Anti-Hypertensive Pharmacology Flashcards Preview

CVPR: Renal > Anti-Hypertensive Pharmacology > Flashcards

Flashcards in Anti-Hypertensive Pharmacology Deck (33)
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1

BP = 

CO x Peripiheral Vascular resistance

2

Factors affecting CO

  • inotropic state
  • HR
  • filling pressure
  • regulated by sympathetic/parasympathetic activity, hormones, volume regulation, posture

3

Factors affecting PVR

  • sympathetic/parasympathetic tone
  • vasoconstrictor/dilator hormones
  • blood viscocisty 
  • blood volume
  • cardiac fxn

4

MOA of ACE inhibitors (+major drugs)

  • major drugs: captopril, enalapril, and lisinopril
  • inhibit ACE (angiotensin converting enzyme) and decrease production of AngII and destruction of bradykinin
  • create a net vasodilatory effect→↓BP.

5

Disadvantages of beta-blockers

  • CHF patients have a limited cardiac reserve and must be titrated up to the correct dose of beta-blockers.
  • Patients may be uncomfortable and feel worse before they start feeling better (remodelling of the heart takes time—up to 3 – 12 months)
  • some patients may never reach the recommended dose
  • may not be tolerated in Class IV HF due to preexisting limitation in cardiac function

6

Major beta-blocker drugs

  • Metoprolol & atenolol: beta1-AR selective agent
  • Propranolol & timolol: Non-selective beta1- and beta2-ARs
  • Carvedilol & labetalol: relatively nonselective inhibitor of both beta1- and beta2- ARs and also alpha1-ARs (may explain vasodilatory action).

7

ACE inhibitors (Lisinopril): Site/MOA

  • Inhibits ACE conversion of AI to AII, blocking AII induced vasoconstriction; results in decreased pre-load and afterload

  • Decreases AII-induced release of aldosterone

  • Decreases bradykinin inactivation, increasing vasodilation

8

ACE inhibitors (Lisinopril): Pharmacokinetics

  • Well absorbed orally

  • onset of action < 1 hr

  • Once daily dosing for most agents 

9

ACE inhibitors (Lisinopril): Uses

  • first line tx of hypertension
  • HF
  • chronic kidney disease
  • diabetic nephropathy

10

ACE inhibitors (Lisinopril): Adverse effects

  • cough
  • hyperkalemia
  • contraindicated in pregnancy
  • hypotension (if hypovolemic)
  • mild increase in serum Cr
  • anemia/angioedema (rare)

11

Angiotensin Receptor Blockers (Losartan): Site/MOA

  • Selective inhibition of AII receptor

  • Similar mechanism of action as ACEIs 

    • prevents vasoconstriction + aldosterone release

12

Angiotensin Receptor Blockers (Losartan): Uses

  • HTN
  • HF
  • chronic kidney disease
  • diabetic nephropathy

13

Angiotensin Receptor Blockers (Losartan): Adverse effects

  • Similar to ACEIs but no cough
  • Contraindicated in pregnancy 

14

Examples of Angiotensin II Receptor Blockers (ARBs)

  • losartan
  • irbesartan
  • candesartan
  • valsartan

15

Calcium channel blockers: examples

  • dihydropyridines (DHP): 
    • amlodipine
    • nislodipine
    • nifedipine
    • felodipine
  • non-dihydropyridines (NDHP)
    • diltiazem
    • verapamil

16

Calcium channel blockers: MOA

  • cause arterial vasodilation via blocking L-type calcium channels => lower peripheral vascular resistance
  • DHP=selective to channels @ vasculature vs. NDHP=channels @ vasculature + heart
    • NDHP = negative chronotropic/inotropic effect

17

Calcium channel blockers: Pharmacokinetics

  • readily absorbed, extensive protein binding
  • liver metabolism
  • drug interact: NDHP >> DHP
    • NDHP = CYP P450 metabolism
    • statins, amiodarone, cyclosporine, warfarin, grapefruit juice, St. Johns wort, macrolides
  • once-daily dosing

18

Calcium channel blockers: Adverse effects

  • NDHP
    • constipation
    • headache
    • conduction defects
  • DHP
    • peripheral edema
    • headache

19

Calcium channel blockers: uses

  • DHP: HTN, migraine prophylaxis
  • NDHP: HTN, migraine prophylaxis, angina, rate control in aFib

20

Beta-blockers: MOA

  • Beta1 selective: compete w/catecholamines @ cardiac ARs => decrease CO, suppress renin
  • Beta1/Beta2 nonselective: impact ARs @ heart, bronchial, and vascular system

21

Beta blockers: pharmacokinetics

  • once/twice daily dosing
  • generally liver metabolism (not atenolol)

22

Beta blockers: Adverse effects

  • fatigue
  • respiratory abnormalities
  • mask sx of hypoglycemia
  • elevate lipids
  • sexual dysfxn

23

Beta blockers: Uses

  • Post-MI/CAD
  • HTN
  • angina
  • HF
  • rate control in aFib

24

Direct vasodilators: Examples/MOA

  • peripheral vasodilation
  • hydralazine
    • alter calcium metabolism 
    • inhibition of calcium movement needed to maintain contract => vasodilation
  • minoxidil
    • K+ channel opener => hyperpolarization of cell membranes

25

Direct vasodilators: pharmacokinetics

  • hydralazine
    • peak levles @ 1-2 hrs
    • half-life: 3-7 hrs
    • liver metabolism
  • minoxidil
    • half-life: 4 hrs
    • no clear dose-response 

26

Direct vasodilators: adverse effects

  • headache
  • anorexia, nausea, vomiting, diarrhea
  • palpitations, tachycardia
  • Hydralazine: SLE-like sx
  • Minoxidil: reflex tachycardia, salt/H20 retention, hair growth

27

Direct vasodilators: uses

  • 3rd or 4th line choice:
  • hydralazine: HTN, HF
  • minoxidil: HTN, hair growth (topical)

28

Alpha-1 blockers: examples/MOA

  • prazosin, terazosin, doxazosin
  • selective block @ alpha-1 ARs => reduced SVR => lowers HTN
  • also acts @ bladder => decreased urethral resistance => may relieve obstruction/improve urine flow/BPH

29

Alpha-1 blockers: adverse effects

  • orthostatic hypotension
  • headache
  • peripheral edema

30

Alpha-1 blockers: Uses

  • Benign prostatic hypertrophy (BPH)
  • HTN (3rd or 4th line)