Week 7 Flashcards
(210 cards)
1
Q
What are the most common types of arthritis?
A
RA and OA
2
Q
What is arthritis?
A
Conditions that affect the musculoskeletal system - specifically the joints where two or more bones meet
3
Q
How many types of arthritis are there?
A
> 100 types of arthritis and related conditions - degenerative, inflammatory, infectious or metabolic in nature
4
Q
Rheumatoid arthritis is a fluctuating condition associated with…?
A
Joint destruction, deformity, disability
5
Q
Is rheumatoid arthritis driven by massive leukocyte infiltration?
A
Yes
6
Q
Does rheumatoid arthritis involve pain, inflammation and loss of function?
A
Yes
7
Q
True or false, rheumatoid arthritis primarily targets synovial tissues?
A
True
8
Q
Who does RA mainly affect?
A
young, middle aged women
9
Q
Is the cause of RA known?
A
No
10
Q
What are some presentations of a joint with RA that a normal joint would not have?
A
Muscle wasting, destruction of bone, inflammation of the synovial membrane and also migration of the synovial membrane onto and into the bone in cartilage.
11
Q
What cells infiltrate to the joint and contribute to damage in RA?
A
macrophages, plasma cells, T + B cells
12
Q
What is a consequence of the infiltration of cells in RA?
A
Damage the synovial membrane they also cause muscle wasting and bone destruction as well. This makes it really difficult and painful for your patient to move.
13
Q
Is RA symmetrical in presentation?
A
Typically, yes
14
Q
Does RA usually affect larger joints of the body?
A
No, it usually affects smaller joints of the body, but it can affect the hips and knees.
15
Q
Is OA symmetrical?
A
No, it is asymmetrical
16
Q
Does erosion of the bone happen more in OA or RA?
A
RA
17
Q
What does limited range of motion lead to?
A
Atrophy of muscles, weakness and deformity
18
Q
Are symptoms of RA often cyclical?
A
Symptoms are often cyclical – spontaneously relapse and remit
19
Q
Are all RA symptoms related to the joints?
A
Not all symptoms are related to joints – because it’s an autoimmune disease it might affected other areas of the body e.g. anaemia and fatigue
20
Q
What are some broad symptoms of RA?
A
RA causes pain for the patient, it also causes stiffness and inflammation. Usually morning stiffness of the joints lasts for more than 30 minutes as well. Joints affected by RA are/ can be warm to the touch, which is a sign of inflammation.
21
Q
Is there a cure for RA?
A
No - so the goal is to maximise an individual’s QOL
22
Q
What are some examples of aims of treatment of RA?
A
- Control symptoms
- Normalise physical function
- Enable participation in social and work-related activities
- Prevent joint damage
- Minimise cardiovascular complications
23
Q
What are ways to manage RA through lifestyle?
A
- Land and water-based exercises
- Strengthening exercises
- Weight bearing exercises
24
Q
Can NSAIDs be used in the management of RA?
A
Yes
25
NSAIDs and RA
- Symptomatic relief only – will not stop joint destruction and deformity
- **paracetamol or opioids are an option but not as effective
26
DMARDs and RA
- Control the disease and the symptoms: induce and maintain remission
- Delayed action and significant side effects
- 2 types: synthetic (conventional) csDMARDs and biological DMARDs (bDMARDs)
27
Glucocorticoids and RA
- May be used systemically or as intra-articular injection
- Decrease pain, inflammation and autoimmune response
- Limited use due to long term side effects; reserved for flare ups
28
What are synthetic (conventional) CSDMARDS
- csDMARDs are immunosuppressants and/or immunomodulators
- most csDMARDs have a unique mechanism of action; often used in combination to improve efficacy
29
Is methotrexate a csDMARD?
yes
30
What is the MOA of methotrexate?
- increase intracellular adenosine levels by inhibiting AICAR transformylase
- adenosine transported out of cells and binds to adenosine receptors on phagocytic immune cells (neutrophils, monocytes and macrophages)
- secretion of cytokines such as interleukins and TNF-a is inhibited
- immunosuppression occurs
31
When is methotrexate taken in the management of RA?
Methotrexate is taken once a week on the same day each week, in order to prevent toxicity
32
Are BDMARDs produced by WBC?
Yes BDMARDs are produced by WBCs and they are major contributors to inflammation and destruction
33
What is a cytokine?
= small protein that has an effect on the immune system and alpha and interleukin on cytokines
34
What is an example of a bDMARD?
Adalimumab
35
What are some details about adalimumab?
- monoclonal antibody to TNFx
- class: TNFx and stops it from being able to bind to receptors
- also causes a decrease production of other pro-inflammatory cytokines: IL-1, IL-6, IL-8 (this will help to prevent further joint damage and destruction)
36
What is a glucocorticoid example?
prednisolone
37
What are the actions of prednisolone?
Anti-inflammatory and immunosuppressive
- decreased production of pro-inflammatory cytokines
- increased synthesis of anti-inflammatory cytokines
- decreased activation of neutrophils, macrophages and mast cells
38
Does prednisolone have a rapid onset of action?
Yes
39
Does prednisolone have multiple dosage forms?
Yes, orally or injection
40
Does prednisolone have unlimited use?
No, due to the acute and chronic adverse effects
41
Is OA a degenerative joint disorder?
Yes
42
What are some common symptoms of OA?
- Pain
- Swelling
- Crepitus – popping, clicking or cracking sound that can happen when the person moves the affected joint
- Stiffness
- Decreased mobility
43
Is OA caused by wear and tear?
N, instead it's because the joint is working overtime
44
Does OA usually affect weight bearing joints?
Yes
45
Is OA considered a normal part of aging?
No
46
How does OA differ from RA?
It differs from RA because it’s a degenerative disease rather than an autoimmune disease and it is often asymmetrical in presentation as well.
47
What are some risk factors for OA?
- Obesity
- Injury
- Malalignment
- Family history
- Occupation
48
Why is obesity a risk factor for OA?
Increased weight puts more pressure on the joints
49
Why is malalignment a risk factor for OA?
Puts more pressure on the joints of the spine
50
Why is occupation a risk factor for OA?
Particularly at risk of OA if they are doing repetitive tasks with certain parts of the body
51
Broadly, what is the pathophysiology of OA?
- Affects whole joint
- Swelling due to osteophyte formation
- Low grade inflammation
52
Does OA usually affect the whole joint?
Yes
53
Why is there swelling in the joint in OA?
Swelling in the joint is also due to osteophyte formation and this is where bony lumps form around the joints.
54
What do osteophytes contribute too?
These osteophytes contribute to bone remodelling and because of the OA and low grade inflammation that’s happening cartilage starts to break down and there’s also hypertrophy of the ligaments, the tendons and the synovial tissue in the joint.
55
Does OA affect a patient's ability to move throughout the day?
Yes
56
What are the aims in managing OA?
OA is not curable and hence the goals are to reduce pain, maximise function and movement, and prevent associated disability
57
What is the effect of exercise on OA?
Exercise has been shown to reduce pain and also improve physical function in people with osteoarthritis. In particular, aerobic exercises seem to be most beneficial for helping with osteoarthritis
58
Does weight loss help in managing OA?
Yes, weight loss will also help as it will reduce the pressure put on the weight bearing joints.
59
What determines the choice between paracetamol and NSAIDs in OA patients?
- The choice between paracetamol and an NSAID for patients is really dependent on how healthy the patient is and their previous medical history and the other medications they’re taking.
60
Are opioids recommended for OA patient's?
Opioids NOT recommended due to adverse effects – particularly because they can make people drowsy
61
Do corticosteroids have a clear role in the management of OA?
No
62
What causes Gout?
Too much uric acid in the blood
63
Is uric acid a normal waste product of the body?
Yes
64
What is too much uric acid called?
Hyperuricaemia
65
What happens when there is too much uric acid in the blood?
- Precipitates out and deposits in joints and soft tissue – formation of urate crystals (due to the accumulation of urate) inflammatory response
66
Is the foot one of the most common places people experience gout?
Yes
67
Is gout a chronic condition?
Yes, yet it has acute flares
68
Are gout flare ups extremely painful?
Yes
69
Does joint damage occur if gout is poorly managed?
yes
70
What are some risk factors for gout?
- Age
- Alcohol consumption
- Obesity
- Meat and seafood
- Medications
71
Why are meat and seafood a risk factor for gout?
(contain purines) (purines are a type of chemical compound and when they are broken down in the body, they form uric acid in the liver)
72
Why are medications a risk factor for gout?
(thiazide diuretics, loop diuretics) – this is because these medicines might affect how the body excretes the uric acid via the kidneys
73
What are tophi?
Solid lumps of urate crystals
74
What are exogenous purines from?
Diet
75
Is endogenous purine synthesis possible?
Yes, these purines are made in the body, usually in the liver
76
What are purines broken down into, in the body?
Broken down to produce this compound called hypoxanthine and hypoxanthine is converted to xanthine and finally to urate by important enzymes called xanthine oxidase.
77
Broadly, what is urate lowering therapy?
- Lower urate levels in body to allow the urate crystals to dissolve
- Prevent formation of new crystals in joints, soft tissues and kidneys
- Typically will be a lifelong medication
- Example: Allopurinol
78
Broadly, what is gout flare treatment?
- Drugs to treat acute attacks
- Typically used for a few days
- Examples: NSAIDs, colchicine, prednisolone
79
What is allopurinol's mechanism?
So the body has to first convert allopurinol to oxypurinol // oxypurinol inhibits the effects of xanthine oxidase // urate isn’t formed // decreased levels of uric acid in the blood
80
When using NSAIDs to treat acute flares of gout, what drug should be avoided?
Aspirin, this is because it competes with uric acid for excretion
81
Is paracetamol an effective drug choice for an acute gout flare up?
No, not particularly, as it doesn't reduce inflammation and hence it isn't as effective as other drugs
82
Colchicine and acute gout flare up..?
- Affects immune cell division and movement
- Inhibits neutrophil migration, chemotaxis and phagocytosis
- Short cause: can be toxic (early signs of N/V/D)
83
What corticosteroids are used to treat gout?
A short course of prednisolone
84
What is cortical (hard) bone?
Dense, outer section in shaft of long bones
85
What is trabecular (spongy) bone?
Interior ‘meshwork’
86
What is the deposit of minerals in bones?
Predominantly calcium and phosphate
Calcium and phosphate forms a complex called hydroxyapatite, which gives bones its strength. Lots of hydroxyapatite forms a nice lattice, this makes the bone nice and strong.
In both the cortical bone and the trabecular bone
87
What are the functions of bones?
- Structure, support and framework for musculature attachments
- Protection of internal and vital organs
- Reservoir for calcium, phosphate and other essential minerals
- Allows and/or limits movement or rotation
88
Are bones continuously formed and reabsorbed?
Yes
89
What is the function of osteoblasts?
bone formation/ builders
new minerals aid down = mineralisation
90
What is the function of osteoclasts?
- bone resorption/ consumption
- dig pits in bone via secretion of acid and enzymes
- helps to release minerals which are then taken back into the bloodstream
91
Is osteoporosis a disruption to the normal balance of osteoblast/ clast function?
Yes
92
What are the main things that happen in osteoporosis?
Bones become thin, weak and fragile, therefore people are at increased risk of a fracture
93
Why are bones remodelled?
- Mechanism to maintain bone strength
- Maintain blood calcium and phosphate levels
- Repair microfractures
- Prepare bone for weight bearing
94
What is the bone remodelling process regulated by?
- Parathyroid hormone (PTH)
- Calcium and vitamin D
- Calcitonin
- Other hormones
95
What are some sources of calcium in the diet?
high calcium content food/drink : milk, sesame seeds, chia seeds, almonds, kale
96
What is calcium's importance in bone formation?
Important to have the right amount of calcium in the blood stream so that it can be delivered to the bones
97
Do calcium and vitamin D work together?
Yes
98
How do calcium and vitamin D work together?
Calcium levels in blood increases with: consumption of calcium and with exposure to vitamin D
Vitamin D from kidneys increases calcium reabsorption, therefore increasing calcium levels in the blood
99
Do oestrogen and testosterone induce bone formation?
Yes
100
Does oestrogen promote bone mineralisation?
Yes
101
When are men's bone the strongest generally?
It is shown in the diagram that testosterone levels peak in the early twenties and decline steadily with age, so naturally bones are strongest when men are in their twenties or so.
102
When does oestrogen tend to peak in women?
Maybe later, into their 30s or 40s
103
Once oestrogen levels drop off, what happens?
Due to this rapid drop off, you can expect that women are more likely to be at risk of osteoporosis and as such, and increased risk of fractures.
104
How is BMD measured?
Measured using a bone densitometry scan (DXA)
105
What is BMD?
- Surrogate measure for bone strength – we can’t actually measure how strong a bone is without an invasive surgery, so this is the best thing we can do without being too invasive
- Bone mineral density
106
What is a T-score?
The T-score basically compares the bone mineral density of a person who’s bone is being scanned against the bone mineral density of a younger person of the same sex.
107
What does a T-score of greater than negative 1 mean?
A normal BMD, with minimal risk of fracture
108
What does a T-score of negative one to negative 2.5 mean?
The patient has osteopenia and has intermediate risk of a fracture
109
What does a T-score of less than negative 2.5 mean?
The patient has osteoporosis and has a high risk of obtaining a fracture
110
What is osteoporosis broadly?
- Compromise of trabecular (spongy) bone
- Loss of ‘bone mineral density’ (BMD): calcium loss quicker than replacement
- Asymptomatic
- Characteristics – low bone mass, microarchitectural deterioration of bone tissue
- Increase fragility and susceptibility to fractures
111
Why is it important that the risk of fractures is minimal?
Fractures result in pain, deformity, disability and loss of independence. (impacting a person’s quality of life)
112
What are the aims in treating osteoporosis?
- Maintain or increase bone strength
- Prevent and or decrease fracture risk
113
How is osteoporosis managed through lifestyle?
exercise: preserves bone mass and stimulates bone growth
114
How is osteoporosis managed with medications, broadly?
usually work in one of these three ways. slow bone resorption, decreased osteoclast activity or increased bone formation
115
Why is calcium a medication for osteoporosis?
- Essential for bone formation and strength
- Mineralised into trabecular meshwork, increasing BMD
116
Why is vitamin D a medication for osteoporosis?
- Hormone, maintains calcium levels
- Increase calcium absorption for GIT, increased mobilisation of calcium for mineralisation into bone, decreased calcium excretion from kidney
117
What is an example of bisphosphonates to treat osteoporosis?
Risedronate
118
What are the basics of the mechanism of risedronate?
Deposited in bone (binds to hydroxyapatite)
When osteoclasts start to resorb bone drug is released and internalised by osteoclasts
Decreased osteoclast function and apoptosis
Decreased bone loss and decreased resorption, increased BMD
119
So broadly, how do bisphosphonates work?
So we can say that also the bisphosphonates reduce bone loss and reduce a bone reabsorption by reducing osteoclast function apoptosis, and overall, they increase bone mineral density as well.
120
What is esophagitis an adverse effect of?
Taking bisphosphonates for osteoporosis
121
How do you avoid esophagitis?
Swallow the medication with a full glass of water and don’t lay down for at least an hour after you take the medication to prevent this, this is because it can get stuck in the throat and cause inflammation.
122
Is osteonecrosis a rare adverse effect of biphosphonates?
Yes
123
What is osteonecrosis?
This is a condition where the bone in a person’s jaw actually becomes necrotic and dies
124
Why is it important people taking bisphosphonates have planned dental work complete before starting the medication?
To avoid osteonecrosis
125
Should bisphosphonates be taken separate to food and drink?
yes, as they have poor oral absorption
126
Should calcium be taken at the same time as bisphosphonates?
No, calcium should be taken at least two hours after bisphosphonates
127
Why should calcium be taken at least two hours after bisphosphonates?
If you take calcium the bisphosphonate will instead bond to the calcium that you have taken and it will form a complex in the GI tract and that complex cannot actually get to your bones and be effective. So really it stops the drug from being to work
128
Is hormone replacement therapy used in post-menopausal women?
Yes
129
Why is hormone replacement therapy used in post menopausal women?
- Aging; decreased estrogen levels, increased osteoclast activity, increase bone resorption and decreased BMD. Therefore an increased risk of osteoporosis.
130
What is the mechanism of estrogen in treating osteoporosis?
Decreased osteoclast activity, decreased bone resorption, prevents further decrease in bone mineral density
131
What are the adverse effects of taking estrogen for osteoporosis?
- Concerns about cardiovascular risks (blood clotting) and cancer (breast and endometrial)
132
Why is denosumab becoming popular in the the treatment in osteoporosis?
It only has to be given once every six months as an injection, which means that people, don’t have to remember to take a tablet all the time.
133
What class of drug is Denosumab?
RANK Ligand (RANK-L) inhibitor
134
What is the mechanism of Denosumab ?
When given, the drug will bind to the RANK ligand and stops the RANK ligand from being able to bind to the RANK receptors on the osteoclast. Because of this we can reduce the production and formation of our osteoclast and that will help to reduce bone resorption.
135
Give a summary of the mechanism of Denosumab ?
- RANK-L usually important for differentiation and activation of osteoclasts
- Prevents RANK-L binding onto RANK receptor
- Inhibits interaction of RANK-L with osteoclast
- Decrease osteoclast synthesis and formation
- Decreased bone resorption
- Most significant BMD elevation.
136
What is the usual role of sclerostin?
- Synthesised by osteocytes
- Inhibits wnt signalling pathway – essential for osteoblast to increase bone formation
- Inhibits bone formation
- Increases bone resorption, decreasing BMD
137
What class is sclerostin in?
anti-sclerostin antibody
138
What is an example of a sclerostin?
Romosozumab
139
What does romosozumab do?
- Inhibits synthesis of sclerostin in osteocytes
- Promotes survival and proliferation of osteoblasts
- Decreased bone resorption and increased BMD
140
Can glucocorticoids induce osteoporosis?
Yes, they can decrease done formation, increase bone resorption and therefore increase fracture risk
141
Can thyroid hormones increase the risk of osteoporosis?
increased osteoblast and osteoclast activity, overall net decrease in BMD
142
Can anti- epileptic drugs increase the risk of osteoporosis?
Yes, they inactivate vitamin D, this decreases calcium absorption, and this interferes with parathyroid gland, increasing bone resorption
143
What are the anti-resoprtive agents in treating osteoporosis?
biphosphonates, hormone replacement therapy and RANK-ligand inhibitor
144
What is the anabolic agent used to treat osteoporosis called?
anti-sclerostin antibody
145
What vitamins and minerals are used to treat osteoporosis?
Calcium and vitamin D
146
What are the methods of cell to cell communication?
Direct, synaptic, paracrine and endocrine
147
What is the mechanism of transmission of direct cell to cell communication?
Direct movement through gap junctions linking the cytoplasm of adjacent cells
148
What is the mechanism of transmission of synaptic cell to cell communication?
Diffusion from a neuron across a narrow space (synaptic cleft) to a cell bearing the appropriate receptors
149
What is the mechanism of transmission of paracrine cell to cell communication?
Diffusion through extracellular fluid to nearby cells bearing the appropriate receptors
150
What is the mechanism of transmission of endocrine cell to cell communication?
Carried in the bloodstream to near or distant cells bearing the appropriate receptors
151
Does the endocrine system control multiple bodily functions?
Yes
152
What are the main regulators in the endocrine system?
The hypothalamus and pituitary gland
153
What are the functions of the endocrine system?
- Maintain internal homeostasis – water and metabolic functions
- Support tissue growth
- Coordinate development
- Coordinate reproduction and fertility
154
What is an endocrine hormone?
- Chemical messenger that travels in the blood to different parts of the body
- Signals the body to act in a certain way
- Each hormone fits exactly into it’s receptor- so only specific parts of the body that have that receptor will be able to respond to the hormone, so this why hormones affect some parts of the body, but not others
155
Does the hypothalamus link the brain to the rest of the endocrine system?
yes
156
How is the pituitary gland connected to the hypothalamus?
Connected through nerves and blood vessels
157
Does the pituitary gland control the functions of other glands?
Yes
158
What is the role of the anterior lobe of the pituitary gland?
makes hormones in response to signals from the hypothalamus
159
What is the role of the posterior lobe of the pituitary gland?
releases hormones made in hypothalamus (ADH + oxytocin)
160
What hormones does the anterior lobe of the pituitary gland release?
Adrenocorticotropic hormone, thyroid stimulating hormone, growth hormone, follicle stimulating hormone, luteinising hormone, prolactin
161
What hormones does the posterior lobe of the pituitary gland release?
Oxytocin, and antidiuretic hormone/ vasopressin
162
Where is the adrenal gland?
On top of the kidney
163
What layer of the adrenal gland is the cortex?
The outer layer
164
What layer of the adrenal gland is the medulla?
The inner layer
165
Is oxytocin involved in a positive feedback loop?
Yes
166
What positive feedback loop is oxytocin involved in?
Breastfeeding, The oxytocin keeps getting released until the baby has stopped feeding, signalling the slow/ stop of milk
167
168
What does the thyroid gland make?
- makes hormones that control heart function, digestion, bone health, muscle function, etc
169
What does calcitonin (CT) control?
Controls calcium and phosphate
170
What is the main hormone produced by the thyroid?
thyroxine (T4)
171
What is more active than T4 (thyroxine)?
Triiodothyronine
172
Where is the thyroid gland located?
The thyroid gland is a small gland that sits in the front of the neck and wraps around the trachea.
173
How is thyroid hormone regulated?
Through a negative feedback loop
174
Broadly, how does the negative feedback loop of thyroid hormone work?
It is signalled that body temperature or T3/4 levels are low. The hypothalamus releases TRH and TSH from pituitary. Then the thyroid releases T3/4 into the bloodstream. Once it is returned to normal the hypothalamus will stop signalling. This results in balanced levels.
175
What is an overactive thyroid called?
hyperthyroidism
176
What is a normal level of thyroid activity called?
Euthyroid
177
What is a low level of thyroid activity called?
hypothyroidism
178
What is hyperthyroidism caused by?
- Grave’s disease, autoimmune condition where the body’s own immune system produces antibodies that stimulate the thyroid gland to produce too much thyroid hormone
- thyroiditis – inflammation due to genetics, virus or medications (amiodarone, lithium)
- thyroid nodules – lumps that might form in the thyroid gland.
179
What are the symptoms of hyperthyroidism?
- mood changes
- intolerance to heat
- increased sweating
- heart palpitations
- fatigue
- increased appetite
- unexpected weight loss
180
What are the classes of hyperthyroidism?
Primary and secondary
181
Briefly explain primary hyperthyroidism:
- decreased TSH but increased thyroid hormones
- example: Grave’s disease – treat anti-thyroid medication and/ or surgery
182
Briefly explain secondary hyperthyroidism:
In secondary hyperthyroidism there’s an external contributing factor causing an increase in thyroid hormone, so this type of hypothyroidism is usually characterised by elevated TSH and elevated thyroid hormone.
- increased TSH and thyroid hormones
- examples: hypothalamic or pituitary dysfunction
183
What is the oral treatment for hyperthyroidism?
- TH synthesis inhibitors: carbimazole, propylthiouracil – carbimazole longer half-life
- Radioactive iodine: destroy overactive cells
184
What is the surgery treatment for hyperthyroidism?
- Thyroidectomy – will need thyroid hormone replacement afterwards.
185
What is hypothyroidism?
An underactive thyroid that cannot produce enough TH
186
What are the symptoms of hypothyroidism?
- Sensitivity to cold temperatures
- Fatigue
- Weakness
- Dry/rough skin
- Hair thinning or becoming brittle
- Constipation
- Weight gain
- Depressed mood
187
What are the two classes of hypothyroidism?
Primary and secondary hypothyroidism?
188
What is primary hypothyroidism?
- Increase TSH but decreased TH
- Examples: Hashimoto’s, thyroidectomy – Hashimoto’s is most common cause of hypothyroidism; autoimmune destruction of thyroid cells
189
What is secondary hypothyroidism?
- Reduced TSH and TH
- Examples: hypothalamic or pituitary dysfunction
190
What is liothyronine's role in treating hypothyroidism?
(manufactured form of T3) helps as it has a rapid onset, short duration of effect. used in severe hypothyroidism
T3: Liothyronine – short duration of action (up to 3 days) – difficult to monitor – plasma concentrations vary
191
What is levothyroxine's role in treating hypothyroidism?
(manufactured form of T4) Drug choice of primary and secondary hypothyroidism. It has a long half life, with a long duration of effect.
T4: Levo(thyroxine) is used most often – long duration of action (up to three weeks) – used in both primary and secondary hypothyroidism
192
What is the MOA of levothyroxine and liothyronine?
actually in some people this might cause mild hypothyroidism. So we get a much better response to the medication if we use T4.
The aim is to suppress TSH levels and replace deficient TH – use synthetic TH
193
What are the adverse effects of levothyroxine and liothyronine?
Hyperthyroidism – usually due to over-treatment
Increased cardiovascular effects:
- Signs and symptoms similar to hyperthyroidism increased BP/HR, tachycardia, arrythmia
Increased osteoporosis risk – decreased BMD leading to increased risk of osteoporosis and fractures
194
What are some common conditions of the adrenal gland?
- Adrenal insufficiency
- Adrenal crisis
- Cushing’s disease – excess glucocorticoids
- Addison’s disease – deficiency of glucocorticoids
195
What is primary adrenal insufficiency?
(Addison’s disease) – autoimmune destruction of cortex
196
What is secondary adrenal insufficiency?
pituitary cant produce enough ACTH – aldosterone not affected – can be due to hypothalamus disorders or prolonged administration of glucocorticoids (due to reduction in endogenous production of hormones)
197
What are some symptoms of adrenal insufficiency?
Fatigue, joint pain, reduced appetite, weight loss, light-headed feeling, diarrhoea
198
What is the goal in treating adrenal insufficiency?
Treatment can be tricky so the goal is to replace hormones and improve symptoms
199
Is mineralocorticoid replacement therapy used to treat adrenal insufficiency?
Yes.
200
What are the uses of fludrocortisone?
- Mineralocorticoid replacement in primary adrenal insufficiency, with a glucocorticoid
- Orthostatic hypotension – because it has fluid retaining properties
201
What are the adverse effects of fludrocortisone?
- Sodium and water retention, oedema, hypertension
- (we need to be careful to make sure the person doesn’t become fluid overloaded)
202
What is adrenal crisis?
- Occurs when a person with adrenal insufficiency is exposed to severe physical or psychological stress – infection, illness, surgery or trauma leading to low levels of cortisol
- Medical emergency
- Treatment – injectable hydrocortisone into muscle or under skin
203
What is cushing's disease?
- Tumour in pituitary gland causes overproduction of cortisol
- Excess adrenocorticotropic hormone (ACTH) – this stimulates the adrenal glands to produce lots of cortisol
- Symptoms: bruising, muscle weakness, weight gain, fluid retention, excess body and facial hair, acne, fat accumulation on neck, rounding of face, low back pain, reduced libido
204
What are the goals of treatment for cushing's disease?
- Return cortisol levels to normal, reverse symptoms and improve QoL
205
What are the treatment options for Cushing's disease?
- Block release of cortisol: ketoconazole
- Block release of ACTH: cabergoline
- Block cortisol having an effect in the body: mifepristone
206
What are the adverse effects of glucocorticoid drugs?
- Adrenocortical insufficiency: suppression of HPA
- Diabetes mellitus
- CNS effects: physiological and behavioural changes
- Impaired wound healing
- Musculoskeletal effects: osteoporosis, increased fracture risk
- Cardiovascular effects: fluid retention, oedema, hypertension
- GI effects: increased acid and pepsin secretion
207
What is the way to reduce undesirable effects of corticosteroids?
Modify the dose or dosage regimen
208
What are ways to modify the dose or dosage regimen of corticosteroids?
- Use lowest dose for shortest duration
- Use only when needed (for certain indications)
- Give in the morning
- Give locally
- Taper slowly – do not abruptly withdraw if high dose or on long term therapy
209
What are the possible withdrawal effects of ceasing glucocorticoid therapy?
- Adrenal crisis, hypotension, hyperglycaemia, muscle aches + pains
- Unlikely with short term use (few days)
210
How is tapering managed in ceasing glucocorticoid therapy?
- Important when used long-term
- No clear guidance for tapering dose
- Usually managed by GP
