Term
| what are guanethidine, guanadrel, and reserpine? |
|
Definition
| these will deplete catecholamine release (specifically norepi) |
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|
Term
| what is the key for classification of HTN? |
|
Definition
| diastolic pressure, b/c the less your vessels can relax - the more likely a stroke or heart attack |
|
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Term
| what is diastolic normal, pre-HTN, HTN 1, HTN 2 generally? |
|
Definition
| normal: <80, pre-HTN: 80-89, HTN 1: 90-99, HTN 2: >100 |
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Term
| what are 4 mechanisms of increased BP? |
|
Definition
| heart/pump-based HTN (more common in young w/hyperkinetic circulation - PR normal), vascular-based HTN (w/age increased PR, vasoconstriction, normal CO), renal/volume based HTN (increased Na/H2O/fluid retention, increased RAA/CO/PR), and neuroendocrine dysfunction (hyperthyroidism, pheochromocytoma, and hyperaldosteronism) *PR in this case means peripheral resistance* |
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Term
| how does the renin system work? can the sympathetic system stimulate this? |
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Definition
| renin leads to angiotensin I which leads to angiotensin II, which stimulates vasoconstriction and fluid retention (via aldosterone) -> resulting in increased BP |
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Term
| what part of the vasculature is primarily responsible for peripheral resistance? |
|
Definition
| the arterioles (which can contract and control afterload) |
|
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Term
| what are the capacitance venules responsible for? |
|
Definition
| returning blood to the heart (by controlling preload) |
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Term
| what does increased Na inside smooth muscle also increase? how does this affect their function? |
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Definition
| increased Na+ inside the smooth muscle will also lead to increased Ca++ inside the smooth muscle as well via the Na/Ca exchange mechanism. |
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Term
| how does lowering dietary Na+ lead to lower BP (nondrug approach)? |
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Definition
| since increased Na+ = increased intracellular Ca++, and higher Ca++ leads to greater smooth muscle sensitivity to norepinephrine, epinephrine and angiotensin II and an increase in constriction/peripheral resistance |
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|
Term
| what are other non drug approaches to reducing BP besides lowering Na+? |
|
Definition
| diruetic therapy, weight loss, exercise, elimination of stress/anxiety/caffeine |
|
|
Term
| what is the baroreceptor reflex arc? |
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Definition
| if you have an increase in pressure, baroreceptors in the carotid sinus will inhibit the sympathetic tone exerted in the nucleus of the tactus soliarius (motor neuron area in brain stem ) to the alpha/beta receptors |
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Term
| what is the sequence of stepped care in tx of HTN? |
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Definition
| step 1 (diuretic/beta blocker/ACE inhibitor), step 2 (other sympathoplegic agents), step 3 (vasodilator) |
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Term
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Definition
| thiazides decrease peripheral resistance by reducing intracellular Na and Ca which causes vasodilation in the long term (in the short term, they lower blood volume as diuretics). |
|
|
Term
| when are thiazides used? loop diuretics? |
|
Definition
| mild to moderate HTN (diastolic between 90 and 99). loop diuretics are used for severe HTN. |
|
|
Term
| what are ADRs associated with thiazides? |
|
Definition
| diuretics can interfere with both compensatory reflexes, the baroreceptors and the RAA |
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|
Term
| when are loop/K+ sparing diuretics indicated for HTN? |
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Definition
| loop/K+ sparing diuretics are combined with thiazides pts with CHF w/decreased renal function to maintain normal K+ levels (spironolactone is particularly useful in CHF) |
|
|
Term
| will thiazides or loops help against osteoporosis? |
|
Definition
| thiazides wouldn't hurt it |
|
|
Term
| when vasodilators are administered, what are the body's automatic reflexes? |
|
Definition
| vasodilator drugs decrease vascular resistance (promote vasodilation) which 1) increases renin in the kidneys, increasing angiotensin II, which increases vascular resistance/aldosterone secretion. 2) the decrease in vascular resistance is also picked up by the baroreceptor reflex in the carotids which leads to increased sympathetic outflow to the heart/arteries |
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Term
| how are the body's automatic reflexes to vasodilator drugs combated with other drugs? |
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Definition
| diuretics can block the effect of renin on increasing BP (by increasing fluid retention) and beta blockers can limit the sympathetic system's ability to raise HR and vascular resistance |
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|
Term
| what is the main action of beta blockers in tx of HTN? |
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Definition
| beta blockers depending on selectivity, metoprolol/atenolol/acebutolol/esmolol are all beta1 selective, meaning HR is decreased, force of contraction is decreased, and velocity of contraction is decreased and by extension decrease renin -> used to interfere with compensatory reflexes |
|
|
Term
| can beta blockers reduce mortality in pts w/LVH? |
|
Definition
|
|
Term
| what are ADRs associated with beta blockers? |
|
Definition
| esp with propanolol, which is lipid soluble (affects CNS): wild dreams, increase in cholesterol, impotence, fatigue, and masking of hypglycemia |
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|
Term
| what is the mechanism of action for labetalol/carvedilol? |
|
Definition
| these are both alpha-1 and beta 1+2 blockers. this decreases PR and CO, and gives a more balanced approach to inhibiting the SNS. |
|
|
Term
| when are labetolol and carvedilol used? ADRs? |
|
Definition
| labetolol and carvedilol are used in HTNsive emergencies, pheocytochroma, and as a second line drug in tx of moderate-severe HTN. ADRs: hypotension, too low of a drop in BP |
|
|
Term
| what is the effect of alpha 1 blocker administration? |
|
Definition
| alpha 1 blockers such as prazosin can be used to maintain BP from HTN. these will decrease peripheral resistance, will block any kind of vasoconstriction on venous beds. in CHF, CO can be increased, b/c it will not have to work as hard. HDLs may be increased as well as some Na+ retention |
|
|
Term
| what are some ADRs associated with prazosin? |
|
Definition
| selective alpha 1 blockers can cause postural hypotension, reflex tachycardia, nasal congestion and impotence |
|
|
Term
| what is the benefit of alpha 2 receptors in terms of HTN? |
|
Definition
| presynaptic alpha 2 receptors in the periphery/CNS bind to receptors - exerting negative feedback and decrease further NE release. postsynaptic alpha 2 receptors in the CNS inhibit SNS outflow from the vasomotor/cardiac centers to decrease vasomotor tone, BP, and HR |
|
|
Term
| how are alpha 2 and beta receptors opposites? |
|
Definition
| both are linked to G proteins, but beta are GS (stimulatory) and alpha are GI (inhibitory) on levels of cAMP release that ultimately controls Ca++ levels |
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|
Term
| what is the main mechanism of clonidine? |
|
Definition
| this alpha 2 agonist inhibits adrenergic outflow to the SNS by stimulating alpha 2 receptors in the CNS-NTS, as well as binding to the nonadrenergic-imidazole binding site that decreases SNS outflow and BP |
|
|
Term
| what is the end result of clonidine administration? how is it administered? |
|
Definition
| decreased BP/HR/renin, and incresed PNS/vagal tone. it is administered IV only |
|
|
Term
| what are ADRs for clonidine? |
|
Definition
| dry mouth, CNS sedation/depression, decreased HR/Na/H2O retention, and post tx syndrome (increased SNS - hypertensive crisis) with abrupt cessation |
|
|
Term
| what is methyldopa? what is it used for? |
|
Definition
| another alpha 2 agonist, which uses the same M/A as clonidine, but has less of an effect on HR (acts as methyl-NE). it is safe in pregnancy. it is usually used as a diuretic to prevent fluid retention |
|
|
Term
| what are ADRs for methyldopa? |
|
Definition
| CNS sedation, autoimmune disorders (*hemolytic anemia*, jaundice, lupus-like syndrome), anemia |
|
|
Term
|
Definition
| a direct-acting arteriolar vasodilator, via decreasing diastolic pressures and peripheral resistance. the exact MA is not known, (may interfere with IP3 action to release Ca from SR) |
|
|
Term
| can hyralazine activated baroreceptor/RAA reflexes? |
|
Definition
| yes, so it usually requires a diuretic + beta blocker |
|
|
Term
| what are ADRs associated with hydralazine? |
|
Definition
| excessive vasodilation, edema flushing, headache, reflex HR, immune reaction resembling lupus syndrome/rash/arthralgia |
|
|
Term
| what is the mechanism for alpha 1 receptors? |
|
Definition
| IP3 – second messenger that releases stored calcium to allow for interaction of myosin light chain kinase |
|
|
Term
| what is minoxidil? when is it used? |
|
Definition
| an arteriolar dilator that opens up K+ channels and hyperpolarizes smooth muscle membranes (similar to adenosine), causing it to relax (harder to fire APs). it is used in severe HTN, when other drugs don't work (has to be combined with diuretic and beta blocker) |
|
|
Term
| what are ADRs for minoxidil? |
|
Definition
| reflex tachycardia, Na+ retention, and hair growth |
|
|
Term
| what drugs are used for HTNsive crises? |
|
Definition
| nitroprusside, diazoxide (infrequent use), and fenolapam (dopamine-1 agonist) |
|
|
Term
| what are hypertensive crises usually caused by? |
|
Definition
| malignant HTN characterized by severe increased BP, papilledema, acute renal insufficiency, encephaolpathy, and a fibroid arterial necrosis (life threatening) |
|
|
Term
| what is the M/A for nitroprusside? |
|
Definition
| nitric oxide activates cyclic GMP, which inactivates the myosine light chain kinase (which is why its very fast acting) |
|
|
Term
| what are ADRs for nitroprusside? |
|
Definition
| hypotension, reflex tachycardia. breaks down into thiocyanate and can be toxic to cause you to have convulsions (can give sodium thiosulfate as an antidote) |
|
|
Term
| what is diazoxide? when is it used? |
|
Definition
| diazoxide is a thiazide-like arteriolar dilator that activates/opens K+ channels (hyperpolarizing the arterial smooth muscle). it has no diuretic activity. *it is used only in emergencies, and requires noncomitant use of a beta blocker to control reflex tachycardia/release of renin |
|
|
Term
| what are ADRs associated with diazoxide? |
|
Definition
| excessive hypotension, tachycardia/angina, and Na/water retention |
|
|
Term
| what are the 2 main groups of Ca channel blockers? |
|
Definition
| verapamil/dilitiazem and nifedipine |
|
|
Term
| what characterizes verapamil and diltiazem? |
|
Definition
| verapamil and diltiazem will decrease HR, AV node conduction, and contraction of the cardiac muscle independent of their effects on the smooth muscle - therefore these drugs are the preferred tx for chronic HTN. verapamil exerts more action on the heart and also may cause *constipation. caution needs to be used if administered in conjunction with beta blockers (risk of excessive depression of contractility) |
|
|
Term
| what are the 3 indications for verapamil so far? |
|
Definition
| anti-anginal, anti-arrhythmic, and anti-HTN |
|
|
Term
| what characterizes the dihydropyridines such as nifedipine? |
|
Definition
| nifedipine functions more as an arterial dilator, it is short acting and is good for IV acute situations. it can trigger reflex increase in HR, exacerbate myocardial ischemia, cause excessive dilation (lightheadness/dizziness), and may increase the risk of MI in certain pts with coronary artery disease |
|
|
Term
| what is the difference between the ACE inhibitors and the angiotensin receptor blockers? |
|
Definition
| the angiotensin converting enzyme inhibitors not only stop progression of angiotensin I -> II, but also the breakdown of bradykinin, which increases prostaglandin synthesis. increased prostaglandin synthesis will then lead to vasodilation. the angiotensin receptor blockers simply block angiotensin from causing vasoconstriction or stimulating secretion of aldosterone (which increases Na/H2O retention) |
|
|
Term
| what is the effect of ACE inhibitor administration? |
|
Definition
| decreased angiotensin II (decreased vasoconstriction/PR), increase bradykinin (increases PG/NO -> vasodilation). both pre- and afterload are decreased, CO in CHF is increased, renal flow/function are increased |
|
|
Term
| what are ADRs associated with ACE inhibitors? |
|
Definition
| GI, hypotension, rash, cough/wheezing/angioedema, K retention/hyperkalemia (due to lack of aldosterone - which usually keeps Na and kicks out K). contraindicated in 2-3 trimester pregnancy and those with bilateral renal stenosis |
|
|
Term
| do ACE inhibitors cause metabolic disadvantages or impotence? |
|
Definition
|
|
Term
| what are the 3 ACE inhibitors we need to know? |
|
Definition
| captopril, enalapril, and lisinopril |
|
|
Term
|
Definition
| a rapid onset/short duration, bioavailability decreased by food, has an SH group, dysgeusia |
|
|
Term
|
Definition
| prodrug, once a day. active metabolite: enalaprilat (pril->lat) |
|
|
Term
|
Definition
|
|
Term
|
Definition
| a competitive angiotensin II receptor (AT-1) blocker. it is an active prodrug, and is particularly effective in the arterial small muscle, kidney, and adrenal gland. |
|
|
Term
| what are ADRs for losartan? |
|
Definition
| similar to ACE inhibitors (except for cough/andioedema), excessive hypotension, dizziness, headache, fatigue, increased liver enzymes (b/c metabolized in the liver), hyperkalemia, and contraindication during pregnancy |
|
|
Term
| does losartan, an angiotensin II receptor blocker increase bradykinin or subsequent prostaglandin synthesis? |
|
Definition
|
|
Term
| what are good AHPT drugs for the african american population? |
|
Definition
| diuretics, Ca blockers. beta blockers/ACEIs are less preferred |
|
|
Term
| what are good AHPT drugs for pts with edema/CHF? |
|
Definition
|
|
Term
| what are good AHPT drugs for pts w/prostatic hypertrophy, CHF, and peripheral vascular disease? |
|
Definition
|
|
Term
| what are NOT good AHPT drugs for pts w/asthma, sick sinus, brittle diabetes? |
|
Definition
|
|
Term
| what are good AHPT drugs for pts with angina? |
|
Definition
| Ca blockers, beta blockers |
|
|
Term
| what are good AHPT drugs for pts with CHF, diabetes, post MI? |
|
Definition
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