Topic: Introduction

Intro:

[Intro music]

Sally:
Welcome to episode one of 'Prescriber Pod', the evidence-based podcast applying pharmacology to prescribing practice.

My name is Sally Porter, I’m a pharmacist and lecturer at the University of York.

Jodie:

Hello I’m Jodie Coulson, I’m a nurse and lecturer at the University of York.

Thanks for joining us for this podcast! 

Sally:

In today’s episode we’ll share why we developed 'Prescriber Pod' and provide a brief introduction to pharmacology.

Introduction to podcast series:

Sally:

I’ve been teaching on the Independent & Supplementary Prescribing for Non-Medical Prescribers…let's call that the NMP programme…since 2019. Our students are all healthcare professionals but their backgrounds can be very different…they could be a specialist nurse working in a hospital or an advanced paramedic working in general practice. They could have studied pharmacology as an undergraduate but it could be totally new…in any case I think it’s fair to say that pharmacology can be a bit scary! There are some complex concepts to get your head around and a lot of terminology. On top of that you have to pass a pharmacology exam to qualify as a prescriber…and the pass mark is 80 percent, which is a high bar. 

The NMP programme at the University of York runs over five months and our students are only released from work one day a week, so it’s an intensive workload. They’re balancing professional and personal responsibilities with part-time study, which can be really challenging.

Jodie, you've been at York longer than me…and you successfully completed the NMP programme here. What would you say is the biggest challenge with studying pharmacology…and your strategy for overcoming it?  

Jodie:

There are some quite complex concepts and a lot of new terminology to navigate. It's important you can apply these to the medicines you'll be prescribing, when qualified, and the cohorts of people you work with in practice. I think it’s really important to become familiar with pharmacological terms as quickly as possible, so that you can interpret sources of drug specific information. This can be done by accessing source material in lots of different ways until you feel comfortable with what key terms mean and how they are used.

So Sally, why a podcast…and why pharmacology?

Sally:

The idea for a pharmacology podcast came from a student. I remember them saying ‘Haven’t you got any podcasts, I could do with something to listen to while I walk the dog’? It stuck with me. I’d say there are two key reasons for making the podcast. The first is that I couldn’t find any pharmacology podcasts designed for NMP students. The second is that it's a bit like the wild west with podcasts…there's no formal peer review process, so you haven’t got the same assurance as say a journal article. Nina Barnett, who was one of my heroines, said pharmacists don’t like uncertainty…which is probably why we like robust evidence that reduces it! 

I brought this affinity for evidence-based practice with me when I moved into academia. I didn’t want to jump straight into recording. I wanted to see what the literature said and use the research to inform the podcast. 

Tony, a nurse who teaches at the University of Hull, was interested in collaborating on research into education for postgraduate healthcare professionals…that’s where the podcast project really got off the ground. We started with a literature search…we didn’t find much in the way of primary research… and most of it related to undergraduate medical or nursing students… but there was a consensus that podcasting supports students to gain knowledge and enhances their learning experience. I was really excited by some of the research…Crooks et al. developed a Parkinson’s awareness podcast for undergraduate nursing students. They used a co-design team that included people with Parkinson’s Disease, carers and nurse specialists. The podcast helped students to empathise and understand the experiences of people living with Parkinson’s Disease. I could see the potential for postgraduate students…they’re pressed for time, so if they can listen to a podcast while they’re doing something else…like driving to work…or walking the dog…it gives them an opportunity to learn without having to set time aside. 

When you have limited time to study, your strategy is really important. When I did my degree, my strategy was essentially maximum time, maximum effort. For my clinical diploma it shifted to maximum effort in available time. Ironically, my motivation to understand how to teach effectively is what improved my understanding of how to learn effectively!

I realise this is a long answer to a short question…but hear me out! Research by Nuthall found that we rarely learn from a single, isolated experience…so you’re unlikely to learn a new pharmacological concept by going to one lecture. We need a sequence of experiences that build on one another. The analogy used is the mind has a valve to protect itself from incidental information. To get through the valve we have to make sense of the information and connect it to related information in our existing frameworks…which takes time. You need opportunities to approach or explore a new concept in different ways. Nuthall’s ‘three-times’ rule predicts that if you read an article, attend a lecture and listen to a podcast, that new concept will be constructed as part of your long-term memory. In fact, only the ‘three-times’ rule predicted whether concepts were learned…ability and intelligence didn’t. I will point out that the research was done in schools but it had incredible predictive power, so it seems like a strategy that’s well worth using as an adult learner. For anyone that wants to know more, I’ve put details of Nuthall’s book The Hidden Lives of Learners and a couple of related blogs in the show notes.

I can answer ‘why pharmacology?’ in three words…assessment drives learning. Our students will probably prioritise studying for the pharmacology exam…so it makes sense that we make a pharmacology podcast.  

Jodie:

Picking up on Nuthall’s ‘three times’ rule, where would you suggest starting if pharmacology is a new subject?

Sally:

Cerbin says that what you know before a lecture is the key determinant of what you learn in a lecture. I think reading the pharmacology chapter in a couple of books on prescribing is a helpful starting point…they provide basic information and they’re concise. I like Independent Prescribing for Paramedics by Blaber, Morris and Collen. The chapter on pharmacology is relevant for all healthcare professionals. It's got a table of key terms, which I find really useful. I’ve put details in the show notes. However, people need to find what works best for them!

Jodie, what’s your favourite and why?

Jodie:

Professional journal articles can be useful because they contain a small amount of focused information on a topic. In addition to this, articles in Nursing Times or Nursing Standard for example are usually quite accessible for those with different levels of foundational knowledge.

What would be your next step?

Sally:

A book on pharmacology. McGavock is my ‘go to’ when I’m teaching. It goes into more detail but it's broken down into manageable chunks. 

A note of caution! You do need to be mindful of when literature was published, because clinical practice may well have moved on!

Jodie:

What did the research say about how to utilise podcasts?

Sally:

That’s an excellent question…but I haven’t got a clear answer to it! It might be helpful to tell you a bit about how participants used podcasts in a couple of the papers that Tony and I reviewed. 

Lien et al. compared how medical students used podcasts and blogs. The podcast group tended to multitask. However, a lower proportion of participants multitasked when listening to the toxicology podcast compared to the asthma podcast, which suggests that topic can influence how a podcast is used. They also looked at whether knowledge gain differed between podcasts and blogs. Interestingly, although the majority of the blog group were just reading or taking notes, this didn’t seem to have a significant effect on knowledge acquisition. 

When Crooks et al. developed the Parkinson’s awareness podcast I mentioned earlier, they found that some students sat down and took notes, while others multitasked. One of the participants indicated that the class weren’t sure how best to use the podcast.

It seems counterintuitive to give a set of instructions when a key benefit of podcasts is being able to choose when and where you learn! Having said that, I think there may be a double-edged sword with podcasts. For example, O’Neill et al. argue that because listening to podcasts is passive, you might enjoy learning even when you feel too tired to study. On the other hand, Freeman et al. found that active learning increases exam performance. 

We’re aiming to get the best of both worlds by providing some deep processing activities, designed to improve understanding and support retention. We’re calling this ‘Postpod learning’. The reason we’re taking this approach is that new information will basically go in one ear and out of the other unless we do something with it! 'Prescriber Pod' is designed to supplement in-class learning, so I think it makes sense to listen after attending the lecture that an episode relates to. Bottom line, there is no sure-fire strategy and in any case adults have a psychological need to be self-directing…we tend to resist being told what to do!

Sally:

So now listeners know where we’re coming from, let’s talk about where we’re going!

Jodie, what are the learning objectives for this episode?

Learning objectives

Jodie:

Well, this episode is like a first date with pharmacology…we’ll be keeping it short and simple!

By the end of the episode you should be able to:

• Distinguish between the two main branches of pharmacology.

• Describe why pharmacology is important for prescribers.

• Explain how pharmacology can inform drug design.

By the end of the NMP programme you’ll need to have achieved all of the competencies in the Royal Pharmaceutical Society, RPS, prescribing competency framework, which sets out what good prescribing looks like. This podcast series aligns with five competencies.
Four are in the consultation domain:

1. Identify evidence-based treatment options available for clinical decision making; 

2. Present options and reach a shared decision;

3. Prescribe;

4. Monitor and review

The fifth, Prescribe safely, is the governance domain.

Overview of pharmacology

Jodie:

Let’s start at the beginning. What is pharmacology?

Sally:

It's the study of drugs and how they interact with the body. This definition is from a two-page introduction to pharmacokinetics by Robertson…details in the show notes.  

Jodie:

What are the two main branches of pharmacology?

Sally:

Pharmacokinetics and pharmacodynamics.

Jodie:

Let’s start with pharmacokinetics. There's a lot of terminology in pharmacology. How might you work out what pharmacokinetics means?

Sally:

If you break the word down, you can work out what it means. Pharmaco- relates to drugs and kinetics relates to movement. So, pharmacokinetics is how a drug moves through the body. Some sources describe this as the body ‘processing’ drugs. I quite like the analogy that Blaber et al. use…pharmacokinetics helps describe the journey of a drug into, around and out of the body.

Jodie, will you run through the four main steps on this journey?

Jodie:

Sure. The four main pharmacokinetics stages are absorption, distribution, metabolism and excretion. You may see the acronym ADME in textbooks.

Sally:

How would you define pharmacodynamics?

Jodie:

Robertson defines pharmacodynamics as the effect, or effects, that a drug has on the body.

Sally:

Why is it important for prescribers to understand the ways that drugs exert their effects?

Therapeutic effects and side-effects

Jodie:

Drugs can have effects we want…and effects we don’t want. For example ibuprofen can relieve pain but it can cause gastrointestinal discomfort.

If we understand how a drug works we can anticipate and evaluate the therapeutic effects on an individual. For example, amlodipine relaxes vascular smooth muscle. We can anticipate this will have an antihypertensive effect and evaluate this by measuring the person’s blood pressure. 

Most common side-effects are linked to pharmacology, which creates an opportunity for prescribers to anticipate and avoid them! For example, atenolol blocks beta receptors in the heart - we’ll talk about receptors in a later episode! Atenolol can be used to slow the heart rate in atrial fibrillation; a condition where the heartbeat is fast and irregular. Heart rate is monitored, to avoid the heart rate becoming too slow.

Prescribers can also apply their understanding of pharmacology to empower people as partners in their healthcare. For example, taking ibuprofen with food or milk makes it less likely to cause gastrointestinal discomfort. Prevention is better than cure!

Sally:

People may well take two or more drugs, which can exert their effects independently or interact. Let’s say George is taking amlodipine for hypertension and starts atenolol for atrial fibrillation. The BNF Interactions Checker tool tells me both drugs increase the risk of low blood pressure. I’m satisfied that the risk: benefit ratio is favourable because George’s blood pressure is slightly above target and I know he’s got a review scheduled, within a week. 

Interactions can be beneficial…George might achieve his target blood pressure when he starts atenolol. However they can be harmful, so it's important that prescribers can identify interactions and either avoid the drug combination or take action to allow safe use. In George’s case, a timely review that includes assessing blood pressure, heart rate and any side-effects.

What do prescribers need to know about the pharmacology underpinning drug interactions?

Drug interactions

Jodie:

Drug interactions can develop through pharmacokinetic or pharmacodynamic mechanisms.

Pharmacodynamic interactions occur between drugs with similar, or opposing, pharmacological effects. They’re usually predictable from the drug’s pharmacology. We’ll stick with George for a worked example! Amlodipine and atenolol both have an antihypertensive effect. We can predict that combining them might increase the risk of low blood pressure. 

Sally:

That’s logical. It’s worth highlighting that generally, pharmacodynamic interactions with one drug are likely to occur with related drugs: The BNF Interactions Checker tool details the same interaction for amlodipine and bisopr-olol, which is in the same drug class as aten-olol. This isn’t necessarily the case for pharmacokinetic interactions.
Pharmacokinetic interactions occur when one drug alters how another drug moves through the body. Ultimately this leads to more or less of the drug being available to exert its pharmacological effects.

We’ll take a more detailed look at drug interactions in the relevant episodes!

Jodie:

How can pharmacology inform the design of drugs?

Drug design

Sally:

Understanding how drugs interact with the body means that they can be targeted, to maximise benefit and minimise risk. For example, morphine is a natural opioid analgesic. It acts on targets in the body that are linked to pain. But…it also acts on other targets…leading to side-effects, like constipation. Synthetic opioids, such as tramadol, have been developed to act more specifically on targets that are linked to pain. Tramadol has fewer of the typical opioid side-effects, like constipation. However, the only way to be sure of avoiding side-effects is not to take any drugs!

Jodie:

So Sally…why did you call this episode ‘Do I know you?’?

Sally:

Because healthcare professionals already know a lot about physiology…and drugs work by speeding up or slowing down physiological processes.

Thinking back to Nuthall, this means they can connect a new pharmacological concept with related knowledge of physiology…which should help to construct the concept in their long-term memory. 

Sally:

We are nearly out of time, so let's summarise the key points from this episode.

Summary of key points

Sally:

Making connections between new knowledge and existing knowledge is key to learning.

Pharmacology is the study of drugs and how they interact with the body.

Pharmacokinetics is what the body does to the drug.

Pharmacodynamics is what the drug does to the body.

Understanding how drugs interact with the body enables prescribers to anticipate and evaluate therapeutic effects. It also assists with anticipating and avoiding side effects…and drug interactions. This understanding links to two RPS competencies: ‘Prescribe safely’ and ‘Monitor and review’.

Designing drugs to act more specifically on targets helps to minimise risk and maximise benefit. With any drug, there is always a balance to be struck between risk and benefit!

To demonstrate the RPS competency ‘Present options and reach a shared decision’, prescribers need to tailor information to the needs of the individual…to empower them to make an informed decision.

Outro:

Jodie:

And that’s all we have time for! Thanks for tuning in to this episode of 'Prescriber Pod'. Remember to check the show notes for additional resources and ‘Postpod learning’. The next episode in the series is ‘Are you taking it all in?’ where we’ll be talking about drug absorption.

Sally:

Thanks Jodie and thanks to everyone listening. Until our next episode, remember knowledge empowers prescribers to empower people.

[Outro music]

Topic: Introduction

Quality assurance (adapted from Lin et al., 2015)

Credibility

Author

Sally Porter BPharm (Hons) PgDip (Pharm) MFRPSII MRPharmS MAPCPharm FHEA, Lecturer-Practitioner in Prescribing and Medicines Optimisation, Department of Health Sciences, University of York, York, YO10 5DD.

Conflicts of interest

None declared.

Bibliography

Blaber, A., Morris, H., and Collen, A. (2018). Independent Prescribing for Paramedics. 1st edn. Bridgwater: Class Professional.

Cerbin, W. (2018). Improving student learning from lectures. Scholarship of Teaching and Learning in Psychology, 4(3), 151-163.

CKS. (2025). Atrial fibrillation. [Online]. National Institute for Health and Care Excellence. Available at: https://cks.nice.org.uk/topics/atrial-fibrillation/ [Accessed 13 March 2025].

Coulson, J. (2021). Understanding the pharmacology of the side effects of medicines for effective prevention of adverse drug reactions. Nursing Standard, 35(3), 60-66.

Crooks, S. et al. (2023). Evaluation of a co-designed Parkinson’s awareness audio podcast for undergraduate nursing students in Northern Ireland. BMC Nursing, 22(1):1–13.

Fink. S. (2013). Pharmacodynamics. [Video]. Available at: https://www.youtube.com/watch?v=QW-88I38SKQ [Accessed 11 November 2024].

Fischer J., et al. (2024). How does assessment drive learning? A focus on students’ development of evaluative judgement. Assessment & Evaluation in Higher Education, 49(2), 233–245.

Freeman, S., et al. (2014). Active learning increases student performance in science, engineering, and mathematics. PNAS, 111, 8410–8415.

Joint Formulary Committee. (2024). British National Formulary / British National Formulary for Children (Version 3.2.21). [Mobile application software]. Available at: https://www.pharmaceuticalpress.com/bnf-publications/bnf-bnfc-app/ [Accessed 21 October 2024].

Lien, K., et al. (2018). A Randomized Comparative Trial of the Knowledge Retention and Usage Conditions in Undergraduate Medical Students Using Podcasts and Blog Posts. Cureus, 10(1), e2065. Available at: DOI: 10.7759/cureus.2065.

Lin, M., et al. (2015). Quality indicators for blogs and podcasts used in medical education: modified Delphi consensus recommendations by an international cohort of health professions educators. Postgraduate Medical Journal, 91, 546-550.

Marton, F. and Säljö, R. (1976). On qualitative differences in learning - outcome and process. British Journal of Educational Psychology, 46, 4-11.

McKechnie, D. (2024). Atrial fibrillation. [Online]. Patient.info. Last updated: 19 December 2024. Available from: https://patient.info/heart-health/atrial-fibrillation-leaflet [Accessed 11 February 2025].

NHS. (2021). How and when to take or use ibuprofen. [Online]. Available at: https://www.nhs.uk/medicines/ibuprofen-for-adults/how-and-when-to-take-ibuprofen/ [Accessed 7 October 2025].

Nuthall, G. (2007). The hidden lives of learners. Wellington: NZCER Press.

O’Neill, S. et al. (2024). ‘SurgTalk’: The Educational Outcomes Associated With Development of a Surgical Podcast for Undergraduate Medical Students. Journal of Surgical Education, 81(2), 202–209.

Robertson, D. (2017). Introduction to pharmacokinetics. Nurse Prescribing, 15(3), 146-148.

Royal Pharmaceutical Society. (2018). Prescribing Competency Framework. [Online]. Royal Pharmaceutical Society. Last updated: September 2021. Available at: https://www.rpharms.com/resources/frameworks/prescribers-competency-framework [Accessed 17 April 2025].

Royal Pharmaceutical Society. (2021). A Competency Framework for all Prescribers. Royal Pharmaceutical Society, London.

Sherrington, T. (2020). Re-reading Nuthall’s Hidden Lives of Learners. Insights from a classic. 15 February 2020. Teacherhead. [Online]. Available at: https://teacherhead.com/2020/02/15/re-reading-nuthalls-hidden-lives-of-learners-insights-from-a-classic/#:~:text=The%20three%2Dtimes%20rule.&text=They%20concluded%20that%3A%20Provided%20a,the%20student's%20long%20term%20memory. [Accessed 12 October 2024].

Still, K. (2021). Hidden Lives of Learners (III). 6 June 2021. Edventures. [Online]. Available at: https://www.kristianstill.co.uk/wordpress/2021/06/06/hidden-lives-of-learners-iii/ [Accessed 12 October 2024]. 

Tidy, C. (2022). Hypotension. [Online]. Patient.info. Last updated: 30 June 2022. Available from: https://patient.info/doctor/hypotension [Accessed 13 April 2025].

Content

Academic rigour

Peer reviewed by Jodie Coulson, Lecturer in Prescribing & Medicines Optimisation, Department of Health Sciences, University of York.

Peer reviewed by Dr Andrea Hilton, Reader/Pharmacist, University of Hull.

Design

Technologies

Learners with standard equipment and software can access this podcast.

Topic: Absorption - part 1

Intro:

[Intro music]

Sally:
Welcome to episode two of 'Prescriber Pod', the evidence-based podcast applying pharmacology to prescribing practice.

My name is Sally Porter, I’m a pharmacist and lecturer at the University of York.

Jodie:

Hello I’m Jodie Coulson, I’m a nurse and lecturer at the University of York.

Thanks for joining us for this podcast! 

Sally:

In the last episode we introduced the two main branches of pharmacology, pharmacokinetics and pharmacodynamics. In today’s episode we’ll be looking at the first step of the pharmacokinetic journey, absorption.

Sally:

Jodie, you usually teach absorption. How will this episode supplement the lecture?

Learning objectives

Jodie:

The lecture covers the processes that feature in drug absorption. Today we’ll review key elements, with a focus on challenging concepts like first-pass metabolism and bioavailability. We’ll also use cases to illustrate how pharmacological principles can be applied to prescribing practice.

By the end of the episode you should be able to:

• Explain why drug absorption is important.

• Define absorption.

• Identify the key processes involved in drug absorption.

• Explain the concept of bioavailability.

• Apply knowledge of absorption to prescribing practice.

Sally:

Shall we have a quick recap on the basics?

Overview of absorption

Jodie:

Sounds like a good place to start!

Sally:

Why is drug absorption important?

Jodie:

Many drugs have to be absorbed, into the body systems, before they can have an effect!

Sally:

Shall we work through an example?

Jodie:

Yes! George has atrial fibrillation; a fast, irregular heartbeat. We reach a shared decision to use atenolol tablets to slow his heart rate. To have this effect, atenolol has to interact with receptors on George’s heart. 

Tablets are taken orally…the atenolol has to get out of George’s gastrointestinal tract and into his blood, so that it can travel to his heart. Absorption is the drug’s movement, from its site of administration into the blood.

Sally:

Shall we have a look at how the atenolol gets into George’s blood?

Processes that feature in drug absorption

Disintegration and dissolution of tablets

Jodie:

Sure. When George takes an atenolol tablet it will disintegrate, then dissolve, in his stomach. Disintegration and dissolution of tablets is the first process in the absorption of many drugs. 

[Segue]

Sally:

Ok. So the atenolol molecules have been ‘released’ from the tablet and form a solution in George’s gastrointestinal, or GI, fluids. But they still need to cross cell membranes in his GI tract, to get into his blood. So… how do drugs cross cell membranes?

Passive diffusion down a concentration gradient

Jodie:

Most drugs pass through cell membranes using passive diffusion, so we’ll focus on this.

Sally:

Shall we have a reminder of what diffusion is? GCSE biology was a long time ago!

Jodie:

Fair point! Diffusion is the movement of molecules from an area of high concentration, to an area of low concentration. Molecules diffuse down their concentration gradient, until the concentrations are equal.

You like a latte, so let’s use coffee as an example. If you take a spoonful of sugar and put it into the bottom of a coffee cup, the sugar molecules will become evenly distributed through the liquid. 

Sally:

Do I need to stir the coffee?

Jodie:

No. Diffusion doesn’t need energy…it's a passive process!

Sally:

Let’s get back to George! He’s taken the atenolol by mouth…so while-ever there are more atenolol molecules in his GI tract than there are in his blood, they will move down their concentration gradient?

Jodie:

Yes…until the concentrations are balanced…then there is no concentration gradient! Bodies like balance!

Sally:

You said that most drugs pass through cell membranes. So the atenolol molecules must pass through the cells lining George’s GI tract, to get into his blood?

Cell membrane and fat-solubility

Jodie:

Yes. Drugs taken by mouth have to pass through the cell membranes of the GI tract to get into the blood.

Cell membranes are mainly made up of lipids. A general rule in chemistry is ‘like dissolves like’. Lipid soluble drugs dissolve in the lipids, so they can pass directly through cell membranes, using passive diffusion. 

Let’s take propranolol as an example. Propranolol is lipophilic…it likes fat. Propranolol is completely absorbed when you take it by mouth because it can passively diffuse through cell membranes.

Sally:

George is taking atenolol though…and that’s hydrophilic; it likes water. What does that mean for absorption?

Jodie:

I know you’re a foodie, so I have a cooking analogy! You’re going to make pasta pomodoro.

Sally:

Nice…simple is good! 

Jodie:

You have a pan of water. If you add some olive oil, will it dissolve?

Sally:

No. That would break the ‘like dissolves like’ rule!

Jodie:

Atenolol has low lipid solubility, so it has difficulty diffusing through cell membranes. Only about half of atenolol makes it into the blood when you take it by mouth.

Sally:

Do all drugs need to cross cell membranes?

Jodie:

Almost all! Intravenous administration puts a drug straight into the blood, so absorption is bypassed. We should clarify that we’re talking about drugs that act systemically…so have to enter the systemic, or general, circulation. 

Sally:

So far we’ve looked at three processes that feature in drug absorption:

1. Disintegration and dissolution of tablets; 

2. Passive diffusion down a concentration gradient;

3. Cell membrane and fat-solubility.

I see three key points, which relate to solubility: 

1. A drug must dissolve before it can be absorbed;

2. ‘Like dissolves like’;

3. Lipid soluble drugs dissolve in the lipids that make up cell membranes. 

The last process we’re going to cover is first-pass metabolism. Perhaps we should start by clarifying why we’re talking about metabolism in an episode on absorption!

First-pass metabolism

Jodie:

Definitely! First-pass metabolism literally means metabolism that happens during the first pass through the liver. I’ll use an example to explain.

You take a propranolol tablet. It disintegrates, then dissolves, in your stomach. Propranolol is lipophilic, so it diffuses through the cell membranes of the GI tract and enters the portal circulation. Then, it travels in the blood to the liver where a proportion of it is metabolised…let’s say it's broken down by enzymes, until the metabolism episode! We’ve ‘wasted’ some propranolol before it even gets to the systemic circulation!

Sally:

I’d say pre-systemic metabolism is a more self-explanatory term…the metabolism happens before the drug reaches the systemic circulation. 

Jodie:

Arguably more accurate too because breakdown can occur in other sites, like the intestinal mucosa! Lots of drugs are broken down in the intestinal villi, before absorption can occur.

Sally:

Why does presystemic metabolism happen?

Jodie:

Broadly, the enzymes for metabolism detoxify chemicals to keep the body functioning optimally. Drugs are chemicals…the body treats most drugs as potential toxins.

Sally:

Why does presystemic metabolism matter?

Jodie:

The proportion of propranolol that doesn’t reach the systemic circulation will never get to its site of action, so can’t have an effect.

Sally:

So to get similar drug levels in the systemic circulation, the dosage of propranolol is higher when it's taken orally, compared to when it's given intravenously. 

Jodie:

Yes. With oral propranolol you need a higher dose to achieve an adequate therapeutic effect, like slowing heart rate. Intravenous administration bypasses first-pass metabolism, by putting the drug straight into the systemic circulation. IV will bypass first-pass!
We should clarify that dosage takes account of first-pass metabolism, so prescribers can use the dose regimens in reliable sources, like the British National Formulary or BNF.

Sally:

Now is probably a good time to talk about bioavailability. 

Bioavailability

Jodie:

Makes sense because first-pass metabolism can decrease bioavailability.
Bioavailability is the fraction, or percentage, of the drug that reaches the systemic circulation unchanged.

Sally:

We probably need to work through that! Let's stick with propranolol as an example.
When taken orally, propranolol is 100% absorbed but enzymes in the liver metabolise up to 90% of the dose, which could mean only 10% reaches the systemic circulation unchanged. In this case, bioavailability would be 10%.

Jodie:

Yes, bioavailability is the amount of active drug entering the systemic circulation and available for therapeutic action.
Bio-available - available to change biology!

Sally:

So, intravenous propranolol is 100% bioavailable because putting a drug straight into the systemic circulation bypasses absorption and first-pass metabolism.

Jodie:

Actually, let’s pick up on the absorption element of bioavailability. I’ll use atenolol as an example.
When taken orally, about half of atenolol makes it out of the GI tract into the portal circulation. Only a small amount of the half that makes it to the liver is metabolised. This is because atenolol is hydrophilic, so it has difficulty getting through cell membranes to the enzymes inside. The bioavailability of atenolol is about 50% but in this case the main reason is poor absorption from the GI tract, not first-pass metabolism.

Sally:

I feel like that was quite a lot to take in! I’ve put a link to a video describing first-pass metabolism and bioavailability in the show notes. It illustrates both concepts and the connection between them. We know from episode 1 that coming at a concept in three different ways helps us to learn effectively. The video includes a bit of maths but there’s no need to get bogged down with the numbers: understanding the concepts is more important.
We’ve looked at four processes that feature in drug absorption and the concept of bioavailability. It’s enough to lightly fry anyone’s brain! 

Before we wrap up, shall we talk about how pharmacology is assessed?

Jodie:

Go on then! There are two strands to assessing pharmacology; an unseen open book exam, which is used to assess cognitive learning and the Royal Pharmaceutical Society Competency Framework for all Prescribers, which is used to assess performance in practice.
We’ll focus on the exam, which assesses how students apply their understanding of pharmacology to prescribing practice. Questions are generally case-based. We provide quite a bit of information, so that students can answer the question regardless of their scope of practice.

Sally:

How about a worked example?

Jodie:

I’m sure George can do that for us!

First we give some information about the case and the drug:
George has atrial fibrillation (fast, irregular heartbeat). You reach a shared decision to use atenolol tablets to slow his heart rate.
Atenolol is hydrophilic.
When taken orally, about half of atenolol makes it into the blood.

Then we ask a question:

Use your knowledge of absorption to reason why, when taken orally, only about half of atenolol makes it into the blood.

Finally, we say how many marks the question is worth: in this case one.

Sally:

I think it would be useful to walk through the answer framework that the marking team uses.

Jodie:

Agreed. The answer framework outlines key points. This gives students scope to answer questions in their own way.

Let’s say the key points for this question are:
Hydrophilic drug > low lipid solubility > difficulty diffusing through cell membranes > difficulty crossing cell membranes in GI tract to get into blood. 

One student might say:

Atenolol likes water, so has difficulty crossing the phospholipid bilayer of cell membranes. Therefore, only about half makes it out of the gastrointestinal tract into the blood. Another might say:

Atenolol is water soluble, which is bad for drug absorption. This is why only about half gets into the bloodstream.
We need students to show they understand that lipid solubility is good for drug absorption, so both would get the mark.

Sally:

Essentially, long questions and short answers!

Jodie:
Yes! One or two sentences is enough. It’s important to remember exam technique. This question highlights hydrophilicity and signposts to absorption; the key is applying knowledge of absorption to the scenario. We’ve talked about four processes that feature in drug absorption. For this question you need to apply knowledge of cell membrane and fat-solubility to reason why atenolol is poorly absorbed from the GI tract.

Sally:

We are nearly out of time, so let's summarise the key points from this episode.

Summary of key points

Sally:

Absorption is the journey of the drug into the circulation.

Unless enough drug is absorbed, it won’t work!

The main processes involved in drug absorption are:

1. Disintegration and dissolution of tablets; 

2. Passive diffusion down a concentration gradient;

3. Cell membrane and fat-solubility;

4. First-pass metabolism.

If there are only three things you take away from this episode: 

1. Lipid solubility is good for drug absorption!

2. Drugs that are absorbed from the GI tract travel to the liver first, where first-pass metabolism can inactivate a proportion, decreasing bioavailability.  

3. Bioavailability is the amount of active drug that can reach its site of action.

Outro:

Jodie:

That’s all we have time for! Thanks for tuning in to this episode of 'Prescriber Pod'. Remember to check the show notes for additional resources and ‘Postpod learning’. The next episode in the series is ‘How much are you taking in… and how fast?’ where we’ll be talking about more drug absorption.

Sally:

Thanks Jodie and thanks to everyone listening. Until our next episode, remember knowledge empowers prescribers to empower people.

[Outro music]

Topic: Absorption - part 1

Quality assurance (adapted from Lin et al., 2015)

Credibility

Author

Sally Porter BPharm (Hons) PgDip (Pharm) MFRPSII MRPharmS MAPCPharm FHEA, Lecturer-Practitioner in Prescribing and Medicines Optimisation, Department of Health Sciences, University of York, York, YO10 5DD.

Conflicts of interest

None declared.

Bibliography

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Content

Academic rigour

Peer reviewed by Jodie Coulson, Lecturer in Prescribing & Medicines Optimisation, Department of Health Sciences, University of York.

Peer reviewed by Dr Andrea Hilton, Reader/Pharmacist, University of Hull.

Design

Technologies

Learners with standard equipment and software can access this podcast.