anti-hypertensives + lipid lowering drugs Flashcards
example of ace inhibitor
captopril
enalapril
lisinopril
“PRIL”
MOA of ACE inhibitor
prevents conversion of angiotensin I to angiotension II
effect:
decreased vasoconstriction
decrease aldosterone
prevent breakdown of bradykinin which forms NO and prostaglandin (vasodilation)
use of ACE inhibitor
hypertenion
HF
renal insufficiency
protective effect after MI
AE of ACE inhibitor
hypotension, renal failure, hyperkalemia
drug cough (bradykinin)
contraindicated: pregnancy
example of ang II type I blocker
candesartan
losartan
“SARTAN”
MOA of ang II type I blocker
block binding of Ang II to receptor
contraindicated: pregnancy
advantage of ang II type I clocker over ACE inhibitor
less/no dry cough
- does not prevent breakdown of bradykinin
MOA of beta blockers
block phosphorylation of ATP to cAMP so Ca2+ channel not activated, blocking calcium induced calcium release to trigger bronchoconstriction
examples of beta blockers
non-selective -> propanolol, carvedilol
cardio-selective -> bisoprolol, metoprolol XL
mixed (3rd gen) -> nebivolol
- at low dose, cardio selective
- at high dose, non-selective
AE of beta blockers
CVS: hypotension, bradycardia, heart block
CNS: depression
Contraindicated: asthmatics (bronchoconstriction esp from non-selective)
examples of calcium channel blockers
dihydropyridines
nifedipine
amlodipine
“DIPINE”
MOA of calcium channel blockers
decrease vascular smooth muscle tone -> decrease BP
decrease contractility ->decrease CO -> decrease BP
Uses: stable angina, HTP, protective effect for MI
AE of calcium channel blockers
hypotension, HF, MI
example of diuretics
thiazides
- hydrochlorothiazide
-indapamide
MOA of thiazides
- block NaCl reabsorption at DCT
- less blood volume
- decrease CO
uses of thiazide
CVS: HTP, congestive HF
Renal: kidney stones due to hypercalciuria
- enhance Ca2- reabsorption to since less cations in reabsorbed
AE of thiazides
- hyponatraemia
- hyperuricemia
- hypokalameia
=> NA+ excretion may trigger aldosterone release which causes excretion of K+
- hypokalameia
- hyperglycaemia
=> decrease K+ in pancreatic B cells keeps K+ channels open which causes hyperpolarisation of cell
=> voltage gated Ca channels remain closed so exoctyosis of insulin granules decreased becasue it is activated by calcium influx
what are 1st line hypertensives
beta blockers
ACE inhibitors
calcium channel blockers
diuretics (thiazides)
what are the 2nd line hypertensives
hydralazine
alpha adrenergic antagonists
mineralocorticoid receptor antagonists
examples of alpha adrenergic antagonists
prazosin, alfuzosin, terazosin
“ZOSIN”
MOA of alpha adrenergic antagonsts
oppose alpha 1 mediated vasoconstriction-> decrease peripheral resistance -> decrease BP
PK:
half-life: 7h
reach peak plasma conc in 2.5h (fast acting)
metabolised in liver
AE of alpha adrenergic antagonist
CVS: reflex tachycardia (moment to moment response is to increase HR)
CNS: depression
Renal: urinary frequency
examples of mineralocorticoid receptor antagonsits
eplerenone, finerenone
“erenone”
6 types of lipid lowering drugs
- HMG CoA reductase inhibitor
- PCSK9 inhibitor
- Fibrates
- bile acid binding resin (cholestyramine)
- ezetimibe
- omega 3 acid ethyl ester
examples of HMG CoA reductase inhibitor
atorvastatin, pravastatin, sinovastatin
“STATIN”
MOA of HMG CoA reductase inhibitor
- inhibit HMG CoA reductase -> decreases cholesterol synthesis
- increase LDL receptor on cell surface -> increase peripheral clearance
when to administer HMG CoA reductase inhibitor
give orally in the evening
- less dietary cholesterol in the evening so need to synthesis cholesterol which makes HMG CoA reductase more activ
AE of HMG CoA reductase inhibitor
Hepatotxicity
Myopathy
GI effects
rhabdomyolysis
Contraindicated: pregnancy, breastfeeding, child -> affect neurodevelopment of foetus
examples of PCSK9 inhibitor
monoclonal antibody: evolocumab, alirocumab
“CUMAB”
MOA of PCSK9 inhibitor
by inhibiting PCSK9, prevent LDL receptor degradation (LDL receptor cannot be endocytosed and degraded in lysosome). More LDL receptors on surface so absorb more LDL into cell
* reduce LDL level in blood to doesnt get stuck in blood vessel
can PCSK9 inhibitor be taken orally
Cannot be taken orally because it will be digested since the body considers protein
AE of PCSK9 inhibitor
hypersensitivity, inflammation at injection site, nasopharyngitis, sinusitis
examples of fibrates
gemfibrozil, fenofibrate
MOA of fibrates
interact with PPAR-alpha protein to increase activity of lipoprotein lipase
lipoprotein lipase splits triglyceride -> decrease in VLDL, TG, increase HDL
AE of fibrates
GI effects
rash
gall stones
myositis
MOA of cholestyramine (bile acid binding resin)
bind to bile salts in small intestine
- bile salts emulsify huge fat globules in small intestine and once done, bile salts will be recycled
- when cholestyramine bind to bile salts, bile salts cannot be recycled so hepatocytes use cholesterol to produce bile salts
RESULT: reduce intracellular cholesterol con and increase uptake of LDL cholesterol
Use: LDL elevation in combined hyperlipidemia
AE of cholestyramine
GI effects (nausea, constipation)
impaired absorption of fat soluble vitamins (ADEK)
MOA of ezetimibe
inhibit sterol transporter -> block absorption of cholesterol at small intestine
USe: decrease LDL (used tgt with simvastatin)
AE of ezetimibe
diarrhoea
rhabdomyolysis
reversible hepatotoxicty
MOA of omega 3 acid ethyl esters (EPA+DHA ethyl ester)
decrease TG synthesis by inhibiting diglyceride acyltransferase -> increases free fatty acid breakdown
EPA and DHA ethyl ester are poor substrates because their fatty acids have lots of kinks so cannot fit properly into enzyme binding site
PK: oral, mtabolised by liver
AE of omega acid ethyl esters
- GI effects (constipation, flatulence, pain, diarrhoea)
- increase LDL cholesterol
- increased bleeding time due to decreased production of thromboxane A2
Contradicated: allergic to fish, ppl on anticoagulants
drug specifically indicated for hypertriglyceridemia
fibrates like gemfibrozil
MOA of hydralazine
vasodilation of arterioles -> decrease afterload -> decrease BP
so compensatory release of NE to increase HR so increase venous return and CO
use: HFrEF (systolic dysfunction)
PK:
oral-> HFrEF, essential hypertension (when 1st line anti-hypertensives dont work) => slow onset but long DOA
IV-> severe post partum hypertension (acute onset and short DOA)
AE of hydralazine
- baroreflex associated sympathetic activation -> flushing, hypotension tachycardia
- hydralazine induced lupus syndrome (HILS)
=> arthalgia, myalgia, serositis, fever
=> dose dependent, > 6 mths use
solution: discontinue hydralazine
Contradiction:
coronary artery disease (due to hydralazine activation of SNS -> increase CO and oxygen demand -> worsen myocardial ischaemia)
AE of sacubitril + valsartan
hypotension, hyperkalemia, renal failure, cough (neprilysin breaks down bradykininO)
can diabetic patients be given beta blockers
sympathetic NS alert person when hypoglycemic (increase HR, feel faint)
beta blockers prevent patients from feeling palpitations because beta blockers block contractility of heart, masking symptoms of hypoglycemia
why can’t ACE inhibitors be used for preganancy
potential teratogenic effects
- for statin, it decreases cholesterol but cholesterol impt for neuro development in child
