Anti-Diabetic & Anti-Thyroid Drugs, and Oral Contraceptives

• Thyroid gland hormones T4 (thyroxine) and T3 (tri-iodothyronine) are under the control of TSH (thyroid-stimulating hormone). Calcitonin is another thyroid gland hormone - it influences calcium levels.

  
• The production of thyroid hormones is dependent upon iodide ions. They are stored as thyroglobulin, which undergoes proteolysis to release hormones. T3 (tri-iodothyronine) is more potent than T4 (thyroxine). T4 undergoes transformation to T3 in the tissues. The hormones proteolysis to release hormones.
• Thyroid hormones regulate growth (like brain development), calorigenic effects (increase oxygen consumption - effect on basal metabolic rate), metabolic effects (cholesterol to bile salts, increase lipolysis - breakdown of fat, and increase blood glucose), and cardiovascular effects (direct and indirect - eg for indirect = increase sensitivity to catecholamines via beta-receptor expression (beta-blockers))
• Disorders of thyroid function = hypofunction:

  • Children
  • Congenital hypothyroidism - present from birth
  • Hashimoto's thyroiditis - autoimmune (usually teens) - most common
  • Adults
  • Autoimmune destruction
  • Post-surgery - surgery to remover hyperfunctioning thyroid gland, for example
  • 'Myxoedema' - puffiness of skin/cause of exopthalmous: deposition of protein and mucopolysaccharides
  • Immune-response impaired
• Thyroid disease:

  • Second most common endocrine disorder after diabetes mellitus
  • Hypofunction
  • Hyperfunction
• Treatment of hypofunction = levothyroxine sodium (orally) for maintenance
• Disorders of thyroid function = hyperfunction:

  • Hyperthyroidism
  • Graves' disease (diffuse goitre)
  • Anxiety
  • Tremor
  • Increased heart rate
  • Muscle weakness
  • Insomnia
• Methods of treating hyperthyroidism:

  • Anti-thyroid drugs
  • Potassium iodide
  • Radioactive iodine
• Drugs in thyroid disease (hyperfunction): carbimazole and propylthiouracil. The "thionamides" or "thiourylenes" prevent incorporation of iodine into T₃ and T₄ propylthiouracil also stops conversion of T₄ to T₃.

  Carbimazole the most commonly used drug to treat hyperthyroidism in UK. Propylthiouracil only used if intolerant or sensitive to carbimazole, drug of choice in 1st trimester of pregnancy.

  Iodine - short term only prior to partial thyroidectomy.

  Beta blockers - may also be used vs cardiovascular effects
• Unwanted effects of anti-thyroid medication:

  • Agranulocytosis, urticarial rash, hepatitis, and arthralgia - all caused by thionamides
  • Hypersensitivity reactions (angioedema) - iodine-containing preps
  • Hypothyroidism - radioactive iodine
• Calcitonin:

  • Influences calcium and phosphate metabolism
  • Secreted by parafollicular cells (c cells) of thyroid
  • Opposes PTH
  • Produces hypocalcaemia and hypophosphataemia
  • Works by inhibition of osteoclasts
  • Used to treat hypercalcaemia and Paget's (increased bone turnover) - salmon, eel, pig, or synthetic human calcitonin - subcutaneous or intramuscular injection
• Dental influence of thyroid disease and treatment:

  • Avoid adrenaline in uncontrolled hyperthyroidism
  • Reduced immune response in hypothyroidism may cause candidiasis
  • Calcitonin, carbimazole, and propylthiouracil may cause taste disturbance
  • Damage to salivary glands by radioactive iodine
• Diabetes mellitus:

  • Type 1 - previously known as insulin-dependent diabetes mellitus (IDDM)
  • Type 2 - previously known as non-insulin-dependent diabetes mellitus (NIDDM)
  • Type 1 due to deficiency of insulin
  • Type 2 due to decreased insulin secretion or resistance to insulin action
• Treatment of diabtes:

  • Supply insulin
  • Increase insulin release
  • Decrease glucose intake
  • Decrease glucose uptake
• Insulin is inactivated by gut enzymes (therefore can't take it orally). It requires parenteral administration (via injection) - sub-cutaneous for maintenance, intravenous for emergency.

  • Experimental stage - insulin patches, oral insulin
  • Animal insulin - porcine/bovine, hypurin
  • Human insulin eg humulin - lab cultured grown with e.coli, humulin
  • Human analogue insulin - sub-group of human insulin, laboratory grown genetically altered creating more rapidly acting or more uniformly acting insulin
• Insulin types:

  • Rapid-acting insulin
  • Short-acting insulin
  • Intermediate-acting insulin
  • Long-acting insulin
  • Combined or mixed insulin

  The duration of action of a particular type varies between individuals so individual assessment is required.
• Examples of insulin regimens:

  • Once-daily insulin regimen = T2 diabetes supplemental to oral hypoglycaemics
  • Twice-daily insulin regimen or Biphasic
  • T1 and T2  - constant daily routine of meals
  • Mix of short and intermediate acting insulin
  • Basal-bolus regimen/multiple daily injection therapy
  • T1 commonly
  • More flexible and tailorable to meal
  • Use of basal intermediate/long acting and separate short or rapid acting insulin
  • Continuous subcutaneous insulin infusion (CSII)/insulin pump therapy
  • T1
  • Rapid insulin continuously
  • Adjustable
• Insulin and dentistry:

  • Soluble insulin may cause pain and swelling of the salivary glands
  • Inhaled insulin may cause dry mouth
  • Major problem is interference with normal control
  • Treat early in the morning
  • If GA then admission to hospital, check local policy for control if starved, usually involves checking HbA1c (glucose haemoglobin level)
  • GKI (glucose, potassium, insulin)
• Drug interactions and insulin:

  • NSAIDs produce hypoglycaemia and should be used with caution
  • Systemic steroids antagonise the hypoglycaemic effect of insulin
• Oral hypoglycaemics:

  • Should only be used after >3 months of diet and exercise to try and control T2 diabetes and afterwards as a supplement to lifestyle factors
  • Sulphonylureas
  • Biguanides
  • Thiazolidinediones (Glitazones)
  • Alpha-glucosidase inhibitors
  • Others
• Sulphonylureas:

  • Used to augment insulin secretion - must have functional beta cells
  • For those not overweight or who cannot take metformin
  • Examples: gliclazide, gliplizide, tolbutamide
  • Can be used in combination with other oral hypoglycaemic drugs
• Biguanides:

  • Only act in the presence of insulin
  • Decrease gluconeogenesis
  • Increase peripheral utilisation of glucose
  • Acts only in presence of insulin so must have beta cell function
  • First choice in overweight pts
  • Example = metformin
• Oral hypoglycaemics and dentistry:

  • Sulphonylureas may cause lichenoid eruptions, erythema multiforme, and oral neuropathy
  • Metformin produces taste disorders
  • Hypoglycaemic episodes
• Treatment of hypoglycaemia:

  • Oral glucose 10-20g
  • 3 sugar lumps
  • 2 tsp sugar
  • 100ml sugary drink, like Coca-Cola
  • Glucogel
  • If unconscious
  • 1mg intramuscular or subcutaneous glucagon
  • Intravenous glucose 20-50ml of a 50% solution (dextrose)
• Oral contraceptives:

  • Combined oral contraceptive
  • Oestrogen and progesterone - 21 days active, 7 days inactive
  • Progesterone only oral contraceptive
  • 'mini' pill - used when oestrogens contraindicated eg predisposition to venous thrombosis - continuous use
  • Depot injection/implant
  • Progesterone only
  • "Morning after" pill
  • Oestrogen only
  • Oestrogen inhibits ovulation via inhibition of FSH
  • Progesterone inhibits release of LH, changes the endometrium to discourage implantation and thickens cervical mucous
• Oral contraceptives and dentistry:

  • Increase plaque-induced inflammation
  • Increase in gingival crevicular fluid
  • Gingival pigmentation
  • Appear to increase the incidence of dry socket
  • Improves severity of oral aphthous ulceration related to menstruation
  • May increase post-operative pain
• Oral contraceptives and drug interactions:

  • Anti-convulsants eg carbamezapine - enzyme induction
  • Antibiotics
  • A problem if the antibiotic is an enzyme-inducer - eg rifampicin - routine "dental antibiotics" are not enzyme-inducers
  • A concern if diarrhoea or vomiting - effect on gut flora and enterohepatic cycling
  • Enterohepatic cycling effects oestrogen pills
  • Recommend additional contraceptive method anyway