Anti-Hypertensives Flashcards
ACE-inhibitors?
ACE-I
Lisinopril, Captopril, Enalapril
MOA
ACE inhibition -> Decrease the conversion of AngI to AngII; reduced vasoconstriction and Aldosterone effects
- AngII does vasoconstriction
- Activates sympathetic nervous system (increase HR, vasoconstriction)
- Stimulation of ADH release
- Increased thirst
Bradykinin potentiation -> NO and PG for vasodilation
Indications
Hypertension, Cardiac Failure, Following an AMI, Renal Insufficiency (i.e. reduces the damage done to the glomeruli by high blood pressure)
ADR and C/I
Severe hypotension, acute renal failure (reduced blood flow to kidneys), hyperkalaemia (aldosterone blockage), dry cough (bradykinin) and angioedema (bradykinin together with substance P and prostaglandins is known to have inflammation-like effects)
C/I - PREGNANCY!
Angiotensin II Type 1 Receptor Blockers?
AT1 (Angiotensin II Type 1 Receptor inhibitor)
Losartan, Valsartan, Candesartan, Irbesartan, Telmisartan
MOA
Blocks the Angiotensin II Type 1 receptor
ADR and C/I
Less / no dry cough
STILL C/I IN PREGNANCY
Beta Blockers?
Beta Blockers
Selective - Atenolol, Bisoprolol, Metoprolol XL (Metoprolol succinate and Bisoprolol are also used in HF)
Non-selective - Propanolol, Pindolol, Carvedilol (Carvedilol ALSO USED IN HF)
Variable (dosage and genetic polymorphism) - Nebivolol (also used in HF!)
MOA
Block Beta-adrenergic receptors, thereby inhibiting the downstream signals that would increase heart rate and contractility, thereby decreasing blood pressure.
Nebivolol also encourages NO (because it starts with N lol) production, causing vasodilation
Indications
Htn, HF, Following MI, Arrhythmias, Anxiety
ADR and C/I
Hypotension, Bradycardia, AVN BLOCK and particularly if AVN has previously been compromised.
Reduced exercise capacity.
Bronchoconstriction - Particularly of note in asthmatics. Beta blocking has a sympatholytic effect!
CNS - Vivid dreams, Clinical depression aka Beta blocker blues
Example of calcium channel blockers?
dihydropyridines
Thiazide MOA?
Blocks Na/Cl cotransporter in DCT => Reducing water uptake, Makes the Na/Ca exchanger on basolateral surface work harder. More Calcium influx from passive uptake channels on apical surface
Thiazide / NSAID interaction?
NSAIDs decrease renal PG synthesis, thereby making thiazide diuretics less effective (thiazide action is in part dependent on PG activity)
Indications for thiazide therapy?
Indications
Htn, CHF, Nephrolithiasis due to idiopathic hypercalciuria (makes sense! Thiazides reduce Ca in urine). Nephrogenic diabetes insipidus (yes, MOA is increased water output, but thiazides actually paradoxically increase water uptake in NDI)
ADR of thiazides?
Hypokalemic metabolic alkalosis
Hyponatraemia
Hyperglycaemia from hypokalaemia
Hyperlipidaemia
Hyperuricaemia
Hypercalaemia
Name second-line anti-hypertensives
Hydralazine, Mineralocorticoid antagonists, Alpha antagonists
Hydralazine?
Hydralazine
MOA - Direct arterial vasodilator by inhibiting IP3-induced Ca release from smooth muscle cell sarcoplasmic reticulum, thereby reducing TPR. However, used more in HF because there is compensatory release in NE/E, thereby increasing venous return and CO
Used in HFrEF with isosorbide dinitrate, PO
Second-line because it is used in essential htn when first-line medications are unsuitable / inadequate
Given IV if you want rapid onset in the case of severe peripartum or post-partum htn
IV has a faster onset and lasts longer. PO has a slower onset and lasts shorter
Peak concentration at 2.5h, half-life 7h
ADR, C/I - Baroreflex-associated sympathetic activation! Flushing, hypotension, tachycardia.
Special: Hydralazine-Induced Lupus Syndrome (HILS) that comprises arthralgia, myalgia, serositis, fever (FAMS).
C/I in CAD because we don’t want to stimulate the sympathetic nervous system to increase CO as this would increase oxygen demand and lead to myocardial ischaemia
E.g. of mineralocorticoid antagonists
spironolactone, eplerenone, finerenone
Alpha antagonists?
Alpha antagonists (prazosin, alfuzosin, terazosin)
MOA - Antagonists at post-synaptic alpha-1 adrenergic receptors, opposing A1-mediated vasoconstriction and lowering vessel tone to reduce TPR and hence BP
PK - Peaks at 2.5h and has a T1/2 of 7h with extensive binding to plasma proteins.
ADR, C/I - No renal DA. Safe in pregnancy. Early adverse effects include reflex tachy, palpitations, orthostatic hypotension. These symptoms reduce with following doses. May also have depression, greater urinary frequency because agonism at A1 inhibits contraction of the bladder. For this reason, it is also indicated as symptomatic relief for urinary retention in BPH
