LT1 Intro & Prevention vs Cure Flashcards
What is pharmacodynamics?
Drug action on biology = how the drug produces its therapeutic effect
What a drug does to the body
The study of the biochemical, physiologic, and molecular effects of drugs on the body
What is pharmacokinetics?
The study of how the body interacts with administered substances for the entire duration of exposure
What the body does to a drug, refers to the movement of drug into, through, and out of the body
What is pharmacogenomics?
The study of how a person’s genes affect how they respond to drugs
What is metabolic disease?
Disease or disorder that dirupts normal metabolism
Problems with ntrient transport, nutrient digestion and build of toxic agents can occur
What is metabolic syndrome?
Combination of risk factors = diabetes, high blood pressure and obesity
Putting a person at higher risk of CVD or T2D
Define metabolism
Process of converting food to energy on a cellular level
What is non-alcoholic fatty liver disease?
Non-alcoholic fatty liver disease (NAFLD) is caused by a buildup of fat in the liver, which prevents it from functioning properly
It’s often linked to being overweight or obese, but other factors can also contribute
Why are T2D numbers inaccurate?
Because there are about 0.5million people undiagnosed with T2D
What is the correlation between obesity and diabetes?
T1D is NOT associated with being overweight/obesity
T2D is CLOSELY assocaited with being overweight/obesity
What occurs in early-stage non-alcoholic fatty liver disease?
Early stage NAFLD doesn’t usually cause harm
BUT
Associated with T2D, high blood pressure and kidney failure
All linked to obesity related metabolic dysfunction
What are the stages of non-alcoholic fatty liver disease?
Early-stage NAFLD
NASH (non-alcoholic steatohepatitis)
Fibrosis = irreversible hardening of liver
Cirrhosis
What is cirrhosis of the liver?
A chronic liver disease that occurs when healthy liver tissue is replaced by scar tissue. This prevents the liver from functioning properly
What is diabetes mellitus diagnosis based on?
Solely on blood glucose concentration
Hyperglycaemia is abover 7mM fasting blood glucose
Euglycemia is 5mM fasting blood glucose
How does the oral glucose tolerance test work?
Measure 2h after 75g glucose load
If glucose levels are abover 11.1 then diabetic
What is the most accurate test for diabetes and why?
HbA1c test
Look at glycated Hb is a more accurate long term measure of glucose control compared to fasting glucose
Because fasting can be inaccurate if people do it incorrectly
What blood glucose concentration counts as pre-diabetic?
Between 6mM - 7mM fasting blood glucose levels
What counts as hypoglycaemic levels?
Below 4mM of fasting blood glucose levels
Why is glucosuria dangerous?
High glucose in urine promotes large osmotic diuresis = a condition where the body produces more urine than normal
This can lead to dehyration, circulatory failure, brain damage and renal & heart failure
Why is high blood glucose dangerous?
Because it promotes glycation of blood proteins = causing dysfunction
This can give indicaiton of duration of hyperglycaemia
How does diabetes cause macro/microvascular damage?
High glucose levels react with proteins in the blood vessels, forming AGEs which can damage the endothelial lining and contribute to inflammation and vascular stiffness
Advanced Glycation End Products (AGEs)
What does macrovascular blood vessel disease cause compared to microvascular?
Macrovascular = atherosclerosis and platelet aggregation and hypercoagulability
Leads to CHD, vascular disease
Microvascular = specific to diabetes and genetic factors appear to contirbute
Leads to nephropathy, retinopathy, and neuropathy
How is T1D autoimmune disease triggered?
The exact cause of T1D is unknown, but it’s thought to be triggered by a combination of genetics and environmental factors.
The process is characterized by the activation of autoreactive T cells that attack the beta cells in the pancreas
What other causes of diabetes are there except for T1D and T2D?
Genetic defects in beta-cell function = MODY
Genetic defects in insulin action (insulin does more than just regualte glucose = higher risk of death)
Gestational diabetes mellitus
Why does gestational diabetes mellitus occur?
Transient diabetes that arises during pregnancy (usually during the 2nd trimester)
In some, it occurs because the body cannot produce enough insulin to meet the extra needs of pregnancy
Affects ~5% of all pregnancies
Women who are overweight/obese are at higher risk of gestational diabetes
What does gestational diabetes mellitus tell us?
Women who have had GDM = 7x more at risk of developing T2D later in life
Esp if they gain weight
Could be linked to insulin insufficiency
GDm is an early warning of weak beta cell response
Why is the criteria for diagnosing gestational diabetes different from other types?
7mM is the limite for T1D and T2D beacuse this is when vascular issues occur
But for GDM fasting plasma glucose level of 5.6mM or above is the limit
This is becuase it would be dangerous for the unborn child
How do hormones respond to fasting?
Glucagon is released from alpha-cell when blood glucose drops
Glucagon primarily stimulates hepatic glucose output by enhancing glycogen breakdown and endogenous glucose production (gluconeogensis)
Blood glucose levels increase and reduce glucagon production
How do hormones respond to food?
Following a meal, blood glucose levels irse
Insulin is release from beta-cells when this ocurrs
Insulin induces glucose removal from blood and storage in teh liver, adipose, and muscle as glycogen and fat
Insulin is cleared by the liver and levels return to basal when blood lgucose levels normalise
How is insulin cleared from out system?
Primarily cleared from the body by the liver, which removes a large portion of it during its first pass through the hepatic portal vein, and to a lesser extent by the kidneys through filtration in the glomeruli
What is the target cell for T2D therapeutics?
Pancreatic beta-cell
What organs does insulin mainly target?
Liver = inhibits gluconeogenesis and promotes GLYCOGEN synthesis
Reduces hepatic glucose output
Muscle = enhances glucose uptake and storage as glycogen
What is the overall action of insulin?
Anabolism = sotrage of energy for times of starvation
Promotes glucose uptake into liver
Promotes glucose storage as inert glycogen in liver and muscle
Promotes use in glycolysis and suppresses gluconeogensis
Promotes glucose conversion into FA (which are shipped to adipose)
Enhances protein production in muscle
Suppresses TAG breakdown in adipose
Are insulin and glucagon part of the same signalling pathways?
No, it not simply induction and inhibition fo same molecular pathways
Do we ever see insulin and glucagon released at the same time?
During T2DM
Indicates severe disruption of signalling sensitivty and regulation of these hormones
What needs to be taken into account with drugs for diabetes?
Lifestype and pharmacological interventions are depenent on the TYPE of diabetes
Interventions change as disease progresses
Addtional drugs added as complication arise, or to prevent compliations
There is no drug that produces a cure and for many patients the drugs are not that helpful
What are concerns from T1D patients?
Hypoglycameic coma
Remembering insulin injection everyday and not getting ‘caught out’
Glucose monitoring (thumb prick or insert monitor)
Fitting into everyday life (sports, work and driving)
Sports = increases fuel usage so hypoglycaemia is more likely
What is needed to take into account when administering drugs?
Drug-drug interactions hwen taking multiple drugs
Pharmacokinetics in patients with renal and vascular problems
Patient compliance (aversion to taking drugs, forgetting, wrong dosage)
NHS cost
What needs to be considered in prevention strategies?
To prevent a disease either change something in the WHOLE population
OR
Target those at high risk and then give preventative intervention
Why is prevention difficult?
Relies on ‘treating’ those WITHOUT the disease
Requires almost constant reinforcement by education
What is diseae prevention foucsed on?
Disease risk of a person
What is potential T1D prevention as well as treatment?***
Immunotherapy
What is potential T2D treatment?***
Targetting obese population
Weight loss improves T2D, even in leaner people
What group is important to focus on for prevention?
Pre-diabetics
How do you identify and engage people at high risk of getting diabetes?
Screen for impaired glucose tolerance (HbA1C), other risk factors (genetics, GDM)
How do you alter the obesogenic env?
Sugar tax
Always need to have clear evidence base and buy-in from government and food industry
How do you deal with health inequalities?
Low income populatoin are highest risk but poorest engagement in current programmes
No easy fix
Digital innovation and local chamions
How do you evaluate if the weight loss programme is working?
Evaluate short term weight improvement
Maintained improvement in weight/adiposity should translate to less T2D in 5-10 years (politiciant was faster results)
Need long-term clinical follow-up
High quality data collection, joined up national approach to intervention allocations and data collection
NHS as research facility
Defne remission
Signs and symptoms of your disease are reduced
Remission can be partial or complete
Complete = all signs and symptoms have disappeared
What defines diabetes is in remission?
HbA1c dropping below 6.5% without hte need to take any T2D medication
Why is prevention so difficult in the NHS?
Limited funding
Short-term political cycles
Focus on treating immediate health issues rather than long-term prevention
Siloed government structures
Lack of incentives for preventative care
The complex social determinants of health that often lie outside the direct control of the NHS
Meaning addressing preventative measures often requires collaboration with other sectors like housing, education, and transport, which can be challenging to coordinate effectively
What is evidence that T2DM can be prevented?***
Weight reduction has a strong correlation with improved diabetes
What are barriers to prevention of T2DM?***
Identifying and engaging people at high risk of getting diabetes
Altering obesogenic env
Dealing with health inequalities (minorities, and low income population)
Evalutaing if the programme is working (diffucult to see on a long-term scale)
What is diabetes insipidus?
Diabetes insipidus is caused by problems with a chemical called arginine vasopressin (AVP), which is also known as antidiuretic hormone (ADH).
AVP is produced by the hypothalamus and stored in the pituitary gland until needed.
The hypothalamus is an area of the brain that controls mood and appetite.
The pituitary gland is located below your brain, behind the bridge of your nose.
AVP regulates the level of water in your body by controlling the amount of urine your kidneys produce.
When the level of water in your body decreases, your pituitary gland releases AVP to conserve water and stop the production of urine.
In diabetes insipidus, AVP fails to properly regulate your body’s level of water, and allows too much urine to be produced and passed from your body.
There are 2 main types of diabetes insipidus:
AVP deficiency (formerly cranial diabetes insipidus) – where the body does not produce enough AVP, so excessive amounts of water are lost in large amounts of urine
AVP resistance (formerly nephrogenic diabetes insipidus) – where AVP is produced at the right levels but, for a variety of reasons, the kidneys do not respond to it in the normal way
