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59-291 Section 3, Lecture 2

Diuretics:-increase in Na+ excretion(naturesis)Thiazide and Related diuretics-decreased PVR due to decreases muscle contraction-an economical and effectivetreatment-protect against osteoporosisLoop diuretics-used in patients with poorkidney function where thiazidederivatives will not be effective

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vasodilators

β-antagonists

β-antagonists

β-antagonists

α-antagonists

Angiotensin IIreceptor antagonists

Angiotensin IIreceptor antagonists

CNS-directedsympatholytics

ACE inhibitors

diuretics

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Hyperkalemic effectincreased by ACE inhibitorsand potassium supplements

HyperkalemiaPotassium-sparingdiuretics

Increase serum levels oflithium. Hypotensive effectdecreased by NSAIDs andaugmented by ACE inhibitors

Blood cell deficiencies,hyperlipidemia, hyperuricemia,hypokalemia, and other electrolytechanges Aggravation of diabetes

Thiazide and loopdiuretics

DiureticsCommon Drug InteractionsCommon Adverse EffectsDrug Classification

Potassium-Sparing Diuretics

-mild diuretic and antihypertensive effect

-Minimize renal-K+ loss thus preventing hypokalemia

-If the patient can’t tolerate these drugs then use thiazide and take KCltablets

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Hypotensive effect increasedby levodopa. Otherinteractions same as those ofclonidine

Autoimmune hemolytic anemia,hepatitis, and lupuslike syndrome.Other adverse effects same asthose of clonidine

MethyldopaSame as clonidineSame as clonidine but milder GuanfacineSame as clonidineSame as clonidine Guanabenz

Hypotensive effect decreasedby tricyclic antidepressantsSedative effect increased byCNS depressants

Dry mouth, fatigue, reboundhypertension, and sedation

Clonidine

Centrally acting drugs

Cardiac depression increasedby diltiazem and verapamil.Hypotensive effect decreasedby NSAIDs

Bradycardia, bronchoconstriction,depression, fatigue, impairedglycogenolysis, and vivid dreams

β-Adrenergic receptorantagonists

Hypotensive effect increasedby β-adrenergic receptorantagonists and diuretics

Dizziness, first-dose syncope, fluidretention, and orthostatichypotension

α-Adrenergic receptorantagonists

Adrenergic receptor antagonists

Common DrugInteractionsCommon Adverse EffectsDrug Classification

Sympatholytics

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vasodilators

β-antagonists

β-antagonists

β-antagonists

α-antagonists

Angiotensin IIreceptor antagonists

Angiotensin IIreceptor antagonists

CNS-directedsympatholytics

ACE inhibitors

diuretics

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24NoneNo15%Candesartan

24None40%25%Valsartan

24Carboxylicacidmetabolite

10%33%Losartan

Angiotensin receptor antagonists

24RamiprilatNo55%Ramipril

24Quinaprilat25-30%60%Quinapril

24NoneNo25%Lisinopril

24FosinoprilatNo36%Fosinopril

24Enalaprilat*No60%Enalapril

12-JunNone30-40%75%Captopril

24BenazeprilatNo37%Benazepril

Angiotensin-converting enzyme inhibitors

Duration ofAction(Hours)

ActiveMetabolite

AbsorptionReduced by Food

OralBioavailability

Drug

Angiotensin Inhibitors

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Angiotensin inhibitors1. ACE inhibitors2. Angiotensin

receptor inhibitors Renin secretion induced by:

1-Symp. Outflow

2-reduction in BP and walltension in renal arterioles

3-reduced NaCl reabsorbtion

AT1AT1

G-proteins– IP3

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ACE inhibitors Adverse effects

• Increase fetalmorbidity andmortality, especiallyduring 2nd and 3thtrimesters

• Renal failure inpatients with bilateralrenal artery stenosis

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Serum levels of drugincreased by cimetidine anddecreased by phenobarbital

HyperkalemiaAngiotensin receptorantagonists

Increase serum levels oflithium. Hyperkalemic effectincreased by potassium-sparing diuretics andpotassium supplements.Hypotensive effectdecreased by NSAIDs

Acute renal failure, angioedema,cough, hyperkalemia, loss oftaste, neutropenia, and rash

Angiotensin-convertingenzyme (ACE) inhibitors

Angiotensin inhibitorsCommon Drug InteractionsCommon Adverse EffectsDrug Classification

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Vasodilators• Organic nitrites and nitrates

– Amyl nitrites; (nitrites), administered byinhalation

– Nitroglycerin (glyceryl trinitrate); sublingual,oral or transdermal administration

• Calcium channel blockers– Amlodipine, felodipine– Diltiazem, verapamil

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Tolerance Aldehyde dehydrogenase releasesNO from nitroglycerin, and this process isaccompanied with formation of superoxideanion free radical (O2

-) that in turn, deactivatealdehyde dehydrogenase

-to avoid periodically interrupt theadministration of the drugs

Pills –sublingual

Sustained release- patches,skin ointments, IV

Adverse effects- headaches,hypotension, dizziness, reflextachycardia, use β-blocker incombination

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Ca2+- channel blockers (CCBs)Suppress cardiac activity andrelax smooth muscles-incombination increase coronaryblood flowSide effects: fatigue, headache, dizziness,flushing, peripheral edemaOccasionally cause gingival hyperplasia

13DiureticOsteoporosis

β-blocker, CCBMigraine headache

α-blockerBenign prostatic hyperplasia

β-blockerCCB, ACEIAsthma

Diuretic, ACEI,ARB, β-blocker,CCB

Diabetes

ACEI, ARBChronic kidney disease

Diuretic, ACEI, ARBRecurrent stroke prevention

Diuretic, ACEI,ARB, β-blocker

Congestive heart failure

β-blocker, ACEI,aldosteroneantagonist

Myocardial infarction

Hydralazine, minoxidilβ-blocker, CCBAngina pectoris

ACEI, ARBMethyldopa,labetalol

Pregnant

β-blockerDiuretic, CCBAfrican heritage

Centrally acting α2

agonistDiuretic, ACEI,CCB

Age over 65 years

Least PreferredDrugs

Most PreferredDrugsPatient Characteristic

Selection of Antihypertensive Drugs for Patients with SpecificTraits or Concurrent Diseases