Antihypertensives Flashcards
What is considered stage I vs. stage II HTN?
- stage I: 130-139/81-89
- stage II: ≥140/90
What are the 8 classes of antihypertensive drugs currently used in the treatment of HTN?
- Diuretics
- ACE inhibitors
- ARBs
- CCBs
- BBs
- Centrally-acting agents
- Alpha adrenergic blockers
- Vasodilators
Which drugs are the first line drugs of choice for treatment of HTN?
- Diuretics
- ACEIs
- ARBs
- CCBs
What are compelling indications for diuretics?
- first-line choice for uncomplicated HTN
- effective for mild/moderate HTN combined w/ lifestyle modifications
- more effective in AAs than ACEIs or ARBs
What are the main adverse effects associated with the thiazides?
- hypokalemia
- hyperuricemia (uric acid is reabsorbed at the PT, and diuretics compete with transport of uric acid back into the lumen at the DT)
What are the tricks to avoid hypokalemia associated with thiazide diuretics?
- decrease dose
- decrease Na+ intake
- increase K+ intake
- combine w/ BBs, ACEIs, or ARBs
What is a contraindication and relative contraindication for thiazides?
- contraindication=hypokalemia
- relative contraindication=pregnancy
Why can thiazide diuretics cause hyperglycemia?
due to K+ loss (K+ normally stimulates insulin release)
How do beta blockers interact with thiazides?
Beta blockers have an effect on glucose (contribute to hyperglycemia). Thiazides can also result in hyperglycemia. This creates a situation of prolonged hyperglycemia, which is dangerous.
Why do the loop diuretics cause such pronounced natriuresis/diuresis?
They block the Na+/K+/Cl- cotransporter, which is responsible for reabsorbing ~50% of the Na+ filtered into the nephron.
What are the major side effects associated with the loop diuretics?
- hypokalemia
- impaired diabetes control (due to hyperkalemia)
- increased LDL/HDL
- ototoxicity (reversible)
- dehydration/hyponatremia
Describe how NSAIDs interact with the loop diuretics.
NSAIDs inhibit prostaglandins, and loop diuretics cause venous dilation via prostaglandins.
Why are the aminoglycosides contraindicated for patients on loop diuretics?
AGs may further exacerbate ototoxicity.
Which drugs are the ENaC blocker K+ sparing diuretics?
triamterene and amiloride
Which drugs are the Aldosterone Receptor Antagonists?
spironolactone and eplerenone
What makes ACE inhibitors such an effective class of drugs?
They block the action of ACE on (1) activating ang II and (2) inactivating bradykinin. No Ang II=less vasoconstriction and less aldosterone. No bradykinin breakdown=more vasodilation.
What are the 2 types of K+ sparing diuretics?
- ENaC blockers: triamterene, amiloride
- Aldosterone Receptor Antagonists: spironolactone, aplerenone
What are the side effects of K+ sparing diuretics?
- hyperkalemia (thus, don NOT use in patients who are on drugs that block RAAS)
- gynecomastia (spironolactone)
Can K+ sparing diuretics be used as monotherapy in HTN patients?
No, they must be combined with other diuretics.
What are the major contraindications for K+ sparing diuretics?
- RAS inhibitors (can add thiazide to counteract hyperkalemia)
- Addison’s disease (decreased aldosterone production)
Which is the most prescribed ACE inhibitor (and the one we should focus on)?
Lisinopril
What are the adverse effects of ACE inhibitors?
- dry cough
- hyperkalemia
- angioedema (rare, can be life-threatening)
- rash
True or false: K+ sparing diuretics combined with ACE inhibitors serves as a good combination for treatment of HTN.
FALSE! K+ drugs used with ACE inhibitors will exacerbate hyperkalemia.
What are the benefits of lisinopril over captopril or enalapril?
Lisinopril is excreted unchanged by the kidney, has a longer HL (allowing for once daily dosing), and has a more predictable onset/duration of action.
What are the major contraindications for ACE inhibitor use?
- pregnancy (can see problems with fetal renal development)
- severe renal disease (bc ang II has a large effect on RBF)
True or false: ACE inhibitors prolong survival in patients with heart failure of LV dysfunction post-MI.
True!
CCBs are a good first choice in:
- AAs with uncomplicated HTN
- Patients with electrolyte, carbohydrate, or lipid metabolism problems
- Ischemic heart disease (due to vasodilatory properties)
- COPD
- Diabetes
- Patients with AFib (specifically the non-dihydropyridines due to ability to decrease HR)
What is the main Angiotensin II Receptor Blocker (ARB), and what is its MOA?
Losartan; it is a selective AT1 receptor antagonist
True or false: ARBs and ACEIs work extremely well when combined.
False– they are equally efficacious and should NOT be combined due to potential for exaggerated hyperkalemia. They have also NOT been proven to be more efficacious when combined.
What are the contraindications of ARBs?
-pregnancy (can cause fetal renal failure)
-severe renal disease
(same contraindications as ACEIs)
Where do the non-dihydropyridines also have an effect (in addition to vascular smooth muscle)?
They also affect Ca2+ channels expressed directly on cardiac myocytes.
What is the MOA of the CCBs?
- All: reduce vascular resistance
- Non-dihydropyridines: reduce pacemaker potentials, AVE node conduction, contractility
What is the first-line CCB in uncomplicated HTN?
Nifedipine
What are the side effects associated with Nifedipine?
- acute tachycardia (reflex, temporary)
- peripheral edema (arteriolar dilation > venodilation)
What are the side effects associated with Diltiazem?
- edema
- bradycardia (due to effects on conducting system)
What are the side effects associated with Verapamil?
- edema
- bradycardia
- constipation
The non-dihydropyridines are not first-line drugs against HTN unless ____________.
patient is also tachycardic
Why is it important to use long-acting formulations of CCBs with slow-release characteristics?
CCBs can lead to MI due to a rapid drop in peripheral resistance (causes decreased perfusion of heart).
What is the implication of beta-blockers being lipophilic?
They can cross the BBB and cause insomnia, chronic fatigue, depression, and nightmares.
Must be withdrawn gradually to avoid rebound hypertension.
beta-blockers
What are the contraindications for beta-blockers?
- cardiogenic shock (bc BBs decrease CO even more)
- sinus bradycardia (bc BBs drop HR and could send patient into heart block)
- asthma (bc BBs can have an effect on beta-2 receptors and cause bronchospasm)
- severe heart failure
What is the main sympatholytic drug to know, and what is its MOA?
clonidine; acts centrally as an alpha-2 adrenergic receptor agonist in medullary cardiovascular center, thus decreasing sympathetic outflow from CNS
What are the 3 main BBs to know, and to which generation do they belong?
- Metoprolol: β1 selective
- Labetolol: Mixed β and α blocker
- Carvedilol: non-selective
What are the pros vs. cons of metoprolol?
pros:
-fewer respiratory side effects due to being β1 selective
-long-acting version good choice for HFrEF
cons:
-slightly lipophilic
What are the pros vs. cons of carvedilol?
pros: -also acts as a vasodilator -anti-oxidant effect -good choice for HFrEF cons: -somewhat lipophilic -non-selective, therefore potential for bronchospasm
What are the pros vs. cons of labetolol?
pros: -can be used for pheochromocytomas cons: -higher incidence of orthostatic hypotension and sexual dysfunction -lipophilic
Which BB is a partial agonist and why is this beneficial?
pindolol; causes less bradycardia than the other BBs
What are the pros vs. cons of propranolol?
pros:
-very affordable
-used as an adjunct to prevent tachycardia
cons:
-lipophilic
-non-selective, therefore potential for bronchospasm
What is the overall MOA of the sympatholytic drugs?
reduce sympathetic-mediated vasoconstriction, CO, and renin release
What are the major side effects associated with clonidine?
sedation, dry mouth, dermatitis, bradycardia
Which centrally acting agent has a longer HL and less chance of rebound?
Guanfacine (very similar to clonidine)
Why is rebound HTN so common with the sympatholytic drugs?
Nerves become increasingly sensitized to excitatory input once they are no longer receiving excitatory input. Sympatholytic agents block sympathetic outflow. Thus, once nerves begin getting sympathetic stimulation again, there can be large increases in vasoconstriction and cardiac contractility, leading to rebound HTN.
MOA of reserpine?
blocks VMAT vesicular transporter, preventing storage of NE centrally and peripherally. This causes decreased ND release and therefore decreased HR/contractility.
List 4 examples of good drug combinations to control hypertension.
- thiazide or loop diuretic + K+-sparing diuretic
- thiazide + ACE inhibitor (normalizes K+ levels)
- thiazide + BB (also normalizes K+ levels)
- CCBs + ACEIs
Which hypertensive drug should be avoided in patients with hyperlipidemia?
beta blockers (instead, try low dose diuretics, as they have little effect on cholesterol and TGs)
Therapy choice for the elderly?
smaller doses w/ small increments, simple regimens, close monitory of side effects
Therapy choice for African Americans?
- CCBs=most efficacious
- monotherapy w/ diuretics also efficacious
Best therapy choice for heart failure patients?
- ACEIs or ARBs (reduce mortality; can also be combined w/ diuretics for congestion)
- BBs and spironolactone reduce remodeling
Best therapy choice for MI patients?
- ACEIs (reduce remodeling and incidence of subsequent MI)
- BBs (reduce arrhyhtmia and remodeling)
Best therapy choice for diabetic patients?
ACEIs (delay progression of renal insufficiency)
Why can reserpine cause depression and suicidality?
It can cross the BBB (esp. at high concentrations) and deplete dopa and NE, thereby causing a disruption in mood regulation.
Which of the antihypertensives decreases LDL/HDL ratio?
alpha adrenergic receptor antagonists
