Pharmacology

Robert Wise

Contents

• Bronchodilators• Anti-Hypertensives• Diuretics• Basal Ganglia disorder agents• Bone agents

Bronchodilators

• A 56 year old lady attends GP with worsening morning wheeziness. She was recently admitted to hospital with respiratory distress after a severe asthma attack.

• She takes salbutamol PRN (Airomir 200um)

• She takes Beclometasone (400ug/12hr)

• What can the GP do next?

Bronchodilators

• Initially add inhaled LABA

• Assess the response

• Can you name a LABA?

Bronchodilators

• Why is it unwise to just increase the inhaled steroid dose until the problem goes away?

• The patient asks about side effects of the Salbutamol. What can you advise her?

Common: Faster heart rate, Headaches, tremorsUncommon: Irritation of the mouth or throat, muscle cramps, palpitations, peripheral vasodilation, hypokalemia

Bronchodilators

• What is the Mechanism of action of Salbutamol?

1. Binds to GPCR activating adenyl cyclase

2. Increases cAMP increasing PKA

3. PKA inactivated MLCK4. Leads to smooth muscle

relaxation

Antihypertensives

• A 58 year old man (ex-smoker), who has rarely attended GP, comes in for a checkup after his friend recently had a stroke.

• His height is 1.75m and 105kg so his BMI is 32.4 Kg/m^2. His BP is 186/110

• The GP uses Qrisk to work out his risk of having a heart attack or stroke in the next 10 years. It’s 13.9%

• What action can the GP take now?

Antihypertensives

What does “C” stand for?

How does a Calcium channel blocker work?

Inhibits L-type calcium channels in the heartReduces Ionotropy and ChronotropyThus lower heart rate and BP

Side effects:FlushingHeadacheMild ankle oedemaGum hyperplasia

Antihypertensives

Outline the action of the RAAS system?

What are the side effects of ACE-I?

DRY COUGHDizzinessPosteral HYPOtension

Less common side-effects include swelling of the lips, eyes or tongue (angio-oedema) and a decline in kidney function.

Diuretics

• The GP chooses to add in a diuretic upon review 12 months later.

• He chooses a THIAZIDE (Bendroflumethiazide)

• How do THIAZIDE diuretics work?

Diuretics

Diuretics

• What is the key side effects of Spiro?

Hyperkalaemia/acidosisGynaecomastia

• What is the key side effects of Furosemide?

Hypokalaemia/AlkalosisIncreased Frequency of urinationDehydrationPostural Hypotension

Basal Ganglia

• What is the first line medication in Parkinsonism and what is it’s MOA?

Pramiplexole – Synthetic agonist that replaces dopamine, acting on the (primarily) D2 receptors

• Four cardinal features of Parkinsonism?Tremor (resting)Rigidity (like bending a lead pipe, cogwheel)Akinesia (bradykinesia)Postural instability

AdditionalMicrographia (small writing)Mask-like faceSleep disturbances (change in dopamine)Aprosodia

Basal Ganglia

• How do we directly replace dopamine centrally?

• Dopa-decarboxylase inhibitors: Benserazide, Carbidopa

• Catechol-O-methyltransferase (COMT) Inhibitors: entacapone

• Monoamine oxidase inhibitors (MAOI-B): Selegiline, Rasagiline

Levodopa

Basal Ganglia

• Why do we give Anticholinergics (Like Orphenadrine) in parkinsonism?

Decrease in dopamine leads to an increase in acetylcholine concentration

To redress the balance anticholinergics (antimuscarinics) may be used

Bone agents

• Define Osteoporosis?

WHO diagnostic criteria: (based on T scores from a DEXA scan)Normal: BMD <1 SD below the young adult mean

Osteopenia: BMD 1-2.5 SD below the young adult mean

Osteoporosis: BMD >2.5 SD below the young adult mean

It is not just the loss of bone, the change in structure (trabeculae) also important

Bone agents

• Name a Bisphosphonate and outline MOA?

Alendronate, Ibandronate, Zoledronate

These are absorbed onto the hydroxyapatite crystalsReduces osteoclast activityThus reduce bone turnover

Bone Remodelling