Antihypertensives Flashcards
0
Q
what is increased cardiac output in blood pressure?
A
- Increased fluid volume, excess sodium intake & sodium renal retention
- Excess stimulation of the RAAS (Renin-Angiotensin-Aldosterone System)
- Over-activity of the SNS
1
Q
what are some factors influencing blood pressure?
A
- Increased cardiac output
* Increased peripheral resistance
2
Q
what increased peripheral resistance?
A
- excess stimulation of the RAAS
- Over-activity of the SNS
- Genetic alterations in cell membranes, e.g. increased intracellular Na/Ca which alters vascular smooth muscle tone.
3
Q
What are the blood pressure goals?
A
- treat to BP < 140/90 in most patients
- treat to BP < 130/80 in pts with diabetes or chronic kidney disease, MI, angina, stroke.
- treat to BP < 125/75 in patients with proteinuria
- treat to BP , 140/90 for isolated systolic HTN also. For patients with SBP > 180, the first goal is to reduce SBP to <160. Monitor closely for hypotension: dizziness, sweating, tachycardia, falls, fatigue, etc. Then attempt to reduce BP to the target goal as long as the patient tolerates this reduction.
4
Q
what are some cardiovascular risks and blood pressure?
A
- HTN increased the risk of stroke, transient ischemic attacks, dementia, retinopathy, myocardial infarction (MI), angina, heart failure, left ventricular hypertrophy, chronic kidney disease (esp. African American, Hispanic, & Native American), peripheral arterial disease, and early death from a cardiovascular cause.
- Starting at BP of 115/75, risk of CV disease doubles with every 20/10 increase.
- SBP is a stronger predictor of CV disease than DBP
- Isolated systolic HTN may result from pathophysiologic changes in arterial vasculature consistent with aging. These changes decrease the compliance of the arterial wall.
- Pulse pressure (SSBP-DBP) may reflect the extent of atherosclerotic disease and measure arterial stiffness. Higher pulse pressure values are correlated with an increased risk of CV mortality
5
Q
what are some drugs that worsen hypertension?
A
- corticosteroids
- Oral contraceptives
- NSAIDs and COX-II inhibitors
- oral decongestants
- Erythropoietin
- Some antidepressants
- Cocaine and cocaine withdrawal
- Ephedra, ma huang
- Nicotine and nicotine withdrawal
- Anabolic steroids
- Narcotic/opioid withdrawal
- Amphetamines
6
Q
What are some complications of HTN?
A
- eye damage & blindness
- heart failure, MI, angina, CAD
- chronic kidney disease, failure
- stroke (hemorrhagic or ischemic)
- TIA (mini stroke), dementia
7
Q
what drugs make up alpha 2 adrenergic agonists?
A
clonidine (Catapres)
methyldopa (Aldomet)
8
Q
What are alpha 2 adrenergic agonists (clonidine & methyldopa) mechanism of action?
A
- preferentially stimulates the alpha 2 receptors of the brain stem associated with autonomic regulation of the cardiovascular system. Remember that activation of the alpha 2 receptor will cause neurons to quit releasing norepinephrine. Thus, alpha 2 receptors are inhibitory in nature. this will result in decreased sympathetic output, decreased blood pressure, & decreased heart rate.
- Clonidine comes in a patch form that is changed weekly. This may be a good option for patients with compliance problems.
9
Q
What are the alpha 2 adrenergic agonists therapeutic uses? (clonidine & methyldopa)
A
- Main use is treatment of chronic hypertension.
- Clonidine tabs chewed & swallowed are effective for hypertensive urgecies.
- Clonidine has been used in the treatment of withdrawal symptoms of nicotine, opiates, benzodiazepines, & alcohol.
- Methyldopa is a drug of choice in pregnancy induced hypertension.
10
Q
What are the adverse effects of Alpha 2 Adrenergic Agonists? (Clonidine & methyldopa)
A
- drowsiness (35%)
- dry mouth (40%)
- constipation
- headache
- impaired ejaculation
- **avoid abrupt withdrawal- will cause severe rebound HTN
11
Q
What drugs are included in the alpha 1 blockers (antagonists)?
A
"zosin" drugs doxazosin prazosin Silodosin terazosin tamsulosin alfuzosin
12
Q
what are the alpha 1 blockers (antagonists) mechanism of action?
A
- competitive blocking of the alpha 1 receptors
- HTN: lowers blood pressure by causing vasodilation. Relaxes both arterial and venous smooth muscle surrounding some blood vessels.
- BPH: These drugs also relax the smooth muscle of the bladder neck & prostate, which improves urine flow in BPH
13
Q
what are the alpha 1 blockers (antagonists) therapeutic uses?
A
- HTN
* urinary retention associated with benign prostatic hyperplasia (BPH), & Raynaud’s disease (vasoconstriction disease)
14
Q
what are the adverse effects of alpha 1 blockers (antagonists)?
A
- Orthostatic hypotension (>10%) warn patient about this!!! FIRST DOSE EFFECT- syncope (fainting) following the 1st dose. To minimize falls, instruct patient about orthostatic hypotension, give at bedtime, and initiate therapy with dosage titration. The BPH selective alpha 1 blockers are less likely to cause orthostatic hypotension.
- reflex tachycardia
- dizziness, lack of energy, drowsiness, nasal congestion, headache, decreased libido, and inhibition of ejaculation.
15
Q
What drugs are included in the First-Generation: Non-selective Beta blockers?
A
“olol” drugs
- propranolol
- Sotalol
- Timolol
- nadolol
- carteolol
- pindolol
- penbutolol
16
Q
what are First-Generation: non-selective Beta blockers mechanism of action?
A
- competitive blocking of the beta 1 & beta 2 receptors
- Cardiovascular effects (beta 1 mediated): decreased hear rate (negative chronotrope); decreased force of contraction (negative inotrope); decreased cardiac workload & oxygen demand.
17
Q
What are the First-Generation: non-selective Beta blockers therapeutic uses?
A
- Cardiac: Hypertension, angina, post MI, heart failure, atrial fibrilation, & tachycardia.
- Some, carteolol & timolol, are used as eye drops to treat glaucoma.
- Other: Hyperthyroidism, migraine prophylaxis, essential tremor, stage fright.
18
Q
What are the adverse effects of First-Generation: non-selective beta blockers?
A
- Beta 1: hypotension, sexual impairment, nightmares, some lower HDL & higher Tg (minor with chronic use). Heart failure, reduced cardiac output (fatigue) arrhythmias, & bradycardia (beta 1 mediated).
- Beta 2: Peripheral vasoconstriction (beta 2 mediated): not a problem for most people unless there is a history of peripheral vascular disease (PVD), Reynaud’s, or non-healing ulcers where there is already some decreased peripheral blood flow.
- bronchoconstriction (beta 2 mediated): This bronchoconstriction is not a problem for most patients. However, patients with COPD or asthma may be adversely affected.
- May mask signs & symptoms of hypoglycemia in diabetics (beta 2)
- Metabolism disturbances (beta 2 mediated): lead to decreased release of glucagon & decreased liver glycogenolysis (decreased conversion of glycogen to glucose). This can decrease a diabetic’s ability to correct hypoglycemia. Again, this is normally not a problem for most people, but can cause prolonged hypoglycemia in diabetics.
- Do not stop abruptly!!! May cause rebound angina, arrhythmias, heart attack, & DEATH.
19
Q
What drugs are included in the group Second-Generation: Cardioselective Beta 1 blockers?
A
"olol" acebutolol metoprolol atenolol bisoprolol betaxolol esmolol
20
Q
What are the mechanism of action for the group Second-Generation: Cardioselective beta 1 blockers?
A
- selectively blocks beta 1 receptors
- These agents have a higher affinity for the beta 1 receptors than the beta 2 receptors. They can lose their selectivity at higher doses.
21
Q
What are the therapeutic uses of Second-Generation: Cardioselective Beta 1 Blockers?
A
- Same cardiac therapeutic uses as the non-selective beta blockers
- Cardiac: Hypertension, angina, post MI, heart failure, atrial fibrillation, & tachycardia.
- Hyperthyroidism, migraine prophylaxis, essential tremor, stage fright
- *less effective for stage fright and migraine prophylaxis.
22
Q
What are the adverse effects of Second-Generation: Cardioselective Beta 1 Blockers?
A
- Same hypotensive, cardia, and sexual side effects as the non-selective beta blockers.
- *hypotension, sexual impairment, heart failure, reduced cardiac output (fatigue) arrhythmias, & bradycardia.
- They are less likely to cause peripheral vasoconstriction, bronchoconstriction, or hypoglycemia, but can still mask hypoglycemia.
- They should also NOT be stopped abruptly
23
Q
What are the drugs included in the group Third-Generation: Beta Blockers with Vasodilating Actions? what receptors??
A
carvedilol (alpha 1, beta 1, beta 2)
labetalol (alpha 1, beta 1, beta 2)
nebivolol (beta 1)
24
What are the therapeutic uses for carvedilol? (Third-Generation: Beta blockers with vasodilating actions)
Hypertension and heart failure
25
what are the side effects of carvedilol?
*it has similar side effects to the alpha 1 blockers (except will not cause reflex tachycardia) & the same side effects as the non-selective beta blockers.
26
What are the uses and effects of labetalol?
It is not used for CHF. It is most commonly used for hypertensive emergencies. It has similar side effects to carvedilol.
Same side effects as non-selective beta blockers and alpha 1 blockers
27
what are the uses and side effects of nebivolol?
Uses: to treat hypertension
* promotes synthesis and release of nitric oxide causing vasodilation.
* beta 2 blockers increase the release of nitric oxide.
28
what drugs make up the group ACE-inhibitors?
```
"pril"
captopril
benazepril
fosinopril
enalapril
ramipril
trandolapril
lisinopril
quinapril
moexipril
```
29
give an overview of the RAAS.
Angiotensin-2 is a potent vasoconstrictor. Angiotensin-2 also stimulates synthesis of other vasoconstrictors, inhibits the synthesis of bradykinin (a vasodilator) & stimulates the secretion of aldosterone, which causes the kidneys to retain Na+ & fluid to waste K+
30
what is the mechanism of action for ACE-inhibitors?
* ACE-inhibitors inhibit the conversion of angiotensin-1 to its more active form, angiotensin-2.
* ACE-inhibitors counteract or inhibit all of the pharmacological effects of angiotensin-2. Thus, ACE-inhibitors cause vasodilation, decrease aldosterone levels, Na+ & fluid wasting K+ retention.
31
What are the therapeutic uses of ACE-inhibitors?
* Chronic Hypertension
* Chew & swallow oral tablets for hypertensive urgencies
* Congestive heart failure: slows the progression of CHF & improves the patient's quality of life.
* Diabetes: slows the progression of renal failure in diabetics, even without HTN.
32
What are the adverse effects of ACE-inhibitors?
*Hypotension (especially with the first dose- give a test dose of captopril to be safe)
*Hyperkalemia (elevated serum K+) - due to aldosterone effects
*Bradykinin related side effects
>>dry hacky cough (can reduce dose & retry) [5%]
>>non-allergic rash
>>rarely angioedema (swelling of lips & face) - immediately discontinue
*Contraindicated in pregnancy
33
what drugs are included in the group Angiotensin-2 receptor blockers? (ARBs)
```
"sartan"
losartan
candesartan
valsartan
irbesartan
telmisartan
olmesartan
eprosartan
```
34
What is the mechanism of action for ARBs? (Angiotensin-2 Receptor Blockers)
Directly bind & block the angiotensin-2 receptors
35
What are the therapeutic uses of ARBs?
* Same therapeutic uses as the ACE-inhibitors
* Chronic Hypertension
* Chew & swallow oral tablets for hypertensive urgencies
* Congestive heart failure
* Diabetes
* Good choice as an alternative to an ACE-I in atients who cannot tolerate ACE-I side effects.
36
What are the adverse effects of ARBs?
* May cause hyperkalemia & hypotension
* Less likely to cause cough, rash, & angioedema due to their lack of efforts on bradykinin.
* also contraindicated in pregnancy
37
What drugs are included in the group direct renin inhibitor?
aliskiren
38
What is the mechanism of action for Direct renin inhibitor?
* Binds tightly with renin and inhibits cleavage of angiotensinogen into angiotensin-1
* Reduces influence of entire RAAS
39
what are the therapeutic uses of direct renin inhibitors?
Chronic hypertension
40
what are the adverse effects of direct renin inhibitors?
Generally well tolerated, diarrhea, contraindicated in pregnancy.
41
what drugs are included in the group Calcium Channel Blockers?
```
"zem" "amil" "dipine"
diltiazem
verapamil
nifedipine
nicardipine
amlodipine
isradipine
felodipine
nimodipine
nisoldipine
```
42
what is the mechanism of action for calcium channel blockers?
* All inhibit entrance of Ca++ into smooth muscle cells of coronary and arterial vessels. Calcium is necessary for strength of muscle contraction & tone.
* *All these drugs are vasodilators
* Calcium channels are also present on the heart, coupled with beta 1 receptors. Diltiazem and verapamil also act on the calcium channels of the heart which causes them to have some effects similar to the selective beta 1 blockers.
43
what are the therapeutic uses of calcium channel blockers.
* Most can be used to treat chronic hypertension & angina
* Like the beta 1 blockers, verapamil & diltiazem can also be used for arrhythmias such as atrial-fibrillation & tachycardia.
44
what are the adverse effects of CCBs.
* flushing, peripheral edema, headache, and reflex tachycardia are common side effects.
* Verapamil & Diltiazem also have side effects similar to the selective beta 1 blockers. They can slow the S-A node & A-V node conduction, causing bradycardia. They can also have negative inotropic effects.
* All CCBs can cause peripheral edema & constipation. Constipation is caused by relaxation of the smooth muscle of the GI tract.
* Gingival enlargement.- gingival hypoplasia.
* Immediate-release/ short-acting nifedipine (10 mg cap) is associated with dangerous ping-ponging blood pressure, reflex tachycardia, arrhythmias, myocardial infarction, & death. Not recommended for PRN use. Sustained-release nifedipine is perfectly safe.
