Case 17 Flashcards
(199 cards)
1
Q
First line drugs for T2DM
A
Metformin
Gliclazide
2
Q
Effect of Metformin
A
Increases insulin-dependent glucose uptake into tissues.
Inhibits gluconeogenesis in liver.
Inhibits GI absorption of CHOs
3
Q
Route of Administration of metformin
A
Oral
4
Q
MOA of Metformin
A
Activates AMP-dependent protein kinase in liver.
Potentiates effects of endogenous insulin.
5
Q
What class of drug is Metformin?
A
Biguanide class hypoglycaemic drug
6
Q
ADRs of metformin
A
Abdominal pain
Anorexia
Diarrhoea
7
Q
Contraindications of Metformin
A
Renal, liver or heart failure
Hypoxaemia
8
Q
Route of administration of Gliclazide
A
Oral
9
Q
Effect of gliclazide
A
Enhances insulin secretion
10
Q
MOA of Gliclazide
A
Blocks K+ efflux from beta cells of pancreas.
Beta cells become depolarised.
Depolarisation causes Ca2+ influx.
Results in IP3 mediated enhanced secretion of insulin.
11
Q
What class of drug is Gliclazide?
A
Sulfonylurea class hypoglycaemic drug
12
Q
ADRs of Gliclazide
A
Haematological disorders
Hypoglycaemia in overdose
13
Q
Contraindications of Gliclazide
A
Severe hepatic impairment
14
Q
Route of administration of Saxagliptin
A
Oral
15
Q
Effect of Saxagliptin
A
Enhanced insulin secretion
16
Q
MOA of Saxagliptin
A
Inhibits dipeptidyl peptidase-IV
Enzyme which breaks down incretins
17
Q
Effect of incretins
A
Enhance insulin secretion
18
Q
Effect of DPP-IV
A
Rapidly breaks down incretins
19
Q
ADRs of Saxagliptin
A
Dizziness Dyspepsia Fatigue Gastritis Gastroenteritis Headache Hypoglycaemia
20
Q
Contraindications of Saxagliptin
A
Severe hepatic impairment
Sensitive to DPP-IV inhibitors
21
Q
Route of administration of Exenatide
A
Subcutaneous injection
22
Q
Effect of Exenatide
A
Increased insulin secretion
Suppresses glucagon secretion
Slows gastric emptying
23
Q
MOA of Exenatide
A
Mimics incretins.
Acts on GLP-1 receptors causing enhanced insulin secretion.
24
Q
ADRs of Exenatide
A
Hypoglycaemia
Injection-site reactions
Abdominal pain
Weight loss
25
Contraindications of Exenatide
Ketoacidotic
| Severe GI pathologies
26
Drugs which can be coprescribed with metformin
Saxagliptin
| Exenatide
27
Drugs which can be coprescribed with Gliclazide
Saxagliptin
| Exenatide
28
The 'thrifty' genotype
Less active
| Storing more energy
29
Heritability
Proportion of observed differences between members of a population that are due to genetic factors
30
Onset of MODY
<25yrs
31
Inheritance pattern of MODY
Autosomal Dominant
32
Distinguishing clinical features of MODY
No obesity
No ketosis
No beta-cell autoimmunity
Onset < 25yrs
33
Mutation which causes MODY 2
Mutation in Glucokinase (GCK)
34
Function of glucokinase
An enzyme which catalyses phosphorylation of glucose.
| Controls rate limiting step of glycolysis.
35
Treatment of MODY
Diet management only
Have a mild, stable fasting hyperglycaemia without complications.
36
Mutation responsible for MODY3
HNF1A
37
Mutation responsible for MODY12
ATP-Binding Cassette (ABCC8)
38
Mutation responsible for MODY13
Potassium channel KCNJ11
39
MODY12 and MODY13 are associated with...
Neonatal diabetes
40
Features of Permanent Neonatal Diabetes
```
IUGR
Symptomatic hyperglycaemia
Onset < 6 months
With ketoacidosis
Lack of insulin throughout life (requires insulin treatment)
```
41
Features of transient neonatal diabetes
Severe IUGR
Symptomatic hyperglycaemia
Onset < 1 month
Lack on insulin which resolves by 18 months
Intermittent childhood hyperglycaemia during illnesses
~50% risk of T2D as adult
42
Potassium channel structure in beta cells of pancreas
4 Kir6.2 subunits forming the channel pore.
| Surrounded by 4 sulphonylurea receptors (SURs) that regulate pore activity.
43
How do potassium channels affect insulin release?
```
Glucose enters pancreatic beta cell.
Causes ATP to increase in cells.
ATP binds to and closes K+ channel
Cell depolarises due to build up of K+
Depolarisation causes insulin.
```
44
MELAS
Mitochondrial Myopathy
Encephalopathy
Lactic Acidosis
Stroke-like episodes
45
Common presenting features of MELAS
```
Diabetes
Deafness
Exercise Tolerance
Muscle weakness
Seizures
```
46
Donahue Syndrome
Mutation in insulin receptor causing profound insulin resistance
47
Inheritance pattern of Donahue Syndrome
Autosomal recessive
48
Distinctive features of Donahue Syndrome
```
Pre and postnatal growth failure
Low subcut adipose
Aged face
Thick lips
Low set ears
Acanthosis Nigricans
Hyperandrogenism (Hirtsutism, enlarged male genitalia, cystic ovaries)
Early mortality
```
49
Epigenetics
Stable, heritable modification of chromosomes, without alterations in DNA sequence
50
Transient neonatal diabetes inherited due to...
Overexpression of imprinted genes at 6q24 e.g. PLAG1
| Usually due to paternal UPD or duplication of paternal chromosome
51
T2DM is more likely to be inherited from (mother/father)
Mother
52
Intergenerational Effects
Both the foetus and her offspring can be affected by poor nutrition/toxic exposure of mother
53
Transgenerational Effects
Epigenetic changes that persist for multiple generations.
54
Tolbutamide is recommended for...
Elderly
55
Gliclazide is recommended for...
Renal impairment
56
MOA of Meglitinides
Insulin secretogogues
| Closure of K+ ATP channels in beta cells
57
Incretins
GIP and GLP-1
Enhance secretion of insulin
58
MOA of statins
Inhibition of HMG-CoA reductase
59
Who is prescribed statins?
Secondary prevention - those at risk of MI and stroke due to atherosclerotic disease (post MI/Stroke, Angina)
Primary prevention - those at high risk of arterial disease due to elevated serum cholesterol.
60
Common ADRs of statins
```
Myalgia
GI disturbance
Raised liver enzymes
Insomnia
Rash
```
61
Severe ADRs of statins
Myositis
| Angioedema
62
Contraindications for statins
Pregnancy
63
Treatment of Familial Hypercholesterolaemia
Atorvastatin
64
Sensitivity
No. of True positives/No. of people with the condition
65
Specificity
No. of true negatives/No. of people without the condition
66
Borders of the femoral triangle
Inguinal ligament
Sartorius
Adductor Longus
67
Contents of femoral triangle
Femoral nerve
Femoral artery
Femoral vein
68
Where can the femoral artery be palpated?
Midway between ASIS and pubic tubercle
69
Femoral nerve lies within a fascial compartment along with...
Iliopsoas
70
Femoral sheath
Fascial extension of abdomen, within which the femoral nerve and artery are contained
71
Contents of Femoral canal
Lymphatic vessels
Deep lymph node
Empty space
Loose connective tissue
72
What is the function of the empty space in the femoral canal?
Allows for distension of the femoral vein so that is can cope with increased venous return.
73
What is the femoral canal?
A rectangular shaped compartment within the femoral triangle.
74
How can you distinguish between a femoral and direct inguinal hernia?
Femoral = lateral to pubic tubercle
| Direct inguinal = medial to pubic tubercle
75
Meralgia Paraesthetica
Compression of lateral cutaneous nerve as it passes through the inguinal ligament. Causing altered sensation in lateral thigh.
76
Cutaneous innervation of medial thigh
Obturator nerve
77
Cutaneous innervation of lateral thigh
Lateral cutaneous nerve of thigh
78
Cutaneous innervation of posterior thigh
Posterior cutaneous nerve of thigh
79
Cutaneous innervation of anterior thigh
Femoral nerve
80
Cutaneous innervation of anteromedial lower leg
Saphenous nerve
81
Cutaneous innervation of anterolateral lower leg and dorsum of the foot
Superficial branch of common fibular nerve
82
Motor component of common fibular nerve
Biceps femoris
| Lateral and anterior compartments of lower leg
83
Cutaneous innervation of heel
Tibial nerve
84
Cutaneous innervation of posterolateral lower leg
Sural nerve (tibial)
85
Saphenous nerve branches from..
Femoral nerve
86
Motor component of femoral nerve
Hip flexors - pectineus, iliacus, sartorius
Knee extensors - quadriceps femoris
87
Sensory component of femoral nerve
Anteromedial thigh
| Medial lower leg and foot
88
Motor component of obturator nerve
Medial compartment of thigh - adductor
89
Sensory component of obturator nerve
Skin of medial thigh
90
Motor component of sciatic nerve
Posterior thigh muscles
91
Motor component of tibial nerve
Posterior compartment of lower leg
92
Sensory component of tibial nerve
Posterolateral side of the lower leg.
Lateral side of foot
Sole of foot
93
Motor component of common fibular nerve
Short head of biceps femoris
| Anterior and lateral compartments of leg
94
Sensory component of common fibular nerve
Skin over upper lateral and lower posterolateral leg.
| Skin of anterolateral leg and dorsum of foot
95
Sensory component of superficial fibular nerve
Skin over dorsum of foot
| Anterior and lateral aspect of inferior third of lower leg
96
Motor component of superficial fibular nerve
Lateral compartment of lower leg
97
Sensory component of deep fibular nerve
Triangular region of skin between 1st and 2nd toes
98
Motor component of deep fibular nerve
Anterior compartment of lower leg
| Some intrinsic muscles of the foot
99
Blood supply to anterior compartment of leg
Anterior tibial
100
Nerve supply of anterior compartment of leg
Deep fibular
101
Blood supply of lateral compartment of leg
Common fibular
102
Nerve supply of lateral compartment of leg
Superficial fibular
103
Blood supply of posterior compartment of leg
Posterior tibial
104
Nerve supply of posterior compartment of leg
Tibial nerve
105
Nerve supply of posterior compartment of thigh
Sciatic nerve
106
Nerve supply of anterior compartment of thigh
Femoral nerve
107
Nerve supply of medial compartment of thigh
Obturator nerve
108
Surgical intervention for compartment syndrome
Fasciotomy
109
Compartment syndrome
Bleeding into one of the osteofascial compartments of limb .
| Causes an increase in pressure which risks ischaemia of the structures in the compartment
110
Muscles of lateral compartment of the foot
Fibularis longus and brevis
111
Action of fibularis longus and brevis
Evert foot and weakly plantar flex ankle
112
Superficial muscles of posterior compartment of leg
Gastrocnemius
Soleus
Plantaris
113
Deep muscles of posterior compartment of leg
Popliteus
Flexor digitorum longus
Flexor hallucis longus
Tibialis posterior
114
Action of superficial posterior muscles of leg
```
Plantar flexion (weakly)
Support longitudinal arch of foot
```
115
Effect of rupture of achilles tendon
Unable to plantar flex foot against resistance
116
Osteofascial Tunnel Posterior to Malleolus
| Tom Dick And Very Nervous Harry
```
Tibialis Posterior
Flexor Digitorum
Artery
Vein
Nerve
Flexor Hallucis Longus
```
117
Lateral and medial plantar arteries arise from...
Posterior tibial artery
118
Vein most commonly affected by varicosities
Great Saphenous Vein
119
Venous supply which is most at risk in a fracture of proximal femur
Medial and lateral circumflex veins which arise from profunda femoris
120
Ankle-Brachial Index
Ratio of systolic blood pressure in ankle compared to that of the brachial artery
Used to diagnose peripheral artery disease
121
Borders of popliteal fossa
Superomedial: Semimembranosus
Superolateral: Biceps femoris
Inferomedial: Medial head of gastrocnemius
Inferolateral: Lateral head of gastrocnemius and plantaris
122
Contents of popliteal fossa
Popliteal artery
Popliteal vein
Tibial nerve
Common fibular nerve
123
Where can the posterior tibial artery pulse be palpated?
Posterior to medial malleolus
124
Where can the dorsalis pedis pulse be palpated?
Lateral to extensor hallucis longus tendon
125
Endocrine pancreatic secretions
Insulin
Glucagon
Somatostatin
Pancreatic polypeptide
126
Exocrine secretions
Digestive enzymes
| Bicarbonate
127
Fasting plasma glucose
4-6mmol/L
128
Plasma glucose 2hrs after eating
7.8mmol/L
129
GLUT2
Low affinity transport of glucose into cells
130
Secretion of Insulin
```
Glucose enters cells via GLUT2
Glucokinase acts on Glc to produce ATP
ATP inhibits K+ efflux via SUR1/Kir6.2 channels
Depolarisation causes Ca2+ influx
High Ca2+ causes insulin release
```
131
Insulin Receptor
Transmembrane Tyrosine-Kinase-Linked Receptor
132
When insulin binds to its receptor....
The receptor is autophosphorylated by tyrosine kinase.
| Results in autophosphorylation of insulin receptor substrates which act globally to reduce plasma glucose.
133
Insulin activates:
```
Protein synthesis
K+ uptake
Glycogen synthesis
Glucose uptake
Glycolysis
```
134
Insulin inhibits:
```
Lipolysis
Gluconeogenesis
Glycogenolysis
Proteolysis
Ketogenesis
```
135
Advanced Glycation End-Products
Produced by Hb glycation
| Cause oxidative damage and impaired macromolecular function
136
HbA1c is a measure of
Glycated Hb
137
Normal HbA1c
<42mmol/mol OR <6%
138
Values of hypoglycaemia
<4mmol/L
139
Values of hyperglycaemia
>6.9mmol/L
140
Lifestyle factors which increase risk of T2DM
Poor diet
Low levels of exercise
Stress
141
Genes associated with T2DM
FTO
| KCNJ11
142
FTO
encodes alpha-ketoglutarate-dependent dioxygenase
143
KCNJ11
encodes the islet ATP-sensitive K+ channel Kir6.2
144
GLUT2 is found in
Pancreatic cells
| Liver cells
145
GLUT4 is found in
Adipocytes
| Muscle cells
146
MOA of Pioglitazon
Thiazolidinedione
Forms a complex with PPAR-gamma. Complex is an adipocyte gene transcriptional regulator resulting in increased glucose uptake
147
Effects of Pioglitazon
Adipocyte differentiation
Increased lipogenesis
Increased fatty acid uptake
Increased glucose uptake
148
ADRs of Pioglitazon
```
GI disturbance
Weight gain
Oedema
Anaemia
Headache
Visual disturbance
Impotence
Haematuria
```
149
Contraindications of Pioglitazon
Hx of Heart failure
Haematuria
Previous or active bladder cancer
150
Disease of exocrine pancreas associated with diabetes mellitus
Pancreatitis
CF
Haemochromotosis
151
Endocrinopathies associated with Diabetes Mellitus
Cushing's Syndrome
Acromegaly
Hyperthyroidism
152
Drugs which may induce DM
Glucocorticoids
Thiazides
Beta blockers
Atypical Antipsychotics
153
Genetic Syndromes associated with DM
Down's Syndrome
Klinefelter Syndrome
Wolframs Syndrome
154
Autonomic symptoms of hypoglycaemia
Sweating
Palpitations
Shaking
Hunger
155
Neuroglycopenic symptoms of hypoglycaemia
Confusion
Drowsiness Odd behaviour
Speech Difficulty
Incoordination
156
Symptoms of hypoglycaemia
Sweating, Palpitations
Odd behaviour, incoordination and speech difficulty
General malaise - headache, nausea
157
Diagnostic criteria for DKA
BG >11mmol/L or known diabetes
HCO3- < 15mmol/L +/- venous pH less than 7.3
Ketonaemia >3mmol/L or significant ketonuria (> 2+)
158
Causes of DKA
Poor compliance with tx
Infection or intercurrent illness
Medical/Surgical/Emotional Stress
MI
159
DKA normally occurs in
T1DM
160
Hyperosmolar Hyperglycaemic State normally occurs in
T2DM
161
Diagnostic criteria for HHS
BG > 30mmol/L without hyperketonaemia and acidosis
162
DR: Microaneurysms
Small red spots, caused by swelling of small capillary vessels
163
DR: Haemorrhages
Red spots caused by small bleeds within retina
164
DR: Cotton Wool Spots
White and fluffy patches caused by scarred nerve fibres near surface of retina
165
DR: Hard exudates
Small, shiny, pale, white or yellow spots
Sharp edged
Caused by fatty deposits (due to leaking fluid)
166
DR: Venous loop
Loop in blood vessel due to poor blood flow
167
Definition of Diabetic Nephropathy
Proteinuria >0.5g/24hrs
168
Risk factors for diabetic nephropathy
```
Genetic and familial predisposition
Elevated blood pressure
Poor glycaemic control
Smoking
Hyperlipidaemia
Microalbuminuria
```
169
Stage I Diabetic Nephropathy
GFR>90
Hyperfiltration
Increased blood flow through kidney
Early renal hypertrophy
Normal renal function
170
Stage II Diabetic Nephropathy
GFR>60-89
Glomerular lesions
Mild reduction of renal function
171
Stage III Diabetic Nephropathy
GFR 30-59 (moderately reduced)
Microalbuminuria
Albumin:Creatinine Ratio 30-300mcg/mg/day
172
Stage IV Diabetic Nephropathy
GFR 15-29 (severely reduced)
Proteinuria > 500mg/24hrs
Creatinine clearance <70ml/min
173
Stage V Diabetic Nephropathy
End Stage Renal Disease
GFR<15
Creatinine Clearance <15ml/min
174
Pathophysiology of Diabetic Nephropathy
Renal hypertrophy associated with increased GFR.
Vasodilation of afferent arteriole - raised glomerular pressure.
Damage to glomerulus = mesangial cell hypertrophy and secretion of mesangial matrix.
Eventual glomerulas sclerosis - thickening of basement membrane, no longer acts as an effective filter.
Leakage of large proteins.
175
Symmetric Polyneuropathy
Pain, paraesthesia, loss of vibration sense in lower extremities (can eventually affect hands).
Can cause unrecognised trauma.
176
Most common form of neuropathy
Symmetric polyneuropathy
177
Acute Painful neuropathy
Burning, crawling pains in feet, shins and anterior thighs
178
Mononeuropathy
Isolated nerve palsies.
| Commonly affects CNIII and CNVI which supply external eye muscles.
179
Diabetic Amyotrophy
Painful wasting of quadriceps.
Knee reflexes absent or diminished.
Usually in older men.
180
Autonomic Neuropathy
Often Asymptomatic.
CV System - tachy at rest, arrhythmia, postural hypotension, warm foot with bounding pulse (peripheral vasodilation)
GI Tract - gastroparesis (D+V)
Bladder - loss of tone , incomplete emptying
Male erectile dysfunction
181
Pathophysiology of Diabetic Retinopathy
Hyperglycaemia damaged retinal pericytes.
Weak capillary walls - microaneurysms.
More permeable capillary walls - exudates and macular oedema.
Ischaemia - cotton wool spots and new vessels (VEGF)
Thin walled new vessels prone to bleeding - vitreous haemorrhage.
Fibrotic bands of collagen along margins of new vessels can contract - retinal detachment
182
Pathophysiology of Neuropathy
Hyperglycaemia causes formation of sorbitol and fructose in schwann cells. Loss of structure and function of schwann cells.
Segmental demyelinisation (reversible but becomes irreversible)
183
Major risk factor for diabetic foot ulcers
Distal Symmetric Neuropathy
184
Symptoms of ischaemic in diabetic foot
Claudication
| Rest pain
185
Symptoms of neuropathy in diabetic foot
USUALLY painless - unrecognised trauma
Some forms of neuropathy are painful
186
Examination of ischaemia in diabetic foot
Dependent rubor - dusky red colouration except when elevated above heart
Trophic changes - soft tissue changes
Cold
Pulseless
187
Examination
```
High arch
Clawing of toes
No trophic (soft tissue) changes)
Warm
Bounding pulse
```
188
Ischaemic ulceration in diabetic foot is usually...
Painful
| In heels and toes
189
Neuropathic ulceration in diabetic foot is usually...
Painless
| Plantar
190
Why is the response to infection less efficient in patients with diabetes?
Vascular disease and neuropathies
Hyperglycaemia
Depression of adherence, chemotaxis and phagocytosis of neutrophils.
191
Why does poor control of diabetes increase susceptibility to infection?
Depression of adherence, chemotaxis and phagocytosis of neutrophils.
192
Usual test for diagnosis of microalbuminuria
Albumin:Creatinine Ratio (Spot collection)
193
Criteria for diagnosis of microalbuminuria
ACR >30mg/min on 2 out of 3 occasions in a 3-6 month period
194
Causes of false positive test for microalbuminuria
```
Short term hyperglycaemia
Exercise
UTI
Marked hypertension
Heart failure
Acute febrile illness
```
195
Urine sample for Albumin:Creatinine Ratio must not be....
First void of the day due to diurnal variation in albumin secretion
196
Screening for diabetic eye disease
Annual DR screening service
| + Visual acuity
197
First line treatment of T2DM
Metformin
198
Treatment for Diabetes when Metformin is contraindicated/not tolerated
DPP-4 inhibitor e.g. Saxagliptin OR
Pioglitazone OR
Sulphonylurea e.g. Gliclazide
199
Why is wound healing impaired in T2DM
Impaired migration, proliferation and differentiation of keratinocytes.
Impaired eNOS activation causing impaired EPC synthesis.
Limited SDF-1alpha expression therefore EPCs not recruited to site.
Fewer EPCs at wound site, reduced neovascularisation (ischaemic wound)
