Endocrine and Metabolic Drugs

The endocrine system regulates metabolism through hormones — chemical messengers that coordinate growth, development, energy utilisation, stress responses, and reproduction. Disorders of endocrine function are common in South Africa: diabetes mellitus affects approximately 4.5 million South Africans, thyroid disorders are prevalent, and adrenal dysfunction, while rarer, has significant clinical consequences. The pharmacist’s role in endocrine pharmacotherapy extends from ensuring access to essential medicines (many endocrine drugs are on the South African Essential Medicines List), to managing complex polypharmacy in diabetic patients with comorbidities, to counselling on insulin storage and administration. For the SAPC examination, candidates must demonstrate thorough knowledge of the major endocrine drug classes — antidiabetics (insulin and oral agents), thyroid agents, corticosteroids, and related metabolic drugs — and the clinical monitoring they require.

This topic builds on pharmacodynamics (pharma-006), pharmacokinetics (pharma-003 through pharma-007), drug interactions (pharma-008), and cardiovascular drugs (pharma-012 for diabetic cardiovascular risk management).

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Diabetes Mellitus

Classification and Diagnosis

Type	Pathophysiology	Typical Age	Management
Type 1 DM	Autoimmune β-cell destruction → absolute insulin deficiency	Children/young adults; can occur at any age	Insulin from diagnosis
Type 2 DM	Insulin resistance + progressive β-cell dysfunction	Adults; increasingly in children	Lifestyle ± oral agents ± insulin
Gestational DM	Glucose intolerance during pregnancy	Pregnancy	Diet ± insulin (oral agents often used)
Other specific types	Monogenic (MODY), pancreatitis, drug-induced (e.g., steroids), pancreatic disease	Variable	Treat underlying cause; insulin often required

Diagnostic criteria (WHO/ADA):

• Fasting plasma glucose ≥7.0 mmol/L (126 mg/dL); OR
• 2-hour plasma glucose ≥11.1 mmol/L (200 mg/dL) during OGTT (75g glucose load); OR
• HbA1c ≥6.5% (48 mmol/mol); OR
• Random plasma glucose ≥11.1 mmol/L with classic symptoms

Antidiabetic Agents

Insulin

Classification by origin and duration:

Insulin Type	Onset	Peak	Duration	Notes
Rapid-acting (aspart, lispro, glulisine)	5–15 min	1–2 hrs	3–5 hrs	Given at mealtimes; bolus
Short-acting (regular/soluble insulin)	30–60 min	2–4 hrs	6–8 hrs	30 min before meals
Intermediate-acting (NPH/isophane)	1–2 hrs	4–8 hrs	12–18 hrs	Basal/coverage; can mix with rapid-acting
Long-acting (glargine, detemir, degludec)	1–2 hrs	Often no peak	20–24+ hrs	Basal insulin; stable coverage
Premixed (e.g., 30% rapid/70% NPH)	Varies	Varies	Varies	Combines mealtime and basal

Insulin regimens:

1. Basal-bolus: Long-acting insulin (basal, once or twice daily) + rapid-acting insulin at each meal. Best approximates normal physiology; provides flexibility.
2. Twice-daily mixed insulin: Fixed combination (e.g., 30/70 mix) before breakfast and dinner. Simpler but less flexible.
3. ** basal-only:** Long-acting insulin once daily (often with Type 2 DM when oral agents insufficient but not yet requiring mealtime coverage).
4. Continuous subcutaneous insulin infusion (CSII): Insulin pump delivering rapid-acting insulin continuously (basal) with boluses at meals.

Insulin initiation in Type 2 DM:

• Start with basal insulin (usually glargine or degludec) at 10 units or 0.1–0.2 units/kg at bedtime
• Titrate based on fasting glucose: adjust by 2–4 units every 3 days until fasting glucose 4.4–7.2 mmol/L
• If HbA1c not at target despite optimised basal insulin, add mealtime insulin

Adverse effects of insulin:

• Hypoglycaemia (most common and dangerous)
• Weight gain (average 2–4 kg with intensified insulin regimens)
• Lipodystrophy at injection site (rotating injection sites prevents this)
• Hypersensitivity reactions (rare; usually to excipients)
• Diabetic ketoacidosis (DKA) with lapses in insulin (especially with rapid-acting analogues)

Insulin storage and handling in South Africa:

• Insulin vials/cartridges in use: store at room temperature (≤25°C for most insulin types); do not freeze
• Unopened vials in refrigerator (2–8°C) until expiry date
• Cold chain integrity important; avoid shaking insulin vigorously (except clear regular insulin)
• Patient counselling: proper injection technique, site rotation (abdomen preferred for most consistent absorption), correct timing of mealtime insulin

Insulin pen devices: Increasingly used in SA private sector and some public sector programmes; easier to use, more accurate dosing, better adherence.

Sulfonylureas

Mechanism: Bind to SUR1 subunit of ATP-sensitive K⁺ channel on pancreatic β-cells → channel closure → depolarisation → Ca²⁺ influx → insulin secretion (glucose-independent, but enhanced by glucose).

Drug	Dose Range	Half-life	Notes
Gliclazide	40–320 mg daily (IR); 30–120 mg daily (MR)	~12 hrs	MR formulation once daily
Glibenclamide (glyburide)	2.5–20 mg daily	4–10 hrs	Potent; higher hypoglycaemia risk; active metabolites
Glipizide	2.5–30 mg daily	2–4 hrs	Shorter acting
Glimeperide	1–8 mg daily	5–8 hrs	Can be taken with or without food

Adverse effects:

• Hypoglycaemia (especially with glibenclamide; risk increases with renal impairment, elderly, skipped meals)
• Weight gain (~1–3 kg)
• Skin reactions (photosensitivity rare)

Contraindications: Type 1 DM, diabetic ketoacidosis; caution in hepatic/renal impairment (gliclazide MR preferred in renal impairment due to mostly hepatic metabolism).

SA public sector: Gliclazide is on the EML; glibenclamide less commonly used due to higher hypoglycaemia risk.

Meglitinides (Glitinides)

Mechanism: Similar to sulfonylureas — close K⁺-ATP channels → stimulate insulin secretion (rapid, short duration).

Drug	Notes
Repaglinide	0.5–4 mg before each main meal; rapid onset; taken with food
Nateglinide	60–120 mg before meals

Advantages over sulfonylureas: Shorter duration → less persistent hyperinsulinism → lower hypoglycaemia risk between meals; preferred in patients with irregular meal times.

Biguanides — Metformin

Mechanism: Activates AMP-activated protein kinase (AMPK) → multiple metabolic effects: ↓ hepatic gluconeogenesis (primary), ↑ insulin sensitivity in muscle and adipose tissue, ↓ intestinal glucose absorption, modest ↓ body weight.

Indications:

• First-line for Type 2 DM (unless contraindicated)
• In PCOS (off-label) for insulin sensitisation and cycle regulation
• Prevention of Type 2 DM in high-risk individuals (impaired glucose tolerance)

Dosing: Start 500 mg twice daily (or 850 mg once daily); increase by 500 mg weekly; max 2 g/day (or 2.55 g/day modified-release).

Adverse effects:

• GI: nausea, diarrhoea (usually transient; take with meals to minimise)
• Vitamin B12 malabsorption (long-term use; check B12 annually)
• Lactic acidosis (rare; risk with renal impairment, hepatic impairment, contrast media, sepsis, dehydration)
• Avoid in renal impairment (eGFR <30 mL/min/1.73m² — contraindicated; 30–60 eGFR — cautious)
• Avoid before iodinated contrast: stop metformin 48 hours after contrast in patients with eGFR <60

Metformin andPregnancy: Category B; increasingly used in gestational diabetes; safe in pregnancy.

SA context: Metformin is the most cost-effective first-line oral hypoglycaemic; on the EML for Type 2 DM.

Thiazolidinediones (Glitazones)

Mechanism: PPAR-γ agonist → ↑ insulin sensitivity in adipose tissue, muscle, liver → ↓ insulin resistance.

Drug	Notes
Pioglitazone	15–45 mg daily; active metabolites; hepatic metabolism
Rosiglitazone	Withdrawn from many markets (CV risk)

Adverse effects:

• Weight gain (fat redistribution → subcutaneous rather than visceral)
• Oedema (1–2 kg fluid retention; contraindicated in heart failure)
• Hepatotoxicity (monitor LFTs — troglitazone withdrawn for this reason)
• Bone fractures (↑ fracture risk in postmenopausal women — pioglitazone)
• Possible increased risk of bladder cancer (pioglitazone — regulatory caution)

SA context: Pioglitazone available in private sector; not on EML for public sector.

DPP-4 Inhibitors (Gliptins)

Mechanism: Inhibit dipeptidyl peptidase-4 → prevent breakdown of GLP-1 → increased GLP-1 levels → ↑ glucose-dependent insulin secretion, ↓ glucagon → improved glycaemic control.

Drug	Dose	Notes
Sitagliptin	100 mg daily	CYP3A4 not significantly involved; renal dose adjustment
Vildagliptin	50 mg BD	Risk of hepatotoxicity; monitor LFTs
Linagliptin	5 mg daily	Minimal renal dose adjustment needed
Saxagliptin	5 mg daily	CYP3A4 substrate; interaction with strong CYP3A4 inhibitors

Adverse effects: Generally well tolerated; rare reports of pancreatitis; hypersensitivity reactions.

Place in therapy: Second-line or third-line; not as potent as metformin or sulfonylureas but weight-neutral and low hypoglycaemia risk.

GLP-1 Receptor Agonists

Mechanism: GLP-1 receptor agonists (exenatide, liraglutide, dulaglutide, semaglutide, lixisenatide) mimic incretin effects → ↑ glucose-dependent insulin secretion, ↓ glucagon, delayed gastric emptying, ↑ satiety.

Drug	Dosing	Notes
Exenatide	5–10 mcg SC twice daily (within 60 min of meals)
Liraglutide	0.6–1.8 mg SC daily	Weight loss ~2–4 kg; cardiovascular outcomes benefit (LEADER trial for liraglutide)
Dulaglutide	0.75–1.5 mg SC weekly
Semaglutide	0.25–2 mg SC weekly	Weight loss ~4–6 kg; oral formulation available (higher dose)
Semaglutide oral	3–14 mg daily	First oral GLP-1 RA

Adverse effects:

• GI: nausea, vomiting, diarrhoea (usually transient; start low and titrate)
• Pancreatitis (rare; avoid in history of pancreatitis)
• Thyroid C-cell tumour risk (contraindicated in MEN2 or personal/family history of medullary thyroid carcinoma) — animal data; uncertain in humans
• Gallbladder disease (weight loss increases cholelithiasis risk)

Place in therapy: Injectable agents for Type 2 DM not achieving targets on oral agents; increasingly preferred for patients with obesity; cardiovascular outcome trials show benefit for some agents.

SA availability: Exenatide, liraglutide, dulaglutide registered; limited availability in public sector; expensive.

SGLT2 Inhibitors

Mechanism: Inhibit sodium-glucose co-transporter 2 (SGLT2) in proximal tubule → ↑ glucose excretion in urine (~70–100 g glucose/day) → improved glycaemic control and weight loss.

Drug	Dose	Notes
Empagliflozin	10–25 mg daily	Cardiovascular outcomes benefit (EMPA-REG OUTCOME); heart failure hospitalisation ↓
Dapagliflozin	10 mg daily	Heart failure outcomes benefit (DAPA-HF — reduced HF regardless of diabetes); kidney outcomes (DAPA-CKD)
Canagliflozin	100–300 mg daily	CV and kidney outcome benefits; amputations risk (controversial)

Adverse effects:

• Genital mycotic infections (vulvovaginitis, balanitis — very common; 10–15%)
• Urinary tract infections (increase in some trials; generally uncomplicated)
• DKA (rare; can occur with insulin dose reduction; euglycaemic DKA is a diagnostic challenge)
• Volume depletion/hypotension (elderly, diuretics)
• Bone fractures (canagliflozin — regulatory warning)

Additional benefits:

• Weight loss (2–4 kg)
• Blood pressure reduction (2–4 mmHg systolic)
• Cardiovascular risk reduction (empagliflozin, canagliflozin, liraglutide, semaglutide have outcome trial evidence)
• Heart failure hospitalisation reduction (empagliflozin, dapagliflozin)
• Kidney protection (slowing of eGFR decline — empagliflozin, dapagliflozin, canagliflozin)

Place in therapy: Second-line or third-line oral agent; particularly useful in patients with heart failure or CKD; not first-line in SA public sector due to cost.

SA context: Dapagliflozin registered; empagliflozin registered; not on EML (public sector cost barrier); increasingly used in private sector.

Acarbose

Mechanism: α-glucosidase inhibitor in intestinal brush border → delays carbohydrate digestion → blunts postprandial glucose spike.

Use: Type 2 DM; less effective than other agents; GI side effects (flatulence, bloating, diarrhoea).

Combination Therapy in Type 2 DM

Initial therapy: Metformin monotherapy (unless contraindicated or not tolerated)

Second-line: Add second oral agent or GLP-1 RA or basal insulin

Third-line: Add third oral agent or GLP-1 RA or basal-bolus insulin

Common fixed-dose combinations in South Africa:

• Metformin + gliclazide (Glucovance)
• Metformin + vildagliptin (Galvus Met)
• Metformin + sitagliptin (Janumet)
• Metformin + empagliflozin (Jardiance Met)
• Metformin + linagliptin (Trajenta Met)

Diabetic Ketoacidosis (DKA)

Presentation: Hyperglycaemia (>13.9 mmol/L), ketosis (urine/serum ketones), acidosis (pH <7.3, bicarbonate <18), Kussmaul breathing, dehydration, altered consciousness, fruity breath (acetone).

Management:

• IV insulin infusion (0.1 units/kg/hour); when glucose <13.9 mmol/L, add 5% dextrose to IV fluids
• Aggressive IV fluid resuscitation (0.9% NaCl initially; then switch to half-normal saline when corrected)
• Potassium replacement (usually needed — total body K⁺ depleted; but not if K⁺ >5.3 mmol/L)
• Monitor: fingerstick glucose every hour; electrolytes (K⁺, sodium, chloride), venous pH/ bicarbonate, phosphate, Mg²⁺
• Treat underlying cause (infection, missed insulin, MI)

Hypoglycaemia

Definition: Blood glucose <3.9 mmol/L (70 mg/dL) — the threshold for counter-regulatory hormone activation.

Symptoms:

• Autonomic (adrenergic): tremor, palpitations, sweating, anxiety, hunger
• Neuroglycopenic: confusion, headache, difficulty concentrating, visual disturbances, seizures, coma

Causes: Excess insulin or oral hypoglycaemic, missed meals, increased exercise, alcohol, renal impairment (reduced insulin clearance), hepatic impairment (reduced gluconeogenesis), drug interactions.

Treatment ( Rule of 15):

• 15 g fast-acting carbohydrate (glucose tablets, sugary drink, fruit juice) → recheck after 15 minutes → repeat if still hypoglycaemic
• For unconscious patient: IM glucagon (1 mg) or IV dextrose (25 mL of 50% dextrose) or SC glucagon
• If caused by long-acting insulin or sulfonylurea: may need prolonged observation and dextrose infusion

Glucagon injection kit: Available in SA; patients on intensive insulin regimens should have one; training for family members on administration is essential.

Diabetes Monitoring

Glycaemic monitoring:

• Self-monitoring of blood glucose (SMBG): fasting and 2-hour postprandial; frequency based on insulin regimen
• HbA1c: every 3 months if unstable, 6-monthly if stable; target <7% (individualised: <6.5% in young patients without comorbidities; <8% in elderly with limited life expectancy)

Chronic complication monitoring:

• Annual: retinal screening (fundoscopy or photography), foot examination (monofilament, vibration sense), urine albumin:creatinine ratio (ACR), eGFR
• Blood pressure (each visit; target <130/80 or lower in some guidelines)
• Lipid profile (annually)

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Thyroid Agents

Hypothyroidism

Cause: Most commonly Hashimoto’s autoimmune thyroiditis in developed countries; iodine deficiency worldwide (including parts of South Africa).

Treatment: Levothyroxine (synthetic T4)

Dosing:

• Start low in elderly or cardiac disease (12.5–25 mcg daily); titrate every 6–8 weeks
• Average replacement dose: 1.6 mcg/kg/day in adults; 4–6 mcg/kg/day in children
• Take on empty stomach (30–60 min before breakfast) for optimal absorption
• Separate from calcium, iron, PPIs by 4 hours (these reduce levothyroxine absorption)

Monitoring:

• TSH: 6–8 weeks after initiation or dose change; once stable, annually
• Target TSH: 0.5–2.5 mIU/L (age-dependent; higher TSH may be acceptable in elderly)
• T4: only needed if central hypothyroidism suspected (pituitary/hypothalamic disease)

Myxoedema coma: Medical emergency; presentation: severe hypothyroidism, hypothermia, bradycardia, hypotension, respiratory depression, altered consciousness. Treatment: IV liothyronine (T3) + IV hydrocortisone + supportive care.

Hyperthyroidism

Causes: Graves’ disease (autoimmune, most common), toxic multinodular goitre, toxic adenoma.

Antithyroid drugs (thionamides):

Drug	Mechanism	Dosing	Adverse Effects
Propylthiouracil (PTU)	Inhibits thyroid peroxidase and peripheral T4→T3 conversion	100–150 mg 8-hourly initially; then 50–150 mg daily maintenance	Hepatotoxicity (rare but severe — monitoring essential); agranulocytosis (rare)
Methimazole (thiamazole)	Inhibits thyroid peroxidase (more potent than PTU)	5–20 mg daily (once daily possible)	Hepatotoxicity; birth defects (first trimester — PTU preferred in pregnancy); arthralgia

Mechanism of thionamides: Inhibit thyroid peroxidase → block iodine organification and iodotyrosine coupling → ↓ thyroid hormone synthesis.

Radioactive iodine (¹³¹I): Definitive treatment for hyperthyroidism and thyroid cancer; contraindicated in pregnancy; causes hypothyroidism (often permanent).

Surgery (thyroidectomy): For large goitres, refractory cases, or when antithyroid drugs contraindicated.

Monitoring: Free T4, TSH every 4–6 weeks until stable; monitor FBC and LFTs with antithyroid drugs.

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Corticosteroids

Endogenous Corticosteroids

Cortisol (hydrocortisone): Primary glucocorticoid; circadian rhythm (highest at 08:00); released in response to stress.

Aldosterone: Primary mineralocorticoid; regulated by RAAS; sodium retention, potassium excretion.

Synthetic Corticosteroids

Drug	Glucocorticoid Potency (relative to cortisol)	Mineralocorticoid Potency	Half-life	Notes
Hydrocortisone	1	1	Short (~8–12 hrs)	Preferred in adrenal insufficiency
Prednisone (prednisolone — active metabolite)	4	0.5	Intermediate	Oral; most commonly used systemically
Methylprednisolone	5	Minimal	Intermediate	IV; less mineralocorticoid effect
Dexamethasone	25	Minimal	Long	High potency; used in cerebral oedema, chemotherapy nausea
Fludrocortisone	0.1	200	Intermediate	Mineralocorticoid replacement only

Glucocorticoid effects:

• Anti-inflammatory (inhibit phospholipase A2 → ↓ prostaglandins and leukotrienes)
• Immunosuppressive (↓ cytokine production, ↓ lymphocyte proliferation)
• Metabolic (↑ gluconeogenesis, ↑ insulin resistance, protein catabolism, fat redistribution)
• Cardiovascular (↑ BP through mineralocorticoid and permissive effects on catecholamines)
• CNS (euphoria, insomnia; can precipitate steroid psychosis)

Mineralocorticoid effects:

• Sodium retention, potassium and hydrogen ion excretion → hypokalaemia, metabolic alkalosis, volume expansion, hypertension

Systemic Corticosteroids (Oral/IV)

Uses: Severe asthma/COPD exacerbation, autoimmune diseases, organ transplantation, adrenal insufficiency, anaphylaxis (adjunct to adrenaline), septic shock (some protocols), cerebral oedema.

Dosing:

• Low dose: ≤7.5 mg prednisone equivalent/day — most adverse effects minimal
• Medium dose: 7.5–30 mg/day — increased side effects
• High dose: >30 mg/day — significant adverse effects
• Pulse therapy: IV methylprednisolone 500 mg–1 g daily for 3–5 days for severe flares

Adverse effects (chronic systemic use):

System	Effect
Metabolic	Hyperglycaemia/diabetes, hyperlipidaemia, weight gain, sodium retention
Musculoskeletal	Osteoporosis (prevent with bisphosphonate if prolonged use), muscle wasting, avascular necrosis
Immunological	Immunosuppression → infections (opportunistic), reactivation of TB
Dermatological	Skin thinning, easy bruising, striae, acne
Ophthalmological	Cataracts, glaucoma
Psychiatric	Insomnia, euphoria, anxiety, depression, steroid psychosis
Gastrointestinal	Peptic ulcer (especially with NSAIDs), pancreatitis
Adrenal suppression	HPA axis suppression; risk of adrenal crisis on withdrawal after >2–3 weeks of systemic therapy

Adrenal insufficiency on withdrawal:

• After >2–3 weeks of systemic steroids, HPA axis is suppressed
• Abrupt cessation → acute adrenal crisis (hypotension, hyponatraemia, hyperkalaemia, shock) → life-threatening
• Taper slowly (e.g., reduce by 2.5–5 mg prednisone every 1–2 weeks below 10 mg; very slow taper below 5 mg)
• Patient counselling: never stop abruptly; carry steroid card/passport

Stress dosing: Patients with adrenal insufficiency (or on >2–3 weeks of systemic steroids) require increased steroid cover during stress (illness, surgery, trauma): double or triple usual dose, or parenteral hydrocortisone 100 mg IV/IM if unable to take orally.

Inhaled Corticosteroids (ICS)

Used for: Asthma (first-line preventer), COPD (in combination with LABA for some patients).

Drug	Low Dose (adult)	Medium Dose	High Dose
Beclomethasone	200–500 mcg	500–1000 mcg	>1000 mcg
Budesonide	200–400 mcg	400–800 mcg	>800 mcg
Fluticasone	100–250 mcg	250–500 mcg	>500 mcg
Fluticasone furoate	100 mcg	200 mcg	—

Adverse effects (inhaled):

• Local: oral candidiasis (rinse mouth after inhalation), dysphonia (hoarse voice)
• Systemic: minimal at low-medium doses; increases with high dose and prolonged use
• Precautions: rinse mouth after use; use spacer for MDI

Topical Corticosteroids

Potency ranges from mild (hydrocortisone 1%) to very potent (clobetasol 0.05%):

Adverse effects: Skin thinning, striae, telangiectasia, contact dermatitis (with specific preparations).

SA context: Wide range available OTC (schedule 1) for mild preparations; prescription for potent preparations.

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Bone and Mineral Metabolism

Osteoporosis and Antiresorptive Agents

Osteoporosis: Low bone mineral density (BMD); increased fracture risk; common in postmenopausal women and elderly.

Bisphosphonates:

• Alendronate (70 mg weekly), risedronate (35 mg weekly), ibandronate (150 mg monthly oral or 3-monthly IV), zoledronic acid (5 mg yearly IV)
• Mechanism: inhibit osteoclast-mediated bone resorption
• Administration: take in the morning on empty stomach, remain upright for 30–60 minutes; take with plain water (not milk or calcium supplements)
• Adverse effects: GI irritation, osteonecrosis of the jaw (rare; after dental procedures), atypical femoral fractures (long-term use)
• Monitoring: BMD (DEXA) every 1–2 years; supplement with calcium and vitamin D

Denosumab:

• Monoclonal antibody against RANKL → inhibits osteoclast formation and activity
• 60 mg SC every 6 months
• Used for osteoporosis in postmenopausal women at high risk, bone metastases
• Adverse effects: hypocalcaemia (ensure vitamin D sufficiency), infections, skin infections

Hormone Replacement Therapy (HRT):

• Oestrogen ± progestogen: effective for osteoporosis prevention; risk-benefit analysis required (breast cancer, cardiovascular risk)
• Less commonly used first-line for osteoporosis alone

Vitamin D and Calcium:

• Calcium: 1000–1200 mg/day (dietary preferred); supplement if dietary intake inadequate
• Vitamin D: 800–2000 IU/day for osteoporosis; ensure vitamin D sufficiency for bisphosphonate efficacy
• Sunlight exposure (UVB) generates vitamin D in skin; particularly important in South Africa where sunlight is abundant but some populations have limited outdoor exposure

Vitamin D Deficiency

Causes: Inadequate sunlight (indoor work/lifestyle), dark skin (melanin reduces vitamin D synthesis), malabsorption, liver/kidney disease (reduced activation), anticonvulsants (carbamazepine, phenytoin accelerate vitamin D metabolism)

Treatment: Vitamin D3 (cholecalciferol) or vitamin D2 (ergocalciferol); loading dose then maintenance; high doses available OTC in SA.

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SAPC Examination Focus Areas

High-yield topics for the SAPC exam:

1. Insulin types and regimens — basal-bolus vs mixed; rapid-acting vs long-acting onset/peak/duration
2. Metformin — mechanism (AMPK), lactic acidosis risk (renal impairment), B12 deficiency, GI side effects
3. Sulfonylureas and hypoglycaemia — mechanism (K-ATP channel closure); risk in renal impairment and elderly; glibenclamide highest risk
4. SGLT2 inhibitors — mechanism (glycosuria), weight loss, genital infections, DKA, cardiovascular/renal benefits
5. GLP-1 agonists — weight loss, GI side effects, pancreatitis, thyroid C-cell tumour contraindication
6. DPP-4 inhibitors — weight neutral, low hypoglycaemia risk, well tolerated
7. DKA management — insulin infusion, fluids, potassium replacement, treat underlying cause
8. Hypoglycaemia treatment — rule of 15; glucagon kit; long-acting insulin/sulfonylurea risk
9. Levothyroxine administration — empty stomach, separate from calcium/iron by 4 hours, TSH monitoring
10. Thionamides (PTU vs methimazole) — PTU preferred in first trimester pregnancy, hepatotoxicity risk, agranulocytosis
11. Systemic corticosteroid adverse effects — osteoporosis, adrenal suppression, infections, metabolic effects
12. Corticosteroid withdrawal — gradual taper, adrenal crisis prevention, stress dosing
13. Inhaled corticosteroids — oral candidiasis prevention (rinse mouth), dose ranges for asthma
14. Bisphosphonates — administration (empty stomach, upright), osteonecrosis of jaw, atypical femoral fractures
15. Diabetes monitoring — HbA1c targets, retinal/foot/kidney screening, SMBG frequency

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Summary of Key Concepts

• Diabetes management: metformin first-line for Type 2 DM; insulin for Type 1 and advanced Type 2; add-on agents based on patient profile (weight, CV risk, CKD, cost)
• Insulin regimens: basal-bolus provides best glycaemic control; proper injection technique and site rotation essential
• Hypoglycaemia is the most acute complication of insulin and sulfonylurea therapy; glucagon kits should be available
• SGLT2 inhibitors and GLP-1 agonists provide cardiovascular and renal protection beyond glucose control
• Metformin: contraindicated in severe renal impairment; monitor B12; lactic acidosis rare but serious
• Thyroid: levothyroxine for hypothyroidism (empty stomach, separate from calcium/iron); thionamides for hyperthyroidism (monitor LFTs, FBC)
• Corticosteroids: chronic systemic use causes significant adverse effects; taper rather than abrupt withdrawal; inhaled steroids first-line for asthma control with rinse-after-use counselling
• Osteoporosis: bisphosphonates first-line; calcium and vitamin D supplementation essential; proper administration (morning, empty stomach, upright)
• Monitoring: regular HbA1c, complication screening (retina, foot, kidney), BP and lipid control
• SA context: EML guides public sector formulary; cost-effectiveness drives first-line choices; CCMDD programme for chronic medicine distribution