Week 8 Flashcards
(127 cards)
1
Q
Very broadly what is type 1 diabetes?
A
Where the body is unable to make insulin
2
Q
Very broadly what is type 2 diabetes?
A
Where the tissues don’t respond to insulin properly
3
Q
What are high blood glucose levels known as?
A
Hyperglycaemia
4
Q
What are the risk factors for diabetes?
A
- Lifestyle
- Low socioeconomic background
- Aboriginal or torres strait islander
5
Q
Why is glucose important?
A
- Main source: carbohydrates from diet
- Major source of energy for most cells of the body
- Brain relies mainly on glucose for fuel: cannot really store glucose
- Can use fats as energy source but glucose usually used first
6
Q
Why do BGL need to be regulated?
A
The main reason is because we want to prevent hyperglycaemia, We should also try and avoid hypoglycaemia, if a person’s BGL falls too low they can fall into a coma. People with diabetes need a BGL above five in order to be able to drive
7
Q
Does the pancreas have exocrine and endocrine tissue?
A
Yes
8
Q
What do the alpha cells promote?
A
promote glucose release
9
Q
What are islets of Langerhans?/
A
are just small islets of endocrine tissue, and they are responsible for secreting hormones into the blood.
10
Q
What do the beta cells do?
A
uptake and storage of glucose
11
Q
Are the alpha and beta cells inside the islets of Langerhans?
A
Yes
12
Q
What state is the beta cell membrane in when BGL are normal?
A
In a resting state, here, the the plasma membrane is hyperpolarised, hence insulin secretion will be low
13
Q
What is the response to an increase in BGL?
A
- Resting state, beta cell membrane is hyperpolarised; insulin secretion is low
- Glucose enters via GLUT2 transporters
- Glucose metabolised to generate ATP; ATP inhibits the K+/ ATP channel causing membrane depolarisation
- Depolarisation activates calcium channels; influx of of Ca2+
- Vesicles containing insulin fuse with membrane and insulin secreted into blood stream
14
Q
What other substances affect BGL?
A
Cortisol, adrenaline, incretin hormones
15
Q
Where is GLP 1 released from?
A
special endocrine cells in the intestine in response to food
16
Q
Should people with T1DM be taught how to calculate carbohydrate intake?
A
Yes
17
Q
Are T1DM patients insulin dependent?
A
Yes
18
Q
What is the broad mechanism of insulins?
A
increase or restore ability to metabolise glucose
19
Q
Is insulin a chain of different amino acids?
A
Yes
20
Q
Do different chains of amino acids make up different types of insulin?
A
Yes
21
Q
How do insulins work broadly?
A
Insulins work because the patient now has insulin in the body and it can bind to receptors on the tissues that allow glucose to enter the tissues and restore the energy.
22
Q
Does giving insulin lower BGL?
A
Yes
23
Q
Is insulin aspart a ultra-short acting-analogue?
A
Yes
24
Q
When is insulin aspart given?
A
Given just before or at the start of a meal
25
What is the activity of insulin aspart?
quick (few mins) and lasts for 3-5 hours
26
Is insulin glargine a long-acting (analogues) insulin?
Yes
27
What is the activity of insulin glargine?
Onset:1-6 hours
Duration: 24+ hours
28
How often is insulin glargine taken?
Given once daily
29
Should glucose normally spike in the body after a meal?
Yes
30
Can insulin be given as an oral medication?
No, insulin must be given through a pump or an injection
31
What are the adverse effects of taking insulin?
Hypoglycaemia
Wight gain
Local reactions
Lipodystrophy
32
What are some methods of non-drug management of T2DM?
Diet (low GI foods, and decreased sugar intake), weight lose (5-10% of body weight) and regular physical activity
33
What is the rationale for drug use in T2DM?
- Symptom relief (polyuria, polydipsia)
- Control of blood glucose concentration – prevent hyperglycaemia
- Prevention or delay of long-term complications
- Some medications have added benefits in decreased CV risk and slowing progression of kidney disease
34
What is an example of a biguanide drug?
Metformin
35
What is the mechanism of metformin?
- Increase sensitivity of tissues to insulin
- Decreased gluconeogenesis
- Increased peripheral glucose uptake
Doesn’t cause hypoglycaemia when used alone
36
What are the adverse effects of metformin?
N/V/D (excreted by kidneys; rarely lactic acidosis)
37
Does metformin make the body produce more insulin?
No
38
What is a drug example of a sulfonylureas?
Gliclazide
39
How does gliclazide work?
Works by inhibiting the SUR1 portion of the potassium ATP channel which is found on the beta cell membrane in the pancreas.
40
Mechanism of Gliclazide simplified:
- Binds to SUR1 subunit of K+/ ATP channel causing closure and membrane depolarisation
- Stimulates beta cell secretion of insulin
- May decrease insulin resistance
- Require residual beta cell activity
41
What are some adverse effects of gliclazide?
hypoglycaemia and weight gain
42
43
What is an example of a SGLT2 inhibitor?
Dapagliflozin
44
What is the mechanism of dapagliflozin?
- Inhibits glucose reabsorption at PCT
- Increased glucose excretion
45
What are the adverse effects of dapagliflozin?
- Weight loss (osmotic diuretic)
- Dehydration
- Genitourinary infections?
46
Is glucose normally filtered out at the glomerulus?
Yes
47
What is the basic way to describe the action of dapagliflozin?
Makes people wee out more glucose
48
Why are people on dapagliflozins at increased risk of a urinary tract infection?
Because there’s a higher amount of glucose in the urine, and some organisms that are usually found in that area of the body, they might actually feed off the extra glucose, causing an infection.
49
What is an example of a GLP-1 Analogue?
Semaglutide
50
What is the mechanism of semaglutide?
- Mimics the effects of endogenous GLP-1
- GLP-1 = incretin hormone; decreased BGLs by:
Increased glucose dependent insulin secretion
Supresses inappropriate glucagon secretion
Delay gastric emptying, decreases appetite
51
Is the action of semaglutide really broad?
Yes, it has effects all over the body
52
What is an example of a DPP-4 inhibitor?
Linagliptin
53
What is the mechanism of linagliptin?
- DDP-4 usually degrades GLP-1
- Prevents breakdown of GLP-1
- Prolongs GLP-1 circulation – increased insulin secretion, decreased glucagon production
54
What are the adverse effects of linagliptin?
Another point that should be noted is that combining a DDp4 inhibitor and GLp-1 analogue is not recommended
combining DDp4 inhibitors and GLP-1 analogue are not recommended because they act on the same pathway. There is also no extra benefits, BGL or weight wise.
55
What medicines/ substances can affect BGL?
Beta blockers, alcohol, antipsychotics, corticosteroids, thiazides(in high doses)
56
How do beta blockers affect BGL?
mask warning symptoms and increase severity of hypoglycaemia
57
How does alcohol affect BGL?
Decrease BG concentration (inhibit glucose output from liver) and increase the risk of hypoglycaemia
58
How do antipsychotics, corticosteroids and thiazides affect BGL?
They all increase BGL
59
What is diabetes mellitus?
- A metabolic disorder of multiple aetiology characterised by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action or both
60
Describe type 1 diabetes
- Autoimmune destruction of pancreatic beta cells
- Juvenile onset
- 10% of cases of diabetes
No insulin is produced
- Can’t process sugars for energy
- Can’t take up and store glucose
61
What is the presentation of type 1 diabetes?
- Thirst, urinary frequency
- Fatigue, blurred vision
- Recurrent infection – yeast (candida) or fungal infections
- Weight loss – this can happen because the body starts to burn fat and muscle instead of being able to use glucose that it would usually use.
62
Describe type 2 diabetes
Adult onset
90% of cases of diabetes
Obesity is a risk factor: 80%
Happens gradually and is characterised by: insulin resistance, tissues less responsive to insulin – and/or pancreas doesn’t produce enough insulin
63
What is the presentation of T2DM?
- Slow and insidious onset of signs and symptoms
- Thirst, urine frequency
- Fatigue, blurred vision
- Ketoacidosis uncommon
- Often overweight and have hypertension and dyslipidaemia = ‘metabolic syndrome’ – increased risk of heart disease, stroke and diabetes
64
What is the macrovascular complication of diabetes?
Atherosclerosis
65
What is the microvascular complications of diabetes?
- Neuropathy
- Nephropathy
- Retinopathy
66
What are risk factors for atherosclerosis?
- Obesity
- Poor diet
- Lack of exercise
- Hypertension
- Dyslipidaemia
67
Explain the microvascular consequence of neuropathy in regards to diabetes
Nerve damage
- Sensorimotor neuropathies – pain tingling, numbness and muscle weakness
- Autonomic nerve damage - cardiovascular (tachycardia, orthostatic hypotension), GI tract, bladder, erectile dysfunction, impotence
68
Explain the microvascular consequence of a diabetic foot infection
- Loss of sensation in the feet
- Reduced sweat/oil gland function
- Reduced resistance to infection
- Poor peripheral circulation – blood vessel + tissue damage
- Minor injury – risk of diabetic foot ulcers, untreated may lead to gangrene; amputation, foot deformities
69
Explain the microvascular complication of pathological mechanisms in nephropathy
- Hyperglycaemia + glomerular hyperfiltration may increase protein filtration
- High levels of protein in urine = proteinuria (a sign of kidney damage)
- Proteins should remain in blood and not be present in urine
- Can contribute to kidney failure
70
Explain the microvascular consequence of retinopathy in regards to diabetes
- Damage to blood vessels of the retina
- Leading cause of blindness
- Glaucoma and cataracts
71
How is diabetes diagnosed?
An oral glucose tolerance test (OGTT)
72
Explain how a BGL finger prick test works?
- Instantaneous, day-to-day
- Fasting BG: 4-8mmol/L
- Postprandial BG: 6-10 mmol/L
- Test more regularly if: medications cause hypoglycaemias, sick or recent changes to medication
73
What is considered to be hypoglycaemia?
BGL below 4mmol/ L
74
How do you treat hypoglycaemia?
if not severe: quick-acting oral glucose – if severe (unconscious): glucagon injection
75
What is the mechanism of glucagon for hypglycaemia?
Increase blood glucose concentration by activating hepatic glucose production.
Works in 10 minutes, lifesaving, need long-acting carbohydrate soon after
76
What is the adverse effects of glucagon for hypoglycaemia?
Decreased GI motility: nausea and vomiting
77
What is insomnia?
Changes to sleep pattern affecting
- Overall sleep quality
- Functioning the next day
78
What are the two classes of insomnia?
Acute and chronic
79
What is acute insomnia?
<3 months, avoid/ withdraw cause (if any)
- Stress, trauma, changes in habits, environment, pain, medication
Consider secondary causes
80
What is chronic insomnia?
>3 months
- Maybe due to chronic condition (pain, mood disorder, sleep apenea, diabetes, nocturia)
81
Is it important to try non-drug treatments first for insomnia?
Yes
82
What are some examples of ways to maintain sleep hygiene?
- Avoid blue light exposure – supresses melatonin secretion
- Limit use of technology
- Establish regular sleep patterns (6-9 hours)
- Limit daytime napping
- Limit caffeine + alcohol (decreased sleep quality)
- Regular physical exercise
- Exposure to sunlight (regulate circadian rhythm)
83
What is the recommended sleep time for people aged 18-25?
7 to 9 (not recommended to get less than 6 or more than 11)
84
What is the recommended sleep time for people aged 26-64?
7 to 9 (no less than 6 or more than 10)
85
What is the recommended sleep time for someone over 65 years of age?
7 to 8 (no less than 5 or more than 9)
86
Does the sedative effect promote calmness?
Yes
87
What are benzodiazepines?
Benzodiazepines potentiate the inhibitory effects of GABA throughout the CNS, resulting in anxiolytic, sedative, hypnotic, muscle relaxant and antiepileptic effects
88
What does GABA stand for?
gamma aminobutyric acid
89
Is GABA an inhibitory neurtransmitter?
yes
90
How do benzodiazepines affect GABA?
GABA is an inhibitory neurotransmitter
K+ efflux of Cl- influx – membrane hyperpolarization – action potential less likely
Benzodiazepines – potentiate the inhibitory effects of GABA, which allows greater Cl- influx – decreased neuronal excitability
Bind to GABAa at allosteric site
GABA receptors found all over the body: affect muscle tone, arousal, memory formation
91
What are the uses of benzodiazepines?
- Anxiety: alprazolam, diazepam, lorazepam, oxazepam
- Pain disorder: alprazolam
- Muscle spasticity: diazepam
- Insomnia: nitrazepam, temazepam
- Other: epilepsy – diazepam
92
What is a panic attack?
intense apprehension + fearfulness in absence of actual danger – physical symptoms – unexpected/ expected
93
What are some signs of a panic attack?
Dizziness, numbness, tingling, trembling, shaking, sweating, chills, hot flashes, nausea, heart palpitations, hyperventilation
94
What are some precautions of putting elderly on benzodiazepines?
falls risk, increased risk of over-sedation, confusion, respiratory depression
95
What are some side effects of benzodiazepines?
Drowsiness, over sedation, light-headedness, slurred speech.
96
Is it required by law to have a cautionary label on a benzodiazepine packet?
Yes
97
Is there an increased risk of falls when taking benzodiazepines?
Yes
98
Why is an increased falls risk on benzodiazepines a problem?
- Injury, hospitalisation, functional decline, decreased QoL – lacerations, hip fractures, head trauma
99
What are some general risk factors for a fall?
age, previous falls, vision impairment, environment
100
What are some drugs used for the short term treatment of insomnia?
Zolpidem and zopiclone
101
What is the mechanism of action of z-drugs for insomnia?
otentiation of inhibitory effects of GABA at GABAa receptors
- Less muscle relaxant and anxiolytic properties
- Short acting, no active metabolites – less daytime sedation and tolerance/ dependence
102
What are some side effects of taking z-drugs for insomnia?
sedation, dizziness, increased falls risk
103
What is a rare adverse effect of zolpidem?
Parasomnia
104
What is parasomnia?
- Worsened insomnia, irritability, agitation, nightmares, hallucinations, sleepwalking and related behaviour
105
What is the mechanism of action of melatonin?
- Endogenous melatonin is associated with control of circadian rhythms and sleep regulation
- Acts at MT1 and MT2 receptors in the brain (and the rest of the body)
106
What is the use of melatonin?
- Short-term use as monotherapy in primary insomnia with poor sleep quality
- Jetlag
107
What are the side effects of using melatonin?
- Headache
- Back pain
- Arthralgia
108
What are some examples of sedating antihistamines?
diphenhydramine, doxylamine
109
What is the MOA of sedating antihistamines?
inverse agonists at H1 receptors
- Affects ability of histamine to regulate sleep + wakefulness, stabilises receptor in it’s inactive state
110
What are the side effects of sedating antihistamines?
- Sedation and falls
- Psychomotor impairment (confusion, next day drowsiness)
- Dizziness
- Anticholinergic effects (dry mouth, constipation)
- Tolerance and dependence (limit use to <10 days)
111
Are consumer sleep technologies helpful?
They are good to increase awareness but an otherwise be inaccurate
112
What is spasticity?
‘feeling of stiffness or involuntary muscle spasms. It can range from relatively mild with a feeling of tightness in the muscles to very severe with large uncontrollable spasms’
113
What are the 4 types of spasm?
flexor spasm, extensor spasm, adductor spasm, spasms of the torso
114
What is a flexor spasm?
limb bends
115
What is an extensor spasm?
The limb extends
116
What is an adductor spasm?
limb is pulled towards the body
117
What is a spasm of the torso?
back or torso arches off a surface
118
What is the cause of spasms and spasticity?
Broken or damaged nerve pathways – (e.g. multiple sclerosis – damage to myelin that coats nerves) – stroke, damage to brain or spinal cord
119
What is the role of medication when treating spasms?
reduce stiffness but not reduce muscle strength excessively (may lead to muscle weakness
120
What are some examples of drugs used to treat spasticity?
'Muscle relaxants'
Includes: Dantrolen, Baclofen, Diazepam
121
What is dantrolene?
a direct acting skeletal muscle relaxant
122
What is the MOA of dantrolene?
- Decreased muscle contraction by interfering with calcium release from sarcoplasmic reticulum
- Antagonises ryanodine receptor (Ryr)
- Prevents calcium binding to troponin on actin; prevents actin + myosin cross bridge formation
123
What is the use of dantrolene?
Chronic spasticity associated with spinal cord injury, head injury, MS, cerebral palsy or stroke
124
What are the adverse effects of dantrolene?
Muscle weakness, malaise, fatigue, photosensitivity
125
What is the MOA of the muscle relaxant baclofen?
- Structural analogue of GABA (very similar structurally)
- GABAb receptor agonist
- Acts at GABAb receptors and inhibits neurotransmission at spinal level and depresses the CNS
126
What is the use of baclofen?
- Chronic spasticity associated with MS and spinal cord lesions
- Chronic spasticity of cerebral origin
127
What are the adverse effects of using baclofen?
Drowsiness, withdrawal
