37.

Diuretic Drugs: Furosemide (Lasix)

Drugs that increases urine production to remove excess fluids from the

body.

1. Generic Name:

* Furosemide

2. Brand Name:

* Lasix

Dosage:

* For Edema:

* Initial dose: 20–80 mg orally once daily.

* The dosage may be increased based on patient response, typically

in 20-40 mg increments.

* For Hypertension:

* Initial dose: 40 mg twice daily.

* Can be adjusted based on individual response.

Available Formulations:

* Tablets:

* 20 mg, 40 mg, 80 mg.

* Oral Solution:
 * 10 mg/mL.

* Injectable Solution:

* 10 mg/mL.

Indications:

* Edema: Used to treat fluid retention due to conditions like heart failure,

liver disease (cirrhosis), and kidney disease.

* Hypertension: Used in the management of high blood pressure, often as

part of combination therapy.

Contraindications:

* Hypersensitivity to furosemide or sulfonamide drugs.

* Anuria (inability to urinate).

* Severe dehydration or electrolyte imbalances, especially hypokalemia.

* Severe liver disease with ascites.

Special Precautions:

* Electrolyte monitoring: Regularly check potassium, sodium, calcium,

and magnesium levels.

* Renal function: Use with caution in patients with renal impairment or

impaired kidney function.

* Pregnancy: Use during pregnancy only if absolutely necessary.

Furosemide passes into breast milk.

* Elderly: Elderly patients may be more sensitive to the drug; start with

lower doses.

Adverse Reactions:

* Common:

* Electrolyte disturbances (hypokalemia, hyponatremia)

* Dizziness, headache, dehydration

* Hypotension (low blood pressure)

* Serious:

* Ototoxicity (hearing loss) especially with rapid intravenous

infusion.

* Renal failure or impairment in severe cases.

* Liver dysfunction (jaundice, hepatitis).

* Severe electrolyte imbalance (e.g., low potassium, sodium).

Monitoring Parameters:

* Electrolyte levels: Regularly monitor for hypokalemia, hyponatremia,

and other electrolyte disturbances.

* Renal function: Check creatinine and BUN levels for kidney function.

* Blood pressure: Particularly important for patients taking furosemide for

hypertension.
* Weight and fluid balance: Monitor fluid retention and changes in weight

for patients with edema.

Overdosage:

* Symptoms of Overdose:

* Severe dehydration

* Electrolyte imbalances (especially hypokalemia)

* Hypotension

* Ototoxicity (hearing loss)

* Management of Overdose:

* Discontinue furosemide immediately.

* Rehydration: Provide IV fluids to correct dehydration and

electrolyte imbalances.

* Electrolyte correction: Administer potassium and other necessary

electrolytes.

* Monitor renal function to avoid renal failure.

* Supportive care for hypotension and dehydration.

Drug Interactions:

* Antihypertensive drugs: May enhance the effect of other blood

pressure-lowering medications.

* Lithium: Furosemide can increase lithium levels, leading to toxicity.

* NSAIDs: May reduce the diuretic effect of furosemide by decreasing

renal blood flow.

* Corticosteroids: Can increase potassium loss, leading to hypokalemia.

* Aminoglycoside antibiotics: Increased risk of ototoxicity (hearing

damage).

Food Interactions:

* High potassium foods: Include potassium-rich foods like bananas,

oranges, and spinach to help prevent hypokalemia.

* Salt substitutes: Should be avoided if they contain potassium, as they

can alter potassium levels.

Mechanism of Action:

Furosemide is a loop diuretic that works by inhibiting the Na+/K+/2Cl −

symporter in the loop of Henle in the kidneys. This prevents the

reabsorption of sodium, potassium, and chloride, which results in

increased urine production (diuresis) and a reduction in blood volume,

thereby lowering blood pressure.

Onset:

* Oral: Typically takes 30 to 60 minutes for the onset of action.

* Intravenous (IV): Begins acting in about 5 minutes.

Duration:

* Oral: The effects generally last for 6 to 8 hours.

* Intravenous (IV): Effects last for about 2 hours.

Pharmacokinetics:

* Absorption: Rapidly absorbed from the gastrointestinal tract after oral

administration.

* Distribution: Distributed widely throughout the body, especially in the

kidneys, lungs, and liver.

* Metabolism: Furosemide undergoes minimal metabolism in the liver.

* Excretion: Primarily excreted unchanged in the urine by the kidneys.

Storage:

* Tablets: Store at room temperature (20°C to 25°C, 68°F to 77°F), in a dry

place away from moisture and light.

* Oral Solution: Store at room temperature, protected from light.

* Injectable Solution: Store refrigerated (2°C to 8°C, 36°F to 46°F) and

protect from light.

38.Anti-Diuretic Drug: Desmopressin

Medications that reduces urine production, helping to retain body fluids.

Generic Name: Desmopressin

Brand Names: DDAVP, Minirin

1. Dosage

* Intranasal: 10 mcg to 40 mcg per dose, administered once or twice daily.

* Oral: 0.1 mg to 0.4 mg per day, divided into one or two doses.

* Subcutaneous/Intravenous: 0.3 mcg/kg body weight (as prescribed by a

healthcare provider).

* Pediatric Dosage: Adjusted based on the age and condition, commonly

0.05 mg to 0.2 mg per day.

2. Available Formulation

* Oral Tablets: 0.1 mg, 0.2 mg, 0.4 mg

* Intranasal Spray: 10 mcg, 20 mcg

* Injection: Available in ampoules for IV or subcutaneous use

* Oral Liquid: Often used in pediatric populations

3. Indications
* Diabetes Insipidus (central)

* Nocturnal Enuresis (bedwetting)

* Hemophilia A and von Willebrand disease (to reduce bleeding episodes)

* Post-surgical bleeding control (particularly in certain surgical

procedures)

* Primary nocturnal enuresis in children

4. Contraindications

* Hypersensitivity to desmopressin or any component of the formulation

* Hyponatremia (low sodium levels)

* Fluid retention disorders or heart failure

* Severe renal impairment (for oral formulations)

* Patients with uncontrolled hypertension (for nasal spray formulation)

5. Special Precautions

* Fluid balance: Monitor fluid intake to prevent water retention and

hyponatremia.

* Renal function: Use with caution in patients with renal impairment or at

risk for renal dysfunction.

* Pregnancy: Category B (generally considered safe during pregnancy, but

should be used only when necessary).

* Lactation: Can be excreted in breast milk; caution advised when used by

nursing mothers.

* Elderly: Risk of water retention and hyponatremia may be increased in

older adults.

6. Adverse Reactions

* Common: Headache, nausea, abdominal cramps, and dizziness.

* Serious: Water intoxication, hyponatremia (low sodium), seizures, and

cardiovascular events.

* Other: Allergic reactions, rash, and potential for nasal irritation

(intranasal form).

7. Monitoring Parameters

* Serum sodium levels: Regular monitoring is crucial to prevent

hyponatremia.

* Kidney function: Monitor renal function, particularly for those with

pre-existing renal conditions.

* Fluid balance: Assess for signs of water retention or edema.

* Blood pressure: Regular monitoring for potential increases in blood

pressure, especially in patients with a history of hypertension.

8. Overdosage

* Symptoms of overdose include water retention, hyponatremia, headache,

nausea, and in severe cases, seizures or coma.

* Ingestion of large amounts of the drug, especially with inadequate fluid

restriction, can lead to serious adverse effects.

9. Management of Overdosage

* Immediate Action: Discontinue the drug immediately.

* Correction of Hyponatremia: Treat with saline infusion and adjust

sodium levels carefully.

* Monitoring: Continuous monitoring of fluid and electrolyte levels,

especially sodium.

* Supportive Care: Depending on the severity, may require hospitalization

for IV fluids, diuretics, or even dialysis in extreme cases.

10. Drug Interactions

* Increased risk of hyponatremia with lithium, antidepressants (SSRIs,

SNRIs), and NSAIDs.

* Diuretics (especially thiazides): May increase the risk of fluid and

electrolyte imbalances.

* Vasopressin receptor antagonists: Counteract desmopressin’s effects.

* Corticosteroids: May increase fluid retention and sodium levels,

requiring careful monitoring.

11. Food Interactions

* Alcohol: Can reduce the effectiveness of desmopressin. Alcohol acts as

a diuretic, which can counteract the drug's effect.

* High-salt foods: Could increase the risk of fluid imbalance or water

retention.

* Caffeine: May interfere with the medication ’ s effectiveness due to its

diuretic properties.

12. Mechanism of Action

* Desmopressin acts as a synthetic analog of vasopressin (antidiuretic

hormone). It binds to V2 receptors in the kidneys, promoting water

reabsorption by the renal tubules, thus reducing urine output and

concentrating urine. This helps manage conditions like diabetes insipidus

and nocturnal enuresis.

13. Onset

* Intranasal: Within 30 minutes to 1 hour.

* Oral: Within 1 to 2 hours.

* Injection: Immediate onset, depending on the route of administration.

14. Duration

* Intranasal: 8-12 hours.

* Oral: 8-12 hours.

* Injection: Duration varies but usually lasts 12-24 hours.

15. Pharmacokinetics

* Absorption: Rapidly absorbed via the nasal mucosa, gastrointestinal

tract (oral), or subcutaneous/IV injection.

* Distribution: Widely distributed in the body, with minimal protein

binding.

* Metabolism: Metabolized primarily by the kidneys.

* Excretion: Excreted in the urine.

16. Storage

* Oral tablets: Store at room temperature (15-30°C / 59-86°F), away from

moisture and heat.

* Nasal Spray: Store upright at room temperature, away from sunlight and

freezing conditions.

* Injection: Store according to manufacturer's guidelines, typically

refrigerated.

This outline provides a thorough overview of desmopressin's

characteristics and usage, helping to guide its safe and effective

administration.
39. Coagulant Drug: Vitamin K

Drugs that promote blood clotting to prevent excessive bleeding.

Generic Name: Vitamin K

Brand Name: RiaSTAP

1. Dosage

* Vitamin K1 (Phytonadione):

* Oral: 2.5–10 mg for adults; 1–5 mg for pediatric patients.

* Intravenous (IV): 1 – 10 mg, depending on the severity of the

bleeding or the INR level.

* Intramuscular (IM): 1 – 10 mg (usually in an emergency or for

prevention of bleeding).

* Subcutaneous: Less commonly used but can be administered.

* RiaSTAP (Fibrinogen Concentrate):

* Dosing: Dependent on the specific condition, such as for bleeding

or clotting factor deficiencies. The exact dosage is typically based on body

weight and clinical presentation, and should be individualized as per

clinical guidelines.

2. Available Formulations

* Vitamin K (Phytonadione):
 * Oral tablets (e.g., Mephyton 5 mg)

* Injectable solution (e.g., Phytonadione 1 mg/mL)

* Intravenous (IV) or Intramuscular (IM) formulations

* Oral liquid preparations

* RiaSTAP (Fibrinogen concentrate) is typically available in injectable

form for patients with bleeding due to fibrinogen deficiencies.

3. Indications

* Vitamin K:

* Warfarin reversal: To reverse the anticoagulant effects of warfarin

(Coumadin).

* Vitamin K deficiency: Common in neonates or in individuals with

malabsorption syndromes.

* Bleeding disorders: Especially in cases involving vitamin

K-dependent clotting factors.

* Newborns: Prophylaxis against hemorrhagic disease of the

newborn.

* RiaSTAP:

* Fibrinogen deficiency: Treatment of bleeding episodes in patients

with congenital or acquired fibrinogen deficiency (e.g., in hemophilia or

liver disease).
4. Contraindications

* Vitamin K:

* Hypersensitivity to vitamin K or its components.

* Warfarin overdose: Caution is needed because excessive vitamin K

administration can precipitate thrombosis (blood clots).

* Active liver disease (except in cases of deficiency where the liver

cannot produce clotting factors).

* RiaSTAP:

* Hypersensitivity to fibrinogen or any component of the

formulation.

* Active clotting disorders where clot formation could exacerbate

conditions like disseminated intravascular coagulation (DIC).

5. Special Precautions

* Vitamin K:

* Renal impairment: Caution is needed in patients with renal

insufficiency.

* Coumarin therapy (Warfarin): Monitor INR carefully during and

after vitamin K administration.

* Pregnancy and lactation: Use vitamin K1 cautiously, especially

during pregnancy unless necessary (usually used in pregnancy to treat

vitamin K deficiency).
* RiaSTAP:

* Renal or liver impairment: Caution in patients with severe renal or

hepatic dysfunction.

* Allergic reactions: Be prepared for potential allergic reactions to

the components of RiaSTAP.

6. Adverse Reactions

* Vitamin K:

* Local irritation: At the injection site (if given IM or IV).

* Hypersensitivity reactions: Rare but may include rash, itching, or

anaphylaxis.

* Hypercoagulation: Excessive administration can lead to the

development of thrombosis.

* RiaSTAP:

* Allergic reactions: Including rash, fever, chills, and anaphylaxis.

* Thrombosis: Due to excessive fibrinogen, may cause unwanted clot

formation.

* Injection site reactions: Pain or irritation at the injection site.

7. Monitoring Parameters

* Vitamin K:

* INR (International Normalized Ratio): To monitor the effectiveness

of warfarin reversal and ensure clotting status is appropriate.

* Prothrombin time (PT): Check clotting time as part of monitoring

therapeutic effects.

* Signs of bleeding or clotting: Assess clinical status after dosing,

particularly in patients with existing clotting disorders.

* RiaSTAP:

* Fibrinogen levels: Monitor levels to adjust dosing and avoid excess

fibrinogen in the blood.

* Signs of bleeding or thrombosis: Closely monitor for signs of clot

formation or any adverse reactions post-infusion.

8. Overdosage

* Vitamin K:

* Symptoms of overdose may include thrombosis, particularly if

administered excessively to patients on anticoagulants.

* RiaSTAP: Overdosing may result in increased clotting risk,

thrombosis, or unwanted coagulation in the blood.

9. Management of Overdosage

* Vitamin K:

* In the case of warfarin reversal, the INR should be monitored

closely. If excessive clotting occurs, anticoagulants should be resumed as

needed.

* Thrombosis management: Anticoagulation therapy (e.g., heparin or

direct oral anticoagulants) might be used to prevent clot formation if

overdose leads to thrombotic events.

* RiaSTAP:

* Thrombosis management: If thrombotic events occur, anticoagulant

therapy or other appropriate interventions may be needed.

* Discontinue the infusion and manage the bleeding/clotting balance

carefully.

10. Drug Interactions

* Vitamin K:

* Warfarin: Vitamin K can reverse the effects of warfarin, leading to

increased clotting.

* Antiplatelet drugs (e.g., aspirin): May increase the risk of bleeding.

* Other anticoagulants: Close monitoring is necessary as vitamin K

could reverse the effects of anticoagulants, leading to clot formation.

* RiaSTAP:

* Antithrombotic therapy: Caution in using RiaSTAP alongside

anticoagulants due to increased thrombotic risks.

* Heparin or LMWH: If administered concurrently, monitor

coagulation levels closely to prevent clotting issues.

11. Food Interactions

* Vitamin K:

* Green leafy vegetables: High in vitamin K, which can counteract

the effects of vitamin K antagonists (like warfarin). Patients on

anticoagulant therapy should maintain a consistent intake of these foods.

* Alcohol: Excessive alcohol intake may affect liver function,

altering the effectiveness of vitamin K or its role in clotting.

* RiaSTAP: No significant food interactions noted, though patients should

follow healthcare provider dietary recommendations if related to the

bleeding disorder or clotting management.

12. Mechanism of Action

* Vitamin K: It is essential for the synthesis of clotting factors (II, VII, IX,

X) in the liver. Vitamin K helps carboxylate glutamate residues on these

proteins, enabling them to bind calcium and function effectively in the

clotting cascade.

* RiaSTAP: Provides fibrinogen directly to the blood, enhancing clot

formation in patients with low fibrinogen levels, a key component in the

coagulation process.

13. Onset
* Vitamin K:

* Oral: 6-12 hours for effects to be seen (in cases of warfarin

reversal).

* IV/IM: Immediate to within 1 hour.

* RiaSTAP:

* Injection: Immediate effects following administration, with

bleeding control seen within minutes.

14. Duration

* Vitamin K:

* Oral: Lasts about 24 hours.

* IV/IM: Duration of action depends on the clinical situation, but

effects can last up to 1-2 days.

* RiaSTAP:

* Effects are temporary, and repeated dosing may be required based

on the patient's clinical response.

15. Pharmacokinetics

* Vitamin K:

* Absorption: Well-absorbed from the gastrointestinal tract,

particularly when taken with food.

* Distribution: Widely distributed in tissues, including liver (its site

of action).

* Metabolism: Hepatic metabolism.

* Excretion: Excreted in the urine.

* RiaSTAP:

* Absorption: Given IV, quickly enters circulation.

* Distribution: Distributed into the bloodstream, contributing to clot

formation.

* Excretion: Excreted via the kidneys.

16. Storage

* Vitamin K:

* Tablets: Store at room temperature (20 – 25 ° C or 68 – 77 ° F) in a

tightly closed container.

* Injectable forms: Keep refrigerated (2–8°C or 36–46°F) and protect

from light.

* RiaSTAP:

* Storage: Store under refrigeration (2–8°C or 36–46°F), protect from

light, and avoid freezing.

This comprehensive overview of Vitamin K and RiaSTAP provides

essential information on their use in promoting coagulation and managing

bleeding disorders.
 40. Anticoagulant: Warfarin

Medications that prevent blood cloth formation to reduce the risk of stroke

and heart attack.

Generic Name: Warfarin

Brand Names: Coumadin, Jantoven

1. Dosage

* Initial Dosage: Typically, 5 mg to 10 mg orally once daily for the first 2

to 4 days, depending on the patient's INR and clinical condition.

* Maintenance Dosage: Usually 2 mg to 10 mg daily, adjusted based on

the INR, with most patients requiring a maintenance dose of 2–5 mg.

* Pediatric Dosage: Dosing is weight-based and should be individualized,

typically starting at 0.2 mg/kg/day.

* INR Monitoring: Frequent monitoring during initiation and dose

adjustment to maintain an INR range of 2.0 to 3.0 for most indications.

2. Available Formulations

* Oral Tablets: 1 mg, 2 mg, 2.5 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7.5 mg, 10

mg.

* Injectable Form (Rarely used): Warfarin is not commonly given as an

injection; it is mostly administered orally.

3. Indications

* Prevention and treatment of venous thromboembolism (deep vein

thrombosis [DVT], pulmonary embolism [PE]).

* Stroke prevention in patients with atrial fibrillation (AF) or a mechanical

heart valve.

* Post-surgical prophylaxis for thromboembolism (after orthopedic

surgeries like hip or knee replacement).

* Prevention of thromboembolism in patients with known thrombotic

disorders.

4. Contraindications

* Active bleeding (e.g., peptic ulcer, gastrointestinal bleeding, intracranial

hemorrhage).

* Hypersensitivity to warfarin or any of its components.

* Pregnancy (except in certain cases): Category X (can cause fetal harm,

including bleeding, birth defects, and miscarriage).

* Severe hepatic disease: Impaired liver function can alter drug

metabolism and coagulation.

* Recent or planned surgery with high bleeding risk.

* Vitamin K deficiency or conditions that affect clotting factors.

5. Special Precautions

* Bleeding risk: Warfarin significantly increases the risk of bleeding.

Patients should be monitored closely, especially when starting therapy or

adjusting doses.

* Renal impairment: Monitor kidney function, especially if there is

co-administration with other drugs affecting renal function.

* Older adults: Increased sensitivity to warfarin, requiring careful dose

adjustments and frequent INR monitoring.

* Pregnancy: Warfarin is contraindicated during pregnancy due to

teratogenic effects. Alternatives (like heparin) are used in pregnancy.

* Liver disease: Since warfarin is metabolized in the liver, monitor liver

function tests and adjust dosages accordingly.

6. Adverse Reactions

* Common:

* Bleeding complications (most significant, including superficial and

deep bleeds, bruising).

* Nausea and vomiting.

* Alopecia (hair loss).

* Serious:

* Major bleeding (e.g., gastrointestinal, intracranial).

* Hematuria (blood in urine).

 * Hemoptysis (coughing up blood).

* Skin necrosis (rare, may occur due to protein C or S deficiency).

* Purple toe syndrome (painful, purplish discoloration of the toes).

7. Monitoring Parameters

* International Normalized Ratio (INR): Key to monitoring

anticoagulation therapy, aiming for a therapeutic range of 2.0–3.0 for most

indications.

* Prothrombin Time (PT): Used alongside INR as an indicator of clotting

status.

* Complete Blood Count (CBC): Monitor for signs of anemia due to

bleeding.

* Liver Function Tests (LFTs): Warfarin metabolism may be affected in

hepatic impairment.

* Renal Function Tests: Especially in patients with concurrent renal

dysfunction or on other medications that affect kidney function.

* Signs of bleeding: Observe for any new signs of bleeding or bruising.

8. Overdosage

* Symptoms of overdosage include excessive bleeding (gastrointestinal,

cerebral, or superficial), hematuria, and prolonged clotting times.

* INR will be elevated in overdose situations, indicating a higher risk of

bleeding.

9. Management of Overdosage

* Minor bleeding: Discontinue or reduce the dose of warfarin and monitor

closely.

* Severe bleeding: Administer vitamin K1 (phytonadione) to reverse the

anticoagulant effects. In urgent cases, fresh frozen plasma (FFP) or

clotting factor concentrates may be used to rapidly reverse bleeding.

* INR monitoring: Frequent INR testing to guide therapy and reversal as

needed.

* Prothrombin complex concentrates (PCC) or activated PCC: Used in

severe cases of bleeding where immediate reversal is necessary.

10. Drug Interactions

* Increased bleeding risk:

* Aspirin, NSAIDs: Increase bleeding risk when used concurrently.

* Antiplatelet agents (e.g., clopidogrel, ticagrelor).

* Other anticoagulants (e.g., heparin, dabigatran, rivaroxaban).

* Antifungals (e.g., fluconazole) and some antibiotics (e.g.,

macrolides like erythromycin) may increase warfarin levels by inhibiting

metabolism.

* Amiodarone, cimetidine, fluoxetine: Can increase warfarin effects

by inhibiting CYP2C9 enzyme activity.

* Decreased warfarin effect:

* Barbiturates, rifampin, carbamazepine, phenytoin: May reduce

warfarin effectiveness by inducing CYP450 enzymes.

* Vitamin K-rich foods (e.g., kale, spinach, broccoli, liver): Can

decrease the anticoagulant effect by increasing vitamin K availability.

11. Food Interactions

* High Vitamin K foods (e.g., leafy green vegetables, broccoli, kale,

cabbage): Can reduce the effectiveness of warfarin by enhancing clotting

factor synthesis, interfering with the anticoagulant effect.

* Alcohol: Chronic alcohol consumption may affect liver metabolism,

potentially increasing warfarin ’ s effect, while acute alcohol intake may

reduce its effect.

* Grapefruit: May increase the effects of warfarin by inhibiting CYP450

enzymes involved in its metabolism.

12. Mechanism of Action

* Warfarin works by inhibiting the enzyme vitamin K epoxide reductase,

which is responsible for regenerating the active form of vitamin K.

Vitamin K is essential for the synthesis of clotting factors II (prothrombin),

VII, IX, and X. By inhibiting this enzyme, warfarin reduces the synthesis
of these clotting factors, leading to a decreased ability of blood to clot.

13. Onset

* Oral administration: Full therapeutic effect typically takes 2– 5 days to

develop, as the body depletes existing clotting factors.

* Immediate anticoagulant effect: Not observed upon initiation, requiring

bridging with other anticoagulants like heparin in the early days.

14. Duration

* Long duration of action: Warfarin has a half-life of about 20–60 hours,

with effects lasting up to several days after discontinuation.

* INR effects: INR will return to baseline within about 2 – 5 days after

stopping warfarin.

15. Pharmacokinetics

* Absorption: Well absorbed from the gastrointestinal tract, but onset is

delayed due to the need to deplete clotting factors already present in

circulation.

* Distribution: 99% protein-bound, primarily to albumin in plasma.

* Metabolism: Metabolized in the liver by cytochrome P450 enzymes,

particularly CYP2C9.

* Excretion: Excreted primarily in urine as metabolites.

16. Storage

* Tablets: Store at room temperature (20-25 ° C or 68-77 ° F) in a tightly

closed container, away from excess heat, moisture, and light.

* Avoid freezing or storing in extreme temperatures.

This comprehensive overview of warfarin (Coumadin, Jantoven) should

help guide its use, considering the benefits of anticoagulation and the risks

of bleeding, with particular attention to monitoring and drug interactions.

41. Fibrinolytic: Alteplase

Drugs that break down existing blood clots to restore normal blood flow.

Generic Name: Alteplase

Brand Name: Activase

1. Dosage

* Acute ischemic stroke:

* Initial dose: 0.9 mg/kg IV (maximum 90 mg).

* Administer as: 10% of the total dose as an initial bolus over 1

minute, and the remaining 90% as an IV infusion over 60 minutes.

* Acute myocardial infarction (MI):

* Initial dose: 15 mg IV bolus, followed by a continuous infusion of

0.75 mg/kg over 30 minutes, then 0.5 mg/kg over 60 minutes.

* Pulmonary embolism (PE):

* Initial dose: 100 mg IV over 2 hours, in some cases, depending on

weight and clinical conditions.

Note: Dosing should be adjusted based on the clinical scenario, weight of

the patient, and condition being treated.

2. Available Formulations

* IV Solution: Alteplase is typically available as a lyophilized powder that

requires reconstitution before intravenous administration.

* Available in vials: Commonly in 50 mg and 100 mg vials, which are

reconstituted for infusion.

3. Indications

* Acute ischemic stroke: To restore blood flow in patients with acute

ischemic stroke due to a thrombus.

* Acute myocardial infarction (MI): For patients with ST-segment

elevation myocardial infarction (STEMI) who are not candidates for

immediate percutaneous coronary intervention (PCI).

* Pulmonary embolism (PE): For patients with massive PE associated

with hemodynamic instability (e.g., shock or hypotension).

* Acute peripheral arterial occlusion: To treat severe, life-threatening

peripheral arterial occlusion.

4. Contraindications

* Active internal bleeding (e.g., gastrointestinal bleeding, intracranial

hemorrhage).

* History of intracranial hemorrhage or other significant bleeding risk.

* Recent stroke: Within the last 3 months, except in certain cases of acute

ischemic stroke.

* Severe uncontrolled hypertension (e.g., systolic BP >185 mm Hg or

diastolic BP >110 mm Hg).

* Recent surgery or trauma: Especially major surgeries, head trauma, or

non-compressible puncture wounds within 3 weeks.

* Known hypersensitivity to alteplase or any of its components.

5. Special Precautions

* Bleeding risk: Alteplase is a potent fibrinolytic, increasing the risk of

significant bleeding, including intracranial hemorrhage, especially in

patients with a high risk of bleeding.

* Blood pressure control: Keep blood pressure below 180/105 mm Hg

during and after administration to reduce bleeding risk.

* Post-treatment monitoring: Carefully monitor for signs of bleeding,

including neurological status in ischemic stroke and cardiovascular status

in myocardial infarction.

* Recent use of anticoagulants: Patients on anticoagulants, such as

warfarin or direct oral anticoagulants (DOACs), should be monitored

closely due to the potential additive risk of bleeding.

6. Adverse Reactions

* Common:

* Bleeding: The most significant side effect, including major bleeds

(e.g., intracranial, gastrointestinal).

* Allergic reactions: Rash, fever, chills, or anaphylaxis (though rare).

* Serious:

* Intracranial hemorrhage: A potentially life-threatening

complication, particularly in the treatment of acute ischemic stroke.

* Hypotension: May occur during or after administration due to the

rapid restoration of blood flow or bleeding complications.

* Arrhythmias: Including ventricular arrhythmias during myocardial

infarction treatment.

7. Monitoring Parameters

* Neurological monitoring: For signs of bleeding in the brain, particularly

in patients treated for ischemic stroke.

* Vital signs: Blood pressure, heart rate, and oxygen saturation, especially
in the early stages of administration.

* Hemoglobin and hematocrit: To monitor for any signs of significant

blood loss.

* Coagulation profile: To check for any bleeding complications, though

routine monitoring of PT, aPTT, or INR is not typically required.

* Electrocardiogram (ECG): Especially for patients receiving alteplase for

MI, as arrhythmias may occur.

8. Overdosage

* Overdose may result in excessive bleeding, including major bleeding

events such as gastrointestinal or intracranial hemorrhage.

* Signs of overdosage: Excessive bruising, prolonged bleeding,

hematomas, or other signs of significant blood loss.

9. Management of Overdosage

* Discontinue alteplase immediately and initiate appropriate measures to

control bleeding.

* Hemostatic agents: If necessary, consider the use of antifibrinolytics

(e.g., tranexamic acid) or other clot-stabilizing treatments.

* Fresh frozen plasma (FFP): May be administered to reverse fibrinolysis

and replenish clotting factors.

* Supportive care: Include fluid resuscitation and blood transfusions to

manage bleeding.

* Intracranial hemorrhage management: In severe cases, consider surgical

intervention to control bleeding if feasible.

10. Drug Interactions

* Anticoagulants (e.g., warfarin, heparin, direct oral anticoagulants):

Increased risk of bleeding when used together.

* Antiplatelet agents (e.g., aspirin, clopidogrel): May enhance the

bleeding risk when combined with alteplase.

* Other fibrinolytics: Caution when used with other thrombolytic agents,

as it can increase the risk of excessive bleeding.

* NSAIDs: Increase bleeding risk, especially in the context of alteplase

administration.

* ACE inhibitors: Can potentially lower blood pressure, so should be used

cautiously in the acute setting.

11. Food Interactions

* No significant food interactions have been reported with alteplase.

However, maintaining a stable blood pressure and avoiding foods that

might increase bleeding risk (e.g., excessive alcohol consumption) is

important during treatment.

12. Mechanism of Action

* Alteplase is a tissue plasminogen activator (tPA). It activates

plasminogen, which converts into plasmin. Plasmin is a protease that

breaks down fibrin in blood clots, promoting clot lysis and restoring blood

flow to tissues affected by thrombus or embolism.

13. Onset

* Immediate effect: Alteplase begins to dissolve clots immediately after

administration.

* In ischemic stroke: The benefit typically appears within 90 minutes to 3

hours post-infusion, though the most significant benefits are seen within

the first 60 minutes.

14. Duration

* Short-term effect: Alteplase works quickly to break down the clot, and

its effect lasts for several hours, with the clot being resolved and blood

flow restored.

* Effect duration: Can be continued with supportive care for the duration

of the acute episode, but its effects generally do not last beyond the

treatment window.

15. Pharmacokinetics
* Absorption: Alteplase is administered intravenously and enters the

bloodstream immediately.

* Distribution: It is widely distributed throughout the bloodstream and

tissues.

* Metabolism: Alteplase is cleared from the system through the liver and

other proteolytic pathways.

* Excretion: It is metabolized in the liver, and its fragments are excreted

primarily through the urine.

16. Storage

* Lyophilized powder: Store at 2–8°C (36–46°F) in a refrigerator. Do not

freeze.

* Reconstituted solution: Once prepared, the solution should be used

immediately or stored at room temperature for up to 8 hours.

* Protect from light: Store the vial in the original carton to protect from

light.

This comprehensive overview of Alteplase (Activase) provides critical

information on its use as a fibrinolytic agent in treating acute thrombotic

events, as well as the risks, dosages, and monitoring requirements

involved.

42.Antifibrinolytic: Tranexamic Acid

Medications that prevent the break down of blood clots, helping to stop

excessive bleeding.

Generic Name: Tranexamic Acid

Brand Names: Cyklokapron, Lysted

1. Dosage

* For heavy menstrual bleeding (Lysteda):

* Oral: 1,300 mg three times a day for up to 5 days, starting during

menstrual bleeding.

* For surgical bleeding (Cyklokapron):

* IV: 10–15 mg/kg body weight as an initial bolus, followed by 1–2

mg/kg/hour as a continuous infusion.

* For trauma-related bleeding (Cyklokapron):

* IV: 1 g over 10 minutes, followed by 1 g every 8 hours for up to 5

days.

* For bleeding disorders (general):

* Oral: 1–1.5 g every 6 to 8 hours.

* IV: 10 mg/kg body weight every 8 hours for bleeding prevention or

treatment.

2. Available Formulations
* Oral Tablets: 500 mg and 1,300 mg (for use in heavy menstrual bleeding

and other bleeding conditions).

* Intravenous (IV) Solution: Available as a 10 mg/mL solution for

injection or infusion.

* Topical Form: Available for certain surgical applications, though less

common.

3. Indications

* Heavy Menstrual Bleeding: To reduce blood loss in women with

menorrhagia.

* Surgical Bleeding: Used during and after surgery to reduce bleeding and

promote clot stability.

* Trauma-Related Bleeding: Reduces bleeding in trauma and accident

patients.

* Postpartum Hemorrhage: In some cases, to control bleeding after

childbirth.

* Bleeding Disorders: For conditions like hemophilia or other clotting

disorders to prevent or treat excessive bleeding.

4. Contraindications

* Active thromboembolic disease: History of deep vein thrombosis (DVT),

pulmonary embolism (PE), or stroke.

* Hypersensitivity: Known allergy or hypersensitivity to tranexamic acid

or any of its components.

* Subarachnoid hemorrhage: Use is contraindicated in patients with

subarachnoid hemorrhage due to the risk of exacerbating the condition.

* Active bleeding from the gastrointestinal tract: Particularly in patients

with gastric ulcers or other forms of GI bleeding.

5. Special Precautions

* Thromboembolic risk: Tranexamic acid should be used with caution in

patients with a history of thromboembolic events, such as DVT, PE, or

stroke.

* Renal impairment: Dose adjustments may be needed in patients with

renal dysfunction, as the drug is primarily excreted by the kidneys.

* Pregnancy: Use with caution in pregnant women, especially during the

first trimester, though its use is generally considered safe for certain

conditions like postpartum hemorrhage.

* Monitor for bleeding: Regularly monitor for signs of bleeding,

particularly in high-risk patients.

6. Adverse Reactions

* Common:

* Gastrointestinal: Nausea, vomiting, diarrhea, and abdominal pain.

 * Headache: A common side effect during treatment.

* Serious:

* Thromboembolic events: Such as DVT, PE, or stroke, due to the

potential prothrombotic effect of the drug.

* Hypotension: Especially when given intravenously in high doses or

rapidly.

* Allergic reactions: Rare, but can include rash, itching, or

anaphylactic reactions.

* Visual disturbances: Occasionally reported in long-term use,

particularly with high doses.

7. Monitoring Parameters

* Renal function: Monitor serum creatinine and renal function in patients

with pre-existing renal conditions.

* Signs of thromboembolism: Monitor for symptoms of DVT or PE, such

as swelling, redness, chest pain, or shortness of breath.

* Bleeding status: Ensure that bleeding is adequately controlled, and

assess for any signs of excessive clotting or new thrombotic events.

* Hemoglobin and hematocrit: Especially in patients receiving tranexamic

acid for bleeding disorders, to monitor the overall blood loss and recovery.

8. Overdosage
* Symptoms of overdosage include visual disturbances, nausea, vomiting,

and hypotension.

* Overdose may increase the risk of thromboembolic events due to

excessive clot formation.

* IV administration may cause hypotension, especially if administered too

quickly or in high doses.

9. Management of Overdosage

* Discontinue tranexamic acid immediately upon recognition of overdose.

* Symptomatic treatment: Treat symptoms like hypotension or nausea.

* Thromboembolic events: Consider administering anticoagulants or

thrombolytics depending on the clinical situation.

* Monitor for thromboembolic complications, and adjust therapy

accordingly.

10. Drug Interactions

* Oral contraceptives: May increase the risk of thromboembolic events

when used with tranexamic acid.

* Antifibrinolytic agents: Caution with other fibrinolytic drugs, as they

may increase the risk of excessive clot formation or reduce the effect of

tranexamic acid.

* Anticoagulants (e.g., warfarin, heparin): Tranexamic acid may reduce

the effect of some anticoagulants, so monitoring of coagulation parameters

is essential.

* Systemic corticosteroids: May increase the risk of bleeding, so care is

needed when used in combination with tranexamic acid.

11. Food Interactions

* No significant food interactions have been reported with tranexamic acid.

However, it's generally advised to take it with food to reduce

gastrointestinal discomfort.

* Alcohol: Chronic alcohol consumption may increase the risk of

gastrointestinal bleeding, so alcohol should be limited while using

tranexamic acid.

12. Mechanism of Action

* Tranexamic acid is a synthetic antifibrinolytic that works by inhibiting

plasminogen activation to plasmin, a key enzyme that breaks down fibrin

in clots. By blocking this process, tranexamic acid stabilizes the clot,

preventing premature dissolution and thus reducing bleeding.

13. Onset

* Oral administration: Effects typically begin within 2 – 3 hours after

dosing, especially for managing heavy menstrual bleeding.

* IV administration: Effects can be seen within 10–30 minutes of infusion

for surgical or trauma-related bleeding.

14. Duration

* Oral form: The effects last for up to 5 days with dosing every 6–8 hours

for the management of heavy menstrual bleeding.

* IV form: Effects typically last 4–6 hours, but this can vary depending on

the surgical or trauma-related context.

15. Pharmacokinetics

* Absorption: Tranexamic acid is well absorbed after oral administration,

with a bioavailability of about 30–50%.

* Distribution: It is widely distributed in the body, including the plasma

and tissues, with high concentrations in the kidneys.

* Metabolism: It is minimally metabolized in the liver.

* Excretion: The drug is excreted primarily unchanged in the urine.

16. Storage

* Tablets: Store at room temperature (20–25°C or 68– 77°F), away from

moisture and heat.

* IV Solution: Store at 2–8°C (36–46°F), avoid freezing, and protect from

light.
This comprehensive overview of Tranexamic Acid (Cyklokapron, Lysteda)

outlines its therapeutic uses, precautions, side effects, and

pharmacokinetics. It highlights the importance of careful monitoring for

thromboembolic events and the management of bleeding in a variety of

clinical settings.

43.Antiplatelet Drug: Aspirin

Drugs that preventing platelet from clumping together,reducing the risk

clot formation.

Generic Name: Aspirin

Brand Names: Ecotrin, Bayer Aspirin

1. Dosage

* For cardiovascular prevention:

* Low dose (81 mg): Commonly used for prevention of heart attacks,

strokes, and other cardiovascular events. The typical dosage is 81 mg once

daily.

* For pain relief (analgesic):

* Adults: 325 – 650 mg every 4 to 6 hours as needed for mild to

moderate pain (not to exceed 4 grams per day).

* For anti-inflammatory conditions:

* Higher doses (2–4 g/day) for conditions like rheumatoid arthritis or

other inflammatory disorders, divided into multiple doses.

* For acute myocardial infarction (MI):

* Initial dose: 160–325 mg chewed and swallowed immediately after

symptoms of a heart attack start.

2. Available Formulations

* Oral Tablets: Available in 81 mg, 325 mg, 500 mg, and 650 mg dosages.

* Enteric-coated tablets: E.g., Ecotrin, which help reduce stomach

irritation and are often prescribed for long-term use.

* Chewable tablets: Available in 81 mg and 325 mg.

* Suppositories: For patients unable to take aspirin orally.

3. Indications

* Primary and secondary prevention of cardiovascular events: Aspirin is

used to reduce the risk of heart attacks, strokes, and other related events in

high-risk individuals.

* Acute myocardial infarction (MI): Used for the management of acute

heart attacks.

* Pain relief: For mild to moderate pain relief, including headaches,

muscle pain, or minor arthritis pain.

* Anti-inflammatory: For conditions like rheumatoid arthritis,

osteoarthritis, and other inflammatory diseases.

* Fever reduction: For treating fever associated with infections or other

causes.

* Prevention of blood clot formation: Especially for patients after certain

surgeries or those with a history of clotting disorders.

4. Contraindications

* Active gastrointestinal bleeding: Aspirin can exacerbate bleeding,

especially in individuals with active peptic ulcers or gastrointestinal

bleeding.

* History of gastrointestinal ulcers: Caution is needed in patients with a

history of stomach ulcers or gastrointestinal disorders.

* Allergy to aspirin or other NSAIDs: Contraindicated in patients with

known hypersensitivity to aspirin, nonsteroidal anti-inflammatory drugs

(NSAIDs), or salicylates.

* Children and teenagers with viral infections: Risk of Reye's syndrome—

a potentially life-threatening condition.

* Severe liver or kidney disease: Aspirin should be avoided or used with

extreme caution in patients with severe liver or renal impairment.

* Hypersensitivity to aspirin: A history of asthma, urticaria, or allergic

reactions after taking aspirin or other NSAIDs.

5. Special Precautions

* Gastrointestinal issues: Use cautiously in individuals with a history of

gastrointestinal problems such as ulcers, gastritis, or gastrointestinal

bleeding.

* Bleeding risk: Aspirin inhibits platelet aggregation and increases

bleeding risk. It should be used cautiously in patients with bleeding

disorders or those undergoing surgery.

* Renal impairment: Dosage adjustments may be necessary, especially in

patients with compromised kidney function.

* Pregnancy: Avoid during the third trimester due to the risk of premature

closure of the ductus arteriosus in the fetus.

* Asthma and nasal polyps: Aspirin should be used with caution in

patients with asthma, as it may cause bronchospasm.

* Chronic alcohol use: Heavy alcohol consumption can increase the risk

of gastrointestinal bleeding with aspirin.

6. Adverse Reactions

* Gastrointestinal: Stomach irritation, indigestion, nausea, vomiting,

peptic ulcers, gastrointestinal bleeding, and perforation.

* Allergic reactions: Rash, swelling, or difficulty breathing. Severe

reactions like anaphylaxis are rare.

* Bleeding: Risk of prolonged bleeding times, nosebleeds, and easy

bruising.

* Renal: In high doses, aspirin may impair renal function, especially in

individuals with preexisting kidney disease.

* Hearing issues: Tinnitus (ringing in the ears) at higher doses.

* CNS effects: Headache or dizziness in some cases.

7. Monitoring Parameters

* Coagulation status: Monitor bleeding time, platelet count, and

prothrombin time (PT) in patients taking aspirin long-term or in those at

high risk for bleeding.

* Gastrointestinal symptoms: Monitor for signs of gastrointestinal

bleeding, especially in patients with risk factors like a history of ulcers.

* Renal function: Monitor kidney function, especially in patients with

preexisting kidney disease.

* Hematocrit and hemoglobin: To assess for potential blood loss or

bleeding complications.

8. Overdosage

* Symptoms of overdosage:

* Tinnitus (ringing in the ears)

* Hyperventilation (rapid breathing)

 * Nausea and vomiting

* Confusion or dizziness

* Metabolic acidosis and respiratory alkalosis

* Severe cases: May lead to coma, seizures, renal failure, and death.

9. Management of Overdosage

* Immediate treatment:

* Activated charcoal: To reduce absorption if the overdose is within a

few hours.

* Alkalinization of urine: With sodium bicarbonate to enhance

aspirin elimination.

* Hydration: Intravenous fluids to help with kidney function.

* Hemodialysis: In severe cases, particularly for individuals with

renal failure.

* Symptomatic treatment: Address symptoms like nausea, vomiting, and

respiratory distress.

10. Drug Interactions

* Anticoagulants (e.g., warfarin, heparin): Increased risk of bleeding due

to additive effects.

* Other NSAIDs: Increased risk of gastrointestinal bleeding and ulceration.

Should not be used together.

* Corticosteroids: Increase the risk of gastrointestinal ulcers when used

with aspirin.

* Alcohol: Increases the risk of gastrointestinal bleeding and ulcers.

* Methotrexate: Aspirin can increase methotrexate levels, increasing the

risk of toxicity.

* ACE inhibitors and diuretics: Aspirin may reduce the effectiveness of

certain blood pressure medications and diuretics, especially in high doses.

11. Food Interactions

* No significant food interactions are known for aspirin. However, taking

aspirin with food may help minimize gastrointestinal irritation.

* Alcohol: Should be avoided or minimized as it increases the risk of

gastrointestinal bleeding, especially with regular aspirin use.

12. Mechanism of Action

* Aspirin works by irreversibly inhibiting cyclooxygenase (COX-1 and

COX-2) enzymes. This inhibition reduces the formation of thromboxane

A2, a molecule that plays a key role in platelet aggregation (clumping) and

vasoconstriction. By reducing thromboxane A2, aspirin prevents platelets

from clumping together and forming blood clots.

13. Onset
* Oral administration: Begins to take effect within 30 minutes to 1 hour for

pain relief.

* For cardiovascular prevention: Aspirin’s effects on platelet aggregation

are immediate after ingestion, but full effects in terms of reducing

cardiovascular events take longer to manifest with consistent use.

14. Duration

* For pain relief: The effects of aspirin typically last 4–6 hours for mild to

moderate pain.

* For cardiovascular protection: Aspirin ’ s effects on platelet aggregation

last for 7–10 days due to the irreversible inhibition of COX-1 in platelets.

15. Pharmacokinetics

* Absorption: Aspirin is rapidly absorbed from the gastrointestinal tract,

with peak plasma concentrations occurring within 30 minutes to 2 hours of

oral administration.

* Distribution: It is widely distributed throughout the body, including the

liver, kidneys, and lungs.

* Metabolism: Aspirin is metabolized in the liver into salicylic acid, which

is the active form.

* Excretion: Aspirin and its metabolites are primarily excreted in the urine.

The half-life of aspirin is approximately 15–20 minutes, but the half-life of

its active metabolite, salicylic acid, is much longer (2–3 hours).

16. Storage

* Tablets: Store at room temperature (20–25°C or 68– 77°F), away from

moisture and heat. Keep out of reach of children.

* Enteric-coated tablets: Should be stored in a cool, dry place, and

protected from light to preserve the coating.

* Suppositories: Store at room temperature or as directed by the

manufacturer.

This comprehensive overview of Aspirin (Ecotrin, Bayer Aspirin) outlines

its critical use in cardiovascular disease prevention, pain relief, and

inflammatory conditions, as well as the precautions, side effects, and

mechanisms of action. It highlights the importance of monitoring for

bleeding risks, especially with long-term use or high doses.

44.Antineoplastic Drug: Methotrexate

Medications used to treat cancer by inhibiting the growth and division of

cancer cells.

Generic Name: Methotrexate

Brand Names: Rheumatrex, Trexall

1. Dosage

* For cancer (e.g., leukemia, lymphoma):

* Oral: 15– 30 mg once weekly (depending on the cancer type and

treatment protocol).

* Intravenous (IV): Doses of 3.3 – 5 mg/m ² per week or higher,

depending on the specific cancer and regimen.

* High-dose regimens: May vary significantly based on the specific

cancer and response to treatment, often administered in cycles.

* For rheumatoid arthritis (RA):

* Oral: 7.5–25 mg once weekly.

* For psoriasis:

* Oral: 10–25 mg once a week or as prescribed based on severity.

* For ectopic pregnancy (medical management):

* Intramuscular (IM): A single dose of 50 mg/m ² , repeated after a

certain period if necessary.

2. Available Formulations

* Oral Tablets: Available in 2.5 mg, 5 mg, and 10 mg.

* Injectable Forms: Available as IV or IM injection in 25 mg/mL and 50

mg/mL concentrations.

* Solution for Injection: Available in concentrations suited for various

routes of administration.

3. Indications

* Cancer treatment:

* Used for various cancers, including leukemia, lymphomas, breast

cancer, head and neck cancer, non-Hodgkin lymphoma, and

choriocarcinoma.

* Autoimmune diseases:

* Rheumatoid arthritis (as a disease-modifying antirheumatic drug).

* Psoriasis (severe, recalcitrant cases).

* Crohn's disease (moderate to severe).

* Ectopic pregnancy: Used to manage medically, in cases of non-ruptured

ectopic pregnancy.

4. Contraindications

* Pregnancy: Methotrexate is contraindicated in pregnancy, especially in

the first trimester, as it is a teratogen.

* Breastfeeding: Methotrexate is excreted in breast milk, and breastfeeding

should be avoided.

* Active infections: It should not be used in patients with active infections

or in those with compromised immune systems.

* Liver disease: Contraindicated in patients with severe hepatic

impairment (e.g., cirrhosis).

* Renal impairment: Use with caution in patients with impaired renal

function, as methotrexate is primarily excreted via the kidneys.

* Hypersensitivity: Known allergy or hypersensitivity to methotrexate or

any of its components.

5. Special Precautions

* Hematologic monitoring: Methotrexate can cause bone marrow

suppression, so regular blood counts (including white blood cells, platelets,

and hemoglobin) should be monitored.

* Liver function: Regular liver function tests (LFTs) are essential,

especially in high-dose regimens or prolonged use.

* Renal function: Methotrexate can accumulate in patients with renal

dysfunction, so renal function should be assessed before and during

treatment.

* Hydration: Ensure adequate hydration, particularly when using

high-dose methotrexate.
* Pregnancy category: Methotrexate is Category X in pregnancy. Women

of childbearing potential should be advised to avoid pregnancy during

treatment and for several months afterward.

* Vaccinations: Live vaccines should be avoided during treatment, as

methotrexate can suppress the immune response.

6. Adverse Reactions

* Gastrointestinal: Nausea, vomiting, stomatitis (inflammation of the

mouth), and diarrhea.

* Hematologic: Bone marrow suppression, leading to anemia, leukopenia,

thrombocytopenia, and increased infection risk.

* Liver: Hepatotoxicity, including elevated liver enzymes, cirrhosis, and

fatty liver.

* Renal: Renal toxicity (particularly in high doses), renal failure in severe

cases.

* Pulmonary: Pulmonary fibrosis, pneumonitis, and other lung-related

issues.

* Dermatologic: Skin rash, alopecia (hair loss), and photosensitivity.

* Neurologic: Headache, dizziness, fatigue, and occasionally, seizures.

* Oral: Ulcers and mucositis (inflammation of mucous membranes).

7. Monitoring Parameters
* Hematologic: Regular blood counts (CBC with differential) to monitor

for bone marrow suppression.

* Liver: Liver function tests (LFTs), including ALT, AST, and bilirubin

levels.

* Renal function: Serum creatinine and blood urea nitrogen (BUN) levels.

* Pulmonary function: Monitor for signs of pulmonary toxicity (cough,

shortness of breath, chest pain).

* Serum methotrexate levels: In cases of high-dose methotrexate, serum

levels may need to be monitored to guide treatment.

* Pregnancy test: For women of childbearing potential, a negative

pregnancy test should be confirmed before starting methotrexate.

8. Overdosage

* Symptoms:

* Severe gastrointestinal distress (nausea, vomiting, diarrhea).

* Hematologic: Bone marrow suppression, bleeding, and increased

infection risk.

* Renal: Acute renal failure.

* Hepatic: Severe hepatotoxicity and liver failure.

* Signs of toxicity may appear within hours to days of an overdose.

9. Management of Overdosage
* Leucovorin (folinic acid): The antidote for methotrexate toxicity.

Leucovorin is given to help reverse the effects of methotrexate on the bone

marrow and gastrointestinal system.

* Hydration: Aggressive intravenous fluids to prevent renal toxicity and

facilitate methotrexate clearance.

* Activated charcoal: May be used in cases of recent ingestion to reduce

absorption.

* Hemodialysis: In cases of severe toxicity or renal failure, hemodialysis

may be necessary to remove methotrexate from the system.

* Supportive care: Treat symptoms such as nausea, vomiting, and bone

marrow suppression.

10. Drug Interactions

* NSAIDs: Increases the risk of methotrexate toxicity due to reduced renal

clearance.

* Salicylates (e.g., aspirin): Can increase methotrexate levels, increasing

the risk of toxicity.

* Penicillins and cephalosporins: May interfere with methotrexate

clearance, leading to increased levels of the drug.

* Probenecid: Decreases methotrexate renal clearance, potentially

increasing methotrexate levels.

* Trimethoprim-sulfamethoxazole (TMP-SMX): Increases the risk of

methotrexate toxicity, especially in high doses.

* Corticosteroids: May decrease the effectiveness of methotrexate in

treating autoimmune diseases.

11. Food Interactions

* Alcohol: Chronic alcohol consumption may increase the risk of liver

damage when used with methotrexate.

* Folic acid: Folate supplementation may reduce the side effects of

methotrexate, especially in the treatment of rheumatoid arthritis and

psoriasis, but should be used cautiously to avoid interfering with

methotrexate's effectiveness in cancer therapy.

12. Mechanism of Action

* Methotrexate is a folate antagonist. It works by inhibiting the enzyme

dihydrofolate reductase (DHFR), which is involved in the conversion of

dihydrofolate to tetrahydrofolate. This is crucial for the synthesis of

nucleotides, which are necessary for DNA and RNA synthesis. By

inhibiting this enzyme, methotrexate interferes with cell division,

especially in rapidly dividing cells like cancer cells, as well as in the

immune system cells involved in autoimmune diseases.

13. Onset
* Cancer treatment: Effects may take weeks to months to become apparent

depending on the tumor type and response.

* Rheumatoid arthritis: Initial effects may take several weeks, with

optimal effects visible after 6–12 weeks.

* Psoriasis: Improvement in symptoms can occur within 4 – 6 weeks of

starting therapy.

14. Duration

* Cancer: The effects last as long as the treatment is ongoing.

Methotrexate is often given in cycles, with treatment intervals lasting

weeks.

* Autoimmune diseases: Long-term treatment may be required to maintain

disease control, often with periodic doses.

* Psoriasis: Treatment duration may vary, depending on the severity of the

condition and response to therapy.

15. Pharmacokinetics

* Absorption: Methotrexate is absorbed rapidly after oral administration,

but bioavailability is variable(approximately 50%).

* Distribution: Widely distributed throughout the body, including the liver,

kidneys, lungs, and cerebrospinal fluid.

* Metabolism: Primarily metabolized in the liver to inactive metabolites.

* Excretion: Methotrexate is excreted primarily unchanged by the kidneys.

Renal impairment can lead to methotrexate accumulation.

16. Storage

* Oral tablets: Store at room temperature (20–25°C or 68–77°F) in a dry

place, away from light.

* Injectable form: Store at room temperature or according to manufacturer

instructions (usually protected from light and moisture).

This comprehensive overview of Methotrexate (Rheumatrex, Trexall)

highlights its critical role in cancer treatment, autoimmune disease

management, and the necessary precautions when using the drug. Regular

monitoring and supportive care are essential to manage adverse reactions

and toxicity, ensuring its safe and effective use.

45.Immunosuppressant Drug: Cyclosporine

Drugs that suppress the immune system to prevent organ rejection or treat

autoimmune

diseases.

Generic Name: Cyclosporine

Brand Names: Neoral, Sandimmune

1. Dosage

* Organ Transplantation:

* Initial Dose: 10–15 mg/kg/day (divided into 2 doses) for solid organ

transplant recipients, such as kidney, liver, or heart transplants.

* Maintenance Dose: 5 – 10 mg/kg/day depending on serum

cyclosporine levels and organ transplant type.

* Rheumatoid Arthritis:

* Oral: 3–5 mg/kg/day.

* Psoriasis:

* Oral: 2.5–5 mg/kg/day.

* Nephrotic Syndrome: 5 mg/kg/day, typically given as a divided dose.

2. Available Formulations

* Oral Capsules: 25 mg, 50 mg, and 100 mg.

* Oral Solution: 100 mg/mL (Sandimmune), 50 mg/mL (Neoral).

* Intravenous (IV) Solution: 100 mg/10 mL.

3. Indications

* Prevention of organ rejection in kidney, liver, and heart transplants.

* Autoimmune diseases such as:

* Rheumatoid arthritis (when other treatments fail).

* Psoriasis (severe, recalcitrant cases).

* Nephrotic syndrome.

* Severe atopic dermatitis.

* Chronic dry eye disease (keratoconjunctivitis sicca), as an adjunct

therapy.

4. Contraindications

* Hypersensitivity to cyclosporine or any of its components.

* Severe renal dysfunction: Cyclosporine can exacerbate renal

impairment.

* Uncontrolled infections: Immunosuppressive effect increases

susceptibility to infections.

* Pregnancy: Use during pregnancy only if the benefit outweighs the risk

(Category C).

* Breastfeeding: Cyclosporine is excreted in breast milk; avoid use during

breastfeeding unless essential.

* Active malignancy: Due to its immunosuppressive nature, cyclosporine

should not be used in patients with active malignancy.

* Liver disease: Severe hepatic impairment requires caution, especially

during initiation of therapy.

5. Special Precautions

* Kidney function: Monitor renal function closely, as cyclosporine is

nephrotoxic. Baseline creatinine levels should be checked before starting

treatment.

* Infection risk: Increased risk of infections due to immunosuppressive

effects.

* Cancer: Long-term use may increase the risk of malignancy (especially

skin cancers, lymphoma).

* Drug interactions: Cyclosporine is metabolized by the CYP3A4 enzyme.

Be cautious when using with drugs that may inhibit or induce this enzyme.

* Hypertension: Cyclosporine may cause or worsen high blood pressure.

* Liver function: Monitor liver function tests during treatment, as liver

toxicity can occur.

6. Adverse Reactions

* Nephrotoxicity: Renal dysfunction is common, including acute renal

failure, hyperkalemia, and hypertension.

* Infections: Increased susceptibility to bacterial, viral, fungal, and

opportunistic infections.

* Hypertension: May develop or worsen existing high blood pressure.

* Gastrointestinal: Nausea, vomiting, diarrhea, and abdominal pain.

* Neurological: Tremors, headache, and, rarely, seizures.

* Hyperglycemia: Cyclosporine may impair insulin secretion, leading to

elevated blood glucose levels.

* Hirsutism: Excessive hair growth, particularly in women.

* Gingival hyperplasia: Overgrowth of the gums.

* Liver: Elevated liver enzymes and potential liver damage.

* Lipids: Increased levels of cholesterol and triglycerides.

7. Monitoring Parameters

* Serum cyclosporine levels: Blood levels should be monitored to ensure

therapeutic range (typically 100– 400 ng/mL depending on the condition

treated).

* Renal function: Regular monitoring of serum creatinine and BUN

(blood urea nitrogen) levels.

* Blood pressure: Regular monitoring to detect hypertension.

* Liver function tests (LFTs): Monitor for elevated liver enzymes (AST,

ALT).

* Lipids: Periodically monitor cholesterol and triglycerides.

* Electrolytes: Potassium and magnesium levels should be monitored, as

cyclosporine can affect electrolyte balance.

* Infection monitoring: Regularly assess for signs of infections, especially

during immunosuppressive therapy.

8. Overdosage

* Symptoms: Acute overdosage can lead to nephrotoxicity, hypertension,

hyperkalemia, and gastrointestinal symptoms like vomiting and diarrhea.

* Treatment: There is no specific antidote for cyclosporine overdose.

Treatment focuses on supportive care, including:

* Intravenous fluids to support renal function and maintain hydration.

* Monitoring of renal and electrolyte status.

* Dialysis may be required in cases of severe toxicity.

9. Management of Overdosage

* Supportive care: Intravenous fluids to hydrate and support renal

function.

* Hemodialysis: Used in severe cases of overdose or renal failure,

although cyclosporine is only partially dialyzable.

* Discontinue cyclosporine: Temporarily stop therapy until levels return to

normal.

* Close monitoring: Regular blood tests to monitor renal function and

cyclosporine levels.
10. Drug Interactions

* CYP3A4 Inhibitors: Drugs like ketoconazole, itraconazole,

clarithromycin, erythromycin, and grapefruit juice can increase

cyclosporine levels, increasing the risk of toxicity.

* CYP3A4 Inducers: Drugs such as phenytoin, rifampin, and

carbamazepine can reduce cyclosporine levels, leading to subtherapeutic

levels and risk of transplant rejection or disease flare.

* Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): Combined use may

worsen nephrotoxicity.

* Other immunosuppressants: Combined use with other

immunosuppressive agents (e.g., corticosteroids) can increase the risk of

infections and malignancy.

* Diuretics: May increase the risk of hypokalemia or hyperkalemia when

used with cyclosporine.

* Statins: Cyclosporine can increase the levels of statins in the blood,

increasing the risk of statin-associated muscle toxicity.

11. Food Interactions

* Grapefruit juice: Grapefruit and grapefruit juice can inhibit the CYP3A4

enzyme, leading to increased cyclosporine blood levels and potentially

increasing the risk of toxicity.

* High-fat meals: May increase the absorption of cyclosporine, potentially

leading to elevated blood levels.

12. Mechanism of Action

* Cyclosporine is a calcineurin inhibitor that works by inhibiting the

activation of T-cells. It binds to cyclophilin, and the

cyclosporine-cyclophilin complex inhibits calcineurin, a protein

phosphatase necessary for T-cell activation. By inhibiting calcineurin,

cyclosporine prevents the transcription of interleukin-2 and other

cytokines, which are essential for the proliferation of T-cells involved in

the immune response.

13. Onset

* Organ Transplantation: Effectiveness typically begins within 4–7 days of

initiating therapy.

* Autoimmune diseases: Clinical improvement may take 2– 4 weeks for

noticeable results.

* Rheumatoid arthritis and psoriasis: Improvement may take several

weeks to achieve clinical benefits.

14. Duration

* Organ transplantation: Lifelong use may be required to prevent organ

rejection.

* Autoimmune diseases: Duration of use depends on the condition and

response to therapy. Can be long-term but typically tapered once disease

control is achieved.

15. Pharmacokinetics

* Absorption: Cyclosporine is well absorbed orally, but bioavailability is

variable and may range from 30% to 60%. Absorption is enhanced when

taken with food (especially high-fat meals).

* Distribution: It is highly protein-bound (around 90%) in the blood and

widely distributed throughout the body.

* Metabolism: Cyclosporine is primarily metabolized in the liver by the

CYP3A4 enzyme.

* Excretion: Excreted primarily in the bile and feces; a small amount is

excreted in the urine.

16. Storage

* Oral capsules and solution: Store in a cool, dry place at room

temperature (20–25°C or 68–77°F). Protect from light and moisture.

* Intravenous solution: Store at room temperature and protect from light.

This detailed profile of Cyclosporine (Neoral, Sandimmune) highlights its

crucial role as an immunosuppressive drug, particularly in preventing

organ rejection and treating autoimmune disorders. Regular monitoring,

cautious management of drug interactions, and vigilant observation for

side effects are critical for safe and effective use.