Pharmacology CAM201 Flashcards
What are the first line treatment options for Heart Failure?
1) ACE Inhibitors
(or Angiotensin II Inhibitors)
2) Thiazides
(or loop diuretics)
3) Digoxin
(only when AF accompanies HF)
What are key signs/symptoms of Right-sided heart failure? And why does this occur?
Systemic congestion:
Odematous feet, ankles, liver, abdomen.
Because R-heart fails to clear blood from venous return
What are key signs/symptoms of Left-sided Heart Failure? And what causes them?
Pulmonary congestion (oedema), causing
- Dyspnoea
- Paroxysmal Nocturnal Dyspnoes
- Orthopnoea - number of pillows
Reduced systemic CO, causing
- fatigue (if not severe enough to cause pre- / syncope)
*Note, if HF slow developing, pulmonary circulation may compensate - to a POINT - by becoming hypertensive, thus preventing oedema.
Explain what happens in Diastolic Heart Failure? When does it tend to occur?
Heart can contract normally
Reduced diastolic compliance
- Often hypertrophic
- Less stretch
- Lower pre-load (lower EDV)
- Blood backs up, can cause pulmonary oedema
Oten occurs with hypertension, or in elderly
Explain what happens in Systolic Heart Failure. What are some common causes?
Reduced / weakened contraction, usually due to dilation of the ventricle.
Associated:
- Decreased Ejection fractioon (<50%)
- Increased LV EDV (due to reduced ejection fraction)
- Thus there is constant overload, leading to dilation of the ventricle
Common causes:
Ishaemic damage, Aortic valve stenosis, Diabetes, Myocarditis, aging
Explain the Renin-Angiotensin Pathway
Renin is released by juxtaglomerular cells in response to decreased tubule filtration (due to low BP and/or blood vol). Renin enters blood, and interacts with Angiotensinogin to create Angiotensin I. Angiotensin I is converted to Angiotensin II by ACE in the lungs. Angiotensin binds to AT 1 receptors. This triggers 3 key motions:
- Angiotensin II is a powerful vasoconstrictor (^BP)
- Triggers release of NA which ^^HR
- Triggers release of Aldosterone from Adrenal cortex which increases reabsorption of Na+, thus ^^blood volume
What are the names of the ACE-Inhibitor drugs?
Elanopril
Capotril
Fosinopril
Lisinopril
What are the names of the Angiotensin II inhibitor drugs?
Candesartan
Irbesartan
Losartan
ACE Inhibitors Mechanism of action
Inhibit the action of ACE, preventing the conversion of Angiotensin I into Angiotensin II. This prevents the (normally) ensuing rise in BP.
Downstream actions prevented include:
- Angiotenin II - AT 1 Receptor binding
- …which normally results in increased blood vol via Aldosterone release from adrenal cortex (increases Na+ reabsorption),
- …and NA release which increases HR
- …and the potent vasoconstrictory actions of Angiotensin II which again increases BP
Angiotensin II Mechanism of action
Prevents the binding of Angiotensin II to AT 1 Receptors on intraglomerular mesangial cells
Preventing all downstream effects of Renin-Angiotensin pathway
Thiazides - what are they?
What are the types?
Diuretics
Hydrochlorothiazide
Chlorthalidone
Thiazides - mechanism of action
Thiazides reduce plasma volume
by increasing urine output (via increasing Na+ excretion) by ~10%
Loop Diuretics - what do they do / when are they generally used?
Treat Fluid Accumulation
Usually used short-term
Digoxin - when is it indicated for HF?
Only when HF is accompanied by AF
Digoxin - Mechanism of action
Negative chronotrope and Positive Inotrope
Competes with K+ for the K+ binding site on Na+/K+ ATP-ase pump.
Leads to high intracellular levels of N+ and thus high levels of intracellular Ca++.
Leads to lengthening of Phase 4 and Phase 0, thus slowing HR (negatice chronotrope)
High intracellular levels of Ca++ also increase contractility (force of contraction) - positive inotrope
