Lecture 6 Flashcards

1
Q

What is the route of administration of a drug primarily determined by?

A
  1. Properties of the drug – water or lipid solubility, ionisation, etc.
  2. Therapeutic objectives – desire for rapid onset of action, need for long term administration, restriction to a local site, etc.
    • “What are you trying to achieve and how can you best achieve it?”
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2
Q

What are some commonly used routes of drug administration?

A
  • Pareneteral: IV, IM, SC
  • Sublingual
  • Inhalation
  • Oral
  • Transdermal patch
  • Rectal
  • Topical
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3
Q

What are the 2 major routes of drug administration?

A
  1. ENTERAL - goes through a hole/orifice
  2. PARENTERAL - inject = break the skin barrier
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4
Q

List some Enteral, Parenteral and other routes of drug administration

A

Enteral

  • Oral; Sublingual; Rectal

Parenteral

  • Intravascular (IV) Intramuscular (IM) Subcutaneous (SC)

Other

  • Inhalation; Intranasal; Intrathecal / intraventricular; Topical; Transdermal
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5
Q

Describe The oral route of drug administration

A
  • mc
  • most variable(effects)
  • most complicated pathway(long) to the tissues
  • easiest for compliance with conscious Pt
  • usually absorbed by the upper GI tract (not stomach) then passes through the portal venous system where it can undergo First-Pass Metabolism
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6
Q

Why would you need to consider other routes of administration instead of Oral?

A
  • If The drug is unstable or is rapidly inactivated in the GI tract.
  • Loss of drug absorbance via the GI tract
  • limited amounts of the drug gets through first-pass metabolism in the liver so an insufficient levels reach the target, vomiting or a disease state.
  • Therapeutic effects demand local administration as systemic absorption would lead to adverse drug effects
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7
Q

Describe FIRST-PASS METABOLISM

A
  • drug is absorbed in upper GI (oral)
  • enters venus sytem must go through hepatic prortal vein to liver where it metabolises and degrades
  • then exits via bile duct and returns to the venus system
  • If drug is administered via IV drip it directly enters venous system and bipasses the liver (1st pass metabolism)
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8
Q

Describe the SUPLINGUAL route of administration

A

placement under tongue allows for drug to diffuse into the capillary network, avoiding first-pass liver metabolism and directly entering the systemic circulation.

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9
Q

Describe the RECTAL route of administation

A
  • Since there is limited portal blood flow (very few BV go to the liver), exposure of drug to first-pass metabolism is less than with the oral route.
  • useful if drug induces vomiting when given orally or if patient is already vomiting
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10
Q

What are some reasons for administering a drug via the PARENTERAL route?

A
  • for drugs that are poorly absorbed from the GI tract
  • for drugs that are unstable in the GI tract
  • in treatment of unconscious patients
  • in treatment where rapid onset of action is required
  • Provides most control over actual dose delivered - (can assume almost 100% gets to target organ)
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11
Q

Describe INTRAMUSCULAR & SUBCUTANEOUS routes of administration

A

both require absorption of drug into tissue. Use of carrier vehicles (such as peanut oil) allows for control of delivery

intramuscular = drug injected directly into skeletal muscle

subcutaneous = absorbtion of drugs from subcutaneous tissues

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12
Q

Describe the INHALATION route of administration

A

allows for rapid delivery of drug across a large surface area (pulmonary/respiratory system). Used for drugs that are gases or aerosols.

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13
Q

Describe the INTRATHECAL/INTRAVENTRICULAR routes of administration

A

Introduction of drugs directly into cerebral spinal fluid.

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14
Q

Describe a TOPICAL route of administration

A

Used when a local effect of the drug is required.

For Example:

  • eye drops
  • ear drops
  • intranasal
  • via skin
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15
Q

Describe a TRANSDERMAL route of administration

A

This administration route achieves systemic effect by application of drugs to skin via a transdermal patch. Although absorption through skin may vary this route is used when sustained delivery is needed.

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16
Q

What two ways can a drug be absorbed on a cellular level?

A
  1. Passive diffusion – depends on a concentration gradient (from high to low) across a membrane separating 2 body compartments.
  2. Active transport – involves specific carrier proteins that span the membranes and is generally an energy requiring process
17
Q

What are some CHEMICAL PROPERTIES & PHYSIOLOGICAL VARIABLES that influence drug absorbtion?

A

Chemical properties:

  • Chemical nature
  • Molecular weight
  • Solubility
  • Partition coefficient

Physiological variables:

  • Gastric motility
  • pH at absorption site
  • Area of absorbing surface
  • Mesenteric blood flow
  • Presystemic elimination
  • Ingestion with/without food
18
Q

What are some other PHYSICAL FACTORS influencing drug absorption?

A
  1. Blood flow to the absorption site: the intestine is the favoured site of absorption as there is greater BF compared to the stomach
  2. Surface area available: the intestinal surface is covered in microvilli making its total surface area 1000 times greater than that of the stomach = greater efficiency of absorption
  3. Contact time at absorption surface: any condition that delays rate of passage of drug from the stomach to the GI tract (e.g. presence of food) = increased contact time. If rate of passage through the GI is incresed (e.g. severe diarrhoea) = reduced efficiency of absorption
19
Q

What is BIOAVAILABILITY and how is it calculated

A

Expressed as the fraction of administered drug that gains access to the systemic circulation in a chemically unaltered form

(how much of a drug is available for biological action)

  • is determined by comparing plasma levels of a drug by a particular route of administration (e.g. oral) with plasma levels achieved by IV administration (which must be 100%).
  • plot graph
    • x axis = time
    • y axis = [plasma] of drug
  • BIOAVAILABILITY = AUC oral/AUC injected x 100
20
Q

Define Vd and how is it calculated?

A

Volume Distribution

Vd = relates the amount of drug in the body to the concentration in the plasma

Vd = (Total amount of drug in the body mg) / (plasma [drug] mg/L)

Units = L

Total body Volume = 42L

  • Intracellular Volume = 28L
  • Extracellular Volume = 14L
    • Interstitial Volume = 10L
    • Plasma Volume = 4L
21
Q

What is the effect of drug binding on Volume Distribution (Vd)

A
  • drugs have to move from a vascular compartment to extravascular compartments of the body to give effect
  • but it is inefficient (low Vd) if the drug cannot get off the protein and into the system
22
Q

As a general rule what kind of drugs can easily and cannot pass through the lipid membrane of a body compartment

A

Easily enter:

  • Lipid soluble drugs enter cells (e.g. ethanol)
  • Weak acids + weak bases (uncharged form)
  • sml organic molecules low MW < 100 generally

Limited entry:

  • Highly ionised drugs are confined to the extracellular fluid (e.g. turbocurarine)
  • Drugs that are highly protein bound or have high molecular weight (e.g. heparin) are retained in the circulation