Week 10 Flashcards
What organ monitors blood glucose?
Pancreas
What happens if blood glucose in low?
Glucagon released from α cells & upper GI to stimulate glycogen breakdown & gluconeogenesis in the liver
What happens if blood glucose is high?
Insulin released from β cells to stimulate liver, adipose & muscle to take up glucose
List the symptoms of diabetes?
- Always tired
- Wounds don’t heal
- Sudden weight loss
- Frequent urination
- Always hungry & thirsty
- Sexual problems
- Blurry vision
- Numb/tingling hands/feet
- Vaginal infections
Describe the difference in diagnosis of type 1 & type 2 diabetes?
TYPE 1- often in childhood
TYPE 2- usually over 30yrs old
Describe the difference in excess body weight association of type 1 & type 1 diabetes?
TYPE 1- NOT associated
TYPE 2- OFTEN associated
Describe the different associations of type 1 & type 2 diabetes?
TYPE 1- higher ketone levels at diagnosis
TYPE 2- high blood pressure &/or cholesterol levels at diagnosis
Describe the differences in treatment of type 1 & type 2 diabetes?
TYPE 1- insulin injections or insulin pump (replacement therapy)
TYPE 2- initially without medication or with tablets
Describe why there is a natural progression from prediabetes to type 2 diabetes?
- Disruption of ability to metabolise glucose
- May have hyperinsulinemia due to lower insulin sensitivity
- Full diabetes progresses when β cell failure surpasses critical threshold ~90%
What is the glucose level aim when treating type 1 diabetes with insulin?
4-7mM (preprandial/ fasting)
What should glucose levels be, in normal people, 2hrs after a meal?
<7.8mM
What glucose level will overload the renal capacity & be detected in urine?
> 10mM
How is insulin now made?
By recombinant DNA technology, allows an identical pure preparation, limiting allergic reactions
How is insulin administered and why?
- Parentally because it’s a protein that would be destroyed/ digested by gut if oral
- Routine use subcutaneously
- IV infusion in emergencies
Insulin formulations can differ in their _____ of action?
Duration
What can altering amino acids in the insulin structure do?
Usefully alter insulin kinetics (designer insulins)
Describe the formulation of Insulin Lispro or Insulin Aspart
- Rapid-acting soluble
- Designer insulins that prevent dimer formation allowing more active monomers to be bioavailable & used rapidly
Describe the formulation & action of Neutral Protamine Hagedorn (NPH)/Isophane Insulin?
Intermediate-acting insulin that precipitates insulin into suspensions which slowly dissolve
Describe the formulation & action of Insulin Glargine?
Longer acting designer Insulin which has decreased solubility at neutral pH, forms aggregates that slowly dissolve.
Describe the formulation & action of Insulin Detemir?
Long-acting designer insulin with a fatty acid- this confers albumin binding, which slowly dissociates prolonging circulation
For type 1 diabetes describe the formulation of insulin replacement?
Intermediate-acting preparation/ long-acting analogue is often combined with short-acting analogue before meals
What 3 types of diabetes is insulin used for?
- Type 1 diabetes
- 1/3rd of Type 2 diabetes
- Gestational diabetes
Describe the pros & cons of FIXED dose insulin regiments?
- PROS: Can be on any injection regiments, simplify understanding of blood glucose results
- CONS: not offer flexibility of how much carbs patient choose to consume each meal
Describe the pros & cons of FLEXIBLE dose insulin regiments?
- PROS: more control of what they eat & how to balance blood glucose, can have different carb quantities in meals
- CONS: patients need to understand glucose metabolism, take time & commitment to learn to adjust insulin dose
Describe the once daily insulin regimen & who it’s appropriate for?
- 1 injection in morning
- Suitable for Type 2
- Long-acting (Glargine) or Intermediate (NPH)
- Less flexible & required basic patient understanding
Describe the twice daily insulin regimen & who its appropriate for?
- 2 injections in morning & evening
- Type 1 & Type 2
- Short-acting mixed with intermediate
- Less flexible & requires basic patient understanding
Describe the basal-bolus insulin regimen & who its appropriate for?
- Multiple injections throughout day
- Type 1 & some Type 2
- Intermediate or long-acting with short-acting
- Flexible & requires high patient understanding
Describe the insulin pump regimen & who its appropriate for?
- Semi-automated as needed throughout the day
- Type 1
- Short-acting insulin
- Flexible & requires medium/high patient understanding
What are Oral Hypoglycemic tablets used for?
To alter glucose metabolism in Type 2 diabetes
What is the principle oral Hypoglycemic drug?
Metformin (biguanide drug)
What are the effects of Metformin (hypoglycemic drug)?
- Potentiate residual insulin by increasing insulin sensitivity
- Reduce gluconeogenesis in liver & opposes action of glucagon
- Increases glucose uptake & utilisation in skeletal muscle
- Slightly delays carb absorption in gut
- Increases fatty acid oxidation
- Suppress appetite
How can Metformin stimulate insulin release?
By combining it with other drugs
What does Metformin’s effect of increased fatty acid oxidation help with?
Obesity associated diabetes & atherosclerosis development
Overall, what does Metformin do?
Alters energy metabolism
What is the action of Metformin on the mitochondria & what does this result in?
- Increase AMP:ATP ratios activate AMP-activated protein kinase
- AMPK increases transcription of genes important for glucose transport fatty oxidation
What are the 2 classes of insulin secretagogues?
- Sulphonylureas (old)
2. Meglitinides (new)
Give 4 examples of Sulphonylurea’s?
- Tolbutamide
- Chlorpropamide
- Glibenclamide
- Glipizide
Describe the action of Sulphonylurea’s?
- Interfere with β cell ion channels to potentiate insulin secretion
- Well tolerated, can lead to weight gain by stimulating appetite
When are Sulphonylurea’s used & why?
Early stages of type 2 diabetes as they require functional β cells
What 2 drugs can Sulphonylurea’s be combined with?
- Metformin
2. Glitazones
What can the interaction between Sulphonylurea’s & other drugs produce?
Severe hypoglycaemia due to competition for metabolising enzymes, plasma binding proteins & excretory pathways.
What is the action of Meglitinides (next generation insulin secretagogues)?
Block K-ATP channels to increase insulin release
What does the short duration of Meglitinides lead to?
Lower risk of hypoglycaemia
Where are the high affinity receptors for Sulphonylurea drugs present
β cell membranes
What are Glitazones also known as?
Thiazolidinediones
Describe the effects of Pioglitazone (Thiazolidinediones/ Glitazone)?
- Increases insulin sensitivity
- Reduces exogenous insulin needed by ~30%
- Reduces blood glucose & free fatty acid conc
- Promote transcription of several genes with products important in insulin signalling
What do Pioglitazone & Rosiglitazone’s (Thiazolidinediones/ Glitazone) act on?
Peroxisome proliferator activated receptor (PPAR-γ) agonists in adipose tissue, muscle & liver
What 2 side effects can Pioglitazone cause?
- Weight gain
2. Fluid retention
What 3 diseases have been linked to Pioglitazone?
- Bladder cancer
- Heart failure
- Osteoporotic fractures
What is the function of PPAR-γ ligand?
Promote transcription of genes important in insulin signalling (lipoprotein lipase, fatty acid transporters, Glut-4 etc)
What is Pioglitazone used for clinically?
Additive to other oral hypoglycaemic drugs ie. Metformin & Sulphonylureas
What is Acarbose?
Inhibitor of intestinal α-glucosidase
What is the effect of Acarbose?
Delays carbohydrate absorption in small intestine reducing the postprandial spike in glucose
When is Acarbose used?
Type 2 diabetes often in combination with other hypoglycemics
What are the 2 side effects of Acarbose?
- Flatulence
2. Diarrhoea
Give 3 examples of selective sodium glucose cotransporter 2 (SGLT2) inhibitors?
- Canagliflozin
- Dapagliflozin
- Empagliflozin
When are selective sodium glucose cotransporter 2 (SGLT2) inhibitors used?
Type 2 diabetes as mono therapy when diet & exercise along not adequate for whom metformin is contraindicated or inappropriate
What are the actions of selective sodium glucose cotransporter 2 (SGLT2) inhibitors?
- Block glucose reabsorption by proximal tubule leading to therapeutic glucosuria
- Controls glycaemia independently of insulin pathways
What do selective sodium glucose cotransporter 2 (SGLT2) inhibitors lead to compared to placebo?
- Reduced HbA1c up to 1.17%
- Well tolerated, reduce weight & systolic BP
What is the side effect of selective sodium glucose cotransporter 2 (SGLT2) inhibitors?
Associated with increased risk of urinary tract infections
Where are glucagon-like peptide-1 (GLP-1) secreted?
L-cells in the gut
Where are gastric inhibitor peptide (GIP) secreted?
K-cells in gut
What are the effects of Incretins?
- Directly stimulate insulin biosynthesis & secretion
- Inhibit glucagon secretion in pancreas, delay gastric emptying, increase cardiac output & satiety signals in brain
- Indirectly increase insulin sensitivity in muscle & decrease gluconeogenesis in liver
What are Incretins rapidly degraded by?
Enzyme called dipeptidyl peptidase-4 (DPP-4)
Give 3 examples of Incretin mimetics? (analogs of extending-4/GLP-1)
- Exenatide
- Exenatide LAR
- Liraglutide
What is the regimen of Exenatide & its side effect?
- Twice daily
- Nausea
What is the regimen of Exenatide LAR & its side effect?
- Long-acting release formulation administered weekly
- Less nausea
What is the action of Liraglutide?
Additional fatty side-chain that confers albumin binding & slows renal clearance
What are the actions of Incretin mimetics/analogs?
Lowers blood glucose after meal by increasing insulin secretion & suppressing glucagon secretion
When would you use dIncretin mimetics/analogs?
Type 2 diabetes in addition to oral agents to improve control & aid weight loss
What is the route of Incretin mimetics/analogs?
Subcutaneously as peptide analogs
What are the potential side effects of Incretin mimetics/analogs?
- Hypoglycemia
- Range of GI effects
Give 2 examples of DDP-4 inhibitors/Gliptins?
- Sitagliptin
2. Vildagliptin
What are the effects of DDP-4 inhibitors/Gliptins?
- Enhance endogenous incretin effects by blocking DPP-4
- Lowers blood glucose by increasing 1st phase of insulin response after meals
Describe Sitagliptin as a drug?
Well tolerated & weight neutral
What are the side effects of Vildagliptin?
- Respiratory tract infections
- Headache
- Serious pancreatitis
What does the adrenal cortex arise from?
Intermediate mesoderm
Describe the location of the adrenal glands?
Retroperitoneally on upper pole of the kidneys
List the 5 layers of the adrenal gland from exterior to interior?
- Capsule (fibrous)
- Zona glomerulosa
- Zona fasciculata
- Zona reticularis
- Medulla
What hormone is produced in the Zona glomerulosa (adrenal cortex)?
Mineralocorticoid (aldosterone)
What hormone is produced in the Zona fasciculata (adrenal cortex)?
Glucocorticoids (cortisol)
What hormone is produced in the Zona reticularis (adrenal cortex)?
Androgens (DHEA & androstenedione)
What hormone is produced in the adrenal medulla?
Epinephrine/Adrenaline
What is the zona glomerulosa controlled by?
Renin-angiotensin
What is the function of the aldosterone release from zona glomerulosa?
Electrolyte & fluid homeostasis
What is the zona fasciculata controlled by?
ACTH
What is the function of the glucocorticoid release from zona fasciculata?
Carbohydrate, lipid & protein metabolism
The adrenal cortex produces _____ hormones?
Steroid
What is the blood supply of the adrenal cortex?
- Superior, middle & inferior adrenal arteries which anastomose under the capsule
- Cortex receives short cortical arteries run in parallel with cords of cells to medulla
What is the blood supply of the adrenal medulla?
- Draining from the cortex
- Fresh arterial blood in long cortical arteries
What does the blood draining from the cortex into the medulla contain?
Adreno-corticosteroids which influence the production of adrenaline by medullary cells
What are the 6 short-term stress responses to increased catecholamines from the adrenal medulla?
- Increased heart rate
- Increased BP
- Liver converts glycogen to glucose & releases it to blood
- Dilation of bronchioles
- Changes in blood flow patterns leading to decreased digestive system activity & reduced urine output
- Increased metabolic rate
What are the 2 long-term stress responses to increased mineralocorticoids from the adrenal cortex?
- Retention of sodium & water by kidneys
2. Increased BP & blood volume
What are the 3 long-term stress responses to increased glucocorticoids from the adrenal cortex?
- Proteins & fats converted to glucose/ broken down for energy
- Increased blood glucose
- Suppression of immune system
What is the major role of cortisol?
Ability to cope with physical (trauma, infection, allergies) or neurological (anxiety, restraint) stresses
What are the 3 pharmacological actions of cortisol?
- Anti-inflammatory
- Anti-allergic
- Anti-immune
What are the 4 possible causes of Cushing’s disease/syndrome (glucocorticoid excess)?
- ACTH-releasing pituitary tumour
- Ectopic ACTH-releasing tumour (usually in lungs, pancreas or kidney)
- Tumour of the adrenal cortex = hyper-secretion of cortisol
- Administration of pharmacological doses of glucocorticoid drugs
What are the 7 clinical features of Cushing’s disease/syndrome?
- Hyperglycaemia
- Muscle wasting
- Increase free fatty acid (FFA) in plasma
- Increased insulin release
- Tissue edema, hypokalemia, hypertension
- GI Tract ulceration
- Decreases in protein synthesis
Why does Cushing’s disease/syndrome result in hyperglycaemia?
- Gluconeogenesis in liver
- Sometimes called adrenal/steroid diabetes
Why does Cushing’s disease/syndrome result in muscle wasting?
Loss of protein synthesis in muscle & bone (& most tissues)
Why does Cushing’s disease/syndrome result in increase FFA in plasma?
Reduced lipogenesis & enhanced lipolysis
What does increased insulin release in Cushing’s disease/syndrome result in?
- Redistribution of fat stores to face, neck, upper trunk
“buffalo hump” - β-cell exhaustion
Why does Cushing’s disease/syndrome result in tissue edema, hypokalaemia, hypertension?
Increased glomerular filtration (glucocorticoid effect) & water & Na+ retention (mineralocorticoid effects)
Why does Cushing’s disease/syndrome result in GI tract ulceration?
Excess H+ secretion & decreased mucous production (alkalosis due to increased H+ loss in GI tract & kidney)
What are the 2 possible treatments for Cushing’s disease/syndrome?
- Surgical removal of tumour
2. Decreases in drug dosage
What 3 pathways stimulate the glomerulosa cells to synthesise aldosterone?
- Increase renin-angiotensin cascade
- Increase ACTH from anterior pituitary
- Increase plasma [K+]
What effects does aldosterone have on the kidney?
- Decrease Na+ & H2O excretion
- Increase [K+] excretion
- Increase effective circulating volume, extracellular fluid volume & BP
What is the Juxta-glomerular apparatus?
- Specialized structure formed by distal convoluted tubule & glomerular afferent arteriole
- Main function is regulate blood pressure & filtration rate of glomerulus
List the structures that form the Juxta-glomerular apparatus?
- Granular cells/ Juxtaglomerular cells on the afferent arteriole (from renal artery)
- Macula densa on the distal tubule
- Extraglomerular mesangial cells
What does the Granular cells/ Juxtaglomerular cells allow?
Renin to pass into the afferent arteriole
What do the macula dense cells detect?
Sodium concentrations in the distal tubule (osmolality)
Describe the suppression of glucocorticoid activity in renal cortical tubular cells?
- 11 beta-HSD metabolises cortisol, making it have little affinity for mineralcortisol receptor (MR)/glucocorticoid receptor (GR). Aldosterone, not metabolised & occupies MR & GR
- Glycyrrhetinic acid inhibits 11 beta-HSD, cortisol is not metabolised & occupies MR & Gr over aldosterone
What are the 4 primary causes of Addison’s disease (primary adrenal cortical insufficiency)?
- Tuberculosis/ metastatic tumours
- Autoimmune adrenalitis –> adrenal failure
- HIV - decreased immunity & increased viral & bacterial infections
- Atrophy due to prolonged steroid therapy
What are the 6 clinical features of Addison’s disease?
- Loss of weight/appetite, muscle weakness, nausea, vomiting
- Low plasma glucose esp. after fasting
- Hyponatriemia & Hyperkalaemia
- Dehydration & hypotension due to 3
- Lethargy & dizziness on standing up due to 4
- Severe present with skin pigmentation
Why in severe cases of Addison’s disease do patients present with skin pigmentation?
Excess ACTH acting as Melanocyte stimulating hormone (MSH)
Describe the 2 possible treatments for Addison’s disease?
- Glucocorticoid replacement therapy- Hydrocortisone administration morning (25mg)/afternoon (12.5 mg)
- IV saline infusion if severely dehydrated & condition life threatening & administration of Fludrocortisone (mineralocorticoid agonist)
What does the adrenal medulla develop from?
Neural crest cells
What important cell does the adrenal medulla contain?
Chromaffin cells (postganglionic sympathetic neurons) which produce catecholamines
What are chromaffin cells directly controlled by?
Preganglionic sympathetic neurons
What 2 catecholamines do the 2 populations of chromaffin cells secrete?
- Epinephrine (adrenaline) - 90/80%
2. Norepinephrine (noradrenaline)
What 2 hormones have chromaffin cells also been shown to secrete?
- Dopamine
2. Enkephalins (pain control)
What 2 ways can we compare groups in evidence?
- Comparing results with gold standard
2. Comparing one sample with another after an intervention
What does the T-test allow for?
Statistically compare means between 2 groups (1 dependent continuous variable ie. height, 1 independent binary categorical variable ie. sex)
What does the Chi-square-test allow for?
Statistically compare frequencies (1 dependent categorical variable ie. alternative drug types, 1 independent categorical variable ie. deprivation category)
What does the T-test give?
Probability (p-value) that such a difference (or greater difference) would be found by chance, if the null hypothesis is TRUE
How do we know when the probability is unlikely?
We chose an arbitrary cut-off p<0.05 (reject the null hypothesis)
Describe the 3 slightly different t-tests?
- Comparison of mean with a single value
- Comparison of means of independent samples
- Comparison of means of paired data
What 2 things should you report in the t-statistics?
- Degrees of freedom (df)
2. Associated probability (p-value)
What does a P<0.05 mean?
Sample means significantly different
What does a P>0.05 mean?
Sample means NOT significantly different
What does a difference in the Chi-square test imply?
A “relationship” or “association” ie. values of one variable may influence values of the other
What is the Chi-square test for independence?
Association between 2 categorical variables (ie. is cholesterol status associated with gender)
What is the Ch-square test for goodness of fit?
Tests the difference between frequencies of a single categorical variable and some hypothesised frequency
What is Correlation?
Measures the strength of relationship between 2 numerical variables measured by the correlation coefficient (r)
What does r= -1 mean?
A perfect negative correlation (as 1 variable increases the other decreases)
What does r= +1 mean?
A perfect positive correlation (as 1 variable increases so does the other)
What do you use for basic correlation?
Continuous data
What is linear regression used to Predict?
Relationship between independent variables & an outcome (dependent) variable
What must there be between independent & outcome for regression?
Linear relationship
What is the regression coefficient?
Slope of the best-fitting straight line through a scatter plot of data
What is linear regression closely related to?
Correlation
What is the linear regression equation?
y= βx + c (intercept) (β= slope of the best fitting straight line)
What does the p-value of the regression coefficient (β) indicate?
- Probability that the “true” slope of the line is= 0 (null hypothesis is NO SLOPE)
- Significant p-value (p<0.05) indicates that there is a significant slope (β NOT equal to 0)
In Scotland, how many people & their families each year will require palliative care?
~40,000
What is palliative care according to WHO?
Improves quality of life of patients & families facing life-threatening illness
through prevention & relief of suffering by
means of early identification & impeccable assessment & treatment of pain & other problems, physical, psychosocial & spiritual
Whats the GMC definition of “Approaching the end of life”?
Likely to die within the next 12 months
End of life, according to GMC guidance, is those facing imminent death & those with what 4 factors?
- Advanced, progressive, incurable conditions
- General frailty (likely to die in 12 months)
- At risk of dying from sudden crisis of condition
- Life threatening conditions caused by sudden catastrophic events
Give 4 examples of non-cancer disease which require palliation of symptoms?
- Motor Neurone disease
- End-stage Cardiac failure
- End- stage COPD
- Advanced renal disease
What are the 4 key themes for palliative care development?
- Early identification of patients who may need palliative care
- Advance/ anticipatory care planning (decisions with cardiopulmonary resuscitation (DNACPR))
- Care in last days/ hours of life
- Delivery of effective & timely care
What are the Liverpool Care pathway (LCP) report findings?
- Where used properly, many people died peaceful, dignified deaths
- But… in many cases it was associated with poor experiences of care
What is the response from the Liverpool Care pathway (LCP) report?
- ‘One chance to get it right’: 5 priorities
for care of dying people - ‘Care for people in the last days & hours of life’
What are the 3 Palliative care aims?
- Whole person approach
- Focus on quality of life, including good symptom control
- Care encompassing the person with the life- threatening illness & those that matter to them
List the 6 principles of good end of life care?
- Open communication
- Anticipating care needs & encouraging discussion
- Effective input from multidisciplinary team
- Symptom control (physical & psycho-spiritual)
- Preparing for death- patient & family
- Providing support for relatives both before & after death
What is Generalist palliative care?
Integral part of routine care delivered by all health & social care professionals to those with progressive & incurable disease, whether at home/ care home/ hospital
What is Specialist Palliative care?
Same principles of palliative care, but can help people with more complex palliative care needs
List the physical symptoms of end of life?
- Pain
- Dyspnoea
- Nausea/vomiting
- Anorexia / weight loss
- Constipation
- Fatigue
- Cough
What are the 4 different physical causes of pain at end of life?
- Cancer related (85%)
- Treatment related
- Associated factors- cancer & debility
- Unrelated to cancer
Describe bone pain?
Worse on pressure or stressing bone / weight
bearing
Describe nerve pain (neuropathic)?
Burning/ shooting/ tingling/ jagging/ altered sensation
Describe liver pain?
Hepatomegaly/ right upper quadrant tenderness
Describe raised intracranial pressure pain?
Headache (&/or nausea) worse with lying down, often present in the morning
Describe colic pain?
Intermittent cramping pain
How effective is the 3-step approach WHO pain ladder?
70-90%
What is the regimen for painkillers in cancer?
- Oral
- Analgesics should be given at regular intervals, not on demand
What are the functions of Adjuvants in the WHO analgesic ladder for cancer pain?
To help calm fears & anxiety, adjuvant drugs may be added at any step of the ladder
Give 3 examples of non-opioids in the 1st step of the WHO analgesic ladder for cancer pain?
- Aspirin
- Paracetamol
- NSAID
Give 3 examples of weak opioids in the 2nd step of the WHO analgesic ladder for cancer pain?
- Codeine
- Dihydrocodeine
- Tramadol
Give 4 examples of strong opioids in the 3rd step of the WHO analgesic ladder for cancer pain?
- Morphine
- Diamorphine
- Fentanyl
- Oxycodone
What are the indications for morphine use (1st line strong opioid)?
- Moderate-severe pain
- Dyspnoea
What are the actions of morphine (1st line strong opioid)?
- Opioid receptor agonist (μ-receptors)
- Centrally acting
What are the cautions of morphine (1st line strong opioid)?
- Longlist in BNF, including renal impairment & elderly
- Avoid in acute respiratory depression
What are the most common side effects of morphine (1st line strong opioid)?
- N&V, constipation, dry mouth, biliary spasm
- Watch for signs of opioid toxicity
How do you administer Morphine (1st line strong opioid)?
- Enterally- oral/ rectal
- Parenterally- IM / SC injections
- Delivery via syringe driver over 24 hours
List the signs & symptoms of opioid toxicity?
- Shadows edge of visual field
- Increasing drowsiness
- Vivid dreams / hallucinations
- Muscle twitching / myoclonus
- Confusion
- Pin point pupils
- Rarely, respiratory depression
Describe the prescription of modified release of morphine?
- ‘Background’ pain relief
- Either twice daily preparation at 12 hourly intervals
- Or once daily preparation at 24 hourly intervals
Describe the prescription of immediate release of morphine?
- ‘Breakthrough’ pain
- As required (PRN)
- Oramorph liquid/ Sevredol tabs
What can you prescribe for the opioid side effect- Constipation?
- Stimulant & softening laxative
- Senna / Bisacodyl + Docusate
- Magrogol e.g. laxido / movicol
- OR Co-Danthramer alone
What can you prescribe for the opioid side effect- Nausea?
- Antiemetic
- Metoclopramide
- Haloperidol (consider QT interval)
What are the 4 principles to go by when moving on to step 3 opioids?
- Stop any ‘Step 2’ weak opioids
- Titrate immediate release strong opioid
- Convert to modified release form
- Monitor response & side effects
What adjunct medication can you give for liver capsule pain/ raised intracranial pressure?
- Steroids (e.g. Dexamethasone)
- Remember to consider gastroprotection
What adjunct medication can you give for neuropathic pain?
- Amitriptyline
- Gabapentin
- Carbamazepine
What adjunct medication can you give for bowel/bladder spasm?
Buscopan (Hyoscine Butylbromide)
What adjunct medication can you give for bony pain/ soft-tissue infiltration?
- NSAIDs
- Radiotherapy for bony metastases
Describe Diamorphone & its uses (other opioid)?
- Semi-synthetic morphine derivative
- More soluble than Morphine → smaller volumes needed
- Used for parenteral administration (injection /syringe driver)
Describe Oxycodone & its use (oxynorm/oxycontin)?
- 2nd line opioid
- Less hallucinations, itch, drowsiness, confusion
Describe Fentanyl patch & its uses?
- Second line opioid
- Lasts 72 hours
- Only use in stable pain
- Useful if oral & SC routes not available
- Useful if persistent side-effects with morphine / diamorphine
Describe the use of syringe drivers for opioids?
- Delivery over 24 hours- usually sub-cutaneous
- Useful when oral route inappropriate
- Often useful for rapid symptom control
- Multiple medications can be added
What does psychospiritual distress exacerbate?
Physical symptoms
What 3 things should you remember to consider regarding psychospiritual distress?
- Uncontrolled physical symptoms
- Depression
- Other medical causes ie. hyperthyroidism
What are the possible management techniques for psychospiritual distress?
- Counselling/ psychology/ cognitive behavioural therapy
- Medication if clinically indicated
What is the common property of antipsychotics/ neuroleptics/ anti schizophrenic drugs/ major tranquillisers?
Antagonising actions of dopamine in the brain
What are the 3 positive symptoms of schizophrenia?
- Delusions
- Hallucinations
- Thought disorders
What are the 2 negative symptoms of schizophrenia?
- Withdrawal from social contact
2. Flattening of emotional responses
What does the clinical potency of antipsychotics correlate with?
D2 blocking action
Describe the dopamine theory?
- ↑ dopamine content in restricted area of temporal lobe of schizophrenics (amygdala)
- ↑ dopamine synthesis & release in striatum of schizophrenics
Describe the Glutamate theory?
- ↓ glutamate & receptor density in post-mortem schizophrenic brains
- Mice with ↓ NMDA receptor expression show stereotypic schizophrenic behaviours & ↓ social interactions. Also respond to antipsychotics
What do glutamate & dopamine do to GABAergic striatal neurones?
Excitatory & inhibitory effects on GABAergic striatal neurones which project to thalamus & constitute a sensory ‘gate’
Too _____ glutamate or too _____ dopamine disables the “gate”?
- Little
2. Much
What does a disabled “gate” do?
Allowing uninhibited sensory input to reach the cortex
What is excess dopamine responsible for?
Positive symptoms of schizophrenia
What is reduced glutamate responsible for?
Negative symptoms of Schizophrenia
List the 3 types of 1st generation or “Classical” Antipsychotics?
- Phenothiazines
- Butyrophenones
- Thioxanthines
What are 3 examples of Phenothiazines (1st generation antipsychotics)?
- Chlorpromazine
- Fluphenazine
- Pipotiazine
What is an example of Butyrophenones (1st generation antipsychotics)?
Haloperidol
What are 2 examples of Thioxanthines (1st generation antipsychotics)?
- Flupentixol
2. Clopenthixol
List the 3 types of 2nd generation or “Atypical” Antipsychotics?
- Benzamides
- Dibenzodiazepines
- Others
What is an example of a Benzamides (2nd generation antipsychotic)?
Amisulpride (selective D2 & D3 receptor antagonist)
What are 2 examples of Dibenzodiazepines (2nd generation antipsychotic)?
- Clozapine
- Olanzapine
(unselective receptor blocking profile)
What are 4 examples of Others types of 2nd generation antipsychotic drugs?
- Risperidone, paliperidone (mixture of receptor types blocked)
- Quetiapine (α adrenoceptor blocker)
- Aripiprazole (Dopamine & 5-HT antagonist)
What are the PROS of ‘Atypical’ or 2nd generation antipsychotics?
- Overcome some of the problems of the classical antipsychotics
- Efficacy in treatment-resistant patients
- Improve negative & positive symptoms
Is there evidence that 2nd generation antipsychotics are more effective than 1st generation in controlling symptoms?
NO
What 4 factors does the distinction between typical & atypical antipsychotics rest on?
- Receptor profile
- Incidence of extrapyramidal side-effects
- Efficacy in treatment-resistant group of patients
- Efficacy against negative symptoms
What group of antipsychotics shows less extrapyramidal side effects?
Atypical 2nd generation antipsychotics
What 6 receptors do antipsychotic drugs act on?1
- Dopamine 1 (D1)
- Dopamine 2 (D2)
- α1
- H1
- mACh (muscarinic ACh receptor)
- 5-HT2A (histamine receptor)
What are the behavioural effects of antipsychotics?
- Apathy & reduced initiative
- Few emotions, drowsy (can be easily stirred from this)
- Aggressive tendencies inhibited
What 2 main types of disturbances to antipsychotics cause?
- Acute, reversible Parkinson-like symptoms due to block of nigro-striatal dopamine receptors
- Slowly developing Tardive dyskinesia (serious problem)
Describe Tardive Dyskinesia?
- Involuntary movements of face & limbs
- After months/years of treatment
- Associated with proliferation of dopamine receptors in corpus striatum
- Treatment generally unsuccessful
- Less common with newer antipsychotics
What are the endocrine unwanted effects of antipsychotics?
Increased prolactin secretion (male/female) by blocking D2 receptors in the pituitary
What are the anti-muscarinic unwanted effects of antipsychotics?
- Blurring of vision, dry mouth & eyes, constipation
- Can help attenuate extrapyramidal actions
What is the α-adrenoreceptor blocking unwanted effect of antipyschotics?
Orthostatic hypotension
What are the H1-receptor blocking unwanted effects of antipsychotics?
Sedative & anti-emetic actions
List the Unwanted effects of antipsychotics?
- Postural hypotension
- Sedation
- Weight gain
- Endocrine actions
- Diabetes
- Autonomic actions (atropine-like)
- Extrapyramidal actions
- Jaundice
- Leucopoenia & agranulocytosis
- Skin reactions (itchy rash)
- Neuroleptic malignant syndrome
How would you go about prescribing an antipsychotic for 1st episode schizophrenia?
- Choice should consider side-effect profile
- Titrate to minimum effective dose
- Adjust dose according to response & tolerability within BNF limits
- Evaluate over 6-8 weeks
What should you do if the antipsychotic drug prescribed is effective?
Continue at established dose, don’t change the brand of drug!
What should you prescribe if both 1st & 2nd generation antipsychotic drug’s are not effective?
Clozapine
What should you do if the schizophrenic patient is not tolerating or has poor compliant for antipsychotic drug?
Prescribe a depot or compliance aid
What antipsychotics can be used for acute behavioural emergencies & mania?
- Chlorpromazine
- Haloperidol
What antipsychotic can be used for treatment of emesis?
Prochlorperazine
What antipsychotics can be used for treatment of Huntington’s disease?
- Olanzapine
- Risperidone
- Quetiapine
What antipsychotic can occasionally be used to treat depression?
Flupentixol
What is the definition of Complementary Alternative Medicine (CAM)?
Group of diverse medical & health care systems, practices & products that are not generally considered part of conventional medicine
What is Complementary or Integrative medicine?
Refers to use of CAM together with conventional medicine
What is Alternative medicine?
Referes to use of CAM in place of conventional medicine
List the different Alternative medical systems?
- Traditional Chinese Medicine (TCM)
- Ayurvedic Medicine
- Homeopathy
- Naturopathy
- Indigenous healing systems
List the different mind-body interventions?
- Meditation
- Yoga
- Deep-breathing exercises
- Qi gong
- Tai chi
- Guided imagery
- Biofeedback
- Dream therapy
List the different biological based therapies?
- Herbal medicine
- Bach flower remedies
- Bee venom therapy
- Chelation therapy
- Vegetable juice therapy
List the different manipulative & body-based methods?
- Osteopathy
- Chiropractic
- Craniosacral therapy
- Alexander technique
- Acupuncture
- Rolfing
- Kinesiology
List the different energy therapies?
- Therapeutic touch
- Healing touch
- Reiki
- Magnet therapy
- Light therapy
- Crystal therapy
- Qi gong
How do you make a homeopathic preparation?
- Principle of similars
- Preparations must undergo potentiation: serial dilutions of mother tincture, succession
What is the common homeopathic dilution?
30C = 1 in 100*30
What is the annual public spend on homeopathy?
~£45m
What are the direct & indirect risks associated with homeopathy?
- DIRECT harm: no risk of interactions with “high potency” medicines
- INDIRECT harm: delay in receiving appropriate treatment, attitudes of practitioner
What are the regulations for homeopathy?
- No legal regulation of homeopaths in the UK: Society of Homeopaths, Faculty of Homeopathy, British Homeopathic Association
- Homeopathic products regulated by EU directive
What is the difference between herbal & homeopathic medicines?
- Both are natural
- Homeopathic is unlikely to have an active ingredient
- Herbal medicine is likely to have an active ingredient that can interact with other medications
List other drugs that St John’s Wort (Hypericum for depression) interacts with?
- Hormonal contraceptives
- Anti-depressives
- Anti-coagulants
- Anti-epilepsy agents
- Heart medications
- Anti-cancer agents
- Anti-virals for HIV
etc. ..
What are the direct & indirect risks associated with herbal medicine?
- DIRECT harm: Adverse drug reactions, Drug interactions, Quality control
- INDIRECT harm: Delay in receiving appropriate treatment
What regulates herbal medicines in the UK market?
MHRA regulations
What 3 things does the MHRA monitor to regulate herbal medicines?
- Safety, quality, efficacy as per any regular medicine- Marketing Authorisation (MA)
- Safety & quality (not efficacy) based on traditional usage- Traditional Herbal Medicines Registration (THR)
- The “herbalist exemption”- Regulation 3 of The Human Medicines Regulations 2012
What does DD Palmer (straight Chiropractor) state about disease?
95% of all diseases are caused by displaced vertebrae
Describe Chiropractic?
- Straight vs Mixer
- Detect “subluxations” & block flow of “innate intelligence”, use of X-rays or gadgets
- Spinal manipulations including high velocity, low-amplitude thrusts, audible “crack”
What gadgets are used in Chiropractic?
- BJ Palmer & Neurocalometers
- E meters & the Church of Scientology
What are the direct & indirect risks of Chiropractic & Osteopathy?
- DIRECT harm: 50% of chiropractic patients suffer an adverse reaction, tearing of artery wall leading to stroke, injury to the spinal cord, Chiropractic X rays
- INDIRECT harm: Delay in receiving appropriate treatment, Attitudes of practitioner, Anti-vaccination
What are the only 2 CAM modalities under statutory regulation?
- General Chiropractic council (GCC)
2. General Osteopathic Council (GOsC)
Describe Acupuncture?
- Ch’i (Qi, “ch-ee”) as a ‘vital energy’: Flows through ‘meridians’ associated with major organs, illness due to disrupted flow of Ch’i
- Insertion of needles along meridians: restores flow of Ch’i, 1-10cm in depth, with/without rotation, left in place for sec/hrs
Describe the diagnosis process during Acupuncture?
- Inspection
- Auscultation
- Olfaction
- Palpitation
- Inquiring
What are the direct & indirect risks of acupuncture?
- DIRECT harm: Infections, Pneumothorax
- INDIRECT harm: Delay in receiving appropriate treatment, Attitudes of practitioner
How can you become a registered acupuncture?
Premises & practitioners must be licensed via local authority (same as tattooing/body piercing)
What are the regulations for Acupuncture?
Voluntary regulation via several organisations ie. British Acupuncture council
What 2 things are tightly controlled in the body’s fluid compartments?
- Volumes
2. Composition
What are the 2 major divisions of the body’s fluid compartments?
- Intracellular
2. Extracellular
What can the extracellular be divided further into?
- Plasma
- Interstitial
(synovial, intra-ocular, CSF etc)
What is composition determined by?
Movement across the plasma membrane
Describe the volume in the major compartments for a 70kg man?
- Total body fluid: 42L
- Intracellular fluid: 28L (incl. ~2L blood cells)
- Interstitial fluid: 11L
- Plasma: 3L
What is the barrier between plasma & interstitial fluid?
Capillary wall
What is the barrier between extracellular fluid & intracellular fluid?
Plasma membrane
How does the body get a gain in fluid?
- Food & water intake
- Oxidation of food
How does the body get losses in fluid?
- Urine (1500ml)
- Faeces (100ml)
- Sweat (50mls)
- Insensible losses (900ml)
What is the average total losses of body fluid’s?
2550ml
What is insensible water loss?
- Transepidermal diffusion: water that passes through the skin & is lost by evaporation
- Evaporative loss from respiratory tract
- Insensible losses are solute free
What are the types of sensor’s which regulate body fluid?
- Osmoreceptors in hypothalamus
- Low pressure baroreceptors in right atria & great veins
- High pressure sensors in carotid sinus/aorta
What happens if the total sodium drops & osmolality start the same?
Total volume falls (including plasma volume)
What happens if the total sodium rises & osmolality stays the same?
Total volume will rise
What are compensatory mechanisms really linked to?
Low volume (low GFR, stimulation of JGA) or high volume (increased GRF & release of ANP)
If you eat too much/too little salt, where is the only controllable route of loss?
Via urine (hormonal control)
What’s the possible non-hormonally controlled increased losses of NaCl?
- Exercise/heat causing increased sweating
- Diarrhoea causing increased loss via faeces
Describe the intake of NaCl?
Normally in excess of need (hedonistic)
Describe the control of plasma Na+?
- Hormones must act on the kidney
- DCT is the area of control in nephron
- No receptors detecting Na+
- Controlled indirectly via volume sensors
- Changes in Na+ lead to changes in blood volume
What is the equation for working out Net sodium excretion?
Na+ filtered (changed via GFR) - Na+ reabsorbed (changed via rate of flow, aldosterone, ANP etc)
What 4 things occur if osmolality rises?
- Increase in thirst
- Increase in release of ADH
- Increase in water intake/retention
- Increase in volume
What 5 things occur if increase in volume leads to an increase in stretch of vascular system?
- Baroreceptors
- Decrease in renin release
- Decrease in aldosterone release
- Increased release of ANP (cardiac myocytes)
- Decreased sodium & water retention
What 7 things occur if decrease in volume leads to a decrease in stretch of vascular system?
- Baroreceptors
- If pressure falls (decreased vol.), influences ADH release & thirst centres
- Increase renin release
- Increased angiotensin II
- Increase aldosterone release
- Decreased release of ANP
- Increased sodium & water retention
What should you remember about K+?
Its an intracellular ion
How is K+ lost?
Predominantly via urine, little lost in sweat/faeces in normal conditions
Describe the control of K+?
- Control at the kidney
- K+ is freely filtered
- Predominantly reabsorbed again in PCT with controlled secretion at the DCT
- Secretion linked to Na+ reabsorption (sodium pump)
What % of K+ is inside cells?
98%
What do we get a significant & variable intake of K+?
From diet
What does intracellular K+ act as?
Reservoir (attenuates change)
What does an increased K+ in plasma do?
- Increases activity of basolateral sodium pump
- More K+ enters
- Increased secretion across simple diffusion channels on apical membrane
- Increased secretion of aldosterone
What are the effects of K+ plasma driven by?
Direct detection of raised K+ levels by the aldosterone-secreting cells of the adrenal cortex
What is the effects of aldosterone on the DCT?
- Increases activity of sodium pump (basolateral)
- Increases no. of Na+ pumps (basolateral)
- Increases no. of Na+ & K+ channels in apical membrane
What is the result of aldosterone on the DCT?
Increased reabsorption of sodium & increased secretion of potassium
Describe Conn’s syndrome?
Hyperaldosteronism leading to 1. hypertension from increased
fluid volume & 2. hypokalaemia
List the 4 types of IV crystalloids fluids?
- 5% Dextrose (glucose)
- 0.18% NaCl 4% Dextrose
- 0.9% NaCl (isotonic saline)
- Plasmalyte
Describe the distribution of IV 5% Dextrose?
- Initially through ISF & plasma, glucose
metabolised so effectively adding just water - Further distributes into cells, ISF & plasma
Describe the distribution of IV Plasmalyte?
Through ISF & plasma, does not enter cells
List the 3 types of IV colloid fluids?
- 4.5% Albumin
- Hydrolysed Gelatin
- Blood
Describe IV 4.5% albumin fluid?
- Supplied in 0.9% NaCl
- Tends to stay in plasma, does not enter cells
- Blood product
Describe IV hydrolysed gelatin fluid?
- Supplied in 0.9% NaCl
- Initially tends to stay in plasma, does not enter cells
- Protein metabolised over time, so equivalent to 0.9% NaCl
Describe the distribution of IV blood fluids?
Stays in vasculature & increases blood volume
What are the 4 questions to ask before prescribing fluids?
- In terms of volume where is my patient starting from?
- Does my patient need IV fluid?
- Am I prescribing
maintenance/ Replacement/ Resuscitation fluid? - Want volume & what type of fluid?
What are the clinical features of Diabetes ketoacidosis?
- Hyperglycaemia: dehydration, tachycardia, hypotension, clouding of vision
- Acidosis: air hunger (Kussmaul’s respiration) acetone breath, abdominal pain, vomiting
What are 4 reasons why a patient may be dehydrated?
- Hyperglycaemia
- Vomiting
- Kaussmaul respiration
- Altered conscious level (reduced intake)
What 3 treatments would you give for a dehydrated adult patient?
- Start: 1000mls 0.9% saline over 1st hr
- IV insulin infusion 6 units/hr
- K+ IV (slowly)
What happens to the K+ during dehydration?
- Potassium has shifted out of cells (serum K+ may be normal)
- Excreted by kidneys (total loss)
- May be additional losses if vomiting
Where does audit come from?
- Department of Health, 1989, ‘Working for Patients’
- Quality improvement in delivery of health care
- Part of the clinical governance agenda
What is your role as a newly qualified doctor in regards to an audit?
- More than tick box exercise
- Audits can improve practice / quality / patient experience
- Audits can be published
What 3 things does the audit do for clinical governance agenda?
- Personal responsibility
- Organisational culture
- Reduce variation between providers
Define the purpose of a clinical audit?
Quality improvement process that seeks to improve patient care & outcomes through systematic review of care against explicit criteria & implementation of change
Define the purpose of research?
Attempt to derive generalisable new knowledge by addressing clearly defined questions with systematic & rigorous methods
Describe how clinical audits & research can interconnect?
- Audit can be the final stage of research project
- Research findings identify areas for audit
- Audit helps with dissemination of research findings
- Audit identify’s gaps in research evidence
What are the questions you ask when performing research or an audit?
- RESEARCH: what should we be doing?
- AUDIT: are we doing it right (does it reach a predetermined standard)?
List the 7 common elements of clinical audit’s & research?
- Professionally led
- Influence on clinical practice
- Formal data collection
- Methodological rigour
- Data analysis / interpretation
- Publishable?
- Ethics
Is there ethics involved in research & clinical audits?
- RESEARCH: YES!
- AUDIT: NO, may be needed if it’s judged to put patients at risk, if uncertain, seek advice from ethics committee
What are the 2 key factors in distinguishing research & audit according to National Research Ethics service?
- INTENT: to generate new knowledge (research) to measure performance against a standard of care (audit)
- ALLOCATION OF TREATMENT SERVICE if by protocol (research)
What question do we ask in qualitative research?
What is the patient experience of receiving this service?
What is the quantitative research hypothesis test?
How do patient outcomes compare between this service (or treatment) & an alternative?
What does PICO (parts to a quantitative research question) stand for?
- Patient/ Precipitants
- Intervention
- Comparison
- Outcome
Define Service Evaluation?
Review process undertaken solely to define/judge current service with the intention of benefiting those who use it, used to inform local practice
What are the 3 components of Service Evaluation?
- Structure (what you need- infrastructure, staff)
- Process (what to do)
- Outcome (what you expect)
What are the 3 service evaluation questions?
- Does the service achieve its objectives?
- Does the service (still) meet pt’s needs?
- Is the service equitable?
What are the 2 main parts of an audit?
- Retrospective- notes review (beware missing data)
2. Prospective- ongoing data collection (beware the “Hawthorne effect”)
List the 8 steps to doing an audit?
- Identify a topic/ problem
- Identify local resources (local audit dept)
- Choose standard, create the audit proforma
- Define the sample
- Collect data
- Compare data with the standard
- Develop & implement change
- Re-audit
What does the “Johnston et al Quality in Health Care 2000” state are the 5 main barriers?
- Lack of resources
- Lack of expertise/ advice in project design & analysis
- Problems between group members
- Lack of an overall plan for audit
- Organisational impediments
What does the “Johnston et al Quality in Health Care 2000” state are the 6 key facilitators?
- Modern medical records systems
- Effective training
- Dedicated staff
- Protected time
- Structured programmes
- Shared dialogue between purchasers & providers
List the different criteria for choosing a topic?
- High cost, volume, or risk to staff or users?
- Evidence of a serious quality problem?
- Evidence available to inform standards ie. systematic reviews/ national clinical guidelines?
- Is problem amenable to change?
- Is the topic a priority?
- Potential for involvement in national audit project?
List the different criteria for choosing a standard?
- Agree the standard (minimal, ideal or optimal)
- Is it evidence based & related to aspects of care?
Describe the minimal, ideal & optimal standards?
- MINIMAL: lowest acceptable level of performance
- IDEAL: care possible under ideal conditions
- OPTIMAL: realistic under normal conditions of practice
List the 4 perceived benefits of an audit?
- Improved communication among colleagues
- Improved pt care
- Increased professional satisfaction
- Better admin & data recording
List the 4 disadvantages of an audit?
- Diminished clinical ownership
- Fear of litigation
- Hierarchical & territorial suspicions
- Professional isolation
Who do you contact in the NHS regarding Audit or Service Evaluation?
Clinical Effectiveness Department- Clinical Effectiveness Manager / Coordinator
Who do you contact in the NHS regarding research?
Research & Development Office:
- R&D Manager
- Research Governance Officer
- Research Advisor (academic support)
Can a study have components of audit, research & service evaluation?
YES
Describe what is involved/what isn’t involved in an audit?
- Never involves a new treatment
- Never involves allocation of pts to groups
- Should not involve anything being done to pts beyond their normal care
- Simple stats
- Results of local relevance
- Influence on clinical practice locally
- Some aspects may require review by an ethics committee
Describe what is involved/what isn’t involved in research?
- May involve pts getting new treatment
- May involve pts being allocated to different groups
- May involve pts receiving experimental interventions
- Can involve complex stats
- Results generalisable
- Influence on clinical practice everywhere
- Always requires ethics review
What level of glycated haemoglobin gives a diagnosis of diabetes mellitus?
≥48mmol/mol
What level of fasting blood glucose gives a diagnosis of diabetes mellitus?
≥7.0mmol/L
What level of 2hr blood glucose gives a diagnosis of diabetes mellitus?
≥11.1mmol/L following OGTT
What level of random blood glucose gives a diagnosis of diabetes mellitus?
≥11.1mmol/L in presence of symptoms
What are the 4 different classifications of diabetes mellitus & how common are they (%)?
- Type 1 diabetes (ß cell destruction) - 10%
- Type 2 diabetes (insulin resistance & deficiency, secretory defect) - 85%
- Other types (genetic, pancreatic/endocrine disease, drugs) - 5%
- Gestational diabetes
When do type 1 diabetes symptoms occur?
When 80% ß cell mass lost
Give an example of an environmental factor with leads to ß cell destruction in type 1 diabetes?
Viral infection
List the 4 areas that autoantibodies act on in Type 1 diabetes (autoimmune)?
- Islet cells
- Insulin
- GAD (GAD65)
- Tyrosine phosphatase
What are the 2 strong HLA associations in Type 1 diabetes?
- Linkage to DQA & DQB genes
2. Influences by DRB genes
What are the 3 environmental factors for Type 2 diabetes?
- Obesity
- Stress
- Reduced physical activity
Describe the classical presentation of Type 1 Diabetes Mellitus?
- Thirst, polyuria
- Malaise, fatigue
- Infections ie. candidiasis
- Blurred vision
- Complications
- Incidental finding
- More visceral fat distribution
Describe Monitoring for diabetes mellitus
- Monitor blood glucose
- Test for ketones
What is Diasend?
Web-based diabetes management system that allows you to store, review & print insulin pump, CGM & blood glucose meter data on the diasend website for monitoring patterns
Describe glycated haemoglobin (HbA1c)?
Form of hemoglobin that is measured primarily to identify the 3-month average plasma glucose concentration
What is CS11?
Continuous subcutaneous insulin infusion
What are the acute complications of diabetes mellitus?
- Diabetic Ketoacidosis
- Hypoglycaemia
- Other emergencies
What are the chronic complications of diabetes mellitus?
- Microvascular: keys, kidneys, nerves (feet)
- Macrovascular: heart, brain, (feet)
What combination of things in the liver make Ketone bodies?
- Amino acids Leucine, Lysine
2. Free fatty acids
In diabetic ketoacidotic patients what electrolyte loss should you monitor and be most concerned about?
The huge Potassium loss/shift, this often kills patients!
Describe the treatment of diabetic ketoacidosis?
- Insulin IV 6U/hr then by sliding scale
- N/Saline initially (4-6L)
- Dextrose 5% subsequently to replace water losses
- Careful monitoring of K+ & replace as required
Describe the symptoms of hypoglycaemia?
- Adrenergic: tachycardia, palpitations, sweating, tremor, hunger
- Neuroglycopaenic: dizziness, confusion, sleepiness, coma, seizures
What is the formal definition of hypoglycaemia?
Blood glucose <= 2.2mmoll-1
What are the 3 possible causes of hypoglycaemia?
- Too much insulin
- Too little food
- Unusual exercise
What is the human counter-regulatory mechanism for fall in blood glucose?
Vagal stimulation –> parasympathetic –> glucagon release –> glycogen release by liver
What is the human counter-regulatory mechanism for neuroglycopaenia?
Adrenal medulla stimulation –> sympathetic –> Adrenaline release –> glycogen release by liver
What is the treatment for hypoglycaemia?
IV 50% dextrose
Describe the emergency- HyperOsmolar Non-Ketotic coma (HONK)?
- Elderly patients
- Often undiagnosed
- Intercurrent stress (MI, chest infection etc)
Describe why Metformin Associated Lactic Acidosis (MALA) is an emergency?
Causes Renal impairment
Describe the process of glycation?
Protein –> Glucose Schiff base –> Ketoamine –> 5-Hydroxymethylfurfural —> Increased cross linking & browning of proteins
What are the 5 stages of nephropathy?
- Hyperfiltration
- Normal
- Microalbuminuria
- Overt nephropathy
- Chronic renal failure
What screening would you do for nephropathy?
- Albustix
- Microalbuminuria
- Creatinine
How would you manage nephropathy?
- Blood pressure: aggressive treatment ACEI/AIIRA, 130/80 or lower
- Hyperlipidaemia: statin
- Good glycaemic control
- Diet
Describe diabetic microangiopathy?
Debris in lumen causes blockage of normal blood supply –> ischaemia –> pain & lack of function
What would you look at on examination of the foot?
- General appearance
- “Architecture”
- Pulses
- Sensation (neurosthesiometer, monofilament)
- Education (patient)
List the 4 stages of diabetic retinopathy?
Background –> Preproliferative –> Proliferative –> Advanced eye disease
What are the 3 types of maculopathy?
- Exudative
- Oedematous
- Ischaemic
Describe the management of diabetic retinopathy?
- Screening: annual if no previous DR
- Methods: ophthalmoscope, retinal camera
- “System”
- Blindness audit