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3rd Year Drugs > Endocrine drugs > Flashcards

Endocrine drugs Flashcards

1
Q

What is fludrocortisone

A

A synthetic mineralcorticoid

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2
Q

Uses of fludrocortisone

A

1) Replace aldosterone in forms of adrenal insufficiency
2) Orthostatic intoleance and postual orthostatic tachycardia syndrome (POTS) –> 1st line to increase Na+ levels
3) Hypotension treatment (if severe)
4) Confirms Conn’s syndrome

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3
Q

What is Conns syndrome

A

An aldosterone producing adenoma

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4
Q

What usually secretes aldosterone

A

The zona glomerulosa of the adrenal cortex

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5
Q

Action of fludrocortisone

A

Binds to mineralcorticoid receptors and mimics the action of aldosteroine
Acts on the distal nephron, promotes Na/K exchange
Sodium retention and urinary loss of K and H+
CL- is absorbed in conjuction with Na –> water follows

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6
Q

Adverse effects of fludrocortisone

A 
FEATURES OF CONNS
Sodium/water retention --> nocturia
Hypokalaemia
Hypertension
Weakness
Nocturia
Tetany
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7
Q

Warnings of fludrocortisone

A

Contraindicated in patients with systemic fungal infections

Steroids can cause immunosuppression

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8
Q

Interactions of fludrocortisone

A

1) Amphotericin B/K+ Depleteing diruiteics –> enhance hypokalaemia
2) oral anticoagulants –> decrease prothrombin time
3) Aspirin –> Increased ulcerogenic effect
4) Antidiabetic drugs –> diminished antidiabetic effect
5) Oestrogen –> oestrogen increases the amoutn of corticosteroid binding globulin (inactivates the drug) BUT balanced by decreased metabolism of corticosteroid hence may need a reduced drug dose.

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9
Q

Name a biguanide

A

Metformin

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10
Q

Metformin indications

A

1) Type 2 DM –> First choice to control it –> use alone or in combo with other oral hypoglycaemiacs or insulin

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11
Q

Action of biguanides

A

NOT A REPLACEMENT FOR LIFESTYLE CHANGES
Increases the response (sensitivity) to glucose
Suppresses hepatic gluconeogenesis and glycogenolysis
Also increases glucose uptae and utilization by skeletal muscle
Suppresses intestinal glucose absoprtion

Overall decreaes blood glucose

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12
Q

What effect do biguanides have on insulin secretion

A

NO EFFECT –> as it doesnt stimulate pancreas insulin secretions, it only makes cells more sensitive to insulin
Hence there is no risk of hypoglycaemic episodes

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13
Q

What effect do biguanides have on weight

A

It reduces weight gain and can induce weight loss (as it doesnt increase insulin secretion)
This prevenet the worsening of insulin resistance and the slow deteorioration of diabetes

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14
Q

Adverse effects of metformin

A

1) GI Upset - common
2) Lactic acidosis - can be fatal. Onlyl occurs if precipitated by illness that causes metformin accumulation (e.g. renal function decreased), or lactate production increased (sepsis, hypoxia, cardiac failure), or decreased lactate metabolism (liver failure)

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15
Q

Contraindications of metformin

A

1) severe renal impairment –> need to significnalty reduce

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16
Q

When should we acutely withhold metformin

A

AKI e.g. sepsis, shock, dehydration
Severe tissue hypoxia e.g. MI, cardiac/resp failure

Withhold in actue alcohol intoxictaion –> may precipiate lactic acidosis

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17
Q

Caution of metformin in

A

1) Hepatic impairment –> decreased lactate clearance

2) Chronic Alcohol overuse –> risk of hypoglycaemia

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18
Q

Interactions of metformin

A

1) IV contrast media –> increased risk of renal impairment
2) Drugs affecting renal function e.g. NSAIDs, ACEi, diuretics
3) Prednisolone, thiazide and loop diuretics –> these elevate blood glucose hence oppose the action and reduce its efficacy

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19
Q

HbA1c target with metformin

A

<58

Also test renal function before and annually

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20
Q

How is metformin excreted

A

Unchanged by the kidneys

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21
Q

Symtpoms of lactic acidosis

A 
Vomiting
Stomach ache/pain
Muscle cramps
Difficutly breathing
Severe tiredness
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22
Q

Link between insulin and weight gain

A

Insulin is an anabolic hormone

This means drugs that increase insulin secretion cause WEIGHT GAIN hence worsening DM over time

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23
Q

Name a sulphnoylurea

A

Glicazide

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24
Q

Indications for sulphonylureas

A

1) Type 2 DM –> a signel agent where metformin CI or not tolerated
2) DM –> in combo with metformin or other agents if BM not adequately controlled

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25
How should you take sulphonylureas
Orally with meals, start low dose and increase gradually
26
How do sulphonylureas work
Stimulate pancreatic insulin secretion They block ATP dependent K+ channels in pancreatic B cell membranes --> this causes depolarisation and opening of voltage gated Ca2+ channels --> the rise in intracellular calcrium causes insulin secretion
27
Adverse effects of sulphonylureas
Weight gain --> as insulin is anabolic GI Upset Hypogylcaemia --> more likely with increased doses Rare hyperesensetitivity reactions e.g. a) Haematological abnormalities (agranulocytosis) b) Hepatic toxicity (cholestatic jaundice) c) Drug hypersensitivity syndrome (rash, fever, internal organ involvement)
28
What happens to insulin resistance in acute illness
Increased insulin resistace Also impairs hepatic and renal function Oral hypoglycaemic become less effective Insulin may be needed temporarily
29
Warnings of using sulphonylureas
1) Hepatic and renal impairment 2) High risk of hypoglycaemia e.g. those with hepatic impairment (reduced gluconeogenesis), malnutrition, adrenal or pituitary insufficiency (lack of counter regulatory hormones) and the elderly
30
Interactions of Sulphonylureas
1) Antidiabetic drugs --> risk of hypoglycaemia | 2) efficacy reduced by drugs that increase blood glucose e.g. steroids, loop and thiazide diuretics
31
What are the syptoms of hypoglycaemia
Dizziness, nausea, sweating, confusoin Take something sugary and then something starchy
32
How are sulphonylureas excreted
Excreted unchanged in the urine
33
Name thyroid hormone repolacement
Levothyroxine | Liothyroxine
34
Indications for thyroid hormones
Hypothyroidism
35
Action of thyroid homrones
Thyroid hormones regulate emtabolism and growth
36
What is levothyroxine
Synthetic T4 - the inactive from --> most common for long term replacement
37
What is liothyroxine
Synthetic T3 --> shorter half life, quicker onset and offset, hence usually reserved for emergency treatment of severe or acute hypothyroidism
38
Adverse affects of thyroid homrones
Usually related to overdose --> GI upset, neurological (tremors, restlessness, insomnia), Cardiac (palpitations, angina, arryhythmia)
39
Warnings of thyroid hormones
1) Coronary artery disease --> can increase heart rate and metabolism 2) Hypopituatism --> must start corticosteroids before thyoird homrones, otherwise may precipitate an addisonian crisis
40
Interactions of thyroid hormones
1) Antacids, Ca2+ or Fe2+ salts reduce the GI absorption of levothyroxine 2) CP450 inducers (phenytoin, carbamazepine) increase speed of elimination 3) DM --> can increase insulin or oral hypoglycaemic requirement due to changes in metabolism 4) Enhances warfarins effect
41
Name calcium and vitamin D replacements
Calcium carbonate, calcium gluconate, colecalciferol, alfacalcidol
42
Indications for calcium and vitamin D
1) Osteoporosis 2) CKD --> treat and prevent secondary hyperparathyroidism and renal osteodystrophy 3) Hypocalcaemia that is symptomatic 4) Vit D deficiency --> Prevents rickets and osteomalacia 5) Severe hyperkalaemia
43
Symptoms of hypocalcaemia
Paraesthesia | Tetany Seizures
44
Action of calcium and vitamin D
Need Ca for normal muscle/bone/nerve function --> controlled by Vit D and PTH Calciutonin decreases serum Ca levels
45
Why do we need calcium and vitamin D in CKD
Impaired phosphate excretion and decreased activation of itamin D cause high phosphate and low potassium --> this stimulates secondary hyperparathyroidism --> leads to osteodystrophy Give oral calcium supplements to bind phopshate in the gut Give alfacalcidol to provide vitamin D that doesn't require renal activation
46
How does calcium treat hyperkalemia
Increaes the myocardial threshold potential, reducing the risk of arryhtmias It has no effect on serum K+ levels
47
Adverse effects of Calcium
Oral - dypspesia and constipation | IV - if given for hyperkalaemia can cause CV collapse or local tissue damage if given too quickly
48
Interactions of calcum
1) Oral Ca --> decreases absorption of many drugs e.g. iron, bisphosphonates, tetracyclines, levothyroxine 2) IV --> MUST MIX WITH SODIUM BICARBONATE --> risk of precipitations
49
What foods should you wait 2 hours with after taking calcium
Spinach Banana Whole cereals
50
Name some bisphosphonates
Alendronic Acids Disodium pamidronate Zoledronix acid
51
Indicatinos of bisphosphonates
1) Osteoporotis fragility fractures risk 2) Severe hypoermcalcaemi of maligancy 3) MYeloma and breast cancer with bone metastases 4) Pagets disease - first line treatment to reduce bone turnover and pain
52
Action of bisphosphonates
Inhibit action of osteoclasts --> decreses bone turnover Similar sturcture to natural pyrophosphate hence incorporated into bone, when bone is resorbed they accumulate in osteoclasts --> inhibit their activity and promote apoptosis NET EFFECT IS REDUCTION IN ONE LESS AND IMPROVEMENT IN BONE MASS
53
Adverse effect of bisphosphonates
1) Osteophagitis - if taken orally 2) hypophosphataemia 3) Jaw osteonecrosis (rare, more likley if high-dose IV) 4) atypical femoral fracture
54
Contraindications of bisphophantes
1) Severe renal impairment - as renally excreted 2) Hypocalcaemia 3) Oral administration in upper GI disorders
55
Caution of bisphosphonates in
Smokers Major Dental disease This is because of the higher risk of jaw osteonecrosis
56
Interactinos of bisphosphonates
1) Calcium salts, antacids and FE --> bind calcium and reduce its absorption
57
How should you take bisphosphonates
Take 30 mins before breakfast --> take with plenty of water --> sit upright for 30 mins after taking it to reduce the risk of oesophagitis
58
Indications of insulin use
1) Type 1 - DM insulin replacement, Type 2 DM --> if oral hypoglycaemics not working/tolerated 2) Diabetic emergencies --> give IV e.g. diabetic ketoacidosis, hyperglycaemic hyperosmolar syndrome and peri-operative hyperglycaemic control 3) Hyperkalaemia --> give with glucose
59
Action of insulin
Stimulates glucose uptake from circulation into tissues Stimulates glycogen, lipid and protein synthesis Inhitis gluconeogenesis and ketogenesis Also drives K+ into cells --> only for short term though
60
Rapid insulin
Insulin apart e.g. novarapid
61
Short insulin
Actrapid
62
Adverse effects of insulin
Hypoglycaemia --> can lead to coma/death | Lipohypertrophy --> if given SC repeatedly at the same site
63
Warning of insulin
Renal impairment --> insulin clearance is reduced hence increased risk of hypo
64
Interactions of insulin
1) other hypoglycaemics | 2) Systemic corticosteroids --> icnreases insulin requirements and steroids increase glcuose
65
When to use carbimazole
Treats hyperthyroidism
66
How does carbimazole work
Acts via its active metabolist methimazole Substrate inhibitor of peroxidase --> which itself is iodinated and degraded within the thyroid --> this diverst oxidized iodine from thyroglobulin hence decreasing thyroid hormone biosynthesis It also has an mmunosuppressant action within the thyroid and interferes with generation of oxygen free radicals in macrophages (and hence antigen presentation)
67
Adverse effects of carbimazole
Usually well tolerated BUT; 1) Pruritis and rashes 2) Neutropenia --> rare 3) Nausea, hair loss, fever, leukopneia, arthralgia
68
Use of carbimazole in pregnancy
Causes aplasia cutis in newborn (absence of portion of the skin)
69
Contraindicatinos of carbimazole
1) hypersensitivity | 2) Severe hepatic insufficiency
70
Warnings of carbimazole
Stop during whil undergoing radio-iodine treatment to acoid a thyroid crisis
71
Interactions of carbimazole
1) Warfarin --> carbimazole is a vitmain K antagonist hence increases anticoagulation 2) Theophylline toxicity --> serum levels can increse if concurrent use without decreases dose of theophylline 3) Prednisolone --> concurrent therapy increases prednisolone clearance 4) Beta-adrenergic blockers --> increases their clearance

3rd Year Drugs (10 decks)

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