week 7 Flashcards
Omeprazole logP. What are its pKa’s
logP= 2.23
pKas 4 and 9
Where is omeprazole absorbed?
small intestine
How may a patient take omeprazole if they are unable to wholly swallow a capsule?
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
which aminosalicylates are converted to sodium salts?
balsalazide and olalazine
Action of sulfasalazine
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
For a base when will it be fully unionised? When will it be ionised?
Fully un-ionised when the pH is 2 units more than the pKa.
Fully ionised when pH is 2 units less than the pKa.
For an acid when will it be fully unionised? When will it be fully ionised?
Fully un-ionised when pH is 2 units less than pKa.
Fully ionised when pH is 2 units more than the pKa.
Absorption of sulfasalazine
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.
increasing particle size is known as what?
what is decreasing particle size known as?
increasing- granulation
decreasing - milling
What is the purpose in sieving?
to select powders of desired size
Cutting methods in particle size reduction
Cutter Mill- the material is cut by one or more blades.
Compression methods in particle size reduction
Compression mill, roller mills. A pressure is applied
Impact methods in particle size reduction
Hammer mill. particles are hit by a moving surface or that moving particles hit a surface.
Attrition methods in particle size reduction
Roller mills - principle is pressure and friction
What are cutter mills good for?
elastic, fibrous materials like roots and woods.
What are attrition methods used for?
Ointments, solid in suspensions and pastes.
What are impact methods used on?
Brittle methods
Direct methods of analysing particle size
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)
Indirect methods of analysing particle size
Sedimentation rate; diameter of particle estimated, Andreasen pipette used.
Permeability
In elutriation methods; what is the direction of fluid and what is the direction of sedimentation
fluid direction is opposite to sedimention direction
What are the 4 types of particle size distrubution?
Monosized, Normal, Positively skewed, Bimodal
What are steroids derived from? Where are they made?
derived from lanosterol and produced in the adrenal glands.
Steroids used in inflammation
are hydrocortisone, budesonide, beclomethasone and prednisolone
What does the addition of a halogen do to lipophilicity and logP?
addition increases the lipophilicity and increase the logP
What does addition of a halogen do to the lipophilicty and logP of a molecule?
increases lipophilicity and logP
Lipinskis rule of 5 - What makes a drug orally absorbable?
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.
How do steroids work? What do they act on?
Steroids work on inflammation by acting at the glucocorticoid receptor which regulates genes controlling inflammation. Also regulates genes that control development, metabolism.
What type of logP do drugs that are administered rectally have?
high logP
What is classed as acute, persistent and chronic diarrhoea?
acute </14 days
persistent >/ 14 days
chronic > 30 days
Inflammatory diarrhoea
due to infection, radiation injury or IBD.
Mucoid and bloody stool, fever, cramps.
Small frequent bowel movements
Histology of GI tract abnormal
Non-inflammatory diarrhoea
water, large volume frequent stool, no blood in stool or fever.
Histology is reserved.
Osmotic and secretory diarrhoea
What is the difference between osmotic and secretory diarrhoea?
Osmotic; Due to malabsorption/maldigestion. Small stool volume. Improves with fasting.
Secretory; altered transport of ions across across mucosa. Doesn’t improve with fasting
How does Cholera cause diarrhoea?
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.
How does Diphenoxylate work to treat diarrhoea?
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.
What is diphenoxylate often formulated with? Why?
Atropine, high doses cause nausea therefore reduced chance of addiction and dependance. Atropine allows the drug to cross the blood brain barrier.
How is codeine formulated to treat diarrhoea?
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)
How does Racecadotril work to relieve diarrhoea and decrease water secretions?
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.
How does Linaclotide work to relieve constipation?
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
How does Lubiprostone work to relieve constipation?
directly activates a Cl- channel (CIC-2). Increased efflux of Cl-. May restore mucosal barrier function
The more potent a drug, the __ the ec50 value.
lower
Determining stock solution equation.
M1 x V1 = M2 x V2
What is an agonist?
binds to a receptor and activates the receptor to produce a biological response.
What is an antagonist? Give example
occupies the receptor site and preventing binding agonist, thus blocks the action of an agonist.
Myprimine
In an mRNA molecule __ are spliced out and __ join together.
introns out
exons join
Does mRNA or DNA contain the base Uracil instead of Thymine?
mRNA contains Uracil
DNA contains Thymine
Stop codons
UAA UGA UAG
What do synonymous and non-synonymous mean in SNP’s
Synonymous; do not change the encoded amino acid
Non-synonymous; change the encoded amino acid
positive mixture
materials that mix spontaneously and irreversibly. Formed from mixtures such as gases and miscible liquids. No energy input required as spontaneously
negative mixture
components tend to separate - e.g. susupensions
neutral mixtures
components neither tend to separate nor to mix. Capable of demixing but requires energy input. Example – powders
What is granulation? Give some advantages
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.
