipril(Univasc)2. Benzepril (Lotension) 8. Perindopril (Aceon)3. Enalapril (Vasotec) 9. Fosinopril (Monopril)4. Ramipril(Altace) 10. Quinapril (Accupril)5. Trandolapril(Mavik)6. Lisinopril(Prinavil Zestril)

These drugs can be used as the first line Anti Hypertensive agents but the use of Thiazide

diuretics are also recommended.

****** African Americans and Older Adults DO NOT RESPOND TO ACE inhibitors until

diuretics are added. SHOULD NOT PRESCRIPED/ADMINISTERED DURINGPREGNANCY (D/T the effect they have of reducing Placental blood flow).

A. Side Effects: Constant irritating cough; Nausea/Vomiting, diarrhea, H/A, dizziness,fatigue, insomnia, Hyperkalemia, and tachycardia.

B. Contraindications: Should not be administered while pregnant will cause fetal harmd/t decrease placental blood flow. Should not be taken with K+ sparing diuretics or salt

substitutes (those that use K instead of Na).


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VI. Angiotension II Receptor Blockers (ARBs): They are similar to the ACE drugs exceptARBs block Angiotension II from Angiotension receptors found in many tissues. ARBs

cause vasodilatation and peripheral resistance. They do not cause the constant irritating

cough. ARBs should not be taken during pregnancy either.

A. Examples: Losartan (Cozaar), Valsartan (Diovan) Irbesartan (Atacand), OlmesaranMedoxomil (Benecar)- these agents block the vasoconstrictor effects of Angiotension II

at the receptor sites. ARBs can be used as a first line Treatment for HTN.

B. Pharmacokinestics: Cozaar is used primarily to manage HTN and to form activemetabolites.

1. Distribution: They are Highly Protein Bond

2. Metabolism: t - 1.2- 2 hours & metabolite half life is 6- 9 hrs.

3. Excretion: In the Urine and Feces

C.

Pharmacodynamics: Losartan (Cozaar) is a potent vasodilator which blocks the binding ofAngiotension II to the Angiotension receptors found in many tissues. PATIENTS WITH

MILD HEPATIC INSUFFICENCY CAN TAKE THESE DRUGS. The Peak time is 6

hrs., Duration is 24 hrs. THEY ARE LESS EFFECTIVE IN AFRICAN AMERICAN and

may cause Angioedema

VII. Direct Renin Inhibitors: Aliskiren ( Tekturna) 1st FDA approved Renin inhibitor.Aliskiren binds with Renin causing a in Angiotension, Angiotension II and Aldesterone

levels. Effective for the treatment of mild to moderate HTN. Can be used alone or with

another antihypertensive agent. Has an added effect in B/P when combined with Thiazide

diuretics or ARBs.

A. Prototype: Losartan ( Cozaar) Angiotension II receptor Blockers . Pregnancy C ( FirstTrimester), D (2nd or 3rd Trimester can use Hyzaar). PO: For HTN- 25- 50 mg/day in single

or divided doses. Maxium dose is 100mg/ day.

Contraindicated: During Pregnancy and while Breastfeeding

Caution: Renal & Hepatic Impairment.

B. Pharmacokinestic:1. Absorption: Rapidly absorbed in blood in 25-30 minutes.2. Distribution: Protein bond 90-95%3. Metabolism: t 1.2- 2 hrs. metabolites in 6-9hrs.4. Excretion: 35% in the urine.5. Side Effects: Dizziness, diarrhea, insomnia, & occ. Cough6. Drug & Lab Interactions: Phenobarbital effect of Cozaar & its metabolites

May increase ALT, AST, ALP ,Bilirubin , Creatinine , Hbg. and Hct.

7. Adverse: Upper Respiratory Infections.C. Pharmacodynamic: Onset: < 1 hr. Peak : 6 hrs. Duration: 24 hrs.


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D. Calicum Channel Blockers: These are a group of drugs that are slow channels found only inmyocardium & vascular smooth muscle. Free Ca+ muscle contractility, peripheral

resistance, & B/P. Ca+ channel blockers also called Calcium anti-agonist promote

vasodilation. Large central arteries are not as sensitive to Ca+

as the coronary, Cerebral and

peripheral arteries are. They are highly protein bond but have a short half- life. 3 groups of

Ca+ blockers. Calcium Channel Blockers lower B/P better in African Americans than

drugs in other categories.

1. Verapamil (Calan): is used for treatment of chronic HTN, angina pectoris & cardiacdysrhythmias. Verapamil and Diltiazem act on the arterioles & the heart. Nifedopine is

used to prevent ischemic brain injury due to vasospasm that often accompanies

subarachnoid hemorrhage. Also used as treatment of choice in Variant angina (Prentz

Metal ) also thought to be caused by vasospasm of the coronary arteries.

2. Nifedipine (Procardia): Decreases B/P in older adults & in those with low serum Reninvalues. In the immediate released capsules (10-20mg) it has been associated with

increased incident of sudden Cardiac Death especially when prescribed for outpatient athigh doses d/t the fact that Ca+ channel blockers cause reflex tachycardia. This tachycardia

is more prevalent with Procardia.

3. Prototype: Amlodipine(Norvasc) : It is used to treat mild to mod. HTN, and AnginaPectoris.

Mode of action: Decreases peripheral vascular resistance (vasodilation), promoting in

B/P. PO 5- 10mg/day or for Elderly 2.5- 5mg/day.

Lotrel is a combination of Amlodipine with Benzepril.

Contra-Indications: Severe hypotension.

Cautious Use: Liver Disease, Heart Failure, Aortic Stenosis, pregnancy & lactation.Drug- Lab Interactions: Drugs bradycardia with Adenosine Labs: May Amlodipine

with Grapefruit juice.

1. Pharmacokinetics:

a. Absorption: > 90% is absorbed; gradually absorbed from the G.I. tract.

b. Distribution: Highly Protein Bond > 95%

c. Metabolism: t 30- 50 hrs. Elderly: t : 50- 100 hrs.

d. Excretion: in urine & feces as inactive metabolites.

2. Pharmacodynamics: Onset is gradual Peak: 6-9 hrs. Duration 24 hrs. Usually

only prescribed once a day.

4. Side Effects : Peripheral edema may occur because of its vasodilator effect, flushing,dizziness and nausea.

5. Adverse: Reflex Tachycardia


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Chapter 44 Anti-Coagulants/Anti- Platelets & Thrombolytics

Thrombosis - Formation of a clot in an arterial or venous vessel.

Arterial clots could be caused by stasis of blood, platelet aggregation (clumping) on vessel

wall. They are usually made up of white & red clots.

White clots: - (Platelets) initiating the process followed by fibrin formation trapping red

blood cells into fibrin. Blood clots of the veins are from platelet aggregation with fibrin that

attaches to red blood cells. Both kinds of thrombosis formation can become dislodged from

the wall of the vessel and lead to embolus.

Platelets dont usually stick together unless there is a break in the endothelial lining of the

blood vessel. When platelets do stick to the lining they synthesize Thromboxane A2 (product

of prostaglandins and protein synthesis). Platelet receptor protein glycoprotein IIb & IIIa.

Thromboxane A2, and adenosine diphosphate (ADP) the activation of this receptor. As

thrombus inhibits blood flow, fibrin, platelets and red blood cells surround the clot building

the clots size and structure. As clots occludes the vessel, tissue ischemia occurs. Thevenous thrombus usually develops because of slow blood flow. Venous clots can occur

rapidly.

Heparin & Warfrin: Act primarily to prevent venous thrombosis whereas Anti-platelet

drugs act to prevent ARTERIAL thrombosis. Both groups of drugs suppress thrombosis in

general.

I. Anticoagulants: Used to inhibit clot formation. They DO NOT dissolve clots likeThrombolytics. They are used in clients with venous & arterial vessel disorders that put

them at high risk for clot formation. They can be administered Orally, Intravenously, or

Subcutaneous.

Venous-deep vein thrombosis, Pulmonary EmboliArterial Coronary artery thrombosis (MI) presence of artificial valves, CVA/Strokes

A. Heparin: Introduced in 1938, it is a natural substance found in the liver. It was used with blood transfusions to prevent clotting. Is indicated for a rapid anti-coagulant effect

when thrombus occurs d/t DVT, Pulmonary Emboli, or an evolving stroke and for open

heart surgery to prevent blood from clotting & in Disseminated Intravascular

Coagulopathy. Heparin works with anti-thrombin III to inactivate Xa thus preventing

thrombus formation. Poorly absorbed through the GI tract and much is destroyed by

Heparinase (a Liver enzyme). IV bolus and or IV fluid for continuous drip Heparin

prolongs clotting time.

Heparin affects Partial Thromboplastin Time - (PTT). Heparin can platelet count

causing Thrombocytopenia.

ANTIDOTE: PROTAMINE SULFATE.

B.Low Molecular Weight Heparin( LMWH) - Lowers the risk for DVT, PulmonaryEmboli after abdominal or orthopedic surgeries. Commonly used to prevent Pulmonary


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Emboli. LMWHs produce more stable responses at recommended doses, therefore frequent

monitoring of PTT is not required. LMWH inactivates factor Xa , but it is less able to

inactivate thrombin like Heparin is able to.

1.4 Types of LMWH are: All can be given subcutaneously and do not requiremonitoring of aPTT. Treatment is injection in the abdomen for 7-14 days. It is

usually started in the hospital 24 hrs. post-operatively. The half life of LMWH are

2 to 4 times longer than that of heparin. Instruct clients not to take aspirin or other

anti-platelet drugs while on LMWH. Bleeding with these drugs is less likely to

occur than with Heparin. If bleeding dose occur Protamine Sulfate is the anti-

dote.(dose would be 1mg of Protamine S. for every 1mg of LMWH given.)

Contra-Indications: Pt. whom have had a stroke, peptic ulcers, or other blood

anomolies

a. Enoxaparin Sodium: (Lovenox)b. Dalteparin Sodium: (Fragmin)c.

Danapar

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Pharmacology II Outline