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Case 11 > Case 11 Pharmacology > Flashcards

Case 11 Pharmacology Flashcards

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1
Q

Plasma glucose normal range

A
  1. 0-6.0mmol/L (72-108 mg/dL) fasting

7. 8mmol/L (140mg/dL) 2 hours after eating

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2
Q

Endocrine secretions of the pancreas

A

Glucagon
Somatostatin
Pancreatic polypeptide

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3
Q

Exocrine secretions

A

Digestive juices and bicarbonate in duodenum

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4
Q

Insulin secretion MOA

A

Regulated by glucose transport into B cells by GLUT-2.
ATP inhibiting K+ATP efflux channels increased by glucokinas.
Ca2+ influx then insulin secretion via IP3 pathways

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5
Q

Insulin regulates metabolism of…

A

Carbs, lipids, proteins

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6
Q

Which type of transmembrane linked receptor is insulin

A

Tyrosine-kinase

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7
Q

Which glucose transporter is a low affinity glucose transporter

A

GLUT-2

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8
Q

What triggers secretion of insulin in the blood stream?

A

Glucose sensing in the pancreatic beta cell

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9
Q

Insulin blocks which processes

A 
Glycogenolysis
Proteolysis
Ketogenesis
Gluconeogenesis
Lipolysis
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10
Q

Insulin causes which processes

A 
K+ uptake
Protein synthesis
Glycogen synthesis
Glucose uptake 
Glycolysis
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11
Q

HbA1c- glycated or glycosylated ?

A

Glycated.

Higher the number- higher the glycaemic control required

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12
Q

AGE full form?

A

Advanced glycation end-products

Glycation is a non-enzymatic reaction that proceeds under hyperglycaemia and aging

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13
Q

Normal HbA1c?

A

<42 mmol/mol (or below 6% of Hb)

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14
Q

Plasma glucose hypo or hyper

A

<4.0 mmol/L- HYPO

>6.9 mmol/L HYPER

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15
Q

Diabetes complications?

A

Macrovascular disease, gangrene, microangiopathy, peripheral neuropathy, chronic renal failure, diabetic nephropathy, diabetic cardiomyopathy

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16
Q

Insulin sensitive effect by which receptor?

A

GLP-1

They are insulin sensitisers, - regulated by DPP-IV

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17
Q

Metformin class and administration

A

Biguanide- orally administered- FIRST-LINE

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18
Q 
Metformin MOA
(only works if there is SOME endogenous insulin production)
A

Insulin sensitizer
Causes reduction of ATP in liver cells, increased AMP- inhibits, glycerol 3-PDH
NADH goes up and gluconeogenesis goes down
Lactate increases
Appetite depressant

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19
Q

Sulfonylureas- eg Gliclazide MOA

A

Binds to the K+ ATP channel receptor .
BLOCKS K+ efflux
B cell depolarises causing Ca2+ influx
IP3 cascade- enhanced insulin granule

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20
Q

GLIPTINS- saxagliptin- MOA

A

Inhibitor of DPP-IV. Therefore GLP-1 has an EXTENDED effect on insulin secretion
Super-sensitises insulin secretion

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21
Q

GLP-1 agonists Incretin mimetics - Exenatide-MOA and route

A

S.c injection
Analogues of the incretins- you have to inject the drug
Activates the GLP-1 receptor
Enhances insulin secretion from B cells, suppresses glucagon secretions and slows gastric emptyping

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22
Q

SGL2-inhibitors- Gliflozins- eg dapagliflozin- MOA

A

Inhibition of the Na+/gllucose symporter in the nephron

Enhanced secretion of glucose in the urine to reduce plasma glucose concentration

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23
Q

Exogenous insulin?

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A

Exogenously prepared insulin may be considered

24
Q

At which HbA1c value should you add a second drug?

25
Initially, how often should HbA1c be checked?
3-6 months until stable, then 6 monthlu
26
Second drug that can be added to metformin when HbA1c rises to 7.5%
Sulfonylurea Gliptin Pioglitzone
27
Drug options when second drug has been added to metformin but HbA1c still above 7.5%?
metformin + gliptin + sulfonylurea metformin + pioglitazone + sulfonylurea metformin + sulfonylurea + SGLT-2 inhibitor metformin + pioglitazone + SGLT-2 inhibitor ○ OR insulin therapy should be considered
28
If triple therapy ineffective?
Combination therapy with metformin, a sulfonylurea and GLP-1 mimetic
29
Patient is not tolerate to metformin/contra- drug options?
Sulfonylurea, gliptin, pioglitazone and sulfonylurea
30
Patient not tolerant to metformin and HbA1c is 7.5%- drug options?
Gliptin+ Pioglitazone Gliptin + sulfonylurea Pioglitazone + sulfonylurea
31
Which treatments lead to an increased risk of hypoglycaemia 6-12 hours after exercise
Sulfonylureas and insulin
32
Which medicine is the best to prevent weight gain?
Metformin
33
Why should metformin be stopped prior to intravascular administration of iodinated contrast agent?
Risk of renal failure and subsequent lactic acidosis
34
Which class of drugs are avoided in pregnancy
Sulphonylureas
35
Why do the effects of sulfonylureas wear off eventually with the progression of diabetes
They rely on patients having a function beta cell mass however the B-cell mass declines with the progression of diabetes
36
Sulfonylureas that should be used and avoided in renal impairment
Used Tolbutamide, Gliclazide | Avoided- Glipizide/glimepiride and chlorpropamide
37
Sulfonylurea with a short half-life
Tolbutamide- use in the elderly
38
Thiazolidines (glitazones) MOA
Reduce insulin resistnace by interaction with PPAR-y, a nuclear receptor that regulates large numbers of genes involved in lipid metabolism and insulin action
39
DPP-4 inhibitors effect on weight and most effectiveness
Weight neutral - most effective in early stage of diabetes
40
GLP-1 agonists clinical disadvantage
Need for subcutaneous injection
41
Short acting insulin use - pre or post meal?
Pre-meal
42
Taking human insulin predisposes patients to what post meal?
Hypoglycaemia
43
Long-acting insulins
Insulin glargine, detemire and degludec
44
NICE recommendation for initial insulin to use in T2DM
NPH
45
NPH and Metformin regimen
NPH at night and metformin during the day /twice daily injections of pre-mixed soluble and NPH insulin
46
What is lipohypertrophy?
Fatty lumps may occur as a result of overuse of a single injection site with any type of insulin
47
Blood glucose level at which hypoglycaemia symptoms form
3mmol/L | Adrenergic- sweating, tremour and a pounding heartbeat
48
Physical signs of hypoglycaemia
Pallor and a cold sweat | In patients who have long-standing diabetes- hypoglycaemic unawareness might form
49
ADRs and Contra indications of insulin
Hypoglycaemia, coma, death | Contra- if on beta-blockers- this enhances and or masks/hypoglycaemia
50
Hydrocortisone use and MOA
For addison's disease. Hydrocortisone is an exogenous form of cortisol- forms active complex with nuclear glucocorticoid receptors- transcriptionally upregulates gluconeogenesis and suppresses inflammatory immune responses
51
ADR and Contra of hydrocortisone
ADR: weight gain, fluid retention, hyperglycaemia, Cushing's syndrome (chronic use) Contra: if immune-suppressed, if active fungal infection, if diabetic
52
Levothyroxine MOA and use
For HYPOTHYROIDISM | Synthetic tyroxine T4 which is converted to T3. T4 and T3 can bind to nuclear thyronine receptors
53
Levothyroxine ADR and contraindication
ADR: tremour, cardiac arrhythmias, excitability, diarrhoea, hot flushes Contraindicated- if ischaemic cardiac disease, if thyroxicosis or Grave's disease
54
Carbimazole- for hyperthyroidism in Grave's disease
Principle therapy for T1DM- auto-immune mediated- destruction of pancreatic beta cells- stops insulin synthesis and secretion PRO-DRUG converted to methimazole which inhibits thyroid peroxidase (blocks iodination of thyroglobulin needed for T3 and T4)
55
ADR and Contra of carbimazole
ADR: joint pain, fever, headache, rash, taste-disturbances | Contra- if a patient is warfarinsed

Case 11 (7 decks)

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