Cardiovascular Drugs Flashcards
What are some examples of cardioselective beta-blockers?
Bisoprolol
Atenolol
What is the mechanism of action for cardioselective beta-blockers?
- Cardioselective beta-1-adrenoceptor antagonist.
- Preferentially blocks beta-1 receptors in cardiac and renal tissue.
- Inhibits sympathetic stimulation of the heart and renal vasculature.
- Blockade of SAN reduces HR(negative chronotropic effect) and blockade of receptors in the myocardium depresses cardiac contractility (negative inotropic effect).
- blockade of beta-1 adrenoceptors in renal tissue inhibits release of renin, depressing vasoconstrictive effects of the RAAS.
What are the indications of cardioselective beta-blockers
- Hypertension
- Angina
- Rate-control in atrial fibrillation
- Carvedilol or Bisoprolol may be used as part of supportive therapy for mild / moderate heart failure.
List the side effects of cardioselective beta-blockers
- Bradycardia
- Hypotension
- Bronchospasm
- Fatigue (Can affect up to 10% of patients)
- Cold extremities
- Sleep disturbances
- Loss of hypoglycaemic awareness
What is important clinically regarding Pharmacokinetics/dynamics for cardioselective beta-blockers?
- Avoid higher doses & use with caution in patients with Asthma COPD – risk of bronchospasm.
- Avoid in patients with Hx of frequent hypoglycaemia.
- Do not combine Beta-Blockers with rate-limiting Ca2+-Channel-Blockers (Verapamil / Diltiazem) in anti-hypertensive therapy, - risk of heart-block.
What information should you tell the patient before starting on a cardioselective beta blocker
- Compliance is important – hypertension is asymptomatic but nonetheless a dangerous risk factor that needs controlled.
- Fatigue and cold extremities are common side-effects.
What are some examples of non-cardioselective beta-blockers?
Propranolol
Carvedilol
What is the mechanism of action for non-cardioselective beta-blockers?
- Propanolol: Non-cardioselective beta-1-adrenoceptor antagonist.
- Carvedilol: Non-selective beta-1, beta-2 and alpha-1-adrenergic receptor antagonistic effects.
- Inhibits sympathetic stimulation in the heart and vascular smooth muscle.
What are the indications of non-cardioselective beta-blockers?
- Hypertension
- Angina
- Anxiety
- Migraine prophylaxis
- Post-MI prophylaxis
- Carvedilol or Bisoprolol may be used as part of supportive therapy for mild / moderate heart failure.
List the side effects of non-cardioselective beta-blockers
- Bradycardia
- Hypotension
- Bronchospasm
- Fatigue (Can affect up to 10% of patients)
- Cold extremities
- Sleep disturbances
- Loss of hypoglycaemic awareness
What is important clinically regarding Pharmacokinetics/dynamics for non-cardioselective beta-blockers?
Caution in diabetic patients – risk of deranged CHO metabolism
Avoid in patients with Asthma & COPD – risk of bronchospasm
Do not combine Beta-Blockers with rate-limiting Ca2+-Channel-Blockers (Verapamil / Diltiazem) in anti-hypertensive therapy.
Propanolol is lipid-soluble and is mostly cleared by the liver. Avoid in liver impairment. Avoid abrupt withdrawal – risk of liver impairment.
What information should you tell the patient before starting on a non-cardioselective beta blocker
- Nightmares and sleep disturbances may occur.
- Compliance is important – hypertension is asymptomatic but nonetheless a dangerous risk factor that needs controlled.
- Fatigue and cold extremities are common side-effects.
What are some examples of ACE Inhibitors?
Ramipril
Enalapril
Lisinopril
Perindopril
What is the MoA for ACE Inhibitors?
- Inhibits conversion of Angiotensin I to Angiotensin II (a more potent systemic vasoconstrictor).
- This inhibits Aldosterone release from the adrenal cortex, depressing renal sodium and fluid retention, thereby decreasing blood volume.
What are the indications for ACE Inhibitors?
- Hypertension
- Heart Failure
- Nephropathy
- Prevention of Cardiovascular events in high risk patients
List some side effects of ACE Inhibitors:
- Dry cough (10% of Patients, causing cessation of treatment in 5%)
- Hypotension
- Hyperkalaemia
- Renal Impairment
- Angioedema
What is important clinically regarding Pharmacokinetics/dynamics for ACE Inhibitors?
Adverse drug reactions are higher in patients with:
High-dose diuretic therapy / Hypovolaemia / Hyponatraemia / Hypotension / Unstable Heart Failure / Renovascular disease
What information should you tell the patient before starting on an ACE Inhibitor
- Blood test required at 1-2 weeks to check electrolyte balance.
- Dry cough is a common side-effect.
What are some examples of Nitrates?
Isosorbide Mononitrate Glyceryl Trinitrate (GTN)
What is the MoA for Nitrates?
• Converted to Nitric Oxide, a potent vasodilator.
Cardioselective, acting predominantly on coronary blood vessels, enhancing flow of blood to ischaemic areas of the myocardium.
• reduces myocardial oxygen consumption by reducing cardiac preload and afterload.
What are the indications for Nitrates?
- Treatment of Angina
* Severe hypertension (intravenous GTN is sometimes used in this setting)
List some side effects of Nitrates
- Headache
- Postural Hypotension/dizziness
- Tachycardia
What is important clinically regarding Pharmacokinetics/dynamics for Nitrates?
- Tolerance develops with long-term use.
- to avoid tolerance, patients should have a daily nitrate-free period.
- Isosorbide Mononitrate: Oral medication, longer duration of action than GTN.
- GTN: Rapidly inactivated by first pass (hepatic) metabolism and therefore cannot be digested – sublingual spray/tablet only. It can also be given IV.
What information should you tell the patient before starting on a Nitrate?
- Headache is a common side effect initially, but incidence decreases the longer the patient is on the drug.
- Take GTN before activity that you know will bring on angina.
What are some examples of rate limiting calcium channel blockers?
Verapamil
Diltiazem
What is the MoA for rate limiting calcium channel blockers?
- Prevent cellular entry of Ca2+ by blocking L-type calcium channels.
- Myocardial and Smooth muscle contractility depressed. Cardiac contractility will be reduced.
- Dilate coronary blood vessels and reduce afterload.
- Antidysrhythmic actions due to prolonged atrioventricular node conduction – depresses heart rate.
What are some side effects of rate limiting calcium channel blockers?
Verapamil:
• Constipation
• Flushing / Headache / Dizziness / Hypotension
Diltiazem: • GI disturbances • Bradycardia • Peripheral oedema • Dizziness / Headache / Hypotension
What is important clinically regarding Pharmacokinetics/dynamics for rate limiting calcium channel blockers?
- Contra-indicated in heart failure and left ventricular dysfunction due to potent negative inotropy.
- Avoid in bradycardia and hypotension.
- Do not use with beta-blockers.
What information should you tell the patient before starting on a rate limiting calcium channel blockers?
- Constipation is a common side effect with Verapamil.
- Ankle swelling is a common side effect with Diltiazem, hot weather making it worse.
- Compliance is important – hypertension is asymptomatic but nonetheless a dangerous risk factor that needs controlled.
what are some examples of non-rate limiting calcium channel blockers?
amlodipine
nifedipine
felodipine
What is the MoA for non-rate limiting calcium channel blockers?
- Prevent cellular entry of Ca2+ by blocking L-type calcium channels.
- Myocardial and smooth muscle contractility depressed – these drugs mainly affect smooth muscle.
- Dilate coronary blood vessels and reduce afterload
- These drugs do not lower heart rate (heart rate may increase)
What are some indications for non-rate limiting CCBs?
Hypertension
Treatment of Angina
What are some side effects of non-rate limiting calcium channel blockers?
Ankle oedema
Abdominal pain / Nausea
Palpitations
Flushing / Headache / Dizziness
What is important clinically regarding Pharmacokinetics/dynamics for non-rate limiting calcium channel blockers?
Avoid in: Cardiogenic shock, Unstable Angina, Significant Aortic Stenosis
What information should you tell the patient before starting on a non-rate limiting calcium channel blockers?
- Compliance is important – Patients may stop CCB f they do not feel any better.
- HPT is asymptomatic but a dangerous risk factor that needs controlled.
- Ankle swelling is a common side effect, hot weather making it worse.
What are some indications for rate limiting CCBs?
Supraventricular arrhythmias
Treatment of angina
Hypertension
What are some examples of HMG CoA Reductase Inhibitors?
Simvastatin
Atorvastatin
Pravastatin
What is the MoA of HMG CoA Reductase Inhibitors?
- Competitively inhibits HMG CoA Reductase; the rate-determining enzyme in the mevalonate pathway synthesis of cholesterol.
- causes increase in LDL-receptor expression, on hepatocyte surface
- Increases hepatic uptake of cholesterol, reducing plasma cholesterol levels.
- Reduces development of athersclerotic plaques.
(Statins may have additional pleotropic effects)
what are the indications for HMG CoA reductase inhibitors?
familial hypercholesterolaemia
prevention of CV events in high risk patients
What are the side effects of HMG CoA reductase inhibitors?
Myalgia
Myopathy (with creatine kinase elevation) and rhabdomyolysis are rare.
GI disturbances
Liver abnormalities – deranged LFT’s
What is important clinically regarding Pharmacokinetics/dynamics for HMG CoA reductase inhibitors?
Myalgia and Rhabdomyolysis are dose-related, begin with low dose, especially in patients with previous side-effects.
Hypothyroidism should be corrected before assessing need for statin use.
What information should you tell the patient before starting on a HMG CoA reductase inhibitors?
Report any unexplained muscle pains to their GP, who will check a creatine kinase blood level.
Diarrhoea and abdominal pain may be present initially.
What is an example of a Cardiac Glycoside?
Digoxin
What is the MoA for Cardiac glycosides?
Increases vagal parasympathetic activity and inhibits the Na+/K+ pump, causing a buildup of Na+ intracellularly.
T try remove Na+, more Ca2+ enters cell by Na+/Ca2+ exchangers.
The buildup of Ca2+ causes increased force of contraction and reduced rate of conduction through AV node.
What are the indications for digoxin?
heart failure
rate control in atrial fibrillation
What are some side effects of Cardiac glycosides?
nausea
vomiting
diarrhoea
constipation
What is important clinically regarding Pharmacokinetics/dynamics for digoxin?
- narrow therapeutic index.
- Symptoms of digoxin toxicity are similar to effects of clinical deterioration.
- plasma-concentration is not a reliable indicator of toxicity.
- Digoxin-specific antibody fragments are used for life-threatening digoxin overdose.
- long half-life and maintenance doses may only be required once-daily.
- Renal function, age and heart disease are major determinants for safe digoxin dosage.
What information should you tell the patient before starting on a Cardiac glycoside?
risk of toxicity
what is an example of an anti-arrhythmic drugs?
amiodarone
what is the mechanism of action for anti-arrhythmic drugs?
Amiodarone blocks cardiac K+ channels, prolonging repolarization of the cardiac action potential.
Restores regular sinus rhythm.
It slows AV nodal conduction.
what is the indication for amiodarone?
supraventricular / ventricular arrhythmias
What are the side effects of anti-arrhythmic drugs?
Photosensitivity skin reactions Hypersensitivity reactions Hyper / Hypothyroidism Pulmonary fibrosis Corneal deposits Neurological disturbances GI disturbances / Hepatitis
What is important clinically regarding Pharmacokinetics/dynamics for anti-arrhythmic drugs?
- long half-life, once daily dosing, can take weeks-months to achieve steady-state amiodarone-plasma concentrations.
- Thyroid function tests before Tx and every six months, or where symptomatic.
- LFTs should be taken during treatment.
What information should you tell the patient before starting on a anti-arrhythmic drug?
Requires good compliance and attendance for monitoring blood tests.
Avoid exposure to the sun, wear protective clothing and sunscreen.
Report presence of rash after use – hypersensitivity risk.
