Anti-Hypertensive Pharmacology Flashcards
(33 cards)
1
Q
BP =
A
CO x Peripiheral Vascular resistance
2
Q
Factors affecting CO
A
- inotropic state
- HR
- filling pressure
- regulated by sympathetic/parasympathetic activity, hormones, volume regulation, posture
3
Q
Factors affecting PVR
A
- sympathetic/parasympathetic tone
- vasoconstrictor/dilator hormones
- blood viscocisty
- blood volume
- cardiac fxn
4
Q
MOA of ACE inhibitors (+major drugs)
A
- 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
Q
Disadvantages of beta-blockers
A
- 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
Q
Major beta-blocker drugs
A
- 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
Q
ACE inhibitors (Lisinopril): Site/MOA
A
- 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
Q
ACE inhibitors (Lisinopril): Pharmacokinetics
A
- Well absorbed orally
- onset of action < 1 hr
- Once daily dosing for most agents
9
Q
ACE inhibitors (Lisinopril): Uses
A
- first line tx of hypertension
- HF
- chronic kidney disease
- diabetic nephropathy
10
Q
ACE inhibitors (Lisinopril): Adverse effects
A
- cough
- hyperkalemia
- contraindicated in pregnancy
- hypotension (if hypovolemic)
- mild increase in serum Cr
- anemia/angioedema (rare)
11
Q
Angiotensin Receptor Blockers (Losartan): Site/MOA
A
- Selective inhibition of AII receptor
- Similar mechanism of action as ACEIs
- prevents vasoconstriction + aldosterone release
12
Q
Angiotensin Receptor Blockers (Losartan): Uses
A
- HTN
- HF
- chronic kidney disease
- diabetic nephropathy
13
Q
Angiotensin Receptor Blockers (Losartan): Adverse effects
A
- Similar to ACEIs but no cough
- Contraindicated in pregnancy
14
Q
Examples of Angiotensin II Receptor Blockers (ARBs)
A
- losartan
- irbesartan
- candesartan
- valsartan
15
Q
Calcium channel blockers: examples
A
- dihydropyridines (DHP):
- amlodipine
- nislodipine
- nifedipine
- felodipine
- non-dihydropyridines (NDHP)
- diltiazem
- verapamil
16
Q
Calcium channel blockers: MOA
A
- 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
Q
Calcium channel blockers: Pharmacokinetics
A
- 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
Q
Calcium channel blockers: Adverse effects
A
- NDHP
- constipation
- headache
- conduction defects
- DHP
- peripheral edema
- headache
19
Q
Calcium channel blockers: uses
A
- DHP: HTN, migraine prophylaxis
- NDHP: HTN, migraine prophylaxis, angina, rate control in aFib
20
Q
Beta-blockers: MOA
A
- Beta1 selective: compete w/catecholamines @ cardiac ARs => decrease CO, suppress renin
- Beta1/Beta2 nonselective: impact ARs @ heart, bronchial, and vascular system
21
Q
Beta blockers: pharmacokinetics
A
- once/twice daily dosing
- generally liver metabolism (not atenolol)
22
Q
Beta blockers: Adverse effects
A
- fatigue
- respiratory abnormalities
- mask sx of hypoglycemia
- elevate lipids
- sexual dysfxn
23
Q
Beta blockers: Uses
A
- Post-MI/CAD
- HTN
- angina
- HF
- rate control in aFib
24
Q
Direct vasodilators: Examples/MOA
A
- 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)
31
Centrally acting agents: examples/MOA
* clonidine
* stimulation of alpha-2 ARs @ CNS, periphery
* reduce sympathetic/increase parasympathetic outflow =\> decreased SVR
* inhibits norephinephrine release
32
Centrally acting agents: adverse effects
* orthostatic hypotension
* dry mouth
* sedation
* rebound HTN w/abrut stop
33
Centrally acting agents: uses
* HTN (3rd or 4th line)
* ADHD
* smoking cessation
* ETOH withdrawal
