Define why action potentials move in one direction?
Because sodium channels have a refractory period following activation during which they cannot open again.
Define the function of interneurons in the spinal cord.
Interneurons are neurons that transmit impulses between sensory
neurons, brain and motor neurons
Describe similarities and differences between the sympathetic and
parasympathetic nervous systems, with reference to their structure, physiology, and the chemical transmitters released?
Similarities
* Are the part of ANS (0.5 mark)
* Originate from the spinal cord (0.5 mark)
* Influence the involuntary physiological process of the body such as respiration, circulation, digestion (0.5 mark)
* Pre-ganglionic neurons use Ach (0.5 marks)
Differences
* The sympathetic system controls “fight-or-flight” responses, increases availability/ capacity and usage. (0.5 mark)
* The parasympathetic system controls Rest and digest’, reduces energy availability/ capacity and usage. (0.5 mark)
* Where nerves originate (leave CNS) OR where the ganglia (cell bodies) are located. (0.5 mark)
* Post ganglion sympathetic neurons use NE or NA, post
ganglion parasympathetic neurons use Ach (0.5 mark)
Describe the difference between equilibrium solubility, dissolution
testing and intrinsic dissolution testing.
- Equilibrium solubility is the drug concentration value that is reached when a drug compound is placed into a solution
- Dissolution testing involves taking multiple samples as a
function of time. It can be performed until the
equilibrium is reached (with excess solid) or with a dosage form where the drug concentration will plateau once it has been expended - Intrinsic dissolution testing, a compacted disc is used as the drug sample. This removes the need to measure the particle size which is released into solution.
Explain the concept of a drug-receptor interaction with respect to the occupational theory.
Drugs act on independent binding sites and activate them, resulting in a biological response that is proportional to the amount of drug-receptor complex formed. The response
ceases when this complex dissociates.
In contrast to the occupational theory, how does the two-state
receptor model explain an agonist and an antagonist?
An agonist has a high affinity for the R* state than for R
and will shift the equilibrium to the right (R*);
An antagonist has equal affinity for R and R* so does not affect the equilibrium
Explain what happens to the blood pH when you hyperventilate?
- The CO2 is being consumed and needs to be compensated.
- H2CO3 will dissociate to compensate the loss in CO2
- The blood pH will increase.
- The blood will be basic (Alkalosis).
Discuss how drug properties are used to assign drugs to the four groups in the Biopharmaceutics Classification System.
- The BCS classification system groups drugs according to their permeability and solubility.
- Drug permeability through Caco-2 cells is used to estimate permeability in vivo. But this approach is inconsistent, so bioavailability measurements are preferred
- Drug solubility is calculated as a fraction of the dose that would be expected to dissolve in 250 mL
- This is calculated by multiplying the solubility in mg or g/mL by 250 mL and dividing by the dose
- Drug solubility can change as a function of pH and other factors, which can change the BCS class.
Define drug solubility and detail three changes that you can make to a solution and describe how these changes will affect
solubility?
Drug solubility is the point at which an equilibrium is
established between a drug compound and a solution
- pH; The solubility of an acidic drug can be
increased with increased pH. - Temperature; Increased temperature can increase
drug solubility - Micelles; Micelles can internalise hydrophobic
drugs, increasing their solubility - Complexation; Complexing agents can increase
drug solubility.
Focusing on insulin, discuss various factors influencing protein structure, stability and activity, and explain the importance of each factor for insulin function.
- The first factor is having the correct amino acid sequence
- Therefore, human insulin have similar function to porcine insulin but different to other species i.e. dog insulin
- The folding of insulin is important for insulin activity and structure
- The correct folding pattern allow insulin to bind to its receptor adequately to initiate the reaction. That would make insulin more
stable - Insulin protein needs to have the correct number of water molecules attached to in the correct places
- This affects their solubility but also affects folding, if water molecules are attached certain fat soluble-hydrophobic amino
acids will move away from these water molecules - This affects folding and the 3D structure of the protein
Cite four strategies to control sedimentation and caking formation
in oral suspensions. You can consider both formulation and/or excipients aspects.
- Particle size reduction
- Reduce particle density
- Increase medium viscosity
- Use of suspending agents
Describe the main differences between oral solution and oral
suspension and explain the reasons for formulating an oral suspension over a solution
A pharmaceutical suspension is a liquid disperse system consisting of particles distributed within a liquid vehicle whereas solution has all solutes dissolved, exhibiting an optically clear appearance. (1.5 marks)
Reasons for formulating an oral suspension:
- To deliver poorly water-soluble drugs which cannot be formulated as aqueous solutions
* To mask the bitter taste of the drug
* To increase drug stability
* To achieve controlled/sustained drug release
Describe the difference between cytoplasmic and nuclear receptors, give an example for each type of receptor.
Mechanism of Cytoplasmic Receptor Activation:
- Receptor located in cytoplasm (0.5 mark)
- Ligand (lipid soluble) enters cell and causes receptor activation (0.5 mark)
- Ligand binding dislodges regulatory/repressor protein (0.5 mark)
- Ligand-Receptor complex enters nucleus and binds to specific DNA sequence (in promoter region) (0.5 mark)
- Gene is transcribed and translated; protein produced Or gene expression inhibited (cellular response) (0.5 mark)
- Example, one of the following: Mineralocorticoid or Glucocorticoid
(0.5 mark)
Mechanism of nuclear receptor activation:
- Receptor located in nucleus (0.5 mark)
- Lipid-soluble hormones diffuse through the plasma membrane and moves to the nucleus and bind to nuclear receptors (0.5 mark)
- The hormone-receptor complex binds to a hormone response element on the DNA, acting as a transcription factor (0.5 mark)
- The binding of the hormone-receptor complex to DNA stimulates the synthesis of messenger RNA (mRNA), which codes for specific proteins (0.5 mark)
- The mRNA leaves the nucleus, passes into the cytoplasm of the cell, and binds to ribosomes, where it directs the synthesis of specific proteins (cellular response) (0.5 mark)
- Example, one of the following: Estrogen
Explain the main difference between the two methods:
uniformity of mass and uniformity of content.
In summary, while uniformity of mass focuses on the physical weight of dosage forms, uniformity of content is concerned with
the concentration of the active ingredient in each individual unit.
Describe three factors that can affect the uniformity of dosage of solid dosage forms. You should consider powder flow and particle properties in your answer.
- Powder segregation during mixing operation.
- Particle size, shape for and density: differences in particle properties may lead to segregation during mixing or affect the flow properties of the powder.
- Mixing processes: Inadequate mixer and mixing times can lead to content non-uniformity.
