WEEK 4: Pharmacology of Hypertension and heart failure Flashcards
State the GOALS OF TREATMENT of hypertension.
-Increase cardiac output: Improve myocardial contractility
-Decrease cardia remodeling: ↓ the afterload and preload
-Slow the progression of the disease and improve survival
State the 3 types of inotropes.
B1 agonist
Phosphosphodiesterase inhibitors
Cardiac glycosides (Digoxin)
Describe the MOA of Beta 1 agonists and give examples as well as adverse effects.
- Binding to Beta-1 Adrenergic Receptors:
- Activation of G-Protein Coupled Receptors (GPCRs):
- Activation of G-Proteins:
- Adenylate Cyclase Activation:
- Conversion of ATP to cAMP:
- Activation of Protein Kinase A (PKA):
- Phosphorylation of Target Proteins:
Effects on Cardiac Function:
*Phosphorylation of ion channels and calcium channels increases the influx of calcium ions into the cardiac myocytes during the action potential, leading to enhanced contractility (positive inotropic effect).
*Phosphorylation of contractile proteins enhances the force of myocardial contraction.
*In the SA node, increased cAMP levels enhance the funny current (If), leading to an increased rate of spontaneous depolarization and subsequent increase in heart rate (positive chronotropic effect).
-Used for acute management of heart failure
-Potential for tachyphylaxis in patients using dobutamine > than 24–72 hours
EXAMPLES
*Dobutamine
Define Tachyphylaxis.
What drug causes tachyphylaxis when using > than 24–72 hours?
Tachyphylaxis, also known as rapid tolerance or acute tolerance, refers to a phenomenon where the response to a drug decrease rapidly upon repeated administration, often within a short period.
Describe the MOA of phosphodiesterase inhibitors, adverse effects and give examples.
Inhibit Phosphodiesterase III in heart & Blood vessels. AND Inhibit cAMP degradation (Increase cAMP)»_space;> Increased contractility and Vasodilation.
Short-term management of heart failure
Associated with increased mortality with long-term use.
Amrinone-induced thrombocytopenia,
EXAMPLES
Amrinone
Milrinone
Cilostazol
Describe the MOA of cardiac glycosides and give examples.
- Inhibition of Na+/K+-ATPase Pump:
-By inhibiting the Na+/K+-ATPase pump, cardiac glycosides disrupt the normal balance of sodium and potassium ions across the cell membrane, leading to an increase in intracellular sodium concentration. - Indirect Inhibition of Na+/Ca2+ Exchanger:
-The increase in intracellular sodium concentration resulting indirectly inhibits the activity of the sodium-calcium exchanger (Na+/Ca2+ exchanger) located on the cell membrane.
-Inhibition of this exchanger by cardiac glycosides leads to an increase in intracellular calcium concentration.
- Increase in Intracellular Calcium Concentration:
The rise in intracellular calcium concentration resulting from Na+/Ca2+ exchanger inhibition has several effects on cardiac myocyte function.
I
*Increased intracellular calcium concentration enhances the contractility (positive inotropic effect) of the cardiac myocytes, leading to stronger and more forceful contractions of the heart muscle.
Other Effects:
Cardiac glycosides may also have additional effects on the heart, including:
*Modulation of autonomic nervous system activity, leading to decreased sympathetic tone and increased parasympathetic tone.
*Alteration of atrioventricular (AV) node conduction, resulting in a slowing of AV nodal conduction and increased refractoriness, which can be beneficial in certain arrhythmias.
EXAMPLE: Digoxin
Outline the adverse effects of cardiac glycosides.
Outline drugs that displace digoxin from the tissue binding sites.
Outline drugs that enhance digoxin toxicity.
Name the substance that form complexes with digoxin that are rapidly cleared from the body.
Adverse effects
*GIT upset
*Cardiac arrythmias
*Hallucinations, Disorientation and blurry yellow vision
Drugs that displace digoxin from the tissue binding sites
amiodarone, quinidine and verapamil
Potassium-depleting diuretics enhance digoxin toxicity.
Anti-digoxin antibody (polyclonal antibodies that form complexes with digoxin that are rapidly cleared from the body)
Outline other drugs used.
Describe their effect.
Angiotensin Converting Enzyme Inhibitors
Beta Blockers
Diuretics
↓ Preload
↓ Afterload
↓ Cardiac remodeling and mortality
Discuss ACE inhibitor’s role in Heart failure.
- By inhibiting angiotensin II production, ACE inhibitors cause arterial and venous dilation, reducing preload and afterload on the heart. This decreases cardiac workload and oxygen demand, thereby improving symptoms of heart failure such as dyspnea and fatigue.
- ACE inhibitors reduce the secretion of aldosterone, a hormone that promotes sodium and water retention by the kidneys. This leads to diuresis and natriuresis, resulting in a reduction in extracellular fluid volume and alleviating fluid overload in heart failure patients.
- ACE inhibitors have been shown to attenuate ventricular remodeling by inhibiting the effects of angiotensin II on cardiac structure and function. By reducing myocardial hypertrophy and fibrosis, ACE inhibitors can help preserve cardiac function and prevent disease progression.
Discuss Beta blocker’s role in heart failure.
By slowing the heart rate and reducing myocardial oxygen demand, beta blockers can help to alleviate symptoms of heart failure such as dyspnea, fatigue, and exercise intolerance.
Beta blockers have been shown to attenuate ventricular remodeling by blocking the effects of catecholamines on cardiac structure and function. By reducing myocardial hypertrophy and fibrosis, beta blockers can help preserve cardiac function and prevent disease progression.
What is hypertension?
Approximately how many % of people have Primary and secondary hypertension?
State the formula for MAP.
State the formula for Cardiac output.
Persistently elevated systolic or diastolic blood pressure
Approximately 90-95% of adults with hypertension have primary hypertension, whereas secondary hypertension accounts for around 5-10% of the cases.
- Mean arterial pressure = Cardiac Output X Total peripheral resistance
- Cardiac Output = Stroke volume X Heart rate
Outline Lifestyle modifications for hypertension.
Lifestyle modifications:
-Weight reduction
-Salt restriction
-Smoking cessation
-Abstaining from alcohol
State the 3 types of ANS drugs.
α1 antagonists
α2 agonists
β Blockers
Discuss the action of α1 antagonists, adverse effects and give examples.
Competitively block of α1-adrenoceptors
-Relax vascular smooth muscle (↓ Blood pressure)
-Relax smooth muscle in the bladder neck and the prostate (↓ lower urine tract symptoms in BPH)
These drugs may produce initial orthostatic hypotension.
Prazosin
Terazosin
Doxazosin
Discuss the action of α2 agonists, adverse effects and give examples.
Methyldopa»_space; α-Methyldopa»_space;>α-methyl norepinephrine
Centrally acting α2 agonists (↓ sympathetic outflow to the periphery)
Methyldopa (Drug of choice for gestational hypertension)
Sedation
Interaction with Tricyclic antidepressants
