5 - Parenteral Flashcards

1
Q

Why is the IM route often chosen over other parenteral routes?

A
  • Relative simplicity

- Lack of need for specially trained personnel

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2
Q

What are the common routes of parenteral administration?

A
  • Intravenous
  • Intramuscular
  • Subcutaneous
  • Intradermal
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3
Q

What are advantages to IV administration?

A
  • Fastest onset of action b/c drug is injected directly into systemic circulation
  • No lag time for drug to be absorbed
  • Provides 100% bioavailability
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4
Q

What is the difference between bolus and infusion?

A
  • Bolus = dose given all at once over short period of time; Cmax achieved almost instantaneously
  • Infusion = drug injected into vein over sustained period; may be intermittent where dose is administered at timed intervals
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5
Q

When and why is a loading dose given? What are examples of drugs that require loading dose?

A
  • For drugs w/ short half-life and narrow therapeutic window
  • Given to achieve therapeutic serum levels faster
  • Ex: heparin, lidocaine (desirable for serum levels to remain constant); nitroglycerin, dopamine (dose adjustments made according to px response)
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6
Q

What are some reasons to choose IV route over oral?

A
  • Drug is subject to first-pass metabolism or destroyed in GI tract
  • Drug not absorbed via GI tract
  • Poor oral absorption and drug is a vesicant (causes blistering)
  • Dose too high to give orally
  • Rapid response is required
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7
Q

What are problems w/ the IV route?

A
  • Some drugs given too rapidly may cause toxicities

- For some products, excipients like alcohol or propylene glycol may be a problem

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8
Q

Which drugs are solubilized using propylene glycol (PG)? What is the problem w/ PG?

A
  • Lorazepam, phenytoin, pentobarbital, and digoxin

- Infants can’t metabolize and excrete PG efficiently, so repeated dosing of these may lead to toxicity

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9
Q

What are side effects of propylene glycol?

A
  • CNS toxicity
  • Hyperosmolarity
  • Hemolysis
  • Cardiac arrhythmia
  • Seizures
  • Agitation
  • Lactic acidosis
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10
Q

What are the common sites of IM injections?

A
  • Deltoid
  • Gluteus
  • Lateral thigh
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11
Q

Why does the IM route produce a longer time to onset of action than IV?

A
  • Drug must move from muscle to systemic circulation

- Distribution to circulation is diffusion controlled

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12
Q

What affects the rate of absorption of IM injections?

A
  • Local blood flow

- Injections to deltoid have faster onset of action than injections to gluteal muscle b/c deltoid has better blood flow

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13
Q

What affects volume of absorption of IM injections?

A
  • Site of injection
  • Gluteal muscles can absorb 4-5 mL
  • Deltoid muscle can absorb 2-3 mL
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14
Q

How are water soluble drugs and water insoluble drugs formulated?

A
  • Water soluble = aqueous solutions; distribute fairly quickly after injection
  • Water insoluble = dissolved in fixed oils; stay at site of injection and slowly release drug as vehicle is metabolized
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15
Q

What is the depot formulation? What is it used for?

A
  • Water insoluble drug + fixed oil (ex: ester or oil-soluble salt dissolved in fixed oil)
  • Used to maintain therapy through prolonged release
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16
Q

What is an example of a depot formulation?

A
  • Fluphenazine, antipsychotic

- Depot formulation allows dosing every 2-6 weeks depending on px response

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17
Q

What is an example of depot injections formulated as an aqueous suspensions? How does it work?

A
  • Penicillin G benzathine / penicillin G procaine w/ carboxymethylcellulose as suspending agent
  • Insoluble drugs hydrolyzed in tissues, releasing free penicillin G which is absorbed systemically
18
Q

Where are subcutaneous injections administered?

A

Into fatty tissue layer just below epidermis and dermis

19
Q

What is the max volume of SC injections? What happens if this volume is exceeded? Which drugs does it deliver?

A
  • Max = 1.5 mL; over 2 mL associated w/ various issues including injection pain and injection site leakage
  • Delivers protein biopharmaceuticals
20
Q

What happens if a drug given SC requires a high dose?

A

Must use a concentrated solution

21
Q

What affects the stability of SC injections? Why?

A
  • Protein concentration

- Increases chance for aggregation and particle formation during shelf-life

22
Q

Are SC injections absorbed slower or faster than IM injections? Why?

A
  • Slower

- Less blood flow to fatty tissue below the skin than to muscle

23
Q

Which drugs are often given by the SC route?

A
  • Insulin
  • Growth hormone
  • Heparin
  • Various vaccines
24
Q

What are the systems used for drugs where toxicity and/or delivery to site is problematical?

A
  • Liposomal systems

- Polymeric systems

25
What are liposomes?
Closed spherical vesicles made of phospholipid bilayer where drug is encapsulated either in the cavity or wall structure
26
What happens when liposomes are administered orally?
Destroyed by stomach acid, bile acids and enzymes of GI tract
27
Which types of drugs can liposomes encapsulate?
- Both lipophilic and hydrophilic | - Lipophilic inserted into bilayer membrane and hydrophilic in aqueous center
28
What are advantages of liposomal systems?
- Biocompatibility - Ability to carry large drug payloads - Can be modified to control biological characteristics through surface modification w/ polymers and ligands - Protect compounds from early inactivation, degradation and dilution in circulation
29
Are liposomes active? Do they produce toxicity?
Inactive and minimal toxicity b/c composed of natural phospholipids
30
What are the 4 key types of liposomal delivery systems?
- Conventional liposomes - Sterically-stabilized liposomes - Ligand-targeted liposomes - Combination of previous
31
What are conventional liposomes?
- Lipid bilayer that can be composed of cationic, anionic, or neutral (phospho)lipids and cholesterol enclosing aqueous center - Reduce toxicity of compounds by modifying PK and biodistribution to enhance drug delivery to diseased tissue - Prone to rapid elimination from bloodstream due to uptake by fixed macrophages of reticuloendothelial system (RES), mainly in liver and spleen
32
What are PEGylated liposomes? What are they used for? What is a disadvantage to this?
- Improve stability and prolong circulation times in blood - Hydrophilic polymer (PEG) used to obtain sterically-stabilized liposomes, which slow uptake by RES thereby prolonging blood residence time, providing accumulation at pathological sites, and attenuating SE - Can reduce ability to interact w/ intended targets
33
How do ligand-targeted liposomes work?
Offer site-specific delivery of drugs to designated cell types which selectively express or over-express specific ligands (like receptors or cell adhesion molecules) at site of disease
34
What are the possible ligands for ligand-targeted liposomes?
Antibodies, peptides/proteins, and carbs
35
Contrast the outer membrane surface of conventional, PEGylated, and ligand-targeted liposomes
- Conventional = negatively and positively charged lipids - PEGylated = PEG attached to hydrophilic heads of membrane - Ligand-targeted = receptors for common ligands (proteins, antibodies, carbs) attached to PEG which is attached to hydrophilic head of membrane
36
Describe the doxorubicin liposome injection. When is it used?
- Doxorubicin encapsulated in PEGylated liposomes - Various types of cancer; found to be effective alternative to conventional doxorubicin in px w/ pre-existing cardiac dysfunction
37
What is the benefit to a doxorubicin liposome injection?
Doxorubicin in PEGylated liposomes minimizes uptake and clearance by RES, prolonging serum and plasma half-life and allows drug to accumulate in tumour tissue rather than non-target healthy tissue
38
Which side effect is reduced w/ the amphotericin-B liposome injection?
Renal toxicity
39
What determines drug release from IM or SC depot injections?
Diffusion or erosion of polymer matrix
40
What are commonly used synthetic biodegradable polymers?
- Polyesters (most common; PLA, PGA, and PLGA w/ PGA releasing drug the fastest) - Polyanhydrides - Polyamides
41
What is leuprolide acetate? When is it used?
- Microsphere formulation where drug is embedded in matrix of PLGA - Used in men to treat symptoms of prostate cancer and in women to treat sx of endometriosis or uterine fibroids
42
What is paclitaxel used for?
Tx of metastatic breast cancer