6 - Diabetes and Drugs Flashcards
What causes the secretion of insulin and what is it inhibited by?
- Protein secreted by B cells which is why it has to be injected not orally
- Stimulated by: increased glucse, glucagon, incretins (GLP-1 and GIP), parasympathetic activity (M3)
- Inhibited by: lowered glucose, cortisol, sympathetic activity (a2)
What are the different functions of insulin in the body?
- Stimulates uptake of glucose into liver, muscle and adipose tissue
- Inhibits gluconeogenesis
- Inhibits glycogenolysis
- Promotes fat uptake
What are some drugs that can be a risk factor for the development of type 2 diabetes? (drug induced diabetes)
What are some symptoms of type 1 diabetes?
- Hyperglycaemia
- Polyuria
- Polydipsia
- Weight loss
- Fatigue/lethargy
Raised plasma glucose without symptoms not sufficient for diagnosis
How is insulin absorbed and administered?
- Absorbed into the blood stream by subcut injection e.g upper arms, buttocks
- Given 15-30 mns before eating as plasma concentration highest 2-3 hours after giving and short half life
- Given IV if emergency
- Has to be straight to blood stream as it is a protein so would be broken down enterally
What substances can be given with insulin to modify its absorption?
- Protamine: makes insulin short acting, broken down quicker
- Zinc: makes insulin long acting, longer time to absorb
What are some side effects of injecting insulin?
- Hypoglycaemia
- Lipodystrophy if using same sites constantly
- Allergies
- Painful injections
- Lipoatrophy
Fill in the following table regarding different formulations of insulin.
Provide an example of the following and when they need to be administered:
- Rapid acting insulin
- Short acting insulin
- Intermediate acting insulin
- Long/very long acting insulin
- Insulin aspart (Novorapid): inject just before eating
- Soluble Insulin (Actrapid or Humulin S): inject at least 15-30 minutes before eating several times daily to cover meals
- Isophane Insulin (NPH)
- Insulin degludec or insulin glargine
What are some contraindications for the use of insulin?
- Increase dose of insulin if patient using steroids
- Be careful with other hypoglycaemic drugs
What are the key challenges for patients with Type 2 diabetes in terms of patient adherence and quality of life?
- Weight gain (or fear of weight gain)
- Risk of hypoglycaemia (or perceived risk)
What is basal bolus dosing?
- Injection at each meal, attempts to roughly mimic how a non-diabetic person’s body delivers insulin and then a basal dose constantly
- Mimics insulin levels in healthy patient
When should you suspect a DKA and how would you treat it?
- First give fluids as diuresis from glucose
- Then give IV insulin
- Give glucose and K as can turn hypokalemic from insulin even though appear hyperkalemic
What are three different regimens that can be used for insulin injections?
- Basal: inject a long acting insulin so you have the same basal level of insulin at all times
- Basal-Bolus: use a long acting insulin but before eating you inject a fast/short acting insulin so insulin levels increase when eating
- Intermediate: 2 injections a day of combined intermediate and short acting
Can get a insulin pump but very expensive
What is the pathophysiology of type 2 diabetes and how can it be treated in general terms?
- Decrease in sensitivity of insulin receptors initially overcome by increased pancreatic insulin secretion
- Glucotoxicity from fatty acids and ROS lead to B cell dysfunction
- Treat: change lifestyle, hypoglycaemic agents and eventually insulin
What are the NICE guidlines for type II diabetics needing glucose lowering therapy?
- HbA1c >6.5% use metformin, if can’t tolerate use DPP-4i or SGLT2i OR a modified release metformin
- HbA1c>7.5% consider dual therapy and if not responding then triple therapy and if still not responding think about insulin therapy
SEE PICTURE FOR DETAILS
What is the mechanism of action of metformin? (biguanide)
FIRST LINE THERAPY
- Decrease hepatic glucose output by decreasing gluconeogenesis and glycogenolysis
- Increases glucose utilisation in skeletal muscle by decreasing insulin resistance
- Suppresses appetite so limits weight gain
- Decrease insulin resistance
What are some side effects of metformin?
- GI symptoms (nausea, loose stools, diarrhoea)
- Vitamin B12 deficiency (uncommon)
- Lactic acidosis (rare
USE MODIFIED RELEASE TO LIMIT SIDE EFFECTS
What are some contraindications for the use of metformin?
- Any drugs that may impair renal function: ACEi, NSAIDs, diuretics
- Thiazide like diuretics as they increase gucose so can reduce metformin action
What is the mechanism of action of suphonylureas and what is an example of this class of drug?
- Gliclazide
- Added on if metformin isn’t working
- Stimulates beta cells to secrete insulin by blocking ATP dependent K channels but need residual pancreatic function for this
- Decreased microvascular risk
What are the side effects of sulphonylureas?
- Weight gain due to anabolic effects of insulin
- Mild GI upset
- Hypoglycaemia (less risk than in metformin)
- Hypersensitivity reactions (rare)
When do you need to use suphonylureas with caution?
- Other hypoglycaemic agents
- Hepatic impairment
- Renal impairment (not so much as metabolised hepatically)
What is the mechanism of action of glitazones and what are some examples?
Pioglitazone and Rosiglitazone
- PPARy receptor agonist which is a transcription factor that increases the sensitivity of fat cells to insulin
- Decrease hepatic glucose output by activating PPARy receptor
Describe the side effects for the following glitazone drugs:
- Rosiglitazone
- Pioglitazone
- Rosiglitazone – CVS concerns
- Pioglitazone – weight gain, fluid retention, heart failure, effects on bone metabolism so fracture risk and bladder cancer
- Be careful using these when also using other hypoglycaemic drugs
What are the mechanism of action of gliflozins (SGLT2 inhibitors) and what are some examples of these drugs?
- Prevent uptake of glucose in the PCT so more glucose in the urine
- Used in type 1 and type 2 diabetes as an add on theray
- Dapagliflozin and Canagliflozin
What are some side effects of gliflozins and when should they be used with caution?
- UTI risk
- Polyuria and polydipsia
- Be careful when using with antihypertensives and other hypoglycaemic agents
What are the effects of GLP-1 (glucagon like peptide) in the body?
- Increase insulin secretion from the beta cells
- Decreases production of glucagon from alpha cells
What is the mechanism of action of GLP-1 agonists and what are some examples of this type of drug?
- Increase glucose dependent synthesis of insulin from B cells by activating the GLP-1 receptor. These agonist can’t be degraded by DDP-4
- Decrease production of glucagon
- Promote sateity as slow gastric emptying so possible weight loss
- Exenatide and Liraglutide
What are the side effects of using GLP-1 agonists and when should you be careful prescribing them?
- GI upset
- GORD
- Painful to inject (subcut injection)
- Small pancreatitis/pancreatic carcinoma risk
- Don’t take if eGFR<30ml/min
- Be careful when patient taking other hypoglycaemic agents
When would you prescribe a GLP-1 agonist?
If triple therapy is ineffective, prescribed at really late stage
What is the mechanism of action of gliptins and give a few examples of this type of drug?
- DPP4 inhibitor therefore stopping the degradation of GLP1 so increase plasma incretin levels and therefore increased insulin
- First line option if metformin not tolerated
- Supresses appetite so weight neutral
- Sitagliptin and Saxagliptin
What are the side effects of using DDP4 inhibitors and when should you be careful prescribing them?
- GI upset
- Pancreatitis risk
- Not as much risk of hypoglycaemia as with GLP1 agonists as not directly making insulin
- Avoid in pregnancy
- Thiazide like/Loop diuretics
- Hypoglycaemic agents
- Drugs that increase glucose
When giving a modified release tablet what do we need the patient to do?
SWALLOW THE TABLET WHOLE - as the coating makes it modified release
What are the pros and cons of giving two oral hypoglycaemic agents in the same drug?
- Increases adherance as only one pill
- Hard to change dosage of just one pill so difficult to finely tune drug regimen
What is diabulimia?
An eating disorder in which people with type 1 diabetes deliberately give themselves less insulin than they need or stop taking it altogether for the purpose of weight loss
How is insulin release controlled at the site of injection?
- By the other substances injected with it, e.g zinc
- As it is made soluble this delays absorption as soluble insulins form hexamers at the site of injection to delay absorption
Why do DPP-4 inhibitors have a low risk of hypoglycameia when administer alone?
- Prevents hypoglycaemia via increased glucagon counterregulation through the incretin hormone glucose-dependent insulinotropic polypeptide (GIP)
- INCRETINS DON’T HAVE AN EFFECT AT LOW GLUCOSE!!! (Don)
Why do sufonylureas promote weight gain?
They cause increased insulin release which has anabolic effects
What is the target cholesterol value once statins have been started?
- Total<4mmol/L for secondary prevention
- LDL<2mmol/L
How would you diagnose myalgia due to the use of statins?
Blood CPK would be more than ten times the normal limit
Why do thiazide like diuretics increase glucose levels?
Hypothesis believes they may cause worsening of insulin resistance, inhibition of glucose uptake, and decreased insulin release
What class of oral hypoglycaemic agent provides long term redution in vascular complications?
SGLT2 inhibitors!!!! (not DDP-4)
If a patient can only tolerate a low dose statin, what else should they be given?
Ezetimibe (only in the enterohepatic circulation, not the systemic)
What diabetic drugs are good to use in renal impairment?
Glicazides as they are hepatically metabolised
What non-pharmacological intervention would be recommended upon diagnosing type II diabetes and what considerations should be discussed when initiating therapy?
- Managed weight reduction
- Warn them about weight gain and hypoglycaemia
