Pharmacology Flashcards
ERP
Effective refractory period
The length of time a cell in its normal condition would remain refractory before responding to a cell next to it
Arrhythmias classification
- Bradyarrhythmia (atrioventricular block)
- Tachyarrhythmia (ectopic beats, tachycardia, fibrillation)
Can conduction blocks cause tachycardia
Yes, as well as bradycardia they can also cause tachycardia- through re-entry arrhythmias
What two things are critical for re-entry arrhytmia to occur
Timing
Refractory state
Classes of anti-arrhythmic drugs
1) Na+ channel blockers
2) B blockers
3) Prolong ERP
4) Ca2+ channel blockers
Adenosine
Digoxin
Effects of anti-arrhythmic drugs
1) Suppress enhanced automaticity (II and IV)
2) Prolong ERP (III)
3) Slow conduction rate (I and II)
4) Depress RMP (adenosine)
Na+ channel blockers
Slow conduction time (reduce conduction velocity) by blocking fast Na+ channels
Lignocaine
Flecainide
Adverse effects of Na+ channel blockers
1) Enhanced risk of arrhythmia
2) More chance of a fatal arrhythmia
B-blockers
B receptors cause increased HR as well as increase sino-atrial automaticity
These drugs reduce automaticity and conduction velocity
“olols”
Prolong ERP drugs (K+ channel blockers)
K+ channel blockers
Delay repolarosation
Amiodarone
Sotalol
Ca2+ channel blockers
Reduce conduction velocity
Suppress automaticity
Three classes of CCBs
1) Dihyropyridines (Verapamil and Diltiazem)
2) Non-dihydropyridines
Side effects of amiodarone
Hypothyroidism
Hyperthyroidism
Pulmonary fibrosis
Adenosine
Adenosine receptors are linked to K+ receptors,
they reduce RMP so that stimulus can’t raise it above the threshold
Three ways to treat hypertension
1) Reduce blood volume
2) Reduce SVR
3) Reduce CO by depressing HR and SV
What does angiotensin II do?
Raises BP
Increases retention of salt and water (through ADH)
What do anti-hypertensives act on in RAS system?
Angiotensin II
What are the classes of drugs- two actions on the renin-angiotensin system?
1) ACE inhibitors (“prils”)
2) Angiotensin receptor blockers (ARBs) (“sartans”)
Side-effects of angiotensin blockers?
Sudden drop in BP
Renal failure (fall in glomerular perfusion pressure)
ACE inhibitor cough (as bradykinin is broken down by ACE in the lungs)
Angioneurotic oedema
All anti-hypertensive drug classes
1) Angiotensin blockers
2) B-receptor blockers
3) a-receptor blockers
4) Ca2+ channel blockers
5) Volume reduction diuretics
B-receptor blockers
Work by reducing CO (decrease HR and contractility)
**Can’t work in the periphery
a-receptor blockers
Prazosin
Blocking causes reduced SVR and vasodilation
**If you block a-receptors on their own, body tries to compensate and reflex tachycardia may occur
Ca2+ channel blockers
Two classes:
- Cardio-selective (Veramapil)
- Cardio and vascular (Diltiazem)
- Vascular selective (Dihydropyridines)
What is the mechanism of action of volume reduction diuretics?
1) Na+: prevent absorption in loop and DCT
**Aldosterone stimulates reabsorption of sodium
ADH
Water reabsorption in collecting duct
Loop diuretics
Inhibit sodium-potassium-chloride co-transporter in the thick ascending limb- leads to water loss and sodium loss
FRUSEMIDE
Thiazide diuretics
Do the same thing but in the distal tubule
HYDROCHLOROTHIAZIDE
INDAPAMIDE
K+ sparing diuretics
Antagonise action of aldosterone (aldosterone receptor antagonists)
EPLERENONE
Potency of diuretics
The diuretics that act earlier on prevent more reabsorption compared to the ones that act later on
K+ wasting diuretics
Both loop and thiazide diuretics that act directly on the channels lead to increased K+ excretion
Initial treatment of hypertension
- Thiazide diuretic with ACE-I or AT1 blocker
- Then add Ca2+ channel blocker
Exogenous and endogenous pathway of lipid transport
Exogenous:
Absorption from diet —-> TG and cholesterol packaged in CM —-> CM circulate around and release TG —-> LDL hydrolyses TG and FFA are released —> CM repackaged and remnant CM removed by liver
Endogenous
TG synthesised by the liver packed into VLDL —-> Processed by LPL in tissues —-> FA taken up by muscles for energy —-> Either become IDL or LDL and go to the LDL receptor on the liver
Reverse cholesterol transport
Process by which cholesterol is removed from the tissues
HDL is the main particle here
Statins
Reduce the synthesis of hepatically produced cholesterol
Upregulate LDL receptors of hepatocytes
Mechanism of statins
They inhibit HMG CoA reductase which eventually also increases the LDL receptors
Side-effects of statins
Hepatic- increase transaminase
Cognitive- memory loss
Diabetes
Myositis
Ezetimibe
Inhibits interaction of NPC1/L1 with clathrin/AP2- preventing endocytosis of cholesterol complex in the small intestine
PCSK9 inhibitors
Prevent recycling of LDL and mark it for degradation
PSCK9 MABS
PSCK9 side-effects
URTI GI Hypertension Neurocognitive Muscle (myositis)
Fibrates
Increases FFA B-oxidation
Niacin
Reduces synthesis of TG via hepatic DGAT reduction
GLP1
Glucagon like peptide 1
Reduces TGs
DPP-4
Prolongs activity of GLP1
Thiazolidinediones
PPARy antagonist
Classes of drugs for heart failure
1) Sympathetic NS activation (B-blockers)
2) Failing pump (Digoxin)
3) Salt and water retention (Diuretics)
4) Cardiac remodelling (RAS inhibitors)
5) Peripheral vasoconstriction (Nitrate)
6) Peripheral vascular resistance (ACE inhibitor)
7) Aldosterone driven remodelling (Aldosterone antagonist)
Three areas where the HF drugs work
1) Failing pump
2) Cardiac remodelling
3) Salt and water retention
4) Peripheral vasoconstriction
What is one abnormality in heart failure
Aldosterone over-production leasing to salt and H2O retention and vasoconstriction
B1 blocker adverse effects
- Bronchospasms
- Bradycardia
- Acute worsening heart failure
- Reduced exercise tolerance
Digoxin
Competes with K+ blocking Na/K ATPase
Less efficient Na/K exchange
Effects:
Slower SA node rate
Slower AV conduction
**INCREASES VAGAL TONE
Digoxin toxicity
Not enough K+ can leave- increases RMP
Greater risk of arrhythmias
Serious arrhythmias
Nausea
Confusion
Visual
Hypokalaemia brings digoxin toxicity
What happens to preload in HF?
It increases
How can you make the heart work less harder?
1) Reduce heart rate
2) Reduce contractility
3) Reduce afterload
GTN
Glyceryl trinitrate- broken down into NO which reduces afterload
Early drug management for ACS
1) Analgesia
2) Limitation of infarct size (coronary thrombolysis)
3) Management of arrhythmias
4) Anti-platelet and anti-coagulant therapy
5) Management of acute heart failure
Goals of asthma therapy
1) Prevent bronchoconstriction
2) Suppress inflammation
3) Prevent mucus hypersecretion
Two short-acting bronchodilators (B2 receptor agonists)
Salbutamol
Terbutaline
Long acting bronchodilators
Eformoterol
Salmetrol (not a good reliever)
ICS + LABA
E.g. seretide
Ipratropium bromide
Muscarinic cholinoceptor antagonists
ICS
Inhaled corticosteroids
Reduce inflammation in asthmatic airways
#1 controllers
Fluticasone
Leukotriene receptor antagonists
Montelukast
Zafirlukast
Anti-IgE antibodies
OMALIZUMAB
Subcutaneous injections and expensive
Other controllers
Cromolyns
Theophylline
**Weak efficacies- good for children
Three things that happen to the airways in asthma
1) Increased thickness of airway wall
2) Increased mucus secretion
3) Increased constriction
