Microzide (capsule), Oretic, Esidrix
Amiloride (potassium sparing diuretic)
Triamterine + HCTZ
Guanabenz (Centrally acting alpha agonist)
Prazosin (Alpha blocker)
Amlodipine + Benazapril
Enalapril + Felodipine
Trandalopril + Verapamil
Amlodipine + Telmisartan
Amlodipine + Valsartan
Amlodipine + Olmesartan
Aliskiren + Amlodipine
Aliskiren + HCTZ
Aliskiren + Amlodipine + HCTZ
Aliskiren + Valsartan
Benazepril + HCTZ
Captopril + HCTZ
Lisinopril + HCTZ
Moexpril + HCTZ
Quinapril + HCTZ
Fosinopril + HCTZ
Candesartan + HCTZ
Eprosartan + HCTZ
Irbesartan + HCTZ
Losartan + HCTZ
Telmisartan + HCTZ
Valsartan + HCTZ
Olmesartan + HCTZ
Atenolol + Chlorthalidone
Bisoprolol + HCTZ
Propranolol + HCTZ
Metoprolol + HCTZ
Nadolol + Bendroflumethiazide
Timolol + HCTZ
Methyldopa + HCTZ
Reserpine + Chlorthiazide
resperine + HCTZ
Hydralazine + HCTZ
Amlodipine, Valsartan and HCTZ
Amlodipine, olmesartan and HCTZ
what are sysmptoms of very high blood pressure?
head ahce ,throbbing, fatcige and SOB
What are the 5 classes of standard antihypertensive drugs?
1. diuretics, 2. _-adrenoceptor antagonists (_-blockers) 3. Ca-channel blockers 4. inhibitors of angiotensin (ACE-inhibitors/AT1-blockers) 5. _-adrenergic blockers
what are the centrally acting antihypertensive drugs?
1. clonidine, 2. methyldopa 3. reserpine
what are the vasodilators?
1. nitrates, 2. nitroprusside 3. dihydralazine
what is a normal SBP?
what is a prehypertension SBP?
what is a stage 1 hypertension SBP?
what is a stage 2 hypertension SBP?
what is a normal DBP?
what is a prehypertension DBP?
what is a stage 1 hypertension DBP?
what is a stage 2 hypertension DBP?
what drugs are indicated for prehypertension without compelling indication?
no antihypertensive drug indicated
what is the initial drug therapy for stage 1 hypertension without compelling indication?
Thiazide diuretics for most.May consider ACEI, ARB, BB, CCB, or combination.
what is the initial drug therapy for stage 2 hypertension without compelling indication?
2 drug combination for most: usually thiazide diuretic and ACEI or ARB or BB or CCB
what is the initial drug therapy for prehypertensive and stage 1 hypertensive patients with compelling indications?
drugs for the compelling indications
What is the initial drug therapy for stage 2 hypertensive patients with compelling indications?
1. drugs for the compelling indications 2. other antihypertensive drugs (diuretics, ACEI, BB, CCB) as needed.
What is the relative risk of stroke in hypertensive vs. normotensive patients?
what is the relative risk of CAD in hyptertensive vs. normotensive patients?
what is the relative risk of heart failure in hypertensive vs. normotensive patients?
what is the relative risk of peripheral vascular disease in hypertensive vs. normotensive patients?
what kind of compound is clonidine?
_2-sympathomimetic drug, 2nd choice in treatment of hypertension, with interesting off label uses
what are the relevant pharmacokinetics of clonidine? How excreted, half life
p.o.; i.v.; transdermal patch:t1/2 = 8-12h mainly renal excretion
what are the relevant pharmacodynamics of clonidine?
1. centrally mediated hypotensive effects: a. reduction of cardiac output b. relaxation of capacitance vessels c. reduction of peripheral resistance 2. renal blood flow maintained 3. initial hypertensive episode may occur 4. various CNS effects 5. pronounced rebound effect after
what are the adverse effects of clonidine?
high doses/predisposition:1. symptomatic bradycardia 2. AV-block 3. functional cardiac failure 4. dry mouth 5. drowsiness 6. sedation 7. constipation 8. mental depression
What is the primary use of clonidine?
second line treatment of hypertension
what are the other (empirical) clinical uses of clonidine?
1. symptomatic treatment of withdrawal syndromes (heroin, alcohol, benzodiazepenes) 2. prevention / treatment of alcoholic delirium 3. postmenopausal syndrome 4. refractory diarrhea (short bowel syndrome) 5. adjunct in analgo-sedation (dexmedetomidine)
What type of compound is methyldopa?
centrally acting antihypertensive drug
is methyldopa safe for use in pregnancy?
what are the relevant pharmacokinetics of methyldopa?
p.o.:t1/2= 4-6h, up to 24h including active metabolites
what are the adverse effects of methyldopa?
centrally mediated hypotensive effects quite comparable, but not identical to clonidine
what are the important prototypical _1-blockers and their half lives?
1. prazosin (3-4h) 2. terazosin (12h) 3. doxazosin (22h)
what are the relevant pharmacokinetics of the _1-blockers?
po or iv
what are the relevant pharmacodynamics of _1-blockers?
1. blockade of _1-receptors in arterioles/venules 2. NO effect on pre-synaptic _2-receptors 3. NO effect on inhibitory feedback for NE release
what are the adverse effects of _1-blockers?
1. first dose phenomenon 2. orthostatic hypotension 3. dizziness 4. palpitations 5. headache 6. tests for ANA may turn positive 7. reflex tachycardia
what are the first choice diuretics in the treatment of hypertension?
thiazides like HCTZ
what are the second choice diuretics in the treatment of hypertension?
K+ sparing diuretics:amiloride, triamterene spironolactone
what is the choice diuretic for treatment of hypertension in patients with GFR < 30ml/min or refractory hypertension?
1. loop diuretic like furosemide2. thiazide type metolazone
what are the rules for routine use of thiazides?
1. low dose thiazide, may already work at sub-diuretic doses within 2-4 weeks; to be taken in the morning2. if hypokalemia is a problem, combine with K+ sparing diuretic but watch for hyperkalemia with this combination 3. keeping the patient "on dry weight" may be a good thing, BUT, dehydration may cause mental confusion, may aggravate COPD, or peripheral arterial occlusive disease 4. important adverse effects: hypokalemia, impaired glucose tolerance, hyperlipidemia
what are the relevant pharmacokinetics of metolazone?
1. oral bioavailability 65% 2. t1/2 = 8-10h 3. duration of action 12-24 h
what are the pharmacodynamic of metolazone similar to?
thiazide diuretics like HCTZ
what is the difference in the pharmacodynamics of metolazone vs. HCTZ?
also effective at GFR <30ml/min
what are the uses of metolazone?
1. hypertension (low dose 1.25 - 2.5 - 5mg) also used in combination treatment 2. edema (10-20 mg) 3. can replace other thiazides in combination treatment of furosemide resistance
what are the _-adrenoceptor antagonists and their respective selectivities?
1. propanolol (_1 + _2, non selective) 2. atenolol (_1 > _2) 3. metoprolol (_1 > _2) 4. pindolol (partial agonist, ISA) 5. labetalol (4 isomers, _-blocker & _ blocker, _2-agonist) 6. carvedilol (2 isomers, _-blocker, _-blocker) 7. esmolol (_1 > _2, short acting, emergency med)
what is the specificity of propanolol?
_1 and _2, non-selective
what is the specificity of atenolol?
_1 > _2
what is the specificity of metoprolol?
_1 > _2
what is the specificity of pindolol?
partial agonist, ISA
what is ISA?
intrinsic sympathomimetic activity
what is the specificity of labetalol?
4 isomers, _&_-blocker, _2-agonist
what is the specificity of carvedilol?
2 isomers, _-blocker, _-blocker
what is the specificity of esmolol?
_1 > _2, short acting, emergency med
when does one NEVER prescribe _blockers and why?
never use beta-blockers in asthma or COPD because _1-selectivity is relative
when are unselective _blockers contraindicated?
1. pregnancy 2. Diabetes Mellitus
in what condition is the use of _-blockers tricky?
what are some of the many conventional contraindications of _-blockers?
1. asthma 2. COPD 3. PAD 4. SA or AV-node abnormalities
what effect do _blockers have on LDL?
what effect do _blockers have on HDL?
what effect do _ blockers have on triglycerides?
what effect do _1blockers have on LDL?
what effect do _1-blockers have on HDL?
what effect do alpha 1 blockers have on triglycerides?
how do _1 blockers affect insulin sensitivity?
they do not affect insulin sensitivity
what changes in cardiac output do _1blockers produce?
minimal changes in cardiac output
do _1 blockers cause cold extremity syndrome?
they do not
do _-blockers cause orthostatic hypotension?
they do not
what are the prototypical calcium channel blockers?
1. verapamil 2. diltiazem 3. nifepidine (and dihydropyridines)
what are the relevant pharmacokinetics of calcium channel blockers?
p.o.; i.v.: highly bound by serum proteins, hepatic metabolism, renal excretion
how are calcium channel blockers eliminated?
1. metabolized in liver 2. excreted by kidney
what are the relevant pharmacodynamics of calcium channel blockers?
1. block L-type calcium channels -->cardiodepressant effects 2. arteriolar vasodilation
what are the adverse effects of dihydropyridines?
due to excessive vasodilation: 1. dizziness 2. headache 3. flushing 4. digital dysaesthesia 5. nausea 6. peripheral edema 7. constipation 8. reflex tachycardia
what are the adverse effects of verapamil and diltiazem?
1. bradycardia 2. slow SA and AV conduction 3. increase digoxin levels in the blood
how do short acting calcium channel blockers affect risk of myocardial infarction?
the use of short acting Ca channel blockers nifedipine, diltiazem, and verapamil was associated with an increased risk of myocardial infarction
what is the onset and duration of verapamil, nifedipine, and diltiazem?
fast onset short acting
what are the 1st generation Ca channel blockers?
verapamil SR nifedipine GITS
what are the second generation calcium channel blockers?
1. amlodipine 2. felodipine 3. nisoldipine 4. isradipine
what are the second generation ca channel blockers which are long acting?
1. amlodipine 2. felodipine 3. nisoldipine
what are the slow onset second generation ca channel blockers?
1. amlodipine 2. felodipine
What are the 2 types of inhibitors of angiotensin?
1. ACE- inhibitors 2. AT1- Blockers
What are the prototypical ACE Inhibitors?
1. captopril 2. enalapril 3. enalaprilat 4. lisinopril 5. benazepril 6. fosinopril 7. moexipril 8. quinapril 9. ramipril
what are the ACE inhibitors used for?
all used to treat hypertension some also labelled for use in CHF
what are the prototypical AT1-blockers?
1. losartan2. valsartan
what is losartan used for?
labelled for hypertension and CHF
what is valsartan used for?
what are the relevant pharmacokinetics of captopril?
po: renal elimination
what are the relevant pharmacodynamics of captopril?
Angiotensin II antagonism: - decrease vasoconstriction - decrease norepinephrine release - decrease aldosterone secretion - Vasodilation Bradykinin related: - no reflex tachycardia - no significant change in cardiac output - no water and sodium retention - some reduction of sympathetic tone
how is captopril eliminated?
what are the effects of captopril on the vasculature?
vasodilation, decrease vasoconstriction
what are the effects of captopril on the sympathetic nervous system?
decrease NE releasesome reduction of sympathetic tone
what is the effect of captopril on aldosterone secretion?
decrease aldosterone secretion
is reflex tachycardia associated with captopril?
is a significant change in cardiac output associated with captopril?
is sodium/water retention associated with captopril?
what are the adverse effects of captopril?
1. hypotension2. dry cough, bronchospasm 3. skin rashes, angioneurotic edema 4. neutropenia, leukopenia 5. taste perversion 6. hyperkalemia 7. proteinuria
what conditions are contraindications of captopril?
1. renal artery stenosis 2. renal failure 3. history of angioedema (asthma, COPD) 4. pregnancy (oligohydramnion)
what are the signs of captopril toxicity?
hypotension without marked tachycardia
what are the unwanted interactions associated with captopril?
1. NSAIDs reduce antihypertensive response by inhibition of the bradykinin pathway2. K+ sparing diuretics aggravate hyperkalemia 3. hypersensitivity reactions to other drugs may be aggravated 4. increased plasma levels of digoxin, lithium
what are the wanted interactions associated with captopril?
K+ wasting diuretics yield over-additive antihypertensive effect
elalapril is the prodrug of what?
how is enalapril converted into enalaprilat?
what are the relevant pharmacokinetics of enalapril?
po:tmax=3-4h t1/2=11h renal elimination start with 2-5mg/d up to a maximum 40 mg/d
what are the relevant pharmacokinetics of enalaprilat?
iv: use in hypertensive emergencies
what is the tmax of enalapril?
what is the t1/2 of enalapril?
how is enalapril eliminated?
how is enalapril dosed?
start with 2.5-5 mg and increase up to 40mg/d
when is enalaprilat used?
iv in hypertensive emergencies
how do the pharmacodynamics and adverse effects of enalapril compare to captopril?
enalapril is: more potent slower onset/longer duration of action compound contains no sulfhydryl group (no taste perversion)
what proportion of ACE inhibitors are prodrugs?
most are prodrugs
what makes fosinopril and moexipril different than all other ACE inhibitors?
fosinopril and moexipril are eliminated by the liver and all others are eliminated by the kidneys
do ACE inhibitors have variable influence on tissue specific AG subsystems?
this remains to be verified
what are the indications for ACE inhibitors?
1. hypertension 2. CHF 3. Myocardial Infarction 4. Progressive renal disease (DM nephropathy)
what type of drug is losartan?
Angiotensin II receptor subtype 1 blocker (AT1 blocker)
what are the relevant pharmacokinetics of losartan?
po: bioavailability=33% t1/2= 2h active metabolite t1/2= 6-9h hepatic elimination usual dose 50-100 mg/d
what are the relevant pharmacodynamics of losartan?
Like ACE inhibitors: - decrease vasoconstriction - decrease NE release decrease aldosterone secretion Unlike ACE inhibitors: no effect on bradykinin
what are the adverse effects of losartan?
Like ACE inhibitors except for bradykinin related AE: no cough - no angioedema
what conditions are contraindicated in the use of losartan?
1. renal artery stenosis2. renal failure 3. pregnancy
What is the first step in the guidelines for treatment for hypertension?
1. Single drug therapy- THIAZIDE or _BLOCKER... or Ca channel blocker or ACEI or Alpha Blocker
what is the second step in the guidelines for the treatment for hypertension?
2. Combination Therapy- a. combine a thiazide with a _blocker/CaChannel blocker/ACEI (or _1 blocker) b. combine Ca channel blocker with a _blocker/ACEI
what is the third step in the guidelines for treatment of hypertension?
3. Triple therapy between drugs listed above (thiazide/_b/CaCB/ACEI/_B)or add furosemide or add clonidine
Which antihypertensives are contraindicated in COPD, Asthma?
_ Blockers ACE inhibitors
which antihypertensives are contraindicated in Bradycardia?
clonidine _ blockers Verapamil/Diltiazem
which antihypertensives are contraindicated in Diabetes Mellitus?
ThiazidesUNSELECTIVE _ Blockers
which antihypertensives are contraindicated in Gout?
which antihypertensives are contraindicated in CAD?
which antihypertensives are contraindicated in peripheral artery occlusive disease?
which antihypertensives are contraindicated in CHF?
Ca++ antagonists HIGH DOSE _Blockers
which antihypertensives are contraindicated in Renal Failure?
Amiloride Triamterene Spirololactone ACE Inhibitors
why are _ Blockers contraindicated in COPD/Asthma?
Induction of bronchospasm
why are ACE Inhibitors contraindicated in COPD/Asthma?
induction of cough, Use AT1 blocker
why are clonidine, _Blockers, Verapamil/Diltiazem contraindicated in Bradycardia?
aggravation, risk of Adams-Stokes syndrome
why are thiazides contraindicated in DM?
reduce glucose tolerance
why are unselective _ Blockers contraindicated in DM?
blunt symptoms of hypoglycemia
why are thiazides contraindicated in Gout?
reduced excretion of uric acid
why are hydralazine, prazosin, and minoxidil contraindicated in CAD?
provocation of angina pectoris (reflectory tachycardia)
why are _ Blockers contraindicated in peripheral artery occlusive disease?
why are Ca++ antagonists and high dose _ Blockers contraindicated in CHF?
why are amiloride, triamterene and spironolactone contraindicated in renal failure?
may cause hyperkalemia
why are ACE inhibitors contraindicated in Renal failure?
plasma concentration increases--> side effect
what are the positive criteria for the selection of Diuretics for Tx of hypertension?
old age black race CHF chronic renal failure (loop diuretics)
what are the positive criteria for the selection of _ blockers in the Tx of hypertension?
youth white race post-MI migraine senile tremor atrial fibrillation PSVT
what are the positive criteria for selection of long acting Ca channel blockers in the Tx of hypertension?
old age black race migraine
what are the positive selection criteria for the selection of ACE inhibitors in the Tx og hypertension?
youth white Diabetes Mellitus Type I w/ nephropathy impotence from other drugs NOT IN PREGNANCY
what are the positive criteria for selection of AT1-blockers in the Tx of hypertension?
conditions for which ACEI are indicated, but can't be used due to hypersensitivity or cough
what are the positive criteria for selection of _ blockers in the Tx of hypertension?
prostatism DM dyslipidemia
What are the favorable combinations of antihypertensives?
1. Thiazide + ACEI 2. Dihydropyridine + _ Blocker 3. K wasting diuretic + K sparing diuretic
why is Thiazide + ACEI a favorable combination?
more effective and reduction of adverse effects
why is dihydropyridine + _blocker a favorable combination?
why is a K wasting + a K sparing diuretic a favorable combination?
reduction of adverse effects
what factors contribute to cardiac output?
what does the PSNS do to HR?
what does the SNS do to HR?
what do catecholamines do to HR?
what factors contribute to blood pressure?
Cardiac output and systemic vascular resistance
what factors contribute to SVR?
direct innervation circulating regulators local regulators
what is the effect of _1Adrenergic receptors on SVR?
increases it by direct innervation
how do catecholamines affect systemic vascular resistance?
how does ATII affect SVR?
what is the effect of NO on SVR?
what is the effect of prostacyclin on SVR?
what is the effect of endothelin on SVR?
how does ATII affect SVR as a local regulator?
what is the effect of O2 on SVR?
what is the effect of H+ on SVR?
what is the effect of adenosine on SVR?
which drugs affect BP by affecting CO by affecting HR?
which drugs affect BP by affecting CO by affecting SV by affecting contractility?
which drugs affect BP by affecting CO by affecting SV by affecting Preload by affecting venous tone?
_1B sodium nitroprusside ACE inhibitors AT1 Antagonist
which drugs affect BP by affecting CO by affecting SV by affecting Preload by affecting Intravascular volume by affecting Na+/H2O retention?
Diuretics ACE inhibitors AT1 Antagonists
which drugs affect BP by directly affecting SVR?
CCB Direct Arterial Vasodilators
which drugs affect BP by affecting SVR by affecting direct innervation?
_1B Central _2 agonists
which drugs affect BP by affecting SVR by affecting circulating regulators?
_1 B central _2 agonists ACE inhibitors AT1 antagonists
which drugs affect BP by affecting SVR by affecting local regulators?
endothelin antagonistssodium nitroprusside ACE inhibitors AT1 antagonists
what is a hypertensive emergency?
clinical situation that requires immediate BP- reduction to prevent or limit target organ damage
what is hypertensive urgency?
any situations in which BP should be lowered within a few hours
what is the general strategy for treating hypertensive emergency?
intensive care monitoring pareneral drugs
what is the general strategy for treating hypertensive urgency?
what is the goal for BP reduction in crisis?
generally no immediate reduction of BP to 'normal' levels
the endothelium modulates vascular resistance through what?
endocrine or paracrine release of vasoactive molecules such as NO and PGI2
in a hypertensive emergency, endothelial control of vascular tone may be overwhelmed, leading to what?
1. end-organ hyperperfusion 2. arteriolar fibrinoid necrosis 3. increased endothelial permeability with perivascular edema
loss of endothelial fibrinolytic activity coupled with activation of coagulation and platelets promotes what?
what are the causes of hypertensive emergencies?
1. essential hypertension2. renal parenchymal disease 3. renovascular disease 4. pregnancy 5. endocrine 6. drugs 7. drug withdrawal 8. central nervous disorders 9. autonomic hyperreactivity
what is the term for hypertensive emergency associated with pregnancy?
what endocrine disorders can cause hypertensive emergency?
pheochromocytomacushings renin-producing tumors
which drugs can cause hypertensive emergencies?
cocainecrack sympathomimetics amphetamines CsA MAO-I+Tyramine
withdrawal of which drugs can cause hypertensive emergency?
which central nervous disorders can cause hypertensive emergencies?
injury stroke tumor
what are the important History items to cover in hypertensive crisis?
1. severity/duration of pre-existing hypertension, details of therapy
what are the important Symptoms to cover in hypertensive crisis?
1. CP (MI, aortic dissection) 2. back pain (aortic dissection) 3. dyspnea (CHF, pulmonary edema) 4. neurology, seizures, altered consciousness (hypertensive encephalopathy)
what are the 5 key parts of an initial assessment of hypertensive crisis?
1. BP2. Fundoscopic exam 3. CV 4. Neuro 5. Lab
what should be considered about BP taken in hypertensive emergency?
take supine and standing take on both arms
what should be considered in fundoscopic exam during hypertensive emergency?
new hemorrhages exudates papilledema
what should be considered in CV assessment during hypertensive emergency?
evidence of CHF
what should be considered in a neuro exam during hypertensive crisis?
consciousness vision visual fields meningeal irritation focal signs
what labs should be checked during assessment of hypertensiv crisis?
urea electrolytes creatinine CBC (hemolysis, schistiocytes) ECG CXR UA plasma renin/aldo
what are the consensus recommendations for Tx of hypertensive crisis?
1. admit ICU, IV drugs 2. arterial BP measure line 3. therapy: a. lower BP =100-110 mmHg c. further reduction of BP within days
which hypertensive crisis drug is toxic in pts with renal impairment?
what is the onset of sodium nitroprusside?
what is the onset of labetalol?
what is the onset of hydralazine?
what is the onset of fenoldopam?
what is the onset of enalaprilat?
what is the onset of nicardipine?
what is the onset of phentolamine?
what is the duration of sodium nitroprusside?
what is the duration of labetalol?
what is the duration of hydralazine?
what is the duration of nicardipine?
what is the duration of phentolamine?
what are the adverse effects of sodium nitroprusside?
hypotension nausea vomiting cyanate toxicity
what are the adverse effects of labetalol?
nausea vomiting heart block bronchospasm
what are the adverse effects of hydralazine?
what are the adverse effects of enalaprilat?
hypotension renal failure
what are the adverse effects of nicardipine?
reflex tachycardia flushing
what are the adverse effects of phentolamine?