Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

DMPK > Lecture 03/04 Key tissues in DMPK > Flashcards

Lecture 03/04 Key tissues in DMPK Flashcards

1
Q

In what part of the body does absorption, metabolism, distribution and excretion processes may happen?

Physiology of the tissue in PK processes

A
  • Gastrointestinal tract (GIT) - Mainly absorption / Metabolism and excretion (through bile)
  • Liver - Metabolism mainly and distribution
  • Kidney - Excretion mainly, minimal metabolism

Absorption in much lesser extent may occur in skin (topical) and lungs (

This is only applicable if you are providing the drug extravascularly

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

GI Tract

Provide a brief explanation of the physiology of the GI tract

How does it work, what is its purpose

A
  • GI tract digests material at the top, extracts useful products and expells waste at the bottom.
  • The whole system is under hormonal control (under the prescence of food in the mouth, a cascade of hormonal actions happens)
  • As food enters, the hormones trigger acid secretions, enzyme release and gut mobility
  • Nutrients are highly absorbed in the GI tract and transported to the liver to be broken down, stored or distributed (metabolism)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

GI tract

What are the major DMPK organs of the digestive system?

A

Stomach and intestine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the parts of the upper GI tract?

A

Oesophagus, stomach and duodenum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the part of the lower GI tract?

A

Small intestine and large intestine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Where are digestive juices producted?

A

In the pancreas and gallbladder

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are the parts of the small intestine?

A

Duodenum, jejunum, and ileum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the parts of the large intestine?

A

Cecum, colon, rectum, anus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the oseophagus for?

A
  • Is a fibromuscular tube that food passes through, aided by peristaltic contractions, the pharynx to the stomach
  • Saliva moistens food, while amylase (found in saliva) starts to break down starch into simple sugars
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What does the stomach do?

A

Secretes protein-digesting enzymes called proteases and strong acids to aid in food digestion, before sending the partially digested food to the small intestine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What does the duodenum do?

A

The first section of the small intestine that may be the principal site for iron absorption

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What hapens in the stomach with the ingested food?

Include pH of stomach and what can be absorbed there

A
  • Highly gastrict juices (pH 1 - 2) and enzymes mix with partially digested food to produce chyme. Muscularised walls help also with mixing.
  • Few substances can be absorbed in the stomach, they are usually broken down by highly acidic conditions (lipophilic drugs and weakly acidic drugs)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What can protect drugs for being broken down by the acid conditions of the stomach?

A

Enteric coating

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

The stomach

Name 2 examples of compounds that can be absorbed in the stomach and why

A

Aspirin and ethanol because they are weakly acidic and become ionised at the low pH of the stomach

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

The stomach

Name the 4 major cell types in the stomach

A

Parietal cells, gastric chief cells and mucous neck and pit cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

The stomach

What is the function of parietal cells?

A

Produce HCl and instrinsic factor (aids absorption of vitamin B12)

Parietal cells in red/pink
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

The stomach

What is the function of gastric chief cells?

A

Production of pepsinogen and lipase

Chief cells in purple
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

The stomach

What is the function of mucous neck and pit cells?

A

Produce mucin and bicarbonate to create a “neutral zone” to protect the stomach lining from acid or irritants in the stomach chyme

Mucous and neck cell in orange
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is the function of G cells

A

Produce the hormone gastrin (CCKB agonist) in response to distention of the stomach mucosa or protein, and stimulate parietal cells’ production of their secretion

G cell in blue
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

The small intestine

What is the function of the duodenum?

A
  • Digestive enzymes from the pancreas and the gallbladder (bile) mix together, break down proteins and emulsify fats into micelles
  • Brunner’s glands that produce bicarbonate
  • Pancreatic juice also contains bicarbonate to neutralize hydrochloric acid in the stomach
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

The small intestine

What is the function of the Jejunum?

A
  • The midsection of the intestine, connecting the duodenum to the ileum
  • Contains the plicae circulares (circular folds/flaps) and villi to increase the surface area of that part of the GI tract
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

The small intestine

What is the function of the Ileum?

A

Has villi, with an enormous surface area, where soluble molecules are absorbed into the blood (through capillaries and lacteals)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

In the small intestine…

What is the mucosa and submucosa?

Mention its composition and its function

A
  • The mucosa is the absorptive and secretory layer
  • It is composed of simple epithelium cells and a thin connective tissue in specialized layout – villi, microvilli
  • The submucosa is relatively thick, highly vascular, and contains lymph vessels (lymphatic system), glands and nerve plexuses
  • The absorbed elements that pass through the mucosa are picked up from the blood vessels of the submucosa

Mucosal increases surface area by 600-fold

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

The small intestine

What is below the mucosa and submucosa and what is its function?

A

The muscolaris and serosa.
* Muscolaris: Responsible for segmental contractions and peristaltic movement in the GI tract
* Serosa: Its a protective layer composed by avascular connective tissue and simple squamous epithelium. It secretes lubricating serous fluid

Note to the two bottom parts
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Absorption routes

How are highly hydrophilic substances absorbed?

A

Absorbed through transporters

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Absorption routes

How and where will weak acids and bases be absorbed?

A

By simple diffusion to a greater extent in the neutral ileum (pH 7-8) in which they exist in the most lipid-soluble (non-ionised) state

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Absorption

Usually to where are hydrophilic substances transported?

Name the organ

A

To the liver by the portal vein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

To where are hydrophobic compounds transported?

Is a system, mention how it is transported there

A

Highly hydrophobic compounds may be absorbed into the lymphatic system via chylomicrons and drained into venous circulation near the heart

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What happens if a drug moves through the GI tract quickly (diarrhoea)?

A

It will not be well absorbed

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What is the largest organ inside the body?

What is its weight?

A

The liver/ 14 kg

Alters in size and shape dependant on the amount of blood present

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What is the percentage of blood flood that goes through the liver?

A

25%

32
Q

Which is the only viceral organ capable of regenerating

A

The liver
~25 % of the original liver mass can regenerate a full size liver

33
Q

What are the two large vessels the liver is conected to and what is their purpose?

A
  • Hepatic portal vein: Carries nutrient rich blood from the GI tract
  • Hepatic artery: Carries oxygenated blood from the aorta
34
Q

Into how many lobes is the liver divided?

Describe them

A
  • Split into four main lobes
  • Each lobe consists of a number of hepatic lobules
  • Lobules are roughly hexagonal, and consist of plates of hepatocytes radiating from a central vein
35
Q

What is the purpose of the central vein in the liver?

A

Carry blood out from the liver

36
Q

The liver

What is a portal triad?

A

A distinctive component of a lobule which can be found running along each of the lobule’s corners

36
Q

The liver

What is the structure of the portal triad?

A

The portal triad, misleadingly named, consists of five structures:
* Branch of the hepatic artery
* Branch of the hepatic portal vein
* A bile duct
* Lymphatic vessels
* Branch of the vagus nerve

37
Q

What are liver sinusoids?

A

They are enlarged capillaries between the hepatocyte plates through which blood from the hepatic portal vein and hepatic artery enters via the portal triads, then drains to the central vein

38
Q

Describe the cells that compose the liver and the % of liver volume they compose

A
  • Parenchymal hepatocytes are 70–85 % of liver volume
  • Non-parenchymal cells constitute 40 % of the total number of liver cells but only 6.5 % of its volume
39
Q

What are the two types of cells the liver sinusoids are lined to?

A

Sinusoidal endothelial cells and phagocytic Kupffer cells

40
Q

What are hepatic stelleate cells?

A

Hepatic stellate cells are non-parenchymal cells found in the perisinusoidal space, between a sinusoid and a hepatocyte

41
Q

Where are intrahepatic lymphocytes found?

A

In the sinusoidal lumen

42
Q

What is the function of hepatocytes in the liver?

A

Perform numerous metabolic, secretary and endocrine functions

43
Q

Why are the hepatocytes considered “power houses” more than any other cell in the body?

A

They contain more rough and smooth endoplasmic reticular, mitochondria and lysosomes than most other cells within the body

44
Q

Describe how hepatocytes are arranged in the liver

A

Hepatocytes are arranged into complex plates called hepatic laminae which are one cell thick and are highly branched
Hepatocytes are lined by vascular spaces called hepatic sinusoids with grooves in their membrane for the canaliculi to secrete bile into

45
Q

Mention some key functions of the liver

A
  • Carbohydrate, lipid and protein metabolism
  • Sodium metabolism – the assimilation of salt from our diet
  • Regeneration
  • Processing drugs and hormones – endocrine function either reacts with or destroys most hormones – detoxification
  • Synthesis of bile salts
  • Excretion of bilirubin
  • In foetus’ and new born babies, the liver produces red blood cells (erythropoiesis)
  • Storage of: glycogen, vitamins A, B12, D, E and K, iron, copper
  • Activation of vitamin D
  • Kupffer cells kill/recycle aged cells and phagocytose pathogens
  • Processing all of the blood within the body
  • Regulation of blood clotting
46
Q

What is induction (in the liver)?

A

Interpreted as an attempt to keep up with the excessive amount of poison that people chuck into their bodies by increasing the number of enzymes within the hepatocytes (ex. when there is an excessive amount of alcohol or drugs in our bodies)

47
Q

What is conjugation (in the liver)?

A

Is the process where hepatocytes create compounds which can be excreted via the biliary system, so the liver also plays an important process when it comes to digesting food and accessing certain nutrients

48
Q

Where are the kidneys situated within the body?

A

High in the abdominal cavity, one on each side of the spine

49
Q

Describe the renal circulation (blood supply)

A

The renal circulation supplies the blood to the kidneys via left and right renal arteries
* The first branches from the abdominal aorta
* Despite their relatively small size, the kidneys receive approximately 20 % of cardiac output
*

50
Q

What are the functions of the kidney?

A
  • Regulation of the water and electrolyte content of the body
  • Retention of substances vital to the body such as protein and glucose
  • Maintenance of acid/base balance
  • Excretion of waste products, water soluble toxic substances and drugs
  • Endocrine functions
    *
51
Q

How is the parenchyma kidney divided? Describe these structures.

A

The parenchyma of the kidney is divided into two major structures
* The outer renal cortex
* The inner renal medulla
Grossly, these structures take the shape of 8-18 cone-shaped renal lobes, each containing renal cortex surrounding a portion of medulla called a renal pyramid (of Malpighi)

52
Q

What are the nephrons?

A

The urine-producing functional structures of the kidney, span the cortex and medulla

53
Q

How are nephrons distributed in the kidney

A

The initial filtering portion of a nephron is the renal corpuscle which is located in the cortex
This is followed by a renal tubule that passes from the cortex deep into the medullary pyramids
Part of the renal cortex, a medullary ray is a collection of renal tubules that drain into a single collecting duct

54
Q

What is the function of a nephron?

A

The unit of the kidney responsible for ultrafiltration of the blood and reabsorption or excretion of products.

55
Q

Describe the 4 recognizable sections of the kidney and their function

A

Four recognizable sections
* Glomerulus: Sieve-like structure that filters the blood (125 ml/min of filtrate formed)
* Proximal convoluted tubule: Controlled absorption of glucose, sodium, and other solutes
* Loop of Henle: Concentration and dilution of urine by utilising a counter-current multiplying mechanism
* Distal convoluted tubule and collecting duct: Responsible for absorbing water back into the body
99% of the water is normally reabsorbed, leaving highly concentrated urine to flow into the collecting duct and then into the renal pelvis

56
Q

What is the function of the proximal tubule in the nephron?

A

Proximal tubule is responsible for controlled absorption
Normally 60 % of all solutes are reabsorbed
* 100 % glucose and amino acids
* 90 % bicarbonate
* 80-­90 % inorganic phosphate and water
It has a ‘leaky’ epithelium
Solute reabsorption active; water is passive

57
Q

How is urine produced?

3 processes

A

Urine is produced in the kidney by three processes
1. Simple filtration
2. Reabsorption: Selective (active) and passive
3. Excretion

58
Q

Which proteins play a role in selective reabsorption and excretion in the kidney?

A

Transporters play a role in selective reabsorption and excretion
Active processes are generally mediated by uptake transporters (e.g. SLC22A8/OAT3)

59
Q

What are the physicochemical proterties of drugs that tend to be eliminated by the urine?

A

Drugs eliminated in the urine tend to be small and hydrophilic

60
Q

Describe how a drug is secreted from the body in the kidneys

A

3 stages:
* Glomerular filtration
* Tubular secretion
* Reabsorption
1. Filtration is passive removal of free drug in solution therefore no concentration occurs
2. Tubular secretion is active therefore drug removed from plasma regardless of concentration gradient
3. Reabsorption from tubule depends on lipid solubility
* Polar/charged molecules retained
* Depends on pH (which can be modified in case of overdose)

61
Q

Where is the respiratory system situated? What is its function?

A

In the thorax. Responsible for gaseous exchange between the circulatory system and the outside world

62
Q

Describe how the air is taken up by the respiratory system

A

Air is taken in via the upper airways (the nasal cavity, pharynx and larynx) through the lower airways (trachea, primary bronchi and bronchial tree) and into the small bronchioles and alveoli within the lung tissue

63
Q

How are the lungs divided

A

The lungs are divided into lobes:
* The left lung is composed of the upper lobe, the lower lobe and the lingula (a small remnant next to the apex of the heart)
* The right lung is composed of the upper, the middle and the lower lobes

64
Q

The lungs

Describe the “bronchial tree”

A

As you descend the trachea branches out into layers of bronchi, bronchioles and ultimately alveoli, where gas exchange occurs

65
Q

What substances can be absorbed by the lungs?

Mention examples of drugs

A

Dry powder: Inhalers
* Fluticasone propionate
* Salmeterol
Aerosols: Nebulized drugs
* Salbutamol
Gases: Inhalation anaesthetics
* Isoflurane
Vapors or volatile liquids
* Benzene
* Carbon tetrachloride

66
Q

What is the organ most penetrable to macromolecules?

A

The lungs

67
Q

Describe absorption in the lungs

A

Absorption is rapid:
* Lipophilic small molecules are absorbed extremely rapidly, t½= 1-2 min
* Water-soluble small molecules are absorbed rapidly t½= 10’s of min
BUT - the epithelium of the lung is a significant barrier to absorption
* The change in cell types and morphology going from trachea, bronchi, and bronchioles to alveoli is dramatic

68
Q

Where does the drug need to reach to be well absorbed in the lungs

A

Drug needs to be delivered deep into the airways to be most efficiently absorbed

69
Q

How does absorption of gases differ from intestinal or percutaneous absorption?

A

Epithelial cells lining the alveoli (type I pneumocytes) are very thin and the capillaries are in close contact with the pneumocytes, so the diffusion distance is very short
Chemicals absorbed by the lungs are rapidly removed by the blood
(3-4 s for blood to pass through the lung capillary network)
*Difficulty in breathing may reduce effectiveness of inhalation route

70
Q

Describe what happens in your lungs when a gas is inhaled

A
  1. When a gas is inhaled into the lungs, gas molecules diffuse from the alveolar space into the blood and then dissolve
  2. The gas molecules partition between the air and blood during the absorptive phase, and between blood and other tissues during the distributive phase.
  3. Note that inhalation bypasses first-pass metabolism
71
Q

Is the skin permeable?

A

Skin is not very permeable and a good barrier for separating organisms from their environment

72
Q

What needs to happen for drugs to be absorbed by the skin?

A

To be absorbed through the skin, substances must pass through the epidermis or the appendages (sweat, sebaceous glands, hair follicles)
Once absorbed through the skin, substances must pass through several tissue layers before entering the small blood and lymph capillaries in the dermis

73
Q

What is the rate-determining barrier in the skin?

A

Epidermis

74
Q

Why are cell walls in the skin chemically resistant?

A

They are 2x thicker than other cells and dry
* Cells are in a keratinous, semisolid state with much lower permeability for substances by diffusion
* The stratum corneum cells have lost their nuclei and are biologically inactive
* Once a substance is absorbed through the stratum corneum, absorption through the other epidermal layers is rapid

75
Q

Describe how substances move across after dermal exposure

A

All substances move across the stratum corneum by passive diffusion
* Polar substances diffuse through the outer surface of protein filaments of the hydrated stratum corneum
* Non-polar molecules dissolve and diffuse through the lipid matrix between protein filaments
The rate of diffusion is proportional to lipid solubility and inversely proportional to molecular weight

76
Q

Do we need to consider first pass metabolism for substances absorbed by the skin?

A

No. Substances absorbed through the skin enter the systemic circulation directly, and therefore bypass first-pass metabolism

DMPK (7 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions