anti-hypertensive drugs Flashcards
Name 5 complications of hypertension
- atherosclerosis
- diabetes
- blindness
- renal failure
- aneurysm and stroke
what is primary htn
aka essential
- unknown origin
- MUCH more common (85%)
- usually asymptomatic
- treatable BUT NOT CURABLE
what is secondary hypertension
- rapid in onset
- more severe
- symptomatic
- endocrine disorders, medications, renal disease, obesity, congenital heart defects, lifestyle
- CURABLE POTENTIALLY (solve acute case)
What is goal of htn therapy
- noramlize blood pressure and prevent end organ damage
Give systolic/diastolic for:
normal
pre-HTN
Stage 1
Stage 2
120/80
120-139/80-89
140-159/90-99
> 160/>100
Name the 5 clases of anti-HTN drugs
- vasodilators
- sympatholytics
- alpha-1 and beta adrenergic blockers
- angiotensin inhibitors
- diuretics
What drugs affect the heart most?
- beta blockers
- peripherally acting sympatholytics
- cardioselective calcium channel blockers
What drugs affect the kidney most
- diuretics
- angiotensin inhibitors
- beta blockers
- peripherally acting sympatholytics
what drugs affect the vessels most
- alpha-1 blockers
- angiotensin inhibitors
- diuretics
- direct vasodilators
- calcium channel blockers
- peripherally acting sympatholytics
what drugs affect brain most
- beta blockers
- centrally acting sympatholytics
What anti htn meds affect co
- beta blockers
- angiotensin inhibitors
- diuretics
- sympatholytics
what anti htn meds affect TPR
- beta blockers (INDIRECTLY..?)
- angiotensin inhibitors
- diuretics (unknown why)
- sympatholytics
- vasodilators
- alpha-1 blockers
how does calcium regulate smooth muscle tone
- calmodulin and MLC kinase is inactive; calcium binding makes it activeand can phosphorylate the myson light chain which can then go through actin-myosin crossbridging to get contraction of muscle scell and the constriciton of the blood vessel
what are the 3 relaxation pathways?
- cAMP (PKA)
- endothelium dependent (cGMP and PKG)
- hyperpolarization ( K+ efflux inhibits L-type CA2+ channel activity)
vasodilator drugs directly only reduce _____
tpr
what is the indirect effect of vasodilators
- compensatory reflex (sympathetic reflex
describe how the compensatory reflex comes about
- vasodilator –> VSMC relaxation –> decrease TPR –> Decreased BP
kidneys sense decrease bp to increase renin and incrase aldosterone, which decreases na+ excretion to increase volume and increase CO while incresaeing bloop pressure
- Barosensors from decreased BP also increase sympathetic tone to increase TPR and to increase the renin
VASODILATORS STILL HAVE A NET WINNING EFFECT EVEN WITH THE COMPENSATORY REFLEX
What are the 3 classes of vasodilator drugs
- potassium channel blockers
- organic and inorganic nitrates
- calcium channel blockers
Prototypicak potassium channel opener and its target
- minoxidil –> Katp channels
give mechanism of minoxidil
- open potassium channels to lead to potassium efflux, cell hyperpolarization… inhibits voltage sensitive L-types to reduce ca2+ and cause relaxation
why are hydralazine and diazoxide unique
- Very direct and very strong vasodilators
main indication of potassium channel openers
- HTN uncontrolled by other drugs
- HTN emergency
- severe HTN
- research
Main side effects of drugs of potassium channel blockers
- strong inducers of sympathetic reflex
- increases volume retention and cardiac rate and contractility… can reveal myocardial ischemia and arrythmia
what are dihydropyridines not good at? why?
- don’t bind well to L-type channels in heart
- because binding is voltage dependent… VSMC RMP are more positive, which dihydropyridines can bind well in… but cardiomyocytes are less polar, and dihydropyridines can’t bind well
amlodipine is a _______
dihydropyridine calcium channel blocker
indications of calcium channel blockers
- mild to moderate HTN
- reduces TPR
- cardiac ischemia
main adverse effects of dihydropyridines… why?
- 2.5 fold incrased risk of death with short acting (quick releasing) dihydropyridines because of sympathetic reflex
What two compounds are broken off of nitrovasodilators by enzymatic activities… what is their fate?
- cyanide – thiolated then sent to renal for elimination
2. nitric oxide- vasodilation
indications of sodium nitroprusside
- Hypertensive emergencies TO REDUCE AFTERLOAD
- reduce bleeding during surgery
- acute cardia ischemia (to decrease preload and afterload, and thus decrease cardiac work
what is the toxicity of sodium nitroprusside
- CN poisoning when high infusion rates overwhelm SCN synthesis
T/F tolerance does not occur with inorganic nitrates like sodium nitroprusside
- False… just different mechanism
Name the two centrally acting sympatholytic drugs
- methyldopa
2. clonidine
both methyldopa and clonidine are _____ receptor selective agonists… what’s the difference between them?
alpha-2; methyldopa is a prodrug, clonidine is direct
give prodrug pathway for methyldopa
methyldop –> methyldopamine –> methylnorepinephrine
what is the overall goal of clonidine and methyldopa?
- inhibiting sympathetic outflow from brainstem
indications of methyldopa/clonidine
- HTN when resistant to other treatments
- decrease TPR and reduce CO
side effects of methyldopa/clonidine
- dampens sympathetic reflexes (sympathectomy)
- sedation
- nausea
- Withdrawal syndrome
almost makes them seem sicker than they are because of side effects
What is the prototypical sympatholytic and what does it do generally?
- trimethaphan (non-depolarizing inhibitors of ganglionic nicotinic cholinergic receptors)
indications of trimethaphan
- create controlled hypotension
2. dampen spinal autonomic reflex during spinal cord injury
What is the classic alpha-1 andrenergic anatagonist and what does it generally do?
- prazosin
- blocks vasoconstrictor effect of sympathetic tone to reduce TPR
indications of alpha-1 blocker uses
- monotherapy for mild to moderate HTN
- symptomatic prostate hypertrophy
Side effects of alpha-1 blocker uses
- first-dose phenomenon –> postural hypotension … worsens and impairs recovery from orthostatic hypotension
describe why postural hypotension occurs
- normally, you have sympathetic activation kicking in after standing up to correct postural hypotension
- with alpha blockers… you’re dropping your blood pressure more AND you can’t get reflex as much.. so you can’t repair as well
name the non-selective beta receptor antagonist
beta -1 selective
mixed alpha1-AR, beta-AR antagonist
- propranolol
- metoprolol
- carvedilol
mechanism of antihypertensive action of betablockers
- negative inotropic and chronotropic effect in heart to reduce cardiac output
what’s the secondary effect of beta blockers
- inhibits sympathetic mediated renin release to indirectly lower TPR
______ is gold standard anti-HTN therapy
- propranolol
________ is better for asthmatics
- metoprolol
side effects of beta blockers
- exercise intolerance, so non-ideal drug for active people (because reduciton of cardiac output)
Impotence
The only cells that produce ACTIVE renin are ______
JG- cells… renal juxtaglomerular
what are triggers of renin-angiotensin system?
- low pressure
- low sodium in distal tubule or low flow
- increased sympathetic nervous system activity
what does renin do?
- converts angiotensinogen to angiotensin I
how is Angiotensin II formed?
what else does this do?
- via ACE… also inactivates bradykinin
what is role of angiotensin II
- binds to AT1 receptor and activates it (at arterioles and adrenal gland_)… you get synthesis of aldosterone at adrenal gland… and you increase resistance at arteries
** aldosterone increases sodium/h20 reabsorption to increase blood pressuer
Name 3 renin-angiotensin system inhibitors
- renin inhibitors –> aliskren
- ACE inhibitor –> “Prils” –> LISINOPRIL
- AT1-R antagonist … sartans (LOSARTAN)
Out of ACE inhibitors, AT-1 antagonists, and Renin inhibitors, which:
- are teratogenic
- disrupt electrolyte homeostasis
- Reduce GFR with renal artery stenosis
- angiodema/cough
- all
- all
- all
- only ACE inhibitors (because you increase bradykinin levels, which causes cough)
Name 3 main diuretics used for HTN… what is the gold standard? when do you use the other 2
- thiazide (GOLD STANDARD FOR MILD HTN)
- K+ sparing (adjuvant)
- Loop diuretics (only in refractory HTN)
why do you get sustained antihypertensive effect from diuretics?
- decrease total peripheral resistance… not really because of change in plasma volume or cardiac output
TPR lowering is the mechanism, although unknown
two examples where you don’t use thiazide
- post myocardial infarction
2. chronic kidney disease (because kdineys aren’t working well anyway
