Exam 3: Drugs for Hypertension and Vascular Tone Flashcards
HTN tx threshold without DM/renal disease:
140/90
HTN tx threshold with DM/renal disease:
130/80
First-line tx for HTN:
Thiazide diuretic (without “compelling indication”)
Best drugs for HTN in pts with heart failure:
Thiazide + β-blocker or ACEI
Best drugs for HTN in pts with MI:
β-blocker
Best drugs for HTN in pts with high CVD risk:
Thiazide, β-blocker, ACEI, CCB
Best drugs for HTN in pts with DM:
Thiazide + ACEI
Best drugs for HTN in pts with CKD:
ACEI or ARB
Best drugs for HTN in pts with recurrent strokes:
Thiazide + ACEI
Best drugs for HTN in pts with isolated systolic HTN:
Thiazide + CCB
Define hypertensive urgency:
DBP > 120 with evidence of end organ damage
Tx for hypertensive urgency:
↓ DBP to 100-105 within 24 hours with clonidine
Define hypertensive crisis:
DBP > 120 with evidence of end organ failure
Tx for hypertensive crisis:
↓ DBP to 100-105 asap using NTG, NTP, labetalol, fenoldapam
Effects of angiotensin II:
Vasoconstriction (arterial)
Na+ retention
Thirst/ADH secretion
Aldosterone secretion
Effect of aldosterone:
↑ Na+ reabsorption
ACEIs are 2nd-line therapy for pts with:
HTN
CHF
Mitral regurg
ACEIs are more effective in pts with:
DM
ACEIs delay the progression of:
Renal disease
AT-1 and AT-2 receptors are:
GPCRs
AT-1 effects > AT-2 effects
AT-1 receptor effects:
Vasoconstriction, esp. in glomerular afferent arterioles
↑ norepi release
Proximal tubule reabsorption of Na+
Aldosterone secretion
MoA of ACEIs:
Block conversion of angiotensin I to II via interaction with zinc ion
Works on ACE in endothelium
Clinical effects of ACEIs:
↓ arterial pressure
↓ cardiac load
Indications for ACEIs:
HTN Cardiac failure Post-MI Diabetic neuropathy CRI
Pre-op hold for ACEIs:
One full day pre-op
S/E of ACEIs:
Intra-op hypotension** Granulocytopenia Angioedema* Proteinuria Cough* Hyperkalemia
Contraindications for ACEIs:
Renal artery stenosis
Cough/angioedema from ACEIs related to:
Bradykinin
Dosage of captopril:
12.5-25mg q8h
Onset and half-time of captopril:
Onset: 15 min
E1/2t: 2 hrs
Advantages of captopril:
Does not interfere with SNS outflow d/t short E1/2t
S/E of captopril:
Rash Loss of taste Antagonized by NSAIDs Hyperkalemia Angioedema
Enalapril vs. captopril:
Enalapril is IV; does not cause rash/renal insufficiency due to lacking sulfhydryl group
Elimination of lisinopril:
Administered in active form; excreted unchanged by kidney
Onset and duration of effect of enalapril/lisinopril/ramipril:
Enalapril/lisinopril: onset 60-120min, effect 18-30hrs
Ramipril: onset 30-60min, effect 24-60hrs
MoA for ARBs:
Competitive binding to AT1 receptors to inhibit action of angiotensin II
S/E of ARBs:
Similar to ACEIs but less cough, no bradykinin accumulation
Contraindications for ARBs:
Renal artery stenosis
Pregnancy
Naming of ARBs:
-sartan
Drug class of hydralazine:
Phthalazine derivative
MoA of hydralazine:
Activates guanylate cyclase causing vasodilation (primarily arterial)
Dosage of hydralazine:
2.5 - 10mg IV
Peak, duration and half-time of hydralazine:
Onset: 10-20 minutes
Duration: 6 hr
E1/2t: 3 hrs
Elimination of hydralazine:
Extensive first-pass effect
IV: 15% excreted unchanged
S/E of hydralazine:
Reflex tachycardia Tolerance/tachyphylaxis Na+/H2O retention Angina w/ EKG changes Drug-induced lupus-like syndrome
Clinical use of hydralazine:
In combination with β-blocker and diuretic to limit SNS activation
MoA of minoxidil:
Directly relaxes arteriolar smooth muscle via influx of potassium –> hyperpolarization
Indications for minoxidil:
Severe HTN due to renovascular disease, renal failure, transplant rejection
Clinical use of minoxidil:
Combined with β-blocker and diuretic
PK of minoxidil:
90% oral absorption
Peak: 1 hr
E1/2t: 4 hrs
10% of drug excreted unchanged by kidneys
S/E of minoxidil:
↑ HR ↑ renin, norepi Na+/H2O retention Pulmonary HTN Pericardial effusion/tamponade
EKG changes with minoxidil:
Flat/inverted T wave
Increased voltage of QRS
Indications for peripheral vasodilators:
Facilitate forward flow in AR, MR, HF
Controlled hypotension in OR
Treat hypertensive crisis
MoA of sodium nitroprusside:
Interacts with oxyhemoglobin to release NO and cyanide