CCB mechanisms
- rl
- non rl
rate limiting Verapamil
- blocks T-type calcium channels in SA/AV node to stop action potential upstroke phase 4
- blocks l-type cc in AV/SA and in myocardium to reduce contractility
Non - RL Amlodipine
- main effect in vessels blocking L-type cc to stop Ca2+ entry
- this stops vascular smooth muscle contraction and lower BP and cardiac output/inotropy
Prodrug Strat
- enalaprilat
Enalaprilat active drug
- low absorption and low LogP
- Add lipophilic Ester group to make prodrug Enalapril
- body has esterase’s to break the ester down and release Enalaprilat once in systemic absorption
Furosemide MOA
- given in HF / stroke
- works in the proximal convoluted tubule
- blocks Na/K/2Cl channel to stop ion reabsorption
- water follows ions so it is excreted with ions, lowering blood volume, lowering BP
Bendroflumethiazide MOA
- 3rd line HTN
- works in distal convoluted tubule
- blocks Na/Cl channel to stop ion reabsorption
- water follows ions so it is excreted , lowering blood volume , lowering BP
Beta Blocker MOA
- blocks B1 receptor in the heart which blocks NA binding
- this decreases SA firing to decrease the heart rate
- it reduces cardiac output and gives LV more time to fill up to increase effectiveness of heart - NA binding activates adenyl cyclase which increases cAMP levels to activate PKA. PKA inc contractility so BB block this
DVT Treatment
Acute Stroke Care
- hospitilisation + ASPIRIN 300mg stat
- CT scan (quicker than MRI) rules out haemorrhagic stroke
- Thrombolysis (alteplase)
- within 4.5hrs of onset
- 0.9mg/kg max 90mg dose
- 10% given bolus 2-3min and 90% given over 6hrs - stop ALL anticoagulants, antiplatelets, NSAID’s or HTN meds because you dont want to limit blood flow
Nitrates & Potassium Channel Activators
isosorbide mononitrate
- decreases coronary vasoconstriction by becoming nitric oxide in body (vasodilator)
Nicorandil at low dose is nitrate
- at high dose opens K+ channels
- opens K+ channels on smooth muscle to hyperpolarise and decrease Calcium entry
Primary Stroke Prevention
- A-E
A - antiplatelet / anticoagulant
- aspirin 300mg stat on admission (avoided for 24hrs post thrombolysis)
- aspirin 300mg daily 14days then clopidogrel 75mg daily
- AF patients this antiplatelet started 10-14days after
B - Blood pressure under 130/80
- If under 55 years old –an ACE inhibitor or anangiotensin receptor blocker (ARB).
- If 55 or older or African – Caribbean origin of any age – a calcium channel blocker
C - cholesterol
- atorvastatin 40-80mg 1st line
- not used in haemorrhagic stroke
D - diabetes
- sliding scale insulin and glucose to keep tight control on blood sugar
E - Exercise
- counselling and lifestyle advice to reduce chance of stroke in future
Sacubatril/Valsartan
- HF treatment
- used when patient displays symptoms despite treatment
- Neprilysin inhibitor / ARB
- Stop ACE-inhibitor minimum 36 hours
- starting dose: 49 mg/51 mg twice daily
SBP>100, K<5.4
- neprilysin breaks down ANP which causes vasodilation
Beta Blocker Binding
- catchecolhydroxyl binds to TM1 serine by hydrogen bonding
- aromatic ring binds to TM6 phenyl
Flecainide
- rhythm control
- sodium channel blocker
- stops sodium coming in at phase 0 prolonging refractory period
Amiodarone
- rhythm control
Class III anti arrhythmic
- potassium channel blocker with some Na and Ca channel blocking effects
Works phase 0- 3 but most effect in phase 3 blocking potassium channels, prolonging refractory period
