Alyson Brown and Amber Robertson
PHAR222 Pharmacology I
Dabigatran for Ischaemic Heart Disease
Kuvakäsikirjoitus Teksti
Title Page
Alyson Brown and Amber RobertsonPHAR222 Pharmacology 1Dabigatran for Ischaemic Heart Disease
1.0 Introduction
So I was thinking after we do some gardening we might go into town?It sure is good to be retired!
1.1 Introduction
WHO ARE YOU!?!?
1.2 Introduction
Never fear! We're pharmacy students, Alyson and Amber. And we're here to teach you about Dabigatran for Ischaemic Heart Disease!
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1.3 Introduction
Nope! Betty, dial 000!
I'm on it Fred!
00:00-00:05 Fred and Betty are enjoying their morning coffee. He sits listening to his wife who is telling him about her plans for the day. Birds are chirping and classical music is playing.
2.0 Demographics
You might want to listen to them! Did you know ischaemic heart disease is the leading cause of death in men and Aboriginal and Torres Strait Islander people in Australia?
00:05-00:10 Suddenly a pair of weirdos appear in their breakfast nook! The music stops and the couple are startled by the strangers' presence.
2.1 Demographics
Oh....well that does interest me....but I still don't know who you are....
Well, she has an accent. I think we should listen to her. Plus, didn't your Doctor say something about your heart health?
00:10-00:20 The pharmacy students, Alyson and Amber (aka the A team) attempt to alay their fears. Erm, no, it's still weird.
2.2 Demographics
You know, it's not just men; ischaemic heart disease is the second leading cause of death in women, and accounts for 10.8% of all deaths in Australia with a median age of 84 years. It affects 17% of adults over 75 years of age.
00:20-00:25 Fred is displeased and Betty is preparing to call the Police. Ominous music plays.
00:25-00:30 Anna-Marie appears to incite fear in the couple, thereby inspiring them to listen. Ominous music stops and becomes more optimistic and hopeful.
00:30-00:40 Fred and Betty decide to hear what the strange people have to say. After all, Anna-Marie has an authoritative accent, and the students are wearing lab-coats. Heck, one even has a stethoscope. So they must know what theyr'e talking about.
00:40-00:55 Anna-Marie exits seeing the couple are in good hands with her students. The students continue their presentation.
3.0 Ischaemic Heart Disease
Ischaemic heart disease is the loss of oxygen and nutrients to the heart muscle due to poor blood flow. Fatty plaques known as "atherosclerosis" may cause this poor blood flow by blocking the arteries. This can cause "ischaemia" and can even kill the heart muscle!
3.1 Ischaemic Heart Disease
Oh man, that sounds bad.
It is bad Fred. Atherosclerotic lesions can rupture or wear causing a cascade of events to occur. This coagulation cascade can result in a blood clot called a thrombus. The thrombus is caused by platelets clumping together.
3.2 Ischaemic Heart Disease
3.3 Ischaemic Heart Disease
That sure is a lot of big words! But I think I follow so far. So how does that drug work?
00:55-01:10 Alyson states dialogue whilst animated images appear on screen. Educational elevator-style music plays in the background. Kind of like the "Jeopardy" thinking music.
4.0 Dabigatran MOA
A thrombus is held together by fibrin. Fibrinogen is converted to fibrin by an enzyme called thrombin. Dabigatran works directly against thrombin. It is a direct-acting reversible competitive antagonist of thrombin. Wow, what a mouthful!
01:10-01:15 Fred and Betty take a seat as the weight of this heavy new info sets in on their shoulders.
4.1 Dabigatran MOA
So, what you're saying is, stop the thrombin from working properly, you can stop the thrombus from forming!
01:15-01:25 Amber continues as Alyson makes herself way too comfortable preparing beverages. An occluded artery with aggregating platelets and red blood cells floats in the kitchen.
4.2 Dabigatran MOA
Exactly! Direct thrombin inhibitors are a group of drugs that bind onto the active site of thrombin. The active site of an enzyme is where molecules can attach to cause a chemical reaction. Occupying this active site results in decreased fibrin formation and reduces thrombin-stimulated platelet aggregation. This prevents the thrombus from forming!
01:25-01:30 Fred and Betty continue to listen and ask questions.
5.0 Contraindications/Precautions
So if we develop heart problems, is this something we might be prescribed?
01:30-01:45 Alyson continues. Amber has been distracted by a cat and won't be back for some time.
01:45-01:50 Despite the medical lingo, Fred and Betty get the gist!
01:50-02:15 Alyson continues whilst animations display on screen.
Dabigatran
Active Site
Thrombin
Fibrin
02:15-02:20 Fred and Betty are now enjoying the presentation and have decided the weirdos are harmless. Upbeat music plays.
5.1 Contraindications/Precautions
Well, that will depend on what your GP and/or Cardiologist find is best for you. There are some contraindications and precautions we can tell you about. Actually, my mouth's a little dry. Amber, can you take it from here?.....Amber?.....?
5.2 Contraindications/Precautions
Oh, sure thing Alyson! So according to the Therapeutic Goods Administration, or TGA, there are a number of contraindications and precautions for Dabigatran. This means a patient either can't take the drug, or their Doctor will need to decide if it's ok for them to take the drug.
5.3 Contraindications/Precautions
You must not take Dabigatran if you have:allergies to Dabigatran or any other ingredientactive bleeding or history of bleedingsevere renal dysfunctionbleeding complicationsincreased risk of bleedingstomach ulcersindwelling/recent spinal/epidural cathetersliver problems/diseasea prosthetic heart valvepregnancy/breastfeeding
5.4 Contraindications/Precautions
You also can't take Dabigatran if you're on any of the following medications:oral ketoconazole or itraconazoledronedaronecyclosporin or tacrolimusglecaprevir/pibrentasviranticoagulants (warfarin, heparin etc)verapamil (can't be started)It also interferes with lots of other medications, so you need to let your Doctor know everything that you take.
02:20-02:30 Alyson continues. Amber is still distracted by the cute, fluffy thing.
6.0 Side effects/Toxicity
Ooooh, so that's why the Doctor's are always asking what we're taking. So what kind of side effects does this drug have?
02:30-02:55 Amber pulls herself together and continues the presentation whilst Alyson silently judges her lack of professionalism.
6.1 Side effects/Toxicity
Well, all medications have potential side effects; some patients might experience some of them, some might not experience any of them!
02:55-03:20 Amber talks through the list of contraindications and precautions on the slide.
6.2 Side effects/Toxicity
• bruising• nose bleeds• stomach ache• itchy skin, rash• diarrhoea• indigestion• feeling sick• cough• painful, swollen joints• sore nasal passages and throat• discomfort when swallowing• hair loss• frequent infections such as fever,severe chills, sore throat or mouthulcers (signs of lack of whiteblood cells).These side effects are usually mild.
To access information on Dabigatran and other medications, you can read the Consumer Medicines Information or CMI, which can be found on the TGA website.Here are some side effects....
03:20-03:50 Alyson takes over for the next list.
6.3 Side effects/Toxicity
...and here are some more. It's also important to regularly check your coagulation markers using tests such as TT (Thrombin Time).
Tell your doctor immediately or goto Emergency at your nearesthospital if you notice any of thefollowing:• long or excessive bleeding• exceptional weakness• tiredness, headaches, dizzinessand looking pale (signs ofanaemia)• chest pain or being short of breath• swelling of hands, ankles and feet• red or dark brown urine• red or black bowel motions.These are serious side effects. Youmay need urgent medical attention.Other side effects not listed abovemay occur in some people.Tell your doctor if you noticeanything else that is making youfeel unwell.
03:50-03:55 Fred and Betty continue to be enthralled by the presentation and are impressed by the students knowledge and ability to relay information.
03:55-04:05 Amber continues.
04:05-04:15 Amber states dialogue in bubble whilst side effects scroll up screen.
04:15-04:25 Alyson states dialogue in bubble whilst side effects scroll up screen.
6.4 Side effects/Toxicity
Those more severe side effects involving uncontrolled bleeding, weakness and dizziness may indicate overdose. This can be tested by checking the coagulation markers, and as Dabigatran is reversible, there is an antidote available, namely darucizumab. If a patient suspects they may have taken too much medication, they should immediately seek medical attention, whether or not they have symptoms. And that's the end of our presentation!
7.0 The End
Wow! Thank you for that amazing impromptu presentation!
7.1 The End
THE END
Thank you! Bye Bye!!!!
References
Australian Bureau of Statistics. (2021). Causes of Death, Australia. 2021. https://www.abs.gov.au/statistics/health/causes-death/causes-death-australia/latest-release#key-statistics.Australian Institute of Health and Welfare. (2021). Coronary heart disease. https://www.aihw.gov.au/reports/australias-health/coronary-heart-disease.Di Nisio, M., et al. (2005). Direct thrombin inhibitors. New England Journal of Medicine 353(10): 1028-1040.Dubois, E. A. and A. F. Cohen (2010). Dabigatran etexilate. British journal of clinical pharmacology 70(1): 14-15.
04:25-04:50 Amber continues speaking.
References continued
04:50-04:55 Fred and Betty leap to their feet and applause!
04:55-05:00 Alyson and Amber leap into the air and in a flash they are gone! Leaving their coffee cups unwashed next to the sink. Rude!
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Ganetsky, M., et al. (2011). Dabigatran: review of pharmacology and management of bleeding complications of this novel oral anticoagulant. Journal of Medical Toxicology 7(4): 281-287.Kunio, N. R. and M. A. Schreiber (2013). Topical hemostatic agents. Consultative Hemostasis and Thrombosis: Third Edition, Elsevier Inc.: 538-545.Severino, P., et al. (2020). Ischemic Heart Disease Pathophysiology Paradigms Overview: From Plaque Activation to Microvascular Dysfunction. International journal of molecular sciences 21(21).Ten Cate, H. and H. C. Hemker (2016). Thrombin Generation and Atherothrombosis: What Does the Evidence Indicate? Journal of the American Heart Association 5(8): e003553.