Drug Delivery Systems Overview

Drug Variables

• Dosage refers to the frequency, size, and number of doses
• Dosage depends on reason for use, potency, pharmacokinetics, route of administration, dosage form, and recipient
• Loading dose: a larger dose at the beginning of drug therapy to attain a rapid blood level of the drug
• Maintenance dose: quantity of drug needed to keep blood levels and/or tissue levels at a steady state

Route of Administration

• Affects drug actions and patient responses
• Rapid response: IV (injected directly into the bloodstream) and IM (produces a fast effect)
• Slow response: Oral (due to first-pass effect)
• Absorption and action vary on drug formulation

Drug-Diet Interactions

• Used therapeutically to decrease food absorption in the intestinal tract
• Examples: Orlistat (Xenical) decreases the absorption of fats from food, and ezetimibe (Zetia) decreases absorption of cholesterol from food
• Undesirable interactions: food often slows absorption of oral drugs, and certain foods react with drugs (e.g., MAO inhibitors, warfarin, vitamin K, dairy, and grapefruit)

Drug-Drug Interactions

• Increase or decrease therapeutic or adverse effects
• Types of interactions:
  • Additive effects: two drugs with similar pharmacological actions (e.g., ethanol and sedative drugs)
  • Synergism: two drugs produce greater effects when taken together (e.g., acetaminophen and codeine)
  • Interference: intensify effects of the second drug
  • Displacement: a drug exchanges with another, increasing the effect of the second drug
  • Antidote: given to antagonize the toxic effects of another drug
  • Decreased intestinal absorption of oral drugs when combined with other drugs

Preparations and Dosage Forms

• Vary according to drug's chemical characteristics, reason for use, and route of administration
• Types of dosage forms:
  • Liquids
  • Tablets
  • Capsules
  • Suppositories
  • Transdermal and pump delivery systems

Medication Administration Process

• Follow the "rights" associated with medication administration consistently
• Learn essential information about each drug to be given
• Interpret the prescriber's order accurately
• Question the prescriber if any information is unclear
• Calculate doses accurately
• Verify the identity of all patients before administering medications

Clopidogrel

• Antiplatelet effects similar to aspirin
• Reversibly blocks the ADP receptor on platelet cell surface
• Indications for use: reduction of myocardial infarction, stroke, and vascular death in patients with atherosclerosis
• Specific uses: prevention of vascular ischemic events, acute coronary syndrome, and thrombosis following placement of an intracoronary stent

Prasugrel and Ticagrelor

• Other ADP receptor antagonists
• Similar to clopidogrel but with different mechanisms and effects
• Uses: reduction of thrombotic cardiovascular events, including stent thrombosis

Heparin

• Pharmaceutical preparation of the natural anticoagulant
• Prototype anticoagulant
• Antidote: protamine sulfate
• Pharmacokinetics: given intravenously or subcutaneously
• Action: combines with antithrombin III to inactivate clotting factors
• Uses: prophylactic prevention of DVT and pulmonary embolism, management of acute thromboembolic disorders, and disseminated intravascular coagulation (DIC)### Heparin Administration
• Heparin therapy requires platelet counts before therapy begins and every 2-3 days during therapy
• If platelet count falls below 100,000 platelets per microliter of blood or to less than half the baseline value, heparin should be discontinued
• Heparin-induced thrombocytopenia (HIT) is a potentially life-threatening complication of heparin administration

Contraindications and Administration

• Contraindications include GI ulcerations, intracranial bleeding, dissecting aortic aneurysm, blood dyscrasias, severe kidney or liver disease
• aPTT (activated partial thromboplastin time) should be maintained at approximately 1.5 to 2.5 times the control or baseline value

Pharmacokinetics and Pharmacodynamics

• Absorption: the process by which a drug enters the body and reaches the bloodstream
• Distribution: the transport of drug molecules within the body to their sites of action, metabolism, and excretion
• Metabolism: the method by which the body inactivates drugs
• Excretion: the elimination of a drug from the body

Pharmacodynamics

• Receptors: proteins located on the surfaces of cell membranes or within cells that bind to drug molecules
• Agonist effect: drugs that produce effects similar to those produced naturally occurring hormones, neurotransmitters, and other substances
• Antagonist effect: drugs that inhibit cell function by occupying receptor sites

Serum Half-life

• Serum half-life: the time required for the serum concentration of a drug to decrease by 50%
• Half-life is determined by the drug's rate of metabolism and excretion
• Four to five half-lives are required to achieve steady-state concentrations and to develop equilibrium between tissue and serum concentrations

Drug-Related Variables

• Dosage: the frequency, size, and number of doses; a major determinant of drug actions and responses
• Route of administration: affects drug actions and patient responses
• Drug-drug interactions: may be increased or decreased
• Drug-diet interactions: used therapeutically to decrease food absorption in the intestinal tract or undesirable because food often slows absorption of oral drugs

Dosage Forms and Drug Preparations

• Dosage forms of systemic drugs include liquids, tablets, capsules, suppositories, and transdermal and pump delivery systems
• Controlled-release tablets and capsules maintain more consistent serum drug levels and allow less frequent administration

Medication Administration Process

• The nurse adheres to the following principles: follow the "rights" associated with medication administration consistently, learn essential information about each drug, interpret the prescriber's order accurately, and calculate doses accurately### Adenosine Diphosphate (ADP) Receptor Antagonists

• ADP receptor antagonists, including clopidogrel, prasugrel, and ticagrelor, have antiplatelet effects similar to aspirin and inhibit the ADP receptor on platelet surfaces.

• Clopidogrel has three shortcomings: delayed onset of action, irreversible inhibitory effects on platelets with no reversing agent or antidote, and significant individual variability in platelet response.

Pharmacokinetics of Clopidogrel

• Clopidogrel is rapidly absorbed after oral administration and undergoes extensive first-pass metabolism in the liver.
• It is converted to its active form by hepatic CYP2C19 and CYP3A4 enzymes.
• Platelet inhibition may occur 2 hours after a single dose, but the onset of action is slow, so an initial loading dose is usually administered.
• The drug has a half-life of about 8 hours and is excreted in the urine and feces.

Action of Clopidogrel

• Clopidogrel irreversibly blocks the ADP receptor on platelet cell surfaces.
• Effective dose-dependent prevention of platelet aggregation can be seen within 2 hours of a single oral dose.
• Platelet inhibition essentially lasts for the lifespan of the platelet (7-10 days).

Use of Clopidogrel

• Indications for use include reduction of myocardial infarction, stroke, and vascular death in patients with atherosclerosis and in those after placement of coronary stents.
• Specific uses include prevention of vascular ischemic events in patients with symptomatic atherosclerosis or with acute coronary syndrome (with or without ST-segment elevation).
• People with atrial fibrillation who are unable to take vitamin K antagonists take clopidogrel instead.

Safety and Precautions of Clopidogrel

• Older adults are more likely than younger ones to experience bleeding and other complications of antiplatelet drugs.
• Clopidogrel may accumulate in people with hepatic impairment.
• Caution is necessary for people with variant forms of CYP2C19, who may be poor or ultrarapid metabolizers of clopidogrel.

Adverse Effects of Clopidogrel

• The most common adverse effects associated with clopidogrel are pruritus, rash, purpura, and diarrhea.
• Thrombotic thrombocytopenic purpura, hemorrhage, and severe neutropenia have also occurred.

Prasugrel and Ticagrelor

• Prasugrel demonstrated improved cardiac outcome compared with clopidogrel for acute coronary syndromes involving percutaneous coronary intervention.
• Ticagrelor is the latest ADP receptor antagonist, used to reduce the rate of cardiovascular death, myocardial infarction, and stroke in patients with a history of myocardial infarction or acute coronary syndrome.
• Ticagrelor differs from clopidogrel and prasugrel in that receptor blockade is reversible.

Heparin

• Heparin is a prototype anticoagulant, used to prevent and treat thromboembolic disorders.
• It combines with antithrombin III to inactivate clotting factors IX, X, XI, and XII, inhibit the conversion of prothrombin to thrombin, and prevent thrombus formation.

Pharmacokinetics of Heparin

• Heparin is administered intravenously or subcutaneously, as the gastrointestinal tract does not absorb the drug.
• After IV injection, the drug acts immediately; after subcutaneous injection, heparin acts within 20-30 minutes.
• Metabolism takes place in the liver and the reticuloendothelial system, and excretion occurs in the urine.

Use of Heparin

• Prophylactically, patients at risk for certain disorders take low doses of heparin to prevent DVT and pulmonary embolism.
• Heparin is used to manage acute thromboembolic disorders, such as DVT, thrombophlebitis, and pulmonary embolism.
• Another use is in disseminated intravascular coagulation (DIC), a life-threatening condition characterized by widespread clotting.

Adverse Effects of Heparin

• Hemorrhage is a major adverse effect of heparin.
• Heparin-induced thrombocytopenia (HIT) is a potentially life-threatening complication of heparin administration, leading to a decrease in platelet count and detectable HIT antibodies.

Contraindications of Heparin

• Contraindications include GI ulcerations, intracranial bleeding, dissecting aortic aneurysm, blood dyscrasias, severe kidney or liver disease.