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Antihypertensives > Antihypertensives > Flashcards

Antihypertensives Flashcards

1
Q

Thiazide

A
  • loop diuretic (Na+ and K+ in for 2 Cl- out)

- inhibit Na+ absorption in DCT by blocking the NCC transporter

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2
Q

Toxicity of Diuretics

A
  • low K+ (hypokalemia)
  • metabolic alkalosis (increased delivery of K to the collecting ducts facilitates the exchange of K for H by the H/K exchangers on the intercalated alpha cells, resulting in loss of H [metabolic alkalosis])
  • hyponatremia
  • hypotension and decreased GFR
  • metabolic alkalosis also due to increased proximal HCO3 reabsorption
  • increased UA/gout
  • hyperglycemia (inhibition of insulin release)
  • hypercalemia (increased proximal calcium reabsoprtion)
  • K-sparring agents –> hyperkalemia
  • gynecomastia/sexual dysfunction (steroid receptor antagonism (spironolactone))
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3
Q

Prazosin

A
  • adrenoreceptor antagonist
  • alpha1 blockage in peripheral arterioles and venules
  • useful for symptoms of BPH
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4
Q

Doxazosin

A
  • adrenoreceptor antagonist
  • alpha1 blockage in peripheral arterioles and venules
  • useful for symptoms of BPH
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5
Q

Toxicity of Adrenoreceptor Antagonists

A
  • dizziness
  • headaches
  • lassitude (a state of physical or mental weariness, lack of energy)
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6
Q

Hydralazine

A
  • vasodilator
  • given both PO and IV
  • dilates arterioles, no veins
  • effective in severe hypertension
  • Toxicity: reflex increase in HR can cause myocardial ischemia; potential for lupus syndrome with pericarditis
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7
Q

Clonidine

A
  • vasodilator
  • centrally-acting
  • alpha-2 agonist
  • onset in 30-60 min
  • useful in hypertensive urgencies
  • very useful for treatment-resistant HTN
  • decreases HR and PVR
  • Toxicity: sudden withdrawal can result in sudden hypertensive crisis; sedation, dry mouth
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8
Q

Amlodipine

A
  • vasodilator
  • calcium-channel blocker
  • can have cardiac depressant effects
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9
Q

Captopril

A
  • ACE inhibitor
  • inhibit peptidyl dipeptidase - affects RAAS and Kallikrein-kinin system
  • Toxicity: ARF in pts with bilateral renal artery stenosis; dry cough; angioedema
  • contraindicated in pregnancy
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10
Q

Enalapril

A
  • ACE inhibitor
  • inhibit peptidyl dipeptidase - affects RAAS and Kallikrein-kinin system
  • Toxicity: ARF in pts with bilateral renal artery stenosis; dry cough; angioedema
  • contraindicated in pregnancy
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11
Q

Losartan

A
  • angiotensin-R blocker
  • AT1 inhibitors; no effect on bradykinin
  • Toxicity: similar effects to ACE inhibitor; less cough and angioedema
  • contraindicated in pregnancy
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12
Q

Valsartan

A
  • angiotensin-R blocker
  • AT1 inhibitors; no effect on bradykinin
  • Toxicity: similar effects to ACE inhibitor; less cough and angioedema
  • contraindicated in pregnancy
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13
Q

Propranolol

A
  • beta blocker
  • non-selective
  • decreased CO to decreased BP
  • Benefits: reduce mortality post-MI; inhibits stimulation of renin release by catecholamines
  • Toxicity: increased airway resistance; reduce IO pressure; impair recovery from hypoglycemia
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14
Q

Metoprolol

A

cardiac selective beta blocker

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15
Q

Atenolol

A

cardiac selective beta blocker

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16
Q

Pindolol

A
  • partial agonist beta blocker
  • decreased SVR (systemic vascular resistance)
  • Benefits: does not change SVR and CO as much
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17
Q

Acebutaol

A
  • partial agonist beta blocker
  • decreased SVR (systemic vascular resistance)
  • Benefits: does not change SVR and CO as much
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18
Q

Labetolol

A
  • beta-blocking and vasodilating effects
  • has both beta and alpha blocking action
  • Benefits: reduced SVR without change in HR or CO
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19
Q

Carvedilol

A
  • beta blocking and vasodilating effects
  • has both beta and alpha blocking action
  • Benefits: reduced SVR without change in HR or CO
  • Toxicity: carvediol is effective in CHF and HTN
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20
Q

Esmolol

A
  • beta-1 selective
  • very rapid; given IV
  • short half-life (~10 min)
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21
Q

Hydrochlorothiazide

A
  • most common diuretic and antihypertensive prescribed (initial or add-on Rx)
  • especially effective in patients with volume expanded/salt dependent/low-renin hypertension - including the elderly, diabetics, and blacks; pts w/ edema
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22
Q

Chlorthalidone

A
  • diuretic
  • more potent than HCTZ
  • reduction in stroke, heart failure, coronary events
  • more expensive to manufacture
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23
Q

Loop Diuretics

A
  • reserved for CHF or resistant edema

- Na+ and K+ in for 2 Cl- out

24
Q

K-sparing agents

A
  • helpful for hypokalemic patients
  • Na+ in for K+ out
  • aldosterone antagonists
  • may have heart failure benefits
25
Q

Direct Vasodilators

A
  • least frequently used for HTN
  • most useful in severe or refractory HTN
  • hypertensive emergencies like in pulmonary edema
  • reflex increased SNS activity, increased HR and CO
  • counters CO effect on HTN, so need to use in combination with beta-blocker
  • BP lowering effect is non-renin dependent
  • decreased renal perfusion leads to increased plasma renin activity and increased sodium-volume retention and edema
  • “pseudotolerance” - almost always requires combination with loop diuretics and beta blockers
26
Q

Minoxidil

A
  • direct vasodilator
  • very potent oral agent
  • Adverse Effects: hypertrichosis (abnormal amount of hair growth), PEs, massive fluid retention, tachycardia
27
Q

Nitroprusside

A
  • direct vasodilator
  • releases NO
  • dilates arterioles and venules (decreased cardiac afterload and preload)
  • Adverse Effect: structure of thiocynate is similar to cyanide and can result in cyanide toxicity
28
Q

Alpha Adrenergic Receptors

A
  • agonists (norepi>epinephrine)
  • alpha-1 receptor (post-synaptic; mediates vasoconstriction)
  • alpha-2 receptor (mostly pre-synaptic; inhibits norepinephrine release at peripheral and CNS sympathetic nerve terminals)
29
Q

Alpha Receptor Antagonists

A
  • inhibit the vasoconstrictor effects of norepi
  • hemodynamic action (decreased TPR) similar to vasodilators, but with less tachycardia
  • usually most effective in combination Rx
  • may increase the sxs of HF as monotherapy
  • Adverse Effects: postural hypotension, headache, edema
30
Q

CNS-acting Sympathetic Inhibitors

A
  • alpha-2 receptor AGONISTS in the medullary brainstem

- act in the CNS to decrease outflow of the SNS

31
Q

Alpha Methyldopa

A
  • CNS-acting sympathetic inhibitor
  • alpha-2 agonist
  • decreases outflow of the SNS
  • given oral and IV
  • used most commonly in pregnancy-associated HTN
  • Adverse Effects: sedation; hepatitis and coombs pos hemolytic anemia
32
Q

beta-1 Adrenergic Receptors

A
  • increase cardiac SA node (increase heart rate)
  • increase cardiac muscle contractility
  • increase renin release (renal JGA cells)
33
Q

beta-2 Adrenergic Receptors

A
  • vascular smooth muscle (dilate)
  • bronchial smooth muscle (bronchodilation)
  • hepatocytes (glycogenolysis)
  • pancreatic islet cells (insulin release)
34
Q

Non-Selective Beta-Receptor Antagonists

A
  • increases rick of bronchospasm, worsening diabetes, hyperlipidemia, risk of prolonged hypoglycemia, symptoms of PVD
  • increased CNS adverse effects (fatigue, depression, ED) due to high lipid solubility
  • may be superior for migraine prevention
35
Q

beta-1 Selective Antagonists

A
  • atenolol, metoprolol, bisoprolol
  • inexpensive, may have fewer adverse effects
  • most common type prescribed today
36
Q

Vasodilatory Beta Blockers

A
  • may have faster onset of BP reduction than other beta-blockers
  • non-selective beta/alpha
  • labetalol
  • carvedilol
  • RCT w/ carvedilol show long-term survival benefit in patients w/ CHF
  • Nebivolol: beta-1 selective agent, releases NO
37
Q

ISA (intrinsic sympathomimetic activity)

A
  • pindolol, acebutolol
  • may prevent extreme decreases HR at rest
  • agonist and antagonist effects
  • some pts on other antihypertensive meds have unusual degrees of bradycardia, so with a drug like pindolol you will have control of BP due to beta-blocker effect, but at night the heart rate will rise to normal levels
38
Q

Indications for Beta Blockers (hypertension)

A
  • often more effective in younger pts, those with signs of greater adrenergic activity or elevated plasma renin
  • less BP reduction in low renin patients - blacks, elderly
  • may have less stroke prevention in the elderly
39
Q

Indications for Beta Blockers (cardiac disorders)

A
  • tachyarrhythmias
  • chronic LV dysfunction (metoprolol XL/carvedilol/bisoprolol)
  • CAD: angina, acute coronary syndrome (ACS), post-MI
  • hypertrophic subaortic stenosis
40
Q

Indications for Beta Blockers (non-cardiac disorders)

A
  • vascular (migraine) headache prevention

- essential tremor and performance anxiety

41
Q

Calcium Channel Antagonists

A
  • Ca channel antagonists bind the alpha-1 subunit of the L channel
  • produce relaxation of VSM/myocardium; and slows SA and AV nodal transmission
  • broad effectiveness as a single or combination Rx
  • metabolically neutral: no effects on glucose, electrolytes, uric acid, lipids
  • no renal, CNS, or pulmonary AEs
42
Q

Diltiazem Hydrochloride

A
  • calcium channel antagonist
  • decreases heart rate
  • decreases myocardial contractility
  • decreases nodal conduction
  • increases peripheral vasodilation
43
Q

Verapamil Hydrochloride

A
  • calcium channel antagonist
  • decreases heart rate
  • greatly decreases myocardial contractility (and CO)
  • greatly decreases nodal conduction
  • increases peripheral vasodilation
44
Q

Nifedipine

A
  • calcium channel antagonist
  • increases heart rate
  • slightly decreases or no effect at all on myocardial contractility
  • NO EFFECT on nodal conduction
  • greatly increases peripheral vasodilation
45
Q

Nicardipine Hydrochloride

A
  • calcium channel antagonist
  • increases heart rate
  • no effect on myocardial contractility
  • no effect on nodal conduction
  • greatly increases peripheral vasodilation
46
Q

Calcium Channel Antagonist AEs

A
  • edema, flushing, lightheadedness, constipation
  • bradycardia and HF (uncommon)
  • skin rash uncommon but can be serious
  • diltiazem and verapamil (but not DHP) inhibit hepatic P450 isozymes
47
Q

AT1 receptor

A
  • vasoconstriction
  • increased aldosterone levels
  • proximal nephron increased Na+ retention
  • JGA cells (inhibits renin release)
  • cardiac and vascular tissue (profibrotic/remodeling)
48
Q

Renin

A
  • synthesis and release by the JGA cells, which are under feedback control
  • decreased renal perfusion pressure leads to increased renin release
  • increased renal SNS stimulation (JGA cell surface beta-1 receptors) leads to increases renin release (why we use beta blockers to help with HTN)
  • angiotensin II negative feedback (JGA AT1 receptors) leads to decreases renin release (so we don’t release too much)
  • increased distal tubular sodium content leads to increased renin release
49
Q

Direct Renin Inhibitors

A
  • inhibition of renin proteolytic action on its substrate and the formation rate of angiotensin I
  • decreased PRA, angiotensin I, angiotensin II, aldosterone
  • increases plasma renin level
50
Q

ACE Inhibitors

A
  • inhibition of the formation of angiotensin II from angiotensin I
  • decrease angiotensin II and aldosterone levels
  • increase levels of vasodilatory pepties (e.g. bradykinin)
  • increase plasma renin levels
  • increase plasma renin activity (PRA)
51
Q

ARBs (angiotensin receptor blockers)

A
  • blockage of angiotensin II (AT1) receptors at tissue sites
  • decrease aldosterone levels
  • increase plasma renin level, PRA, and angiotensin II levels
52
Q

Aldosterone Antagonists

A
  • blockage of mineralocorticoid/aldosterone receptors in the kidney and other sites
  • Adverse Effect: hyperkalemia
53
Q

Potential Adverse Effects of ACEi, ARB, DRI

A
  • hyperkalemia (aldosterone inhibition)
  • hypotension
  • worsen renal insufficinecy (disproportionate glomerular efferent arterial vasodilation)
  • fetal injury (angiotensin II important for fetal cell differentiation)… all inhibitors of RAA are contraindicated in pregnancy!
  • ACEi - cough (5-10%) and angioedema (<1%)… ACE has many substrates (angiotensin I, bradykinin, substance P, neuropeptide Y, etc.)
54
Q

Conditions that May Worsen with Certain Drug Therapies

A
  • Pregnancy (RAA agents absolutely contraindicated!)
  • Depression (beta blockers, central inhibitors)
  • Sexual Dysfunction (beta blockers, central inhibitors, spironolactone)
  • Asthma (beta blockers… especially non-selective)
  • Gout (diuretics)
  • Constipation (verapamil)
55
Q

Conditions that May have Favorable Effects From BP Rx

A
  • BPH (alpha blockers)
  • essential tremor; performance anxiety; cardiac awareness (beta blockers)
  • migraine headache (beta blockers, CCBs)
  • osteoporosis (thiazides)
  • kidney stones (thiazides)
  • Raynaud’s Syndrome (DHP, CCBs)
  • Chronic Diarrhea (verapamil… causes constipation)
  • Hyponatremia/Hypercalcemia (loop diuretics (+IV saline)

Antihypertensives (1 decks)

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