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Toxicology > Lecture 1 > Flashcards

Lecture 1 Flashcards

1
Q

What does ADME stand for?

A

Absorption
Distribution
Metabolism
Excretion

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2
Q

There are 4 main routes for systemic administration of drugs

A
  • Enteral route
  • Parenteral route
  • Inhalation
  • Transdermal route
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3
Q

Enteral routes of administration

A

Sublingual
Oral
Rectal

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4
Q

Parenteral routes of administration

A

Intravenous (IV)
Intramuscular (IM)
Subcutaneous (SC)
Intradermal injection

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5
Q

Topical routes of administration

A

Epidermic
Irrigation
Instillation

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6
Q

Inhalation routes of administration

A

Vaporization
Gas inhalation
Nebulization

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7
Q

What is the difference between enteral and parenteral?

A

The difference between parenteral and enteral routes of administration is that the parenteral route
completely bypasses the digestive system, eliminating the effects of first-pass metabolism. In contrast,
enteral routes use the digestive system, including the mouth, stomach, small intestine, and anus

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8
Q

What are the two types of mucus membranes

A
  1. Respiratory mucosa (lines most of the nasal cavity)- Pseudostratified ciliated columnar epithelium, scattered goblet cells
  2. Seromucus nasal glands- contain mucous secreting cells and serous cells
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9
Q

Where does intranasal absorption occur

A

Absorption occurs through thin mucus membranes that line the nasal passages

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10
Q

What are some important properties for nasal delivery

A

molecular size and weight
pH
partition coefficient

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11
Q

What size do particles need to be to reach the alveolar sacs?

A

0.5-1 um. Particles outside this range are either
exhaled or deposited on larger bronchial
airways

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12
Q

Advantages of intrathecal therapy

A

Better analgesia with fewer side effects and a lower dose of drugs
administered as the drug is taken directly to the receptors with a good impact on severe spasticity in adults and children

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13
Q

Angles for administration of injection

A

Intramuscular injection- 90 degrees
Subcutaneous injection- 45 degrees
Intravenous injection- 25 degrees
Intradermal injection- 10-15 degrees

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14
Q

What is the bioavailability of intravenous

A

100%

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15
Q

Intramuscular injections are used when?

A

The intramuscular route is used where effects are desired over a longer period of time than can be
expected after intravenous injection, for drugs that are too irritant to be given subcutaneously, or for oily
solutions, which cannot be given intravenously

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16
Q

The skin is comprised of three primary layers

A
  1. The epidermis (provides waterproofing and serves as a barrier to infection)
  2. The dermis (serves as a location for the appendages of skin)
  3. The hypodermis (subcutaneous adipose layer)
17
Q

What is the stratum corneum?

A

The stratum corneum is the outermost layer of the epidermis and is
composed mainly of dead keratinised cells (from lack of oxygen and
nutrients).

18
Q

What is the dermis?

A

The dermis is the layer of skin beneath the epidermis. It contains the
hair follicles, sweat glands, sebaceous glands, apocrine glands,
lymphatic vessels and blood vessels.

19
Q

What is the hypodermis?

A

Its purpose is to attach the skin to underlying bone and
muscle as well as supplying it with blood vessels and nerves. The main
cell types are fibroblasts, macrophages and adipocytes (the
hypodermis contains 50% of body fat).

20
Q

Factors that affect the absorption of an epidermal
administered drug

A
  1. Damage in the stratum corneum (layer)
  2. Region of the body
  3. High lipid-water partition coefficient (and small molecular size)
  4. Cleansing of the skin (and friction)
21
Q

How do transdermal drug delivery systems work?

A

Transdermal drug delivery system delivers the drugs through the skin portal to
systemic circulation at a predetermined
rate and maintain clinically the effective
concentrations over a prolonged period of
time.
The drug must traverse three layers, the
stratum cornium, the epidermis, and the
dermis. Of these, the toughest barrier is the
stratum corneum, which consists of 10-25
layers of keratinized cells.

22
Q

What are the four types of wearable transdermal delivery systems?

A
  1. Mechanoresponsive delivery systems
  2. Electrically activated delivery skins
  3. Bioresponsive delivery systems
  4. Light triggered delivery patches
23
Q

Factors in skin permeation

A
  1. Thickness of the skin layer- thickest on palms and soles and thinest on the face
  2. Skin condition- permeability of skin is affected by age, disease state or injury.
  3. Skin temperature- permeability increases with increase in temp.
  4. Hydration state- the greater the hydration, the higher and better the absorption of substances, in particular polar
    substances.
24
Q

What does sublingual mean?

A

Drug is placed under tongue

25
Q

What does buccal mean?

A

Drug is placed between gums and lips

26
Q

How long does it take for the effects of sublingual drugs occur

A

Immediately

27
Q

Orally administered drugs are most absorbed where?

A

Drug molecules are mostly absorbed from duodenum,
jejunum and upper ileum

28
Q

What are the two main
processes for the oral administered drugs before the
absorption process?

A

Disintegration and dissolution

29
Q

What is bioavailability?

A

The fraction of toxin or drug reaching the systemic circulation after
administration

30
Q

Bioavailability varies between

A

0-100% (or 0-1)

31
Q

What is first-pass metabolism

A

Reduced drug concentration that enters the
circulation as a result of metabolism by the liver

32
Q

How do you work out bioavailability?

A

The bioavailability (F) of a drug delivered via other routes of administration can be determined by the mass of the drug delivered to the plasma divided by the total mass of the drug administered:

F = mass of the drug delivered to the plasma ÷ total mass of the drug administered

In pharmacologic contexts, an area under the curve graph (AUC) plots the plasma
concentration of a drug on the y-axis versus time following drug administration on the
x-axis. The area under the curve is directly proportional to drug absorption. Recall
that the bioavailability of any drug delivered intravenously is theoretically 100%, or 1.
This allows for convenient calculation of the bioavailability of drugs not delivered intravenously. By dividing the area under the curve of a drug delivered orally, for example, by the area under the curve for the same dose of that same drug delivered intravenously, one may successfully calculate the bioavailability of the oral drug.

F = AUC for X route of administration ÷ AUC for IV administration
Bioavailability

33
Q

Drug Related Factors That Affect Bioavailability

A
  • Particle size,
  • Crystalloid structure,
  • Salt compound / free,
  • Degree of hydration,
  • Drug formulation affects the dissolution and disintegration
34
Q

Patient Related Factors That Affect Bioavailability

A
  • Differences in first-pass metabolism,
  • drug metabolism differences between individuals (pharmacogenomics),
  • diseases that affect the GI motility,
  • age,
  • gender,
  • body weight,
  • drug-drug or drug-food interactions
35
Q

Physiological Factors That Affect the Absorption from GI Tract

A
  • Stomach emptying time
  • Taking pills on a full or empty stomach (generally doesn’t affect the absorption ratio but it affects the absorption rate)
  • Drug-food interactions may be important.
  • Absorption of drugs which are taken on an empty stomach starts earlier and it
    reaches the effective plasma concentration earlier than expected.
  • Some drugs are recommended to be taken with food to minimize the irritant effect of the drug to the gastric mucosa.
  • The motility of intestines (constipation or diarrhoea)
36
Q

Advantages of rectal routes of administration

A

*Can be used when oral route is unsuitable (e.g severe vomiting, uncooperative or unconscious patient)
* Useful when the drug causes GIT irritation
*NO first-pass elimination

37
Q

Disadvantages of rectal routes of administration

A
  • Absorption can be irregular and unpredictable
  • Less convenient than other route
  • Low patient acceptability in the UK
    *Risk of rectal bleeding
    *Increased bacteremia risk for immunosuppressive patients
    *Decreased absorption in diarrhea and constipation.

Toxicology (8 decks)

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