week 7

Question 1

Omeprazole logP. What are its pKa’s

Answer 1

logP= 2.23
pKas 4 and 9

Question 2

Where is omeprazole absorbed?

Answer 2

small intestine

Question 3

How may a patient take omeprazole if they are unable to wholly swallow a capsule?

Answer 3

recommend taking drug out of capsule and washing it down with an acidic liquid such as orange juice. Chewing should not be promoted as this will break the coating which helps the drug to work

Question 4

which aminosalicylates are converted to sodium salts?

Answer 4

balsalazide and olalazine

Question 5

Action of sulfasalazine

Answer 5

a prodrug with a site of action and breaks down in the colon. It breaks down to the active 5-aminosalisilic acid (5-ASA) (mesalazine). Breakdown to 5-ASA done by gut flora. Inhibits prostaglandin and leukotriene biosynthesis

Question 6

For a base when will it be fully unionised? When will it be ionised?

Answer 6

Fully un-ionised when the pH is 2 units more than the pKa.
Fully ionised when pH is 2 units less than the pKa.

Question 7

For an acid when will it be fully unionised? When will it be fully ionised?

Answer 7

Fully un-ionised when pH is 2 units less than pKa.
Fully ionised when pH is 2 units more than the pKa.

Question 8

Absorption of sulfasalazine

Answer 8

no absorption in stomach as logD is 0.
in ileum molecule does not absorb; too large and so passes to colon
in colon; cleaved to 5-ASA by gut flora. absorbs through aqueous gaps in-between epithelial cells - small molecule.

Question 9

increasing particle size is known as what?
what is decreasing particle size known as?

Answer 9

increasing- granulation
decreasing - milling

Question 10

What is the purpose in sieving?

Answer 10

to select powders of desired size

Question 11

Cutting methods in particle size reduction

Answer 11

Cutter Mill- the material is cut by one or more blades.

Question 12

Compression methods in particle size reduction

Answer 12

Compression mill, roller mills. A pressure is applied

Question 13

Impact methods in particle size reduction

Answer 13

Hammer mill. particles are hit by a moving surface or that moving particles hit a surface.

Question 14

Attrition methods in particle size reduction

Answer 14

Roller mills - principle is pressure and friction

Question 15

What are cutter mills good for?

Answer 15

elastic, fibrous materials like roots and woods.

Question 16

What are attrition methods used for?

Answer 16

Ointments, solid in suspensions and pastes.

Question 17

What are impact methods used on?

Answer 17

Brittle methods

Question 18

Direct methods of analysing particle size

Answer 18

Sieving
Microscopy; light microscopy(2D images) and electron microscopy (3D images give information on shape but is expensive and a high level of operator expertise is needed)

Question 19

Indirect methods of analysing particle size

Answer 19

Sedimentation rate; diameter of particle estimated, Andreasen pipette used.
Permeability

Question 20

In elutriation methods; what is the direction of fluid and what is the direction of sedimentation

Answer 20

fluid direction is opposite to sedimention direction

Question 21

What are the 4 types of particle size distrubution?

Answer 21

Monosized, Normal, Positively skewed, Bimodal

Question 22

What are steroids derived from? Where are they made?

Answer 22

derived from lanosterol and produced in the adrenal glands.

Question 23

Steroids used in inflammation

Answer 23

are hydrocortisone, budesonide, beclomethasone and prednisolone

Question 24

What does the addition of a halogen do to lipophilicity and logP?

Answer 24

addition increases the lipophilicity and increase the logP

Question 25

What does addition of a halogen do to the lipophilicty and logP of a molecule?

Answer 25

increases lipophilicity and logP

Question 26

Lipinskis rule of 5 - What makes a drug orally absorbable?

Answer 26

A molecular weight less than 500 No more than 5 H bond donor groups No more than 10 H bond acceptor groups A calculated log P value less than +5.

Question 27

How do steroids work? What do they act on?

Answer 27

Steroids work on inflammation by acting at the glucocorticoid receptor which regulates genes controlling inflammation. Also regulates genes that control development, metabolism.

Question 28

What type of logP do drugs that are administered rectally have?

Answer 28

high logP

Question 29

What is classed as acute, persistent and chronic diarrhoea?

Answer 29

acute / 14 days chronic > 30 days

Question 30

Inflammatory diarrhoea

Answer 30

due to infection, radiation injury or IBD. Mucoid and bloody stool, fever, cramps. Small frequent bowel movements Histology of GI tract abnormal

Question 31

Non-inflammatory diarrhoea

Answer 31

water, large volume frequent stool, no blood in stool or fever. Histology is reserved. Osmotic and secretory diarrhoea

Question 32

What is the difference between osmotic and secretory diarrhoea?

Answer 32

Osmotic; Due to malabsorption/maldigestion. Small stool volume. Improves with fasting. Secretory; altered transport of ions across across mucosa. Doesn't improve with fasting

Question 33

How does Cholera cause diarrhoea?

Answer 33

Cholera toxin, released from Vibrio cholerae enters the enterocytes of the gastrointestinal tract and directly activates a G protein. The G protein activates adenylyl cyclase, this increases cellular cAMP and leads to activation of protein kinase A. PKA causes phosphorylation of chloride channels resulting in their activation. There is increased efflux of chloride ions into the gastrointestinal lumen therefore causing diarrhoea.

Question 34

How does Diphenoxylate work to treat diarrhoea?

Answer 34

Diphenoxylate is a mew opioid receptor agonist. It activates opioid receptor on neuronal varicosities, which decrease acetylcholine release. Peristaltic activity is decreased due to the reduction in acetylcholine release. There is also an increase in segmental concentration, which will slow gastrointestinal motility.

Question 35

What is diphenoxylate often formulated with? Why?

Answer 35

Atropine, high doses cause nausea therefore reduced chance of addiction and dependance. Atropine allows the drug to cross the blood brain barrier.

Question 36

How is codeine formulated to treat diarrhoea?

Answer 36

Formulated as the phosphate salt as it contains a tertiary amine with pKa of approximately 9. Codeine metabolised to morphine, which is mew opioid agonist (will inhibit neurotransmitter release)

Question 37

How does Racecadotril work to relieve diarrhoea and decrease water secretions?

Answer 37

Antisecretory drug. Activation of delta opioid receptors decreases the cellular cAMP level. Decreased secretion of Cl- leading to decreased water secretion. Enkephalins are the endogenous activator of delta opioid receptors. Racecadotril is a (pro drug) metabolised to thiorphan – an enkephalins inhibitor that prevents the breakdown of enkephalins.

Question 38

How does Linaclotide work to relieve constipation?

Answer 38

activates guanylate cyclase C (GC-C). increases cellular cGMP and activation of protein kinase G (PKG). phosphorylation of Cl- channel. Increased efflux of Cl- (and water) therefore giving laxative effect

Question 39

How does Lubiprostone work to relieve constipation?

Answer 39

directly activates a Cl- channel (CIC-2). Increased efflux of Cl-. May restore mucosal barrier function

Question 40

The more potent a drug, the __ the ec50 value.

Answer 40

lower

Question 41

Determining stock solution equation.

Answer 41

M1 x V1 = M2 x V2

Question 42

What is an agonist?

Answer 42

binds to a receptor and activates the receptor to produce a biological response.

Question 43

What is an antagonist? Give example

Answer 43

occupies the receptor site and preventing binding agonist, thus blocks the action of an agonist. Myprimine

Question 44

In an mRNA molecule __ are spliced out and __ join together.

Answer 44

introns out exons join

Question 45

Does mRNA or DNA contain the base Uracil instead of Thymine?

Answer 45

mRNA contains Uracil DNA contains Thymine

Question 46

Stop codons

Answer 46

UAA UGA UAG

Question 47

What do synonymous and non-synonymous mean in SNP's

Answer 47

Synonymous; do not change the encoded amino acid Non-synonymous; change the encoded amino acid

Question 48

positive mixture

Answer 48

materials that mix spontaneously and irreversibly. Formed from mixtures such as gases and miscible liquids. No energy input required as spontaneously

Question 49

negative mixture

Answer 49

components tend to separate - e.g. susupensions

Question 50

neutral mixtures

Answer 50

components neither tend to separate nor to mix. Capable of demixing but requires energy input. Example – powders

Question 51

What is granulation? Give some advantages

Answer 51

process in which homogenous mixtures of primary powder particles form larger, still homogenous particles called granules. Advantages include; improves powder flow, prevents segregation and improves compaction, more convenient for storage. They have a reduced generation of dust which is important for toxic compounds.