Anti-Hypertensive Pharmacology Flashcards
BP =
CO x Peripiheral Vascular resistance
Factors affecting CO
- inotropic state
- HR
- filling pressure
- regulated by sympathetic/parasympathetic activity, hormones, volume regulation, posture
Factors affecting PVR
- sympathetic/parasympathetic tone
- vasoconstrictor/dilator hormones
- blood viscocisty
- blood volume
- cardiac fxn
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.
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
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).
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
ACE inhibitors (Lisinopril): Pharmacokinetics
- Well absorbed orally
- onset of action < 1 hr
- Once daily dosing for most agents
ACE inhibitors (Lisinopril): Uses
- first line tx of hypertension
- HF
- chronic kidney disease
- diabetic nephropathy
ACE inhibitors (Lisinopril): Adverse effects
- cough
- hyperkalemia
- contraindicated in pregnancy
- hypotension (if hypovolemic)
- mild increase in serum Cr
- anemia/angioedema (rare)
Angiotensin Receptor Blockers (Losartan): Site/MOA
- Selective inhibition of AII receptor
- Similar mechanism of action as ACEIs
- prevents vasoconstriction + aldosterone release
Angiotensin Receptor Blockers (Losartan): Uses
- HTN
- HF
- chronic kidney disease
- diabetic nephropathy
Angiotensin Receptor Blockers (Losartan): Adverse effects
- Similar to ACEIs but no cough
- Contraindicated in pregnancy
Examples of Angiotensin II Receptor Blockers (ARBs)
- losartan
- irbesartan
- candesartan
- valsartan
Calcium channel blockers: examples
- dihydropyridines (DHP):
- amlodipine
- nislodipine
- nifedipine
- felodipine
- non-dihydropyridines (NDHP)
- diltiazem
- verapamil
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
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
Calcium channel blockers: Adverse effects
- NDHP
- constipation
- headache
- conduction defects
- DHP
- peripheral edema
- headache
Calcium channel blockers: uses
- DHP: HTN, migraine prophylaxis
- NDHP: HTN, migraine prophylaxis, angina, rate control in aFib
Beta-blockers: MOA
- Beta1 selective: compete w/catecholamines @ cardiac ARs => decrease CO, suppress renin
- Beta1/Beta2 nonselective: impact ARs @ heart, bronchial, and vascular system
Beta blockers: pharmacokinetics
- once/twice daily dosing
- generally liver metabolism (not atenolol)
Beta blockers: Adverse effects
- fatigue
- respiratory abnormalities
- mask sx of hypoglycemia
- elevate lipids
- sexual dysfxn
Beta blockers: Uses
- Post-MI/CAD
- HTN
- angina
- HF
- rate control in aFib
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
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
Direct vasodilators: adverse effects
- headache
- anorexia, nausea, vomiting, diarrhea
- palpitations, tachycardia
- Hydralazine: SLE-like sx
- Minoxidil: reflex tachycardia, salt/H20 retention, hair growth
Direct vasodilators: uses
- 3rd or 4th line choice:
- hydralazine: HTN, HF
- minoxidil: HTN, hair growth (topical)
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
Alpha-1 blockers: adverse effects
- orthostatic hypotension
- headache
- peripheral edema
Alpha-1 blockers: Uses
- Benign prostatic hypertrophy (BPH)
- HTN (3rd or 4th line)
Centrally acting agents: examples/MOA
- clonidine
- stimulation of alpha-2 ARs @ CNS, periphery
- reduce sympathetic/increase parasympathetic outflow => decreased SVR
- inhibits norephinephrine release
Centrally acting agents: adverse effects
- orthostatic hypotension
- dry mouth
- sedation
- rebound HTN w/abrut stop
Centrally acting agents: uses
- HTN (3rd or 4th line)
- ADHD
- smoking cessation
- ETOH withdrawal
