Anti Hypertensives Flashcards
Classes of drugs used as anti hypertensives
1.ACE-i, ARBs
2.Beta blockers
3.Calcium channel blockers
4.Diuretics (Thiazides)
(2nd line)
5.A-adrenoceptor blocking agents
6.Hydralazine
Which class of drugs end with -pril?
ACE inhibitors
Lisinopril, Captopril, Enalapril
MOA of Lisinopril
- Inhibits ACE which converts Angiotensin I to Angiotensin II
- Decrease in angiotensin II = decrease in aldosterone secretion and decrease in vasoconstriction
- Decrease in aldosterone decreases Na+ and H2O retention
- Since arterial blood pressure = CO x peripheral resistance
- Decrease blood volume (decrease CO) and decrease vasoconstriction (decrease peripheral resistance) → decrease blood pressure
- Prevents the breakdown of bradykinin to its inactive states
- Bradykinin accumulation results in the activation of prostaglandins and nitric oxide (NO) → further vasodilation
Clinical uses of ACE Inhibitors
- Hypertension
- Cardiac failure
- Following myocardial infarction (protective effect)
- Renal insufficiency
Adverse effects of ACE INHIBITORS
- Severe hypotension
- Acute renal failure
- Hyperkalaemia
- Angioedema and dry cough (due to
- bradykinin accumulation)
- Contraindicated in pregnancy
Which patients are ACE inhibitors and ARBs contraindicated in?
PREGNANT
What does AT1/ARBs blockers end in?
- sartan
Valsartan, Losartan, Candesartan, Telmisartan
MOA of Valsartan
- Blocks angiotensin II type 1 receptor (AT1)
Prevents the binding of angiotensin II to AT1 to exhibit its effects (vasoconstriction, ADH secretion, aldosterone production, stimulate thirst) → decrease BP
Does sartans cause dry cough?
No, as they no longer affect the bradykinin pathways
What is one side effect observed in use with ACE inhibitors but not AT1 blockers
DRY COUGH
Beta blocker MOA
B1-blockers bind to the beta receptors and decrease myocyte contractility
Decrease contractility and heart rate thus reducing bp
Examples of beta blockers
Non-selective: propranolol, pindolol, carvedilol
Beta 1 selective: atenolol, bisoprolol, metoprolol XL
Dose-dependent: Nebivolol (beta 1 selective in low doses, non selective in high doses, also has vasodilatory effects through NO release)
Example of non selective beta blockers
propranolol, pindolol, carvedilol
Example of selective beta blockers
Beta 1 selective: atenolol, bisoprolol, metoprolol XL
Dose dependent selectivity beta blocker example
Dose-dependent: Nebivolol (beta 1 selective in low doses, non selective in high doses, also has vasodilatory effects through NO release)
Beta blockers contraindicated in which patients?
- Avoid giving ASTHMATICS patients non-selective beta blockers as they can bind to b2 receptors and cause beta-blocker associated bronchoconstriction
- Contraindicated in DIABETICS as it can mask the symptoms of hypoglycaemia
(Beta blockers can mask some of the typical symptoms of low blood sugar (hypoglycemia), such as rapid heartbeat and tremors. This can make it challenging for individuals with diabetes to recognize when their blood sugar is too low and may delay appropriate intervention.)
Clinical uses of beta blockers
- Hypertension
- Cardiac failure (HR decreases, increasing ventricular filling, more CO)
- Following myocardial infarction
- Abnormal heart rhythm
- Anxiety disorders
Adverse effects of beta blockers
- Bradycardia
- Reflex tachycardia
- AV nodal block
- Reduced exercise capacity (heart does not pump as much)
- Bronchoconstriction (CONTRAINDICATED IN ASTHMATICS)
- Beta-blocker blues: clinical depression
What kind of CCB is used in HTN?
DHP CCB
Nifedipine, amlodipine
MOA of Nifedipine, Amlodipine
Blocks the calcium channel → prevent entry of Ca2+ into cell
Prevent formation of Ca2+-calmodulin complex → MLCK inactivation → no myosin LC activation
No contraction of cell
Relax blood vessels (vasodilation) + Decrease cardiac contractility and CO
Decrease BP
Clinical uses of DHP CCB
- Hypertension
- Stable angina (amlodipine)
- Reduce risk of MI and stroke (amlodipine)
Adverse effects of DHP CCB
- Hypotension
- Heart failure
Which channels do Thiazides act on
Blocks the Na/Cl channel at the distal convoluted tubule
Inhibits Na+ reabsorption and therefore decreased fluid reabsorption
Decrease blood volume → decrease CO → decrease blood pressure
Side effect of Thiazide on Ca2+ reabsorption
Since the Na+/Ca2+ channel at the basolateral aspect, is working better, more Ca2+ is drawn out from the lumen in exchange for Na+ –> hypercalcaemia
Uses of Thiazide
- Hypertension
- Congestive heart failure
- Nephrolithiasis due to idiopathic hypercalciuria (kidney stones)
- Nephrogenic diabetes insipidus
Adverse effects of thiazide
- Hypokalemic metabolic alkalosis
- Hyponatraemia
- Hyperuricemia
- Hyperglycaemia (contraindicated in diabetics)
- Hyperlipidaemia
- Hypercalcaemia
What are 2nd line drugs for HTN
- Alpha adrenergic antagonists
- Hydralazine
Which class of drugs end with -zosins
Alpha adrenergic antagonists
Prazosin, Alfuzosin, Terazosin
MOA of Prazosin
A-adrenergic antagonists oppose a1-mediated vasoconstriction
Keeps the vessel tone lower, reducing peripheral vascular resistance → reduces BP
Can alpha adrenergic antagonists be used in pregnancy
yes
Adverse effects of a adrenergic antagonists
Reflex tachycardia (due to reduced BP)
Depression
Urinary frequency
Flushing
Palpitations
Clinical uses of a adrenergic antagonists
- Symptomatic relief of urine retention due to benign prostate hyperplasia
- Hypertension
MOA of Hydralazine
- Direct arterial vasodilator → decreases peripheral vascular resistance
Inhibits IP3-induced release of Ca2+ from smooth muscle cell sarcoplasmic reticulum - Can trigger compensatory NE/adrenaline release by the sympathetic NS (thus increasing CO and useful in HFrEF)
Clinical uses of Hydralazine
- HFrEF (in combination with isosorbide dinitrate, orally, 1st line)
- Essential hypertension (2nd line)
- Acute-onset, severe peripartum or postpartum hypertension (IV)
Adverse effects of Hydralazine
- Symptoms associated with baroreflex-associated sympathetic activation: Flushing, tachycardia
Hypotension - Hydralazine-induced lupus syndrome (HILS):
- autoimmune- like symptoms
- can be resolved by stopping hydralazine - Contraindicated in coronary HD (because hydralazine stimulates the SNS → increase CO → increase oxygen demand → triggering angina)
