Cardiovascular pharmacology Flashcards
List 4 types of drugs that fall under cardiac therapy
Cardiac glycosides
Antiarrhythmics
Cardiac stimulants
Vasodilators (cardiac disease)
List 3 non-selective beta blocking agents
Propranolol
Sotalol
Timolol
List 5 B1 selective drugs
Atenolol
Bisoprolol
ESMOLOL
Metoprolol
Nevibilol
Name 2 drugs that are vasodilatory non-B1 selective
Carvedilol
Labetalol
Which Beta-blocking agents are cardioselective and are preferred in angina?
B1-selective
Which beta blockers are contra-indicated in asthma and COPD?
Non-selective beta blockers
Which beta blockers are preferred in CCF
Vasodilatory non-B1 selective
Which specific drug is cautioned in asthma?
Carvedilol
Which class is preferred in acute coronary syndrome/acute MI, and arrhythmias
B1 selective
Which B blocking agent is used as 5th line treatment of Hypertension?
B1 selective agent
4 indications for the use of non-selective agents
Essential tremor
Symptomatic anxiety
Adjunct in thyrotoxicosis
Migraine prophylaxis
Which beta blockers are lipid soluble (3)
propranolol, metoprolol, labetalol
Which beta blockers have the least lipid-solubility? What is the advantage of low lipid-solubility?
Atenolol and sotalol
Advantage: fewer CNS adverse effects
6 side effects of beta blockers
Bradycardia
Bronchospasm
Masking hypoglycaemia
Fatigue
Cold extremities
Cholesterol dysregulation
Name 2 CNS effects associated with beta blockers
insomnia, depression
Lipid soluble: propranolol,
metoprolol, labetalol (MPL - mnemonic)
Contra-indications/cautions of beta blockers
Asthma & COPD
Heart block
Diabetes mellitus
Depression (non-selectives)
Name 3 alpha-1 blocking agents
Doxazosin
* Prazosin
* Terazosin
3 Indications of alpha-1 blockers
Hypertension 4th line (not monotherapy)
Pheochromocytoma-associated hypertension
Benign prostatic hypertrophy (BPH)
What type of formulation is used in alpha1 blockers?
Controlled release formulation (daily dose)
Explain metabolism and elimination of alpha1 blockers
Extensively metabolised in the liver and excreted mainly as
metabolites in the faeces
COntraindications of alpha-1 blockers
Contraindications: Hypersensitivity,
* For controlled-release tablets: history of GI obstruction, oesophageal
obstruction, decreased lumen diameter of GIT
when should alpha 1 blockers be cautioned?
In hepatic impairment
Adverse effects of alpha1 blockers (10)
First dose hypotension, hypotension, dizziness, vertigo, headache, fatigue
* Orthostatic hypotension, palpitations, nausea
What are the 3 functions of the RAAS system?
Coordinate renal and
cardiovascular functions
* Homeostatic control of blood
volume
* Electrolyte balance
* Vascular resistance
What is renin, and where is it stored?
Proteolytic enzyme
* Stored in juxtaglomerular cells in
kidneys
What causes the release of renin?
Released; response to :
1. sympathetic activation of B1 receptors,
2. systemic hypotension,
3. decreased tubular Na+
What is the mechanism for the release of renin?
↓ arterial pressure = ↓ renal
perfusion + baroreflex mediated
sympathetic activation of renal β1
induce release of renin
What is the function of aldosterone?
Mineralocorticoid
* Increase sodium reabsorption
(promote sodium retention)
Function of ADH
ADH (also known as vasopressin)
is a posterior pituitary peptide hormone.
* Antidiuretic action on the kidney and powerful vasoconstrictor.
What is an example of class 2 Angiotensin-Converting Enzyme inhibitor? (ACEI)
Enalapril
What is an example of Angiotensin II receptor blockers (ARBs)
Losartan
MOA of ACE-Inhibitors
Inhibit ACE1 which converts angiotensin I to angiotensin II
Where do ACE-Is act?
Act preferentially on angiotensin-sensitive vascular beds including
kidney, heart and brain
Antihypertensive effectiveness is increased by what?
Antihypertensive effectiveness increased by
* Low salt diet
* Enhanced renin secretion (patients
on diuretics
What are the indications of ACEIs? (6)
Indications:
* Hypertension (enhanced by low salt diet) – in Black patients they are less effective in the absence of diuretics
* Reduce mortality in patients with heart failure
* Prevent post-infarct heart failure
* Reduce cardiovascular outcomes in patient at high risk of IHD
* Renoprotective in patients with diabetes mellitus (diabetic
nephropathy) and renal disease with proteinuria
* Prevent progression of chronic kidney disease
Why are ACEIs preferred in diabetic pts?
Lack negative effects on glucose tolerance and blood lipids
* Reduce microalbuminuria
Why are ACEs preferred in patients in congestive heart failure?
Counteract overall metabolic-hormonal abnormalities
* Indirect diuretic effect via inhibition of aldosterone production
5 contraindications of ACEIs
Pregnancy - teratogenic
* History of angioedema and hyperkalaemia
* Bilateral renal artery stenosis or stenosis of an artery to a dominant/single kidney
* Aortic valve stenosis
* Severe renal impairment (eGFR <30ml/min) – unless specialist dose-adjusted
What are the general cautions for the use of ACEIs?
- Angioedema rare, but important adverse effect (caused by inhibition of
bradykinin degradation) – more common in Black patients and those with history
of allergy - Combination with ARBs should be avoided
5 adverse effects of ACEIs
Adverse effects:
* Dry cough
* Angioedema
* Hyperkalaemia (due to reduced
aldosterone secretion)
* Hypotension
* In patients with bilateral renal artery
stenosis: precipitate renal failure,
because AT2 usually constrict
efferent arterioles and maintains
pressure in the glomerulus for
filtration
ROA of ACEIs
Administer orally (bioavailability ranges from 25%-75%)
Metabolism of ACEIs
Varying degrees of first pass hepatic metabolism, several has active
metabolites
How is enalapril excreted?
Excreted predominantly in the urine as enalaprilat (active metabolite)
and unchanged drug
What are the adverse effects of enalapril? (3)
Dry cough most common usually happen in early phase of tx (can
happen after many years on tx)
* Angioedema (can happen after many years on tx)
* Hyperkalaemia
3 Contraindications of enalapril
Bilateral renal artery stenosis, hyperkalaemia, pregnancy
Drug interactions with enalapril
Other antihypertensives (hypotension)
* Potassium-sparing diuretics / potassium supplements
* ARBs
* High-dose aspirin & all NSAIDs
* Digoxin & lithium
* Trimethoprim
MOA of angiotensin receptor blockers (ARBs)
Selectively block AT1 receptors (antagonising effects of ATII)
* Reduce vasoconstriction, aldosterone secretion, sodium reabsorption by the proximal tubule and norepinephrine release from sympathetic nerve terminals
What is an advantage of using ARBs instead of ACEIs?
Equally effective (as ACEIs) in treating hypertension and rarely cause dry cough.
Safe to use in diabetes mellitus (do not affect serum glucose), gout (do not increase serum uric acid levels), dyslipidaemias (do not increase cholesterol levels), ACEI-mediated angioedema (only 8% cross-reactivity)
Adverse effects of ARBs (3)
Adverse effects: hyperkalemia, neutropenia, increase hepatic
aminotransferase enzymes
I contraindication and 1 caution of ARBs
Contraindication: pregnancy – cause foetal injury and death
* Caution in patient with renal artery stenosis
Lorsatan metabolism
First pass metabolism to an active metabolite
Half life of Losartan vs half-life of its active metabolite
Half-life (losartan): 1.5-2.5 hours
* Half-life (active metabolite): 6-9 hours
PPB of Losartan
99% PPB
Maximal effect of Losartan
Maximal antihypertensive effect: 3-6 weeks of tx
T/F: Losartan is not uricosuric
F
Contraindications of Losartan (3)
Bilateral renal artery stenosis, hyperkalaemia, pregnancy
Cautions of losartan
- Unilateral renal artery stenosis, pre-existing renal insufficiency,
hypersensitivity (angioedema) to ACEIs
Adverse effects of Losartan
- Dizziness, dose-related orthostatic hypotension
- Hyperkalaemia, raised liver enzymes
