DENT 3005: Introduction to Pharmacology - Endocrine drugs: Diabetes¹²

Diabetes Mellitus

Diabetes mellitus: high blood glucose
- Different to diabetes insipidus
- Insulin: hormone made by pancreas helps bring glucose into cells
- Diabetic patients: not enough insulin or insulin not effective $\to$ glucose cannot reach the cells
- Complications: eyes, kidneys, nerves, heart, cancer
Types
- T1DM
- T2DM
- Insulin resistant
- Gestational diabetes
- Other

Classification of Diabetes³

Type 1 DM	Type 2 DM	Gestational	Other
- Autoimmune destruction of B-cells	- Insulin resistance & B-cell dysfunction	- During pregnancy in women who did not have DM	- Genetic defects of B-cell function
- Young children & adults	- Pancreas loses ability to produce insulin	- Increase risks of mother & child developing T2DM later	- Genetic defect in insulin action
- Life-long insulin therapy	- Obesity, physical inactivity, genetic		- Disease of exocrine pancreas
			- Endocrinopathies
			- Many more

Other types (Rare) (cont.)⁴

Diseases of the Exocrine Pancreas
- Conditions that damage the pancreas – pancreatitis, cystic fibrosis, hemochromatosis, pancreatic cancer
- Exocrine pancreas – responsible for producing digestive enzymes; damage to this part – impairs insulin production
Endocrinopathies
- Hormonal disorders that affect endocrine system
- E.g. Cushing’s syndrome (excess cortisol), acromegaly (excess growth hormone), hyperthyroidism
- Cause insulin resistance – leading to hyperglycemia
Drug/ Chemical-induced Diabetes
- Certain medications and chemicals can impair insulin secretion or action
- E.g. glucocorticoids (used in the treatment of inflammation), antipsychotics, immunosuppressants – can cause hyperglycemia
- a-interferons – used in the treatment of hepatitis, can lead to diabetes, in genetically predisposed individuals
Infection-Related Diabetes
- Some infections damage the pancreas or lead to insulin resistance
- E.g. Rubella, cytomegalovirus
Uncommon forms of Immune-Mediated Diabetes
- Immune system attacks insulin or insulin-producing cells, different from Type-1 diabetes
- E.g. stiff-man syndrome – antibodies attack insulin-producing cells in the pancreas
Other Genetic syndromes associated with Diabetes
- Certain genetic syndromes have a higher incidence of diabetes due to associated insulin resistance or $β$ -cell dysfunction
- E.g. Down syndrome, Turner syndrome, Klinefelters syndrome, Prader-Willi syndrome
Post-transplant Diabetes Mellitus (PTDM)
- Occur after organ transplantation – due to the use of immunosuppressive drugs like corticosteroids or calcineurin inhibitors
- Cause insulin resistance or $β$ -cell dysfunction

Comparison of Diabetes Types⁵

Type 1 Diabetes Mellitus	Type 2 Diabetes Mellitus
Autoimmune-mediated $β$ -cell destruction	No Autoimmune-mediated $β$ -cell destruction; Insulin resistance / Decline in Insulin production over time
Autoantibodies like anti-GAD and Islet cell antibodies that attack pancreatic $β$ -cells present	Autoantibodies absent
Genetic link	Stronger genetic link
Age of onset- younger (children/adolescents/young adults) than 25-30 years	Age of onset usually in adults over 40-45, but seen in younger people due to obesity
Faster onset of symptoms & can be severe – excessive thirst, frequent urination, unintended weight loss, fatigue	Slower onset of symptoms & maybe less noticeable
Lifelong insulin therapy – as pancreas produce little to no insulin	Diet control & oral hypoglycemic medications often sufficient for control, Insulin therapy required if disease progresses
Patients often normal weight, or may experience weight loss before diagnosis	Most patients are overweight/obese
High risk of diabetic ketoacidosis (DKA) – life threatening	DKA is rare, but hyperosmolar hyperglycemic state (HHS) can occur

Glucose metabolism pathway⁶

The processes involved in the utilization and regulation of glucose
Glucose: primary source of energy for cells, regulated by hormones like insulin & glucagon
Stages
- Digestion
- Absorption
- Glycolysis
- Krebs cycle
- Oxidative phosphorylation
- Gluconeogenesis

Insulin⁷

Proinsulin synthesized in the $β$ -cells of the pancreas
- consists of insulin peptide and C- peptide
In the $β$ -cells, proinsulin is cleaved $\to$ active insulin and inactive C- peptide
Active insulin peptide released into the bloodstream to regulate blood glucose levels
Indication: Diabetes mellitus
- **Not Diabetes insipidus
Hypoglycaemia: most frequent & common serious adverse effect

Types of Insulin⁸

RAPID-ACTING INSULIN

Onset ~5 minutes
Duration 4–5 hours
NOVORAPID®
HUMALOG®
APIDRA®
FIASP®
- Ultra-rapid acting, can be given just after meal

SHORT-ACTING INSULIN

Onset 30 minutes
Duration Up to 6 hours
ACTRAPID®
HUMULIN R®

LONG-ACTING INSULIN

Onset 2–4 hours
Duration ~24 hours (longer for Toujeo)
TOUJEO®
OPTISULIN®

PREMIX INSULIN (HUMAN)

Onset 30 minutes
Duration 10–16 hours
MIXTARD 30®
MIXTARD 50®

PREMIX INSULIN (ANALOGUE)

Onset 5–15 minutes
Duration 10–16 hours
NOVOMIX30®
HUMALOG MIX 25®
HUMALOG MIX 50®
RYZODEG 70® (degludec lasts >24 hours)

Delivery Systems

Infusion set
Continuous Glucose Monitor
Insulin pump

Insulin Profiles⁹¹⁰

Insulin type (brand®)	Activity¹	Comments
Ultra-short-acting (analogues)
faster-acting insulin aspart (Fiasp)	onset: 5–15 minutes peak: 0.5–1.5 hours duration: 3–5 hours	give at start of meal, or up to 20 minutes after starting it clear solution do not mix with other insulins; inject separately compared to standard insulin aspart: marginally faster time to effect (but unclear if this is clinically meaningful) may increase infusion site reactions and need for non-routine change of infusion pump
insulin aspart (NovoRapid)	onset: 10–15 minutes peak: 1–1.5 hours duration: 3–5 hours	give immediately before meals clear solution
insulin lispro² (Humalog)
insulin glulisine (Apidra)

Insulin type (brand®)	Activity¹	Comments
Short-acting
neutral insulin³ (Actrapid, Humulin R)	onset: 30 minutes peak: 2–3 hours duration: 6–8 hours	give within 30 minutes before meal soluble insulin clear solution
Long-acting
isophane insulin (Humulin NPH, Protapnane)	onset: 1–2.5 hours peak: 4–12 hours duration: 16–24 hours	also known as intermediate-acting insulins give once or twice daily cloudy solution
Long-acting (analogues)
insulin detemir (Levemir)	onset: 1–2 hours peak: 6–8 hours duration: 12–24 hours	give once or, more commonly, twice daily (effect often wears off before 24 hours) clear solution do not mix with other insulins; inject separately
insulin glargine 100 units/mL (Optisulin), 300 units/mL (Toujeo)	onset: 1–2 hours (100 units/mL); 1–6 hours (300 units/mL) no peak duration: 24 hours (100 units/mL); 24–36 hours (300 units/mL)	give once daily provides a constant basal insulin level do not mix with other insulins; inject separately clear solution the 2 strengths are not directly interchangeable

Insulin type (brand®)	Activity¹	Comments
Mixed (short-acting with long-acting)
neutral insulin with isophane (Humulin 30/70)	onset: 0.5–1 hours peak: 2–12 hours duration: 16–24 hours	give within 30 minutes before meal(s) also known as biphasic insulins give once or twice daily cloudy solution
Mixed, analogues (ultra-short-acting with long-acting)
insulin aspart with aspart protamine (NovoMix 30)	onset: 10–15 minutes peak: 1 hour duration: 16–18 hours	also known as biphasic insulins give once or twice daily give immediately before meal(s) cloudy solution
insulin lispro with lispro protamine (Humalog Mix25, Humalog Mix50)
insulin aspart with degludec (Ryzodeg)⁴	onset: 10–15 minutes peak: 1.25 hours duration: >24 hours	also known as biphasic insulin give once or twice daily give immediately before largest carbohydrate meal(s) clear solution degludec is an ultra-long acting insulin: it provides a constant basal insulin level its glucose-lowering effect persists longer than that of insulin glargine

Metformin¹¹¹²

First line
MOA: Reduces hepatic glucose production; increases peripheral utilisation of glucose
ADR: taste disturbance
No weight gain ☺

Generic name	Brand Name
Metformin IR	Diabex, Diaformin, Metex
Metformin MR	Diabex XR, Diaformin XR, Metex XR

Metformin combinations

Alogliptin with metformin
Dapagliflozin with metformin
Empagliflozin with metformin
Linagliptin with metformin
Metformin with glibenclamide
Saxagliptin with metformin
Sitagliptin with metformin
Vildagliptin with metformin

Sulfonylureas¹³

MOA: Increase pancreatic insulin secretion
ADR: hypoglycaemia, weight gain
- Taste alteration (metallic)

Generic name	Brand Name
Glibenclamide	Daonil
Gliclazide	Diamicron
Glimepiride	Glimepiride
Glipizide	Minidiab

Dipeptidyl peptidase 4 inhibitors

Inhibit dipeptidyl peptidase-4 (DPP-4)
ADR: headache, musculoskeletal pain
- Hypoglycemia: combination w/ insulin or sulfonylurea
Drugs
- Alogliptin
- Alogliptin with metformin
- Linagliptin
- Linagliptin with metformin
- Saxagliptin
- Saxagliptin with dapagliflozin
- Saxagliptin with metformin
- Sitagliptin
- Sitagliptin with metformin
- Vildagliptin
- Vildagliptin with metformin

Glucagon like peptide 1 analogues¹⁴

Analogues of glucagon-like peptide-1 (an incretin)
ADR: gastrointestinal sx, hypoglycaemia (+SU/insulin)

Generic name	Brand Name
Dulaglutide	Trulicity
Liraglutide	Saxenda
Semaglutide	Ozempic

Sodium-glucose co-transporter 2 inhibitors

Inhibit sodium-glucose co-transporter 2, reducing glucose reabsorption in the kidney (and increasing its excretion in the urine)
ADR: genital infections, polyuria, dysuria, UTI, dyslipidaemia, hypoglycaemia (+SU/insulin)

Generic name	Brand Name
Dapaglifozin +metformin	Forxiga Xigduo
Empaglifozin +linagliptin +metformin	Jardiance Glyxambi Jardiamet

Other drugs for diabetes¹⁵

Acarbose
- Inhibiting alpha-glucosidase enzymes in the small intestine
- ADR: flatulence, diarrhoea, abdominal pain and distension
Pioglitazone
- Agonist of peroxisome proliferator-activated receptor gamma
- ADR: peripheral oedema, weight gain, headache, dizziness +++
Tirzepatide
- Agonist at glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors
- ADR: gastrointestinal sx, hypoglycaemia (+SU/insulin)

Drug List Summary

Acarbose
Insulins
Metformin
Metformin with glibenclamide
Pioglitazone
Tirzepatide

Management of hypoglycaemia in dental practice¹⁶

(Figure 13.49)

If the patient is conscious and cooperative:

Stop dental treatment.
Give glucose if available:
- adult: 15 g
- child 5 years or younger, or up to 25 kg: 5 g
- child 6 years or older, or more than 25 kg: 10 g
If glucose is not available, give a fast-acting glucose-containing food or drink [NB1].
If after 15 minutes the blood glucose concentration has not returned to normal or the symptoms have not improved, repeat the dose of glucose.
If three or more portions of glucose are needed to restore the blood glucose concentration to normal, seek medical advice.
If symptoms have improved, the patient should eat a longer-acting carbohydrate (eg sandwich, dried fruit, yoghurt) to prevent recurrence of hypoglycaemia.
Keep the patient under observation until recovered. Do not allow them to drive home. Strongly advise medical review.

If the patient is drowsy, uncooperative or unconscious:

Stop dental treatment.
Call 000.
If the patient is unconscious, start basic life support (for ‘Basic life support flow chart’, see Figure 13.43).

NB1: Examples of food and drink containing 15 g of glucose include: 15 g of easily absorbed carbohydrate (eg 6 to 7 regular glucose jelly beans, 4 large glucose jelly beans); three teaspoons of sugar or honey; 125 mL of fruit juice (approximately one glass or a small popper or box); 150 mL of soft drink (not ‘diet’); 100 mL of oral glucose solution (eg Lucozade).

Diabetes Dental implications¹⁷

Drug implications: not many
- Hypoglycemic effects: learn management
- Taste disturbance
Lowered resistance to infections
Routine dental visits
Oral manifestations
- Periodontal disease
- Tooth decay
- Oral candidiasis
- Taste disturbances
- Xerostomia
Patient’s considerations
- Blood glucose control
- Hypoglycemia

DENT 5003: Introduction to Pharmacology - Endocrine drugs: Thyroid disorders¹⁸

Dr Thuy Linh Truong thuy.truong@uwa.edu.au

Learning Outcomes¹⁹

Learning objectives

Broad understanding of the pituitary gland
Broad understanding of thyroid disorders
Understand implications of thyroid disorder in the dental setting
Identify drugs used for thyroid disorders and recognise oral and dental side effects of these drugs
Understand drugs interactions with dental medications
Applied knowledge to clinical scenarios

Anatomy and Physiology²⁰

The pituitary gland

RECAP $\to$ A major endocrine gland!
- Produces a wide variety or hormones that travels to regulate other glands & organs in the body
Anterior lobe: GH, ACTH, TSH, FSH, LH
Posterior lobe: ADH, oxytocin

The thyroid gland

Regulates key metabolic processes
Produces two main hormones
- Triiodothyronine (T3)
- Thyroxine (T4)
Controlled by Thyroid-Stimulating Hormone (TSH) from the anterior pituitary gland!
Proper thyroid function is crucial for metabolic balance and overall health

A diagram illustrating the pituitary gland, its connection to the brain, and the hormones it secretes to regulate other glands and organs in the body (Mammary glands, Gonads, Thyroid gland, Adrenal gland, Bones/Muscles/Adipose Tissue) is shown to the right, along with a detailed illustration of the thyroid gland in the neck region, including front and back views with labeled structures: Right lobe, Left lobe, Isthmus, and Parathyroid glands (on the back view).

graph LR
    A[Brain] --> B(Pituitary Gland)
    B -->|PRL| C[Mammary glands]
    B -->|GH| D[Bones, Muscles, Adipose tissue]
    B -->|ACTH| E[Adrenal gland]
    B -->|TSH| F[Thyroid gland]
    B -->|FSH & LH| G[Gonads]

Thyroid disorders²¹

Thyroid disorders can be overactive (hyperthyroidism) or underactive (hypothyroidism)
TSH elevation $\to$ hypothyroidism
Rationale for treatment: relieve sx, restore & maintain euthyroid state
- Hypothyroidism: maintain normal growth & intellectual development in children

	Hypothyroidism	Hyperthyroidism
Drug Therapy	Thyroid hormones (Levothyroxine, liothyronine)	Antithyroid drugs
		Levothyroxine
		Iodine
		Beta blockers: short term sx relief

Comparison of Thyroid Disorders²²

	Hypothyroidism	Hyperthyroidism
Symptoms	Tiredness and low energy levels Weight gain Constipation Dry, coarse skin Puffy face Hair loss Slowed heart rate Muscle aches and weakness Depression Problems with concentration Intolerance to cold	Rapid or irregular heartbeat Unexplained weight loss Increased appetite Anxiety and irritability Sleep problems Sweating Fine, brittle hair Diarrhea Sensitivity to heat Weak/less frequent menstrual period
Causes	The immune system attacking the thyroid gland Damage to the thyroid during treatment for an overactive thyroid or thyroid cancer	Graves' disease Toxic nodular goitre Thyroiditis Post-partum thyroiditis Taking too much thyroid medicine Having too much iodine in your system

Drugs for thyroid disorders²³

Thyroid hormones
- Levothyroxine T4: hypothyroidism, block-replacement regimen in hyperthyroidism
- Liothyronine: severe hypothyroidism
Anti-thyroid drugs: block thyroid hormone synthesis
- Carbimazole
- Propylthiouracil: inH T4 $\to$ T3 conversion
Iodine
- Transiently inhibits thyroid hormone release
- Indication: short-term use before surgery for graves disease

Generic name	Brand Name
Levothyroxine	Eutroxisg, Thyroxine, Oroxine
Liothyronine	Tertroxin
Carbimazole	Neo-mercazole, Thirazol
Propylthiouracil	PTU
Iodine	Iodine sol aq

Thyroid drugs: Dental implications²⁴

Levothyroxine & Liothyronine
- ADR associated w/ excessive dosages, corresponds to sx of hyperthyroidism
- Manage accordingly

Thyroid disorder: Dental implications²⁵

Hypothyroidism
- Affects younger population
- Delayed eruption of primary and permanent teeth
- Malocclusion (misalignment of teeth)
- Skeletal growth retardation
- Tongue enlargement (macroglossia) and scalloping
Hyperthyroidism
- Osteoporosis of the alveolar bone $\to$ tooth mobility, complications with extractions, increased risk of periodontal disease
- Higher incidence of dental caries and periodontal disease
- Accelerated development of jaws and teeth in children
- Early eruption of permanent teeth / Early loss of deciduous teeth
- Gingival changes: inflammation, enlargement, tenderness

DENT 3005: Introduction to Pharmacology - Endocrine drugs: Adrenal insufficiency²⁶

Dr Thuy Linh Truong thuy.truong@uwa.edu.au

Learning Outcomes¹⁹

Learning objectives

Broad understanding of the pituitary gland $⊙$
Broad understanding of adrenal insufficiency
Identify drugs used for adrenal insufficiency and recognise oral and dental side effects of these drugs
Understand drugs interactions with dental medications
Broad understanding of other endocrine drugs
Applied knowledge to clinical scenarios

The pituitary Gland²⁷

A teenie tiny gland at the base of the brain: small but mighty!
A major endocrine gland!
- Produces a wide variety or hormones that travels to regulate other glands & organs in the body
Anterior lobe: GH, ACTH, TSH, FSH, LH
Posterior lobe: ADH, oxytocin
PRL
- Mammary glands
FSH & LH
- Gonads
GH
- Adipose, bone, and muscle
ACTH
- Adrenal glands
TSH
- Thyroid gland

Adrenal Insufficiency²⁸

Adrenal insufficiency: insufficient production of cortisol & aldosterone
Hypothalamus releases CRH $\to$ anterior pituitary release ACTH $\to$ adrenal gland to produce cortisol
Function of cortisol
- Regulate blood pressure, blood glucose, body’s response to stress
- Too much $\to$ Cushing’s
- Too little $\to$ Addison’s or hypopituitarism

Symptoms

Extreme fatigue
Muscle weakness
Loss of appetite and weight loss
Low blood pressure
Nausea and vomiting
Abdominal pain
Hyperpigmentation (darkening of skin) in some cases
Salt cravings

flowchart TD
    A[Hypothalamus] -->|releases CRH| B(Pituitary gland)
    B -->|releases ACTH| C(Adrenal gland)
    C -->|produces| D[Cortisol]
    D --> E{To immune system}
    D 	--> F[The hypothalamus responds to level of cortisol]

Drugs for adrenal insufficiency²⁹

Corticosteroids $⨀$ replacement therapy
Hydrocortisone & cortisone preferred: glucocorticoid replacement
Fludrocortisone: mineralocorticoid replacement w/ one of the above
Monitor adverse effect & titrate dose accordingly
Increase dose during intercurrent illness & periods of stress
- Major stress req parenteral administration

Generic name	Brand Name
Cortisone	Cortate
Fludrocortisone	Florinef
Hydrocortisone	Hysone, Solu-Cortef inj

Corticosteroids ADRs³⁰

Infection
Delayed wound healing
Steroid rosacea
Perioral dermatitis
Skin atrophy
Bruising
Acne
Facial flushing
Pupura
Depigmentation
Telangiecstasia
Steroid induced crushing’s

Adrenal insufficiency: Dental implications³¹

Immunosuppression
Adrenocortical suppression
- Dose & duration varies btw patients
- Oral pred 10mg od >3wks → suppression
- High dose inhaled, topical or intra-articular → suppression
Risks: Addisonian Crisis!
Plan morning appointments
Ensure patient is looked after for remainder of day
Seek urgent medical attention: sx of acute adrenal insufficiency

Adrenal insufficiency: Dental management³²

Non-invasive procedures: examination, impressions, diagnostic radiographs
- Advise patient to take usual dose of their corticosteroid
Invasive procedure <1hr (outpatient setting)
- Scale, restorative, extraction, debridement, implant
- Patient at risks of suppression: req increase corticosteroid dose
- Consult their medical GP for dosing strategy
- Start dose on morning of procedure
Invasive procedure >1hr or requiring sedation, GA or fasting
- DEFER & REFER!!!

Other endocrine drugs³³

Drugs for other endocrine disorders
Androgens
	Testosterone (men)
	Testosterone (women)
Antidiuretic hormone agonists and antagonists
	Argipressin
	Demeclocycline
	Desmopressin (endocrine)
	Terlipressin
Growth hormone
	Somatrogon
	Somatropin
Nonselective alpha-blockers
	Phenoxybenzamine
	Phentolamine
Somatostatin analogues
	Lanreotide
	Octreotide

Other endocrine drugs: testosterone³⁴

Androgens aka anabolic steroids: testosterone
- Men: Confirmed androgen deficiency in men due to hypothalamic-pituitary or testicular disorder, Male delayed puberty (seek specialist advice)
- Women: Postmenopausal low libido with associated distress (hypoactive sexual desire dysfunction) when other measures (eg education, addressing modifiable biopsychosocial factors) have failed
Misuse: athletes to increase muscle mass BUT serious adverse effects!
- Aggressive behaviour, psychological dependence, withdrawal symptoms, sodium and water retention, oedema
- Men: Testicular atrophy, impotence or priapism
- Women: amenorrhoea, clitoral enlargement, voice change, virilisation or hirsutism
Brand Names
- Men: Androforte, Testogel, Testavan, Reandron 1000, Primiteston Depot, Sustanon inj
- Women: Androfeme

Anti-diuretic hormones agonists & antagonists³⁵

	Argipressin aka ADH/vasopressin	Demeclocycline (tetracycline AB)	Desmopressin	Terlipressin aka triglycyl-lysine-vasopressin
MOA	Increase tubular reabsorption of water, vasoconstrict	Antagonises the effect of antidiuretic hormone on renal tubules, promoting excretion of free water	Increases tubular reabsorption of water; increases factor VIII and von Willebrand’s factor coagulation activity.	Vasoconstrictor
Indication	Central diabetes insipidus	Persistent marked SIADH resistant to fluid restriction and high salt intake	Central diabetes insipidus Nocturnal enuresis Nocturia due to idiopathic nocturnal polyuria Control of bleeding in patients with mild or moderate haemophilia and type I von Willebrand’s disease	Bleeding oesophageal varices Type 1 hepatorenal syndrome
Brand	Pitressin inj	Only available through SAS	Minirin, Octostim	Glypressin inj, Terlipressin inj

Growth hormones³⁶

MOA: Promotes growth of skeletal, muscular and other tissues; stimulates protein synthesis and influences fat, carbohydrate and mineral metabolism.
Indications: As detailed in the PBS Growth Hormone Program

Non-selective alpha blockers

MOA: Block the effects of adrenaline and noradrenaline at alpha $_{1}$ and alpha $_{2}$ receptors
Indications: Phaeochromocytoma

Somatostatin analogues

MOA: Inhibit release of growth hormone and of various peptides of the gastro-entero-pancreatic endocrine system
Indications: Acromegaly, relief of symptoms associated with gastro-entero-pancreatic neuroendocrine tumours

Drug List

Generic name	Brand Name
Growth hormones
Somatrogon	Ngenla inj
Somatropin	Saizen inj
NSABs
Phenoxybenzamine	Dibenyline
Phentolamine	Only thru SAS
Somatostatin analogues
Lanreotide	Mytolac inj
Octreotide	Sandostatin inj

Other Dental implications³⁷

Androgens: worsening of sleep apnea
Demeclocycline (applies for all tetracyclines)
- Children: teeth discolouration, enamel dysplasia
- Pregnancy: discoloration of deciduous teeth in babies
Terlipressin: drug interaction w/ erythromycin
- May trigger irregular beating of heart
Growth hormones: watch for limping
- May indicate development of a slipped capital epiphysis $\to$ direct patient to see their MGP
Non-selective alpha blockers: orthostatic hypotension, dizziness, drowsiness

DENT 3005: Introduction to Pharmacology - Endocrine Drugs: Drugs for Infertility³⁸

Dr Thuy Linh Truong thuy.truong@uwa.edu.au

Learning Outcomes¹⁹

Learning objectives

Broad understanding of drugs for infertility and their dental implications
Understand drugs interactions with dental medications
Applied knowledge to clinical scenarios

Drugs for infertility³⁹

Highly specialist tx
Clomiphene: 1st line for anovulatory infertility
- Letrozole accepted (aromatase inH) main indication for hormone receptor +ve breast cancer
Metformin: may be added in PCOS
Assisted reproductive technology (IVF) may include GnRH agonists
Progesterone: used for luteal phase support in assisted conception cycle

GnRH agonists⁴⁰

AKA LH releasing hormone agonists
MOA: GnRH initially stimulates synthesis of FSH and LH
Indications
- Endometriosis
- Uterine fibroids
- Endometrial thinning before endometrial ablation
- Pituitary down-regulation to prepare for controlled ovarian stimulation
- Central precocious puberty
- Prostate cancer
- Breast cancer

Generic name	Brand Name
Goserelin	Zoladex inj
Leuprorelin	Eligard inj, Lucrin depot
Nafarelin	Synarel nasal spray
Triptorelin	Decapeptyl inj Dephereline inj

Other drugs for infertility⁴¹

Clomiphene
- MOA: Competitively antagonises estrogen receptors in the hypothalamus
- Indication: anovulatory infertility
ADR (dental implications)
- Clomiphene: dizziness
- Letrozole: vertigo, dry mouth
- Metformin: see diabetes lecture

Generic name
Clomiphene
Letrozole
Metformin
Progesterone

Infertility drugs: Dental implications⁴²

Hormonal changes
- Infertility medications can cause hormonal imbalances, which can affect the tissues in the mouth, making them more susceptible to inflammation and gum disease
- Some patients are not comfortable taking intraoral radiographs, patient education is important but routine radiographs may have to be deferred especially if the patient has gone through a lot of difficulty to conceive they are most likely going to be extremely worried a lot of things
Triptorelin and letrozole: dry mouth
Clomiphene: Watch out for dizziness & light headedness

References⁴³

Ritter JM, Flower RJ, Henderson G, Loke YK, MacEwan D, Robinson E, editors. Rang & Dale’s pharmacology. 10th ed. Edinburgh: Elsevier; 2023
Australian Medicines Handbook Online [Internet]. Adelaide (AU): Australian Medicines Handbook Pty Ltd;2000. Endocrine; [updated 2025; cited 2025]. Available from: UWA Onesearch
Pharmaceutical Society of Australia. Australian Pharmaceutical Formulary and Handbook: A Guide to Best Practice. 25th ed. Canberra: Pharmaceutical Society of Australia; 2021
Ali K. Clinical dental pharmacology. 1st ed. Oxford: Wiley-Blackwell; 2023
Bullock S, Manias E. Fundamentals of pharmacology. 8th ed. Frenchs Forest, NSW: Pearson Australia; 2017
MIMS Australia. eMIMSelite: Consumer medicine information, specific clinical monograph [Internet]. Sydney: MIMS Australia; [updated 2025; cited 2025 Apr 17]. Available from: UWA Onesearch

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DENT 3005: Introduction to Pharmacology - Endocrine drugs: Diabetes12

Diabetes Mellitus

Classification of Diabetes3

Other types (Rare) (cont.)4

Comparison of Diabetes Types5

Glucose metabolism pathway6

Insulin7

Types of Insulin8

RAPID-ACTING INSULIN

SHORT-ACTING INSULIN

LONG-ACTING INSULIN

PREMIX INSULIN (HUMAN)

PREMIX INSULIN (ANALOGUE)

Insulin Profiles910

Metformin1112

Metformin combinations

Sulfonylureas13

Dipeptidyl peptidase 4 inhibitors

Glucagon like peptide 1 analogues14

Sodium-glucose co-transporter 2 inhibitors

Other drugs for diabetes15

Drug List Summary

Management of hypoglycaemia in dental practice16

If the patient is conscious and cooperative:

If the patient is drowsy, uncooperative or unconscious:

Diabetes Dental implications17

DENT 5003: Introduction to Pharmacology - Endocrine drugs: Thyroid disorders18

Learning Outcomes19

Learning objectives

Anatomy and Physiology20

The pituitary gland

The thyroid gland

Thyroid disorders21

Comparison of Thyroid Disorders22

Drugs for thyroid disorders23

Thyroid drugs: Dental implications24

Thyroid disorder: Dental implications25

DENT 3005: Introduction to Pharmacology - Endocrine drugs: Adrenal insufficiency26

Learning Outcomes19

Learning objectives

The pituitary Gland27

Adrenal Insufficiency28

Symptoms

Drugs for adrenal insufficiency29

Corticosteroids ADRs30

Adrenal insufficiency: Dental implications31

Adrenal insufficiency: Dental management32

Other endocrine drugs33

Other endocrine drugs: testosterone34

Anti-diuretic hormones agonists & antagonists35

Growth hormones36

Non-selective alpha blockers

Somatostatin analogues

Drug List

Other Dental implications37

DENT 3005: Introduction to Pharmacology - Endocrine Drugs: Drugs for Infertility38

Learning Outcomes19

Learning objectives

Drugs for infertility39

GnRH agonists40

Other drugs for infertility41

Infertility drugs: Dental implications42

References43

Footnotes

Graph View

Table of Contents

DENT 3005: Introduction to Pharmacology - Endocrine drugs: Diabetes¹²

Classification of Diabetes³

Other types (Rare) (cont.)⁴

Comparison of Diabetes Types⁵

Glucose metabolism pathway⁶

Insulin⁷

Types of Insulin⁸

Insulin Profiles⁹¹⁰

Metformin¹¹¹²

Sulfonylureas¹³

Glucagon like peptide 1 analogues¹⁴

Other drugs for diabetes¹⁵

Management of hypoglycaemia in dental practice¹⁶

Diabetes Dental implications¹⁷

DENT 5003: Introduction to Pharmacology - Endocrine drugs: Thyroid disorders¹⁸

Learning Outcomes¹⁹

Anatomy and Physiology²⁰

Thyroid disorders²¹

Comparison of Thyroid Disorders²²

Drugs for thyroid disorders²³

Thyroid drugs: Dental implications²⁴

Thyroid disorder: Dental implications²⁵

DENT 3005: Introduction to Pharmacology - Endocrine drugs: Adrenal insufficiency²⁶

Learning Outcomes¹⁹

The pituitary Gland²⁷

Adrenal Insufficiency²⁸

Drugs for adrenal insufficiency²⁹

Corticosteroids ADRs³⁰

Adrenal insufficiency: Dental implications³¹

Adrenal insufficiency: Dental management³²

Other endocrine drugs³³

Other endocrine drugs: testosterone³⁴

Anti-diuretic hormones agonists & antagonists³⁵

Growth hormones³⁶

Other Dental implications³⁷

DENT 3005: Introduction to Pharmacology - Endocrine Drugs: Drugs for Infertility³⁸

Learning Outcomes¹⁹

Drugs for infertility³⁹

GnRH agonists⁴⁰

Other drugs for infertility⁴¹

Infertility drugs: Dental implications⁴²

References⁴³