Drugs Acting On The

Cardiovascular &
Renal system
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Group D
Welcome To Our Presentation

ANDRAD CARILLO, DAMEY, DE LLANETA, PINKIYEN, SALANG- TIMBREZ WASHIN

A, JETT JEDREK JACKIELO CASTRO, DUSTIN YVONNE OY, A, GTON,
U FIONA KURK MAE ZAINE LOVELYN LUIS JR.
[as]
Topic 1 DRUGS AFFECTING BLOOD COAGULATION

Blood coagulation
- Complex process that involves
vasoconstriction, platelet clumping or
aggregation, and a cascade of clotting
factors produced in the liver that
eventually react to break down fibrinogen
(a protein also produced in the liver) into
insoluble fibrin threads.
- When a clot is formed, plasmin (another
blood protein) acts to break it down.

- Blood coagulation can be affected at any

step in this complicated process to alter
the way that blood clotting occurs.
 Definition of terms

01. Vasoconstriction

02. Platelet Aggregation

03. Intrinsic Pathway

04. Extrinsic Pathway

1. Vasoconstriction
• Narrowing (constriction) of blood vessels by small muscles
in their walls
• The first reaction to a blood vessel injury
• If the injury to the blood vessel is very small, this
vasoconstriction can seal off any break and allow the area
to heal

2. Platelet Aggregation
• Injury to a blood vessel exposes blood to the collagen and other substances under the
endothelial lining of the vessel. This exposure causes platelets in the circulating blood to stick
or adhere to the site of the injury.
• Adenosine Diphosphate (ADP)is also a precursor of the prostaglandins, from which
thromboxane A2 is formed.
• Thromboxane A2causes local vasoconstriction and further platelet aggregation and adhesion.
This series of events forms a platelet plug at the site of the vessel injury. In many injuries, the
combination of vasoconstriction and platelet aggregation is enough to seal off the injury and
keep the cardiovascular system intact
•
03. Intrinsic Pathway

• As blood meets the exposed collagen of the injured blood vessel, one of the
clotting factors, Hageman factor (also called factor XII), a chemical substance
that is found circulating in the blood, is activated.
• The activation of Hageman factor starts several reactions in the area: The clot
formation process is activated, the clot-dissolving process is activated, and the
inflammatory response is started.
• The activation of Hageman factor first activates clotting factor XI (plasma
thromboplastin antecedent) and then activates a cascading series of coagulant
substances called the intrinsic pathway that ends with the conversion of
prothrombin to thrombin.
• Activated thrombin breaks down fibrinogen to form insoluble fibrin threads, which
form a clot inside the blood vessel. The clot, called a thrombus, acts to plug the
injury and seal the system.
04. Extrinsic Pathway

• While the coagulation process is going on inside the blood vessel

via the intrinsic pathway, the blood that has leaked out of the
vascular system and into the surrounding tissues is caused to clot
by the extrinsic pathway.
• Injured cells release a substance called tissue thromboplastin,
which activates clotting factors in the blood and starts the clotting
cascade to form a clot on the outside of the blood vessel.
• The injured vessel is now vasoconstricted and has a platelet plug,
as well as a clot on both the inside and the outside of the blood
vessel in the area of the injury. These actions maintain the closed
nature of the cardiovascular system.
Topic 1 Drugs Affecting Clot Formation and Resolution

01.ANTIPLATELET AGENTS

02. ANTICOAGULANTS

03.THROMBOLYTIC AGENTS
 ANTIPLATELET AGENTS
• It decreases the formation of the platelet plug by decreasing the responsiveness of
the platelets to stimuli that would cause them to stick and aggregate on a vessel wall.
Drug Name Dosage Usual Indication
Generic Name: 0.25 mg/kg intravenous (IV) bolus 10–60 min before Prevention of acute cardiac events during
abciximab procedure, then continuous infusion of 10 mcg/kg/min for 12 transluminal coronary angioplasty when used in
Brand Name: h conjunction with heparin and aspirin; early
(ReoPro) Angina: 0.25 mg/kg by IV bolus, then 10 mcg/kg/min IV for treatment of unstable angina and non–Q-wave
18–24 h myocardial infarction (MI)

Generic Name: 0.5 mg PO q.i.d. or 1 mg PO b.i.d., may increase by 0.5 mg/d Treatment of essential thrombocythemia to
anagrelide each week; maximum dose 10 mg/d or 2.5 mg as a single reduce elevated platelet count and decrease the
Brand Name: dose risk of thrombosis
(Agrylin)

aspirin 1,300 mg/d PO to decrease transient ischemic attacks (TIAs); Reduction of the incidence of TIAs and strokes in
(generic) 300–325 mg/d PO to reduce MI risk men; reduction of the risk of death or nonfatal
MI in patients with a past history of MI or with
angina

cilostazol (Pletal) 100 mg PO b.i.d. Reduction of symptoms of intermittent

claudication, allowing increased walking distance
in adults
clopidogrel (Plavix) 75 mg/d PO Treatment of patients who are at risk for ischemic
events; patients with a history of MI, peripheral
artery disease, or ischemic stroke; and patients
with acute coronary syndrome

dipyridamole (Persantine) 50 mg PO t.i.d. for angina; 75–100 mg PO q.i.d. for heart valve Prevention of thromboembolism in patients with
patients; 0.142 mg/kg/min IV over 4 min for diagnosis artifi cial heart valves when used in combination with
warfarin; aids diagnosis of coronary artery disease
(CAD) in patients who cannot exercise; may be used
in treatment of angina (found to be only “possibly
effective” by the U.S. Food and Drug Administration)

eptifibatide (Integrilin) 180 mcg/kg IV over 1–2 min, then 2 mcg/kg/min IV for up to 72 h Treatment of acute coronary syndrome; prevention
for acute coronary syndrome; 135 mcg/kg IV bolus before of ischemic episodes in patients undergoing
procedure, then 0.5 mcg/kg/min IV for 20–24 h percutaneous coronary interventions

ticagrelor (Brilinta) 180 mg PO loading dose then 90 mg PO bid with daily aspirin To reduce the rate of thrombotic coronary collateral
0.325 mg loading dose, then 75–100 mg/d vessels events in patients with acute coronary
syndrome
ticlopidine (Ticlid) 250 mg PO b.i.d. Reduction of the risk of thrombotic stroke in patients
with TIAs or history of stroke who are intolerant to
aspirin therapy

tirofiban (Aggrastat) 0.4 mcg/kg/min IV over 30 min, then continuous infusion of 0.1 Treatment of acute coronary syndrome and
mcg/kg/min prevention of cardiac ischemic events during
percutaneous coronary intervention; used in
combination with heparin
Therapeutic Actions and Indications
• It inhibits platelet adhesion and aggregation by blocking receptor sites on the platelet
membrane, preventing platelet–platelet interaction or the interaction of platelets with
other clotting chemicals.

Pharmacokinetics
• Abciximab, eptifibatide, and tirofiban are administered intravenously (IV).
• Antiplatelet agents that are administered orally include anagrelide, aspirin, cilostazol,
clopidogrel, ticagrelor, and ticlopidine.
• Dipyridamole is used orally or as an IV agent.
• These drugs are generally well absorbed and highly bound to plasma proteins. They
are metabolized in the liver and excreted in urine, and they tend to enter breast milk.
Contraindications and Cautions
• Contraindicated in the presence of allergy to the specific drug to avoid hypersensitivity
reactions.
• Caution should be used in the following conditions:
 Bleeding disorder because of the risk of excessive blood loss;
 Recent surgery because of the risk of increased bleeding in unhealed vessels;
 Closed head injuries because of the risk of bleeding from the injured vessels in the brain.
• Contraindicated with pregnancy because of the potential for increased bleeding: they should
be used during pregnancy only if the benefits to the mother clearly outweigh the potential
risks to the fetus.
• Contraindicated during lactation because of the potential adverse effects on the fetus or
neonate; if they are needed by a breast-feeding mother, she should find another method of
feeding the baby.
Contraindications and Cautions
• Contraindicated in the presence of allergy to the specific drug to avoid hypersensitivity
reactions.
• Caution should be used in the following conditions:
 Bleeding disorder because of the risk of excessive blood loss;
 Recent surgery because of the risk of increased bleeding in unhealed vessels;
 Closed head injuries because of the risk of bleeding from the injured vessels in the brain.
• Contraindicated with pregnancy because of the potential for increased bleeding: they should
be used during pregnancy only if the benefits to the mother clearly outweigh the potential
risks to the fetus.
• Contraindicated during lactation because of the potential adverse effects on the fetus or
neonate; if they are needed by a breast-feeding mother, she should find another method of
feeding the baby.
Adverse Effects
• The most common adverse effect seen with these drugs is bleeding, which often occurs
as increased bruising and bleeding while brushing the teeth.
• Other common problems include headache, dizziness, and weakness;
• Nausea and gastrointestinal (GI) distress may occur because of direct irritating effects
of the oral drug on the GI tract.
• Skin rash, may be related to direct drug effects on the dermis
• Bone Marrow Suppression
ANTICOAGULANTS
• are drugs that interfere with the normal coagulation process by interfering with the
clotting cascade and thrombin formation.
Drugs Name: Usual Dosage: Usual Indication
Antithrombin Dose must be calculated using body weight and Replacement in hereditary antithrombin III deficiency;
(Thrombate III ) baseline levels, given every 2–8 d treatment of patients with this deficiency who are to
undergo surgery or obstetrical procedures that might put
them at risk for thromboembolism
Argatroban 2 mcg/kg/min IV until the desired effect is seen; Treatment of thrombosis in heparin-induced
(Acova) then dose is adjusted thrombocythemia
Bivalirudin 1 mg/kg IV bolus, then 2.5 mg/kg/h IV for 4 h Prevention of ischemic events in patients undergoing
(Angiomax) and 0.2 mg/kg/h IV as a low-dose infusion transluminal coronary angioplasty when used in
combination with aspirin
Dabigatran 150 mg PO b.i.d. Reduction in the risk of stroke and systemic embolism in
(Pradaxa) patients with nonvalvular atrial fibrillation
Desirudin 15 mg by subcutaneous injection q12h Prevention of deep vein thrombosis (DVT) in patients
(Iprivask) beginning 5–15 min before surgery and undergoing elective hip replacement
continuing for 9–12 d
Fondaparinux Prevention: 2.5 mg/d by subcutaneous Prevention and treatment of venous thromboembolic events
(Arixtra) injection starting 6–8 h after surgical closure following surgery for hip fracture, hip replacement, or knee
and continuing for 5–9 d Treatment: 5–10 mg/d replacement; used with warfarin when appropriate
by subcutaneous injections for 5–9 d
Therapeutic Actions and Indications
• Warfarin, an oral drug in this class, causes a decrease in the production of vitamin K–
dependent clotting factors in the liver. The eventual effect is a depletion of these clotting factors
and a prolongation of clotting times. It is used to maintain a state of anticoagulation in
situations in which the patient is susceptible to potentially dangerous clot formation.
• Rivaroxaban (Xarelto) is a factor Xa inhibitor that stops the coagulation cascade at this early
step. It is approved to prevent deep vein thrombosis, which might lead to pulmonary embolism,
in patients undergoing knee or hip replacement surgery.
• Heparin, argatroban, and bivalirudin block the formation of thrombin from prothrombin. The
usual indications for heparin include acute treatment and prevention of venous thrombosis and
pulmonary embolism; treatment of AF with embolization; prevention of clotting in blood samples
and in dialysis and venous tubing; and diagnosis and treatment of disseminated intravascular
coagulation.
• Fondaparinux is a newer anticoagulant. It inhibits factor Xa and blocks the clotting cascade to
prevent clot formation. It is supplied in prefilled syringes, making it convenient for patients who
self-administer the drug at home.
Pharmacokinetics
Route Onset Peak Duration
IV Immediate Minutes 2-6 h
Subcutaneous 20-60 h 2-4 h 8-12 h

Contraindications and Cautions:

 Allergy to the drugs to avoid hypersensitivity reactions.
 Hemorrhagic disorders
 Recent trauma
 Spinal puncture
 GI ulcers
 Recent surgery
 Intrauterine device placement
 Tuberculosis
 Presence of indwelling catheters
Adverse Effects:
• Loss of hair, bruising, chills, fever, osteoporosis, suppression of renal function (with long-
term use). See the later section Anticoagulant Adjunctive Therapy for information on
lepirudin (Refludan), a drug developed for the treatment of rare allergic reaction to
heparin
THROMBOLYTIC AGENTS
• break down the thrombus that has been formed by stimulating the plasmin system.
This process is called clot resolution.
Drugs Name: Usual Dosage: Usual Indication
Alteplase 100 mg IV given over 2 h Treatment of MI, acute pulmonary embolism, and acute
(Activase) ischemic stroke; restoration of function in occluded
central venous access devices
Reteplase 10 International Units + 10 International Units Treatment of coronary artery thrombosis associated
(Retavase) double-bolus IV, each over 2 min, 30 min with an acute MI
apart
Tenecteplase (TNKase) 30–50 mg IV over 5 s Reduction of mortality associated with acute MI
Urokinase (Abbokinase 4,400–10,000 units/min for up to 2 h, based Lysis of pulmonary emboli; treatment of coronary
on clinical response thrombosis; for clearing occluded intravenous catheters

Therapeutic Actions and Indications

• If a thrombus has already formed in a vessel (e.g., during an acute MI), it may be necessary to
dissolve that clot to open the vessel and restore blood flow to the dependent tissue.
• All of the drugs that are available for this purpose work to activate the natural anticlotting system—
conversion of plasminogen to plasmin.
• The activation of this system breaks down fibrin threads and dissolves any formed clot.
• The thrombolytics are effective only if the patient has plasminogen in the plasma.
Pharmacokinetics
• These drugs are given IV and are cleared from the body after liver metabolism. They
cross the placenta, but it is not known whether they enter breast milk.
Contraindications and Cautions
• Allergy to any of these drugs to prevent hypersensitivity reactions.
• They also should not be used with any condition that could be worsened by the dissolution of
clots, including:
 Recent surgery
 Active internal bleeding,
 Cerebrovascular accident (CVA) within the last 2 months,
 Aneurysm, obstetrical delivery
 Organ biopsy
 Recent serious GI bleeding, rupture of a noncompressible blood vessel
 Recent major trauma (including cardiopulmonary resuscitation)
 known blood clotting defects
 Cerebrovascular disease
 Uncontrolled hypertension
 Liver disease (which could affect normal clotting factors and the production of
plasminogen).
Adverse Effects:
• Bleeding
• Cardiac arrhythmias (with coronary reperfusion)
• Hypotension.
• Hypersensitivity reactions are not uncommon; they range from rash and flushing to
bronchospasm and anaphylactic reaction
Topic 1 OTHER DRUGS AFFECTING CLOT FORMATION

01.Low-Molecular-Weight Heparins

02.Anticoagulant Adjunctive Therapy

Agents

03.Hemorrheologic Agent
Low-Molecular-Weight Heparins
• These drugs inhibit thrombus and clot formation by blocking factors Xa and IIa. Because
of the size and nature of the molecules, these drugs do not greatly affect thrombin,
clotting, or the PT; therefore, they cause fewer systemic adverse effects.
• They have also been found to block angiogenesis, the process that allows cancer cells
to develop new blood vessels. They are being studied as possible adjuncts to cancer
chemotherapy.
• These drugs are indicated for very specific uses in the prevention of clots and emboli
formation after certain surgeries or prolonged bed rest.
• The nursing care of a patient receiving one of these drugs is similar to that of a patient
receiving heparin. The drug is given just before (or just after) the surgery and then is
continued for 7 to 14 days during the postoperative recovery process.
• Caution must be used to avoid combining these drugs with standard heparin therapy;
serious bleeding episodes and deaths have been reported when this combination was
inadvertently used.
• Low-molecular-weight heparins include dalteparin, enoxaparin, and tinzaparin.
Anticoagulant Adjunctive Therapy Agents
• Used in anticoagulant adjunctive therapy include lepirudin, protamine sulfate, and
vitamin K.
• Lepirudin (Refludan) is an IV drug used to treat a rare allergic reaction to heparin. In
some patients, an allergy to heparin precipitates a heparin induced thrombocythemia
with associated thromboembolic disease.
• Lepirudin directly inhibits thrombin, blocking the thromboembolic effects of this
reaction. A 0.4 mg/kg initial IV bolus followed by a continuous infusion of 0.15 mg/kg
for 2 to 10 days is the usual treatment. The patient needs to be monitored for bleeding
from any site and for the development of direct hepatic injury

Hemorrheologic Agent
• These effects can decrease blood clot formation and increase blood flow through
narrowed or damaged vessels.
• The mechanism of action by which pentoxifylline does these things is not known.
• It is one of the very few drugs found to be effective in treating intermittent
claudication, a painful vascular problem of the legs.
Topic 2 DRUGS USED TO TREAT ANEMIA

Anemia
- is a common or hereditary abnormality
of RBCs or its percursor, or it may be a
manifestation of an underlying non
hematologic disorder.

Hematopoiesis
- the production of erythrocytes,
platelets, and leukocytes from
undifferentiated stem cells.
- It requires a constant supply of
essential nutrients on,
cyanocobalamin, folic acid and
presence of hematopoietic growth
factors.
Topic 2 DRUGS USED TO TREAT ANEMIA

What causes anemia?Signs and Symptoms of Anemia:

• Any process that can disrupt the
normal life span of a red blood cell
may cause anemia.
• Anemia is caused essentially through
two basic pathways. Anemia is either
caused:
By a decrease in production of red blood cell
or hemoglobin
By a loss or destruction of blood
 CLASSIFICATION OF ANEMIA:

Anemia associated with decrease

RBC production for:
1. iron deficiency anemia
2. megaloblastic anemia
3. Thalassemia
4. anemia due to chronic
disease and renal failure

Anemia due to increased RBC

destruction:
1. hemolytic anemia
2. sickle cell anemia
 Anti anemia Drugs

1. Iron - is required for Hb production

Iron deficiency occur due to:
i. inadequate dietary intake as in vegetarians, malnourished patients
ii. due to blood loss in women with heavy menstruation
iii. when iron requirement is increased as in pregnancy and in growing children
iv. acute or chronic blood loss
Iron preparation: oral iron or parental iron
Oral iron:
Ferrous sulfate - 325mg - 65mg elemental iron
Ferrous gluconate - 320mg - 37mg elemental iron
Ferrous fumarate - 325mg - 106mg elemental iron

Mechanism of action: Iron combines with porphyrin and globin chains to form hemoglobin,
which is critical for oxygen delivery from the lungs to other tissues.
 Anti anemia Drugs

Indications: Iron deficiency anemia, blood loss related to pregnancy or GI bleeding

(NSAIDs), hookworm infestation, or excess coffee

Contraindications: Patients with hemochromatosis, hemosiderosis or hemolytic anemia

Nursing Responsibilities: assess nutritional status, bowel function

 monitor hemoglobin, hematocrit, iron levels
 monitor patient for bleeding and hemoglobin levels and other major signs and
symptoms…assessing diet, menstrual cycles etc.
 Anti anemia Drugs

Parenteral iron: iron dextran 50mg elemental iron/ml

Mechanism of action: Same as ferrous sulfate (but has a different route of administration)

Indications: Seldom used now (newer orally effective agents including iron sucrose & ferric
gluconate complex are most commonly used).
- Ferric gluconate & iron sucrose are two alternative parenteral forms of iron that can be
given i.v., but should NOT be given intramuscularly.

Contraindications: Hypersensitivity to the product; all anemias except iron-deficiency

anemia. Safe use during pregnancy (category C) is not established.

Nursing Responsibilities: Don’t give iron dextran with oral iron drug
Monitor Hb level, hematocrit, and reticulocyte count
Maximum daily dose should not exceed 2mL undiluted iron dextran
 Anti anemia Drugs

2 - 3. Cyanocoblamin (Vit B12) and folic acid (Vit B9)- are required for normal DNA synthesis
• Deficiency of either of these vitamins resukts in impaired production andabnormal
maturation of RBCs giving rise the characteristics blood and bone marrow picture known
as megaloblastic anemia.
Cyanocoblamin (Vit B12)
Mechanism of action: A cofactor for several essential biochemical reactions.

Indications: Used to treat or prevent deficiency of Vit B12.

 The most common causes of Vit B12 deficiency are:
i. Pernicious anemia (results from defective secretion of intrinsic factor by the gastric
mucosal cells)
ii. Fish tapeworm infection
iii. Partial or total gastrectomy
iv. Various intestinal disorders that impair absorption of Vit B12.
 Antianemia Drugs

Contraindications: Sensitivity to cobalt and/or vitamin B12 due to the risk of anaphylaxis
 Patients with early Leber disease suffered severe and rapid optic atrophy when they
received treatment with cyanocobalamin
Aluminum is present in the preparation of cyanocobalamin. CNS and bone toxicity secondary
to aluminum accumulation is possible in patients with renal impairment. Thus, it is a relative
contraindication to cyanocobalamin

Nursing Responsibilities:
 monitor vital signs in patients with cardiac disease and in those receiving parenteral
cyanocobalamin, and be alert to symptoms of pulmonary edema, which generally occur
early in therapy.
 Obtain a complete diet and drug history and inquire into alcohol drinking patterns for all
patients receiving cyanocobalamin to identify and correct poor habits
 Obtain a careful history of sensitivities. Sensitization to cyanocobalamin can take as long
as 8 y to develop.
 Anti anemia Drugs

Folic acid (Vit B9)

Mechanism of action: Essential cofactor for synthesis of amino acids, purines and DNA

Indications: Treatment of megaloblastic anemias due to a deficiency of folic acid as may be

seen in tropical or non-tropical sprue, in anemias of nutritional origin, pregnancy, infancy, or
childhood.
A reduced form of folic acid known as citrovorum factor (or leucovorin) is given to replenish
endogenous folic acid in patients on methotrexate (which inhibits dihydrofolate reductase).
Citrovorin (leucovorin) is better absorbed compared to folic acid.

Contraindication: Folic acid should not be given alone in patients with pernicious anemia
without knowing whether they also have a Vit B12 deficiency. The danger is that folic acid
supplements can mask the signs of Vit B 12 deficiency, yet not prevent the development of
irreversible neurological disease due to Vit B12 deficiency.
 Anti anemia Drugs

Nursing Responsibilities: Women who are planning a pregnancy should be advised to take
folic acid daily before conception to prevent occurrence of neural tube defects.

 A woman is at higher risk of having a baby with a neural tube defect if she has previously
had a child with a neural tube defect; if she has a neural tube defect herself; if her partner
or a first-degree relative has a neural tube defect; or if she has coeliac disease or
epilepsy. In these cases higher doses of folic acid are recommended.
 Anti anemia Drugs

4. Erythropoietin and colony stimulating factors - are hormones that regulate blood cell
development and proliferation in the bone marrow.

Mechanism of action: a glycoprotein that stimulates red blood cell production. Epoetin alfa
is a 165 amino acid glycoprotein manufactured by recombinant DNA technology, and has the
same biological effects as endogenous erythropoietin
- Hypoxia is the primary physiological stimulus for erythropoietin production in the body

Indications: treatment of anemia in:

chronic renal failure patients
zidovudine-treated HIV-infected patients
cancer patients on chemotherapy
reduction of allogeneic blood transfusion in surgery patients. Erythropoietin deficiency can
result from compromised renal function (it's primary site of production). Erythropoietin
deficiency results in a normocytic anemia.
 Anti anemia Drugs

Contraindications: Uncontrolled hypertension or known hypersensitivity to either

mammalian cell-derived products or to human albumin.

Nursing Responsibilities: Control BP adequately prior to initiation of therapy and closely

monitor and control during therapy. Hypertension is an adverse effect that must be controlled
Monitor for premonitory neurological symptoms (i.e., aura, and report their appearance
promptly).
Monitor for hypertensive encephalopathy in patients with CRF during period of increasing
Hct.
Do not breast feed while taking this drug without consulting physician.

Mechanism of action: Darbepoetin alfa stimulates erythropoiesis by the same mechanism

as endogenous erythropoietin. Erythropoietin interacts with progenitor stem cells to increase
red cell production.

Indications: Anemia Due To Chronic Kidney Disease.

• Anemic due to chemotherapy inpatients with nonmyeloid malignances
 Anti anemia Drugs

Contraindications: Contraindicated in patients hypersensitive to drug or its components, in

those with uncontrolled HTN, and in patients with pure red cell aplasia that begins after
treatment with Aranesp or other erythropoietin protein drugs.

Nursing Responsibilities: Control BP adequately prior to initiation of therapy and closely

monitor and control during therapy.
 Notify physician of a rapid rise in Hgb as dosage will need to be reduced because of risk
of serious hypertension
 If patient has a minimal response or lack of response at recommended dose, check for
deficiencies in folic acid, iron, or vitamin B12.
 Anti anemia Drugs

AGENTS USEDTO TREAT SICKLE-CELL DISEASE - the drug apparently increases fetal
hemoglobin levels; process takes several months.
Hydroxyurea - makes your red blood cells bigger. It helps them stay rounder and more flexible
— and makes them less likely to turn into a sickle shape.

Mechanism of action: May inhibit DNA synthesis

Indications: Carcinoma of the head (excluding lip) and neck, with radiation(Hydrae)
 Resistant chronic myelocytic leukemia
 To reduce frequency of painful crises and need for blood transfusions in adult patients with
sickle cell anemia with recurrent moderate to severe painful cries(Doxia, Skilos)

Contraindications: Contraindicated in patients hypersensitive to drug or its components

Use cautiously in patients with renal dysfunction and in elderly
Don't initiate treatment if bone marrow function is markedly depressed
 Anti anemia Drugs

Nursing Responsibilities: Monitor I&O. Advise patients with high serum uric acid levels to drink
at least 10–12 240 mL (8 oz) glasses of fluid daily to prevent uric acid nephropathy.
 Lab tests: Determine status of kidney, liver, and bone marrow function before and
periodically during therapy; monitor hemoglobin, WBC, platelet counts at least once weekly.

Pentoxifylline - ability to increase red blood cell deformability and inhibit platelet aggregation.

Mechanism of action: increases red blood cell flexibility by increasing erythrocyte ATP and
cyclic nucleotide levels.

Indications: Management of symptomatic peripheral vascular disease (intermittent

claudication).

Contraindications: contraindicated in patients with intracranial bleeding or retinal bleeding

Pentoxifylline is contraindicated in patients who have exhibited intolerance to pentoxifylline or
methylxanthines (e.g., caffeine, theophylline, theobromine).
Renal failure, renal impairment
 Anti anemia Drugs

Pentoxifylline - ability to increase red blood cell deformability and inhibit platelet aggregation.

Mechanism of action: increases red blood cell flexibility by increasing erythrocyte ATP and
cyclic nucleotide levels.

Indications: Management of symptomatic peripheral vascular disease (intermittent

claudication).

Contraindications: contraindicated in patients with intracranial bleeding or retinal bleeding

 Pentoxifylline is contraindicated in patients who have exhibited intolerance to pentoxifylline
or methylxanthines (e.g., caffeine, theophylline, theobromine).
 Renal failure, renal impairment
Topic 3 RENAL SYSTEM

• The urinary system, also known as the renal system, produces, stores and eliminates urine,
the fluid waste excreted by the kidneys. The kidneys make urine by filtering wastes and extra
water from blood.

• Urine travels from the kidneys through two thin tubes called ureters and fills the bladder.
When the bladder is full, a person urinates through the urethra to eliminate the waste.

• The urinary system works as a filter, removing toxins and wastes from your body through urine. It
uses a series of tubes and ducts to pass this waste. These tubes are connected to your blood
vessels and digestive system. Your urinary system helps the rest of your body work properly
Topic 3 RENAL SYSTEM

Organs of the Renal System

• Kidneys - Kidneys are the most complex and critical part of the urinary system
• -it removes waste products of metabolism, excess water and salts from blood and maintain the
pH .

• Nephrons - are the main functional component inside the parenchyma of the kidneys, which filter blood to
remove urea, a waste product formed by the oxidation

• Ureter - Urine passes from the renal tube through tubes called Bladder

• Urethra - The female and male renal system are very similar, differing only in the length of the urethra

• organ system that includes the kidneys, where urine is produced, and the ureters, bladder, and urethra for
the passage, storage, and voiding of urine.
Topic 4 Diuretic Agents

Diuretics
-Diuretics are drugs that primarily
increase the excretion of sodium.
To some extent, they also
increase the volume of urine
produced by the kidneys.
- effective in relieving symptoms
and edema in heart failure (HF)
and hence, are currently
considered to be the first-line
treatment for HF. The four main
classes of diuretics are: loop
diuretics, thiazide diuretics,
potassium sparing diuretics, and
carbonic anhydrase inhibitors.
Diuretics: Generic and Brand Names
Classification Generic Name Brand Name
Thiazide diuretics Bendroflumethiazide Naturetin
Chlorothiazide Diuril
Hydrochlorothiazide HydroDIURIL
Hydroflumethiazide Saluron
Methyclothiazide Enduron

Thiazide-like diuretics Chlorthalidone Hygrotol

Indapamide Lozol
metolazone Mykrox, Zaroxolyn

Loop diuretics Bumetanide Bumex

Ethacrynic acid Edecrin
Furosemide Lasix
Torsemide Demadex

Carbonic Anhydrase Inhibitors Acetazolamide Diamox

Methazolamide Glauctabs, MZM, Neptazane

Potassium-sparing Diuretics Amiloride Midamor

Spironolactone Aldactone
Triamterene Dyrenium

Osmotic Diuretics Mannitol Osmitrol

Therapeutic Action
•It causes active pumping out of chloride from the cells lining the ascending limb of
Loop of Henle and distal tubule by blocking the chloride pump.
Indication
•Considered to be a milder form of diuretics compared to loop diuretics.
•First-line drugs for management of essential hypertension
Pharmacokinetics
Route Onset Peak Duration

Oral 2h 4-6 h 6-12 h

T1/2: 5.6 – 14 h
Metabolism: liver
Excretion: urine
Contraindications and Cautions
 Allergy to loop diuretics.
 Prevent severe hypersensitivity reactions.
Fluid and electrolyte imbalances.
 Can be potentiated by the changes in fluid and electrolyte levels caused by diuretics.
Severe renal failure, anuria.
 May prevent diuretics from working; can precipitate crisis stage due to blood flow
changes brought about by diuretics.
Systemic lupus erythematosus (SLE).  
 Can precipitate renal failure because the disease already causes changes in
glomerular filtration.
Glucose tolerance abnormalities and Diabetes mellitus.
 Worsened by glucose-elevating effect of some diuretics
Gout.
 Already reflects abnormality in tubular reabsorption and secretion.
Liver disease.
•Could interfere with drug metabolism and lead to drug toxicity.
Bipolar disorder.
•Can be exacerbated by calcium changes brought about by the use of this drug.
Pregnancy, lactation.
•Can cause potential adverse effects to the fetus and baby. Routine use of this drug in
pregnancy is not appropriate and should be used only when there is underlying pathological
conditions. For lactating women, an alternative method of feeding should be instituted.

Adverse Effects
CNS: weakness
CV: hypotension, arrhythmias
GI: GI upset
GU: hypokalemia (can precipitate hyperglycemia), hypercalcemia, hyperuremia, slightly-
alkalinized urine (can lead to bladder infections)
Loop Diuretics
Therapeutic Action
•Blocks the action of chloride pump in the ascending limb of the loop of Henle, where 30% of
sodium is normally reabsorbed.
•Exerts the same effect on the descending limb of loop of Henle and distal tubule causing
sodium-rich urine.
Indications
•Indicated for treatment of acute HF, acute pulmonary edema, and edema associated with HF or with
renal or liver disease, and hypertension.
•Drug of choice when rapid and extensive diuresis is needed. It can produce a fluid loss up to 20
pounds per day.
•Proven to be effective even with the presence of acid-base disturbances, renal failure, electrolyte
imbalances, and nitrogen retention.
•Also used in the treatment of pulmonary edema but its effect only influences the blood that reaches
the nephrons.
•Ethacrynic acid is used less frequently in the clinical setting because newer drugs are more potent
and reliable.
Pharmacokinetics
Route Onset Peak Duration
Oral 60 min 60-120 min 6-8 h
IV, IM 5 min 30 min 2h
T1/2: 120 min
Metabolism: liver
Excretion: urine

Contraindications and Cautions

Glucose tolerance abnormalities and diabetes mellitus.
Allergy to thiazides and sulfonamides.
 Worsened by glucose-elevating effect of some diuretics
 Prevent severe hypersensitivity reactions. Gout.
Electrolyte depletion.  Already reflects abnormality in tubular reabsorption and
 Can be potentiated by the changes in fluid secretion.
and electrolyte levels caused by diuretics. Hepatic coma.
Severe renal failure, anuria.  Exacerbated by fluid shifts associated with drug use.
 Exacerbated by the effects of the drug. Pregnancy, lactation.
 Can cause potential adverse effects to the fetus and baby.
Systemic lupus erythematosus (SLE).  
Routine use of this drug in pregnancy is not appropriate and
 Can precipitate renal failure because the
should be used only when there is underlying pathological
disease already causes changes in conditions. For lactating women, an alternative method of
glomerular filtration. feeding should be instituted.
Adverse Effects
CNS: dizziness
CV: hypotension
GI: GI upset
GU: hypokalemia (can precipitate hyperglycemia), increased bicarbonate excretion (can lead to
alkalosis), hypocalcemia and tetany
EENT: ototoxicity, reversible loss of hearing
Carbonic Anhydrase
Inhibitors
Therapeutic Action
 Inhibits the action of the enzyme carbonic anhydrase, the catalyst for the
formation of sodium bicarbonate stored as alkaline reserve in the renal tubules
and is important for the excretion of hydrogen.
 It slows down the movement of hydrogen ions which leads to greater amount
of sodium and bicarbonate lost in the urine.
Indications
•Most often used for the treatment of glaucoma. Inhibition of carbonic
anhydrase results in decreased secretion of aqueous humor of the eyes.
•Also used as adjunct to other diuretics when more intense diuresis is needed.
Pharmacokinetics
Route Onset Peak Duration
Oral 1h 2-4 h 6-12 h
Sustained-release oral 2h 8-12 h 18-24 h
IV 1-2 min 15-18 min 4-5 h
T1/2:  5-6 h
Metabolism: N/A
Excretion: urine (unchanged)

Contraindications and Cautions

Allergy to carbonic anhydrase inhibitors, thiazides, antibacterial sulfonamides.
•Prevent severe hypersensitivity reactions.
Chronic noncongestive angle-closure glaucoma.
•Not effectively treated by this drug.
Fluid and electrolyte imbalance, renal or hepatic disease, adrenocortical insufficiency,
respiratory acidosis, chronic obstructive pulmonary disease (COPD).
•Could be exacerbated by fluid and electrolyte changes caused by these drugs.
Pregnancy, lactation.
•Can cause potential adverse effects to the fetus and baby. Routine use of this drug
in pregnancy is not appropriate and should be used only when there is underlying
pathological conditions. For lactating women, an alternative method of feeding should be
instituted.
Adverse Effects
CNS: paresthesia, confusion, drowsiness
CV: hypotension
GU: hypokalemia (can precipitate hyperglycemia), increased loss of
bicarbonate (can lead to metabolic acidosis).
Potassium-Sparing Diuretics
•They are weak diuretics usually prescribed in combination with other types of
diuretics.
•They are used to increase the amount of fluid passed from the body In urine,
whilst also preventing too much potassium being lost with it. Side-effects are
uncommon when routine low doses are used.
Therapeutic Action
•This type of diuretics causes a loss of sodium while promoting the retention of
potassium.
Indications
•This is often used as adjuncts with thiazide or loop
diuretics or in patients who are especially at risk if hypokalemia
develops.
•Spironolactone is the drug of choice for treating
hyperaldosteronism typically seen in patients with liver
cirrhosis and nephrotic syndrome.
Pharmacokinetics
Route Onset Peak Duration

Oral 24-48 h 48-72 h 48-72 h

T1/2:  20 h
Metabolism: liver
Excretion: urine (unchanged)

Contraindications and Cautions

o Allergy to potassium-sparing diuretics. Prevent severe hypersensitivity reactions.
o Hyperkalemia, renal disease, anuria. Exacerbated by the effects of the drug.

Pregnancy, lactation. Can cause potential adverse effects to the fetus and baby. Routine use of
this drug in pregnancy is not appropriate and should be used only when there is underlying
pathological conditions. For lactating women, an alternative method of feeding should be instituted
Osmotic Diuretics
•This type of diuretic exerts their therapeutic effect by pulling water into the renal
tubule without loss of sodium.
•Only one osmotic diuretic is currently available
mannitol (Osmitrol).

Therapeutic Action:
•Mannitol is a sugar that is not well reabsorbed by the tubules and it acts to pull
large amounts of fluid into the urine due to the osmotic pull exerted by large sugar
molecule.
•This pulls fluid into the vascular system from extravascular spaces like aqueous
humor.
Indications
•Mannitol is used in acute situations when it is necessary to decrease IOP prior to
eye surgery or during acute attacks of glaucoma.
•Diuretic of choice in cases of increased cranial pressure or acute renal failure
due to shock, drug overdose, or trauma.
•Also available as an irrigant in transurethral prostatic resection and other
transurethral procedures.
Pharmacokinetics
Route Onset Peak Duration

IV 30-60 min 1h 6-8 h

Irrigant Rapid Rapid Short

T1/2:  15-100 min

Excretion: urine (unchanged)
Contraindications and Cautions
•Renal disease, anuria, pulmonary congestion, intracranial bleeding,
dehydration, HF. Exacerbated by large shifts in fluid related to drug use.
•Pregnancy, lactation. Can cause potential adverse effects to the fetus
and baby. Routine use of this drug in pregnancy is not appropriate and
should be used only when there is underlying pathological conditions. For
lactating women, an alternative method of feeding should be instituted.
Adverse Effects
•CNS: light-headedness, confusion, headache
•CV: hypotension, cardiac decompensation, shock
•GI: nausea, vomiting
•GU: fluid and electrolyte imbalance
Topic 5 Drug affecting Urinary Tract and the Bladder

Urinary Tract Infections

• Second most common in
the U.S.
• More common in female
• Patients with indwelling
catheters or intermittent
catherization are at risk
Signs and symptoms of UTI
 Urinary frequency
 Urgency
 Burning on urination (associated with cystitis)
 Chills, fever, flank pain, and tenderness (associated with acute pyelonephritis)

Treatment for UTI

• Antibiotics
• Specific agents to sterilize the urinary tract
• Drugs that:
-Block spasm of the urinary tract muscle
-Decrease urinary tract pain
-Protect the cells of the bladder from Irritation
-Treat enlargement of the prostate gland in
men
Anti-Infectives used to treat UTI
• Cinoxacin (Cinobac): Interferes with DNA replication in gram-negative bacteria
• Norfloxacin (Noroxin): Effective against even more gram-negative strains than in
cinoxacin
• Fosfomycin (Monurol): Has the convenience of only one dose
• Nadilixic Acid (NeGram): Older drug, not effective against as many strains of gram
negative bacteria
• Nitrofurantoin (Furadantin): Older drug with very short half-lifen
Anti-Infective that acidify the urine
Methylene Blue (Urolene Blue)
-Is widely distributed, metabolized in the tissues, and excreted in
urine, bile and feces
Methanamine (Hiprex)
-Undergoes metabolism in the liver and is excreted in urine
-Has established dosage guidelines for children and comes in
suspension form
Anti-infectives
• Indications
-Chronic UTI
-Adjunctive therapy in acute cystitis and pyelonephritis
• Actions
-Act specifically within the urinary tract to destroy bacteria
-They act either through direct antibiotic effect or through acidification

Anti-Infectives (cont.)
• Pharmacokinetics • Drug to drug interactions
-vary with each drug -Vary with each agent
• Contraindications • Adverse Effect
-Allergy -Nausea, vomiting, anorexia, bladder
• Caution irritation, and dysuria, Pruitus, urticaria,
-Renal dysfunction headache, dizziness, nervousness, and
-Pregnancy and lactation confusion
Urinary Tract Antispasmodics
• Actions
-Block the spasm of the urinary tract muscle
-Blocking parasympathetic activity
-Relaxing the detrusor and other urinary tract muscles
• Indications
-Bladder spasm and dysuria

Urinary Tract Antispasmodics (cont.)

• Pharmacokinetics • Caution
-Rapidly absorbed, widely distribute -Renal or hepatic dysfunction
-Metabolized in the liver and excreted in the urine -Pregnancy and lactation
• Contraindications • Adverse Effects
-Allergy -Related blocking of parasympathetic system
-Recent surgery • Drug to Drug interactions
-Obstructive urinary tract problems -Phenothiazines
-Haloperidol
Urinary Tract Analgesia
• Actions
-When phenazopyridine is excreted in urine, it exerts a direct topical analgesic effect on the
urinary mucosa
• Indications
-Relieve symptoms related to urinary tract irritation from infection, trauma, or surgery

Urinary Tract Analgesia (cont.)

• Pharmacokinetics • Adverse Effect
-Rapidly absorbed and has a very -GI upset, headache, rash, reddish-
rapid onset of action orange coloring of the urine
-Widely distributed -Renal and hepatic toxicity
-Metabolized in liver and excreted in • Drug to drug interactions
the urine -Antibacterial agents
• Contraindications
-Allergy and renal dysfunction
• Caution
-Pregnancy and lactation
Bladder Protectants
• Actions
-Heparin-like compound that has coagulant and fibrinolytic effects
-Adheres to the bladder wall mucosal membranes and acts as a buffer to control cell
permeability, preventing irritating solutes in the urine form reaching the bladder wall cells
• Indications
- Interstitial cystitis

Bladder Protectants (cont.)

• Pharmacokinetics • Caution
-Very little of drug is absorbed -Hepatic or splenic dysfunction
-Metabolized in the liver and spleen, -Pregnancy or lactation
and excreted in the urine • Adverse Effect
• Contraindications -Bleeding that may progress to
-Condition that involve a risk of hemorrhage
bleeding -Headache, alopecia, GI
-Heparin induced thrombocytopenia disturbances
• Drug to drug interactions
-anticoagulants, aspirin
Drugs for treatment of Benign Prostatic Hyperplasia
• Actions
-Varies with drug
• Indications
-Treats benign prostatic hypertrophy
• Pharmacokinetics
-Varies with drug
• Contraindications
• -Allergy
Drugs for treatment of Benign Prostatic Hyperplasia (cont.)
• Cautions
-Hepatic/Renal dysfunction
• Adverse Effect
-Varies with drug
-Headache, fatigue, dizziness, hypotension, tachycardia, lethargy
-Decreased libido, impotence, and sexual dysfunction
• Drug to drug interactions
-Theophylline
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Thank You !