Draft exam 1 Flashcards
Define what action the ‘lubb’ and ‘dumb’ sound represents.
Lubb - closing of the AV valves - tricuspid and bicuspid valves - bicuspid before the tricuspid .
Dubb - closing of the semilunar valves with a split sound representing aortic before pulmonary.
Outline the journey of an orally administered tablet formulation to its extracellular site of action in the blood.
- patient will swallow capsule with water and it will travel down oesophagus to stomach.
- capsule then breaks down to release the drug solid.
- Drug will begin to dissolve in gastric fluid with a rate dependent on is physiochemical properties.
- Gastric emptying will control rate of movement from the stomach to ileum.
- Drug will then be absorbed through the gut wall and travel through the portal vein to the liver.
- There it will be metabolised by phase 1 and phase 2 liver enzymes at a rate dependant on its physiochemical properties.
- Drug compound will then leave the liver and may complex with blood proteins before reaching its target.
Describe he mechanism of a drug targeting an intracellular nuclear receptor.
- Drug activating the intracellular receptor is lipid soluble and must pass through plasma membrane to bind to intracellular receptor.
- Receptor located in the cytoplasm.
- Drug binding causes activation of the receptor and a conformation change - often forming a homodimer or heterodimer
- Receptor then translocates to the nucleus of the cell where it binds to DNA.
- Binding to a specific DNA sequence in promotor region of target gene.
- The receptor acts as a transcription factor and target gene transcribed and translated or gene expression inhibited.
Administration of a drug targeting a cell surface kinase-linked
receptor is associated with a rapid but short-lived response.
Define the key steps involved in this signalling pathway and
indicate factors which are responsible for this drug’s action being
rapid but short-lived.
- Binding of the drug to the receptor activates a signal transduction pathway involving an amplifier enzyme (PKA) that produces
second messenger (cAMP) which phosphorylates a
series of proteins, leading rapidly to an amplified cellular response. - The proteins phosphorylated in this pathway are already present
and do not need to be newly synthesised following receptor binding. Therefore, even a small amount of a soluble drug can produce a significant cellular change extremely rapidly, in
matter of seconds to minutes. - Conversely, disengagement of the drug from the receptor leads to
a quick cessation of activation of signal transduction pathway,
causing the response to be short-lived.
With reference to the 3-point binding model, and using an appropriate diagram, briefly explain how one enantiomer can
have activity, whilst the mirror image has no such anti- convulsant activity.
All enzymes and receptors in body are chiral because formed from amino acids (chiral) - enantiomers of biological molecules
bind with different affinity due to 3-D fit, enantiomers of pharmaceuticals bind with different affinity due to 3-D fit
One enatiomer of vigabatrin can bind with high affinity to receptor as all groups are correctly aligned with
binding sites of receptor – the mirror image does not have all binding sites correctly aligned and therefore does not bind with a high affinity.
Explain how the different hybridization states of the two carbon atoms in acetylene and ethane affect the acidity of the hydrogen
atom(s) attached.
- Ethane is SP 3 hybridised (25% s-character).
- Acetylene is SP hybridised (50% s-character)
- Higher the percentage of s-character of the hybrid orbital in Acetylene.
- The closer the lone pair is held to the nucleus.
- The more stable the conjugate base.
- Proton donation is boosted.
- The more acidic the compound will be.
Discuss three differences between the vaginal and rectal routes of drug administration, considering their anatomical and physiological characteristics that can affect drug absorption.
- Motility of rectal wall. Rectal wall muscle activity may influence the rate of dissolution within the rectum whereas in the vaginal there is no motility influence.
- The rectal mucosa has a relatively larger surface area
compared to the vaginal mucosa, which leads to higher permeability than the vaginal mucosa, and potentially faster drug absorption. - Drug ionization characteristics may differ in rectal compared to the vaginal environment. The vaginal pH is acidic, ranging
from approximately 3.5 to 4.5, that can also lead to drug degradation in some cases. The rectal pH is slightly alkaline, ranging from around 7.0 to 8.0. - In the vaginal route, the patient may have the influence of menstrual cycle and hormonal variations, whereas in the rectal route, contents (faeces) in the rectum may reduce drug absorption.
Not all compounds are infrared active. Explain why a molecule of hydrogen bromide is IR active but a molecule of oxygen is
not.
only HBr is
polar / oxygen is non polar
Define the principle of pharmacogenetics and the concept of an individual being either a poor-metaboliser or an ultra-rapid-metaboliser phenotype, contextualising this with polymorphisms in
the cytochrome P450 gene. [6 Marks]
- Pharmacogenetics is the difference in genetic sequence between
individuals leading to different polymorphisms of same protein, which affects its activity - In case of CYP enzymes, polymorphism affects enzymatic rate of
conversion. - A poor metabolizer phenotype associates with reduced metabolic
efficacy, leading to reduced metabolism of drugs (1 Mark) and subsequently increased systemic levels (1 Mark). - An ultra-rapid metabolizer would convert active drug quicker to its metabolites (1 Mark). and reduced systemic levels, causing it to have potentially poorer efficacy
Provide two examples of strategies used with in pharmaceutical formulation to enhance the solubility of poorly water-soluble drugs in solution formulations? Explain the mechanisms by which the strategies increase drug solubility.
- cosolvent system (0.5 marks): the addition of water-miscible organic solvents can increase drug solubility. “Like dissolves
like rule”. Non-polar solvents dissolve non-polar solutes, like the hydrophobic drug. (2 marks) - use of surfactants or micellar solubilization (0.5 marks): surfactants when used above their CMC, will self-assemble to form micelles. Hydrophobic drug is solubilized by the hydrophobic core of the micelles, which have a hydrophilic outer shell. (2marks)
