pharmacology robert wise. contents bronchodilators anti-hypertensives diuretics basal ganglia...
TRANSCRIPT
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
• 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
• 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