10) Hypertension and Anti-Hypertensives Flashcards
(132 cards)
1
Q
Hypertension is recognized as a major risk factor for several potentially lethal cardiovascular conditions, including
A
- Myocardial infarction
- Heart failure
- Stroke
2
Q
Elevated systolic pressure is considered
A
- 120-130 mmHg
3
Q
Stage 1 hypertension systolic pressure
A
- 130/80 to 140/89 mmHg
4
Q
Stage 2 hypertension systolic pressure
A
- 140/90 mmHg +
5
Q
Systemic vascular resistance (SVR)
A
- Resistance to blood flow offered by all of the systemic vasculature
- Excluding the pulmonary vasculature
- AKA total peripheral resistance
6
Q
SVR is determined by mechanisms that cause
A
- Vasoconstriction which increase SVR
- Vasodilation which
decrease SVR
7
Q
Although SVR is primarily determined by changes in blood vessel diameters, changes in
A
- Blood viscosity also affect SVR
8
Q
Cardiac output (CO)
A
- Amount of blood pumped by the heart per minute
- Amount of work performed by the heart in response to the body’s need for oxygen
9
Q
Drugs used in hypertension
A
- Diuretics
- Sympathoplegics
- Vasodilators
- Angiotensin antagonists
- Renin inhibitors
10
Q
Sympathoplegics are blockers of
A
- A/B receptors
- Nerve terminals
- Ganglia
- CNS sympathetic outflow
11
Q
Vasodilator examples
A
- Calcium blockers
- Parenteral vasodilators
- Older oral vasodilators
12
Q
Angiotensin antagonist examples
A
- ACE inhibitors
- Receptor blockers
13
Q
The diuretics most important for treating hypertension are
A
- Thiazides (eg, chlorthalidone, hydrochlorothiazide)
- Loop diuretics (eg, furosemide)
14
Q
Nephron (basic structural unit of the kidney) function
A
- Regulate concentration of water and soluble substances (like Na+) by filtering the blood
- Reabsorbs what is needed
- Excretes the rest as urine
15
Q
Segments of the nephron
A
- PCT: Proximal convoluted tubule
- TAL: Thick ascending loop of Henle
- DCT: Distal convoluted tubule
- CCT: Cortical collecting duct
16
Q
Diuretics acting on PCT
A
- Carbonic anhydrase inhibitors (acetazolamide)
17
Q
Diuretics acting on TAL
A
- Loop diuretics (furosemide)
18
Q
Diuretics acting on DCT
A
- Thiazides (hydrochlorothiazide)
19
Q
Diuretics acting on CCT
A
- K+ sparing diuretics (spironolactone)
20
Q
Duretics modify
A
- Salt secretion
21
Q
Drugs that modify water excretion
A
- Osmotic diuretics (mannitol: also modifies salt excretion)
- ADH agonists (desmopressin)
- ADH antagonists (conivaptan)
22
Q
Loop diuretics
A
- Furosemide, Bumetanide, Torsemide (all sulfonamide derivatives)
- Ethacrynic acid (not a sulfonamide)
23
Q
Loop diuretics usually induce
A
- Hypokalemic metabolic alkalosis
- Large amounts of sodium are presented to the collecting tubules, potassium wasting may be severe
24
Q
Loop are very efficacious. They can cause
A
- Hypovolemia
- Cardiovascular complications
25
Distal convoluted tubule
- Pumps Na+/Cl- out of the lumen of the nephron via the
Na+/Cl– carrier (NCC)
- Channel is target of thiazide diuretics
26
Calcium is also reabsorbed in the DCT under the control of
- Parathyroid hormone (PTH)
27
Thiazides are sulfonamide derivatives; the ones that lack typical thiazide ring in their structure are therefore considered
- Thiazide-like which also contain sulfonamide
28
Because they act in a diluting segment of the nephron, thiazides may reduce
- Excretion of water and cause dilutional hyponatremia
29
Loop diuretic names
- Bumetanide
- Bumex
- Furosemide
- Lasix
- Torsemide
- Ethacrynic acid
30
Bumetanide and Bumex metabolism
- Partially hepatic, then urine excreted
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Furosemide and Lasix metabolism
- Mainly renal
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Torsemide metabolism
- Mainly hepatic
33
Ethacrynic acid metabolism
- Partially hepatic
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Thiazide diuretic names
- Chlorothiazide
| - Hydrochlorothiazide
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Chlorothiazide and hydrochlorothiazide metabolism
- Not metabolized
| - Excreted unchanged in urine
36
Thiazide-like diuretic names
- Chlorthalidone
- Indapamide
- Metolazone
37
Chlorthalidone and Metolazone metabolism
- Not metabolized
| - Excreted unchanged in urine
38
Indapamide metabolism
- Hepatic
39
Loop diuretic side effects
- LFT increased
- Hypomagnesemia
- Hypokalemia
- Hypocalcemia
- Photosensitivity
- Nephrotoxicity
- Ototoxicity (dose-related)
40
Thiazide-like diuretic side effects
- Hypokalemia
- Hypercalcemia
- Hypercholesterolemia
- Hypertriglyceridemia
- Increase LDL
- Azotemia
41
Diuretic side effects (shared by both kinds)
- Fluid and electrolyte loss
- Hypovolemia (dehydration)
- Hypotension
- Hyperglycemia
- Hyperuricemia
- Hypochloremia
- Hyponatremia (dilutional)
- Metabolic alkalosis
42
Final segment of the nephron
- Cortical collecting tubule
| - Controlled by aldosterone
43
Aldosterone
- Steroid hormone secreted by the adrenal cortex
| - Responsible for sodium reabsorption (2–5%)
44
The reabsorption of sodium occurs via
- Epithelial sodium channels (ENaC)
| - Accompanied by loss of potassium or hydrogen ions
45
The collecting tubule is the primary site of
- Acidification of the urine
| - Last site of potassium excretion
46
The aldosterone receptor and the sodium channels are sites of action of the
- Potassium-sparing diuretics
47
Reabsorption of water occurs in the
- Collecting tubule
| - Under the control of antidiuretic hormone (ADH)
48
Most diuretics act from the
- Luminal side of the membrane (except aldosterone receptor antagonist group)
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Aldosterone receptor antagonist group (diuretics)
- Spironolactone and eplerenone
- Enter the collecting tubule from the basolateral side
- Bind to cytoplasmic aldosterone receptor
50
Carbonic anhydrase inhibitor (Acetazolamide) method of action
- Inhibit carbonic anhydrase
- In proximal tubule, bicarbonate reabsorption is blocked and Na+ is
excreted with HCO-
51
Carbonic anhydrase inhibitor (Acetazolamide) toxicities/interactions
- Metabolic acidosis
| - Hyperammonemia in cirrhosis
52
Loop diuretics
| (furosemide, bumetanide and torsemide, ethacrynic acid) method of action
- Inhibit Na+/K+/2Cl- transporter in thick ascending limb of loop of Henle
- Cause powerful diuresis and increased Ca2+ excretion
53
```
Loop diuretics
(furosemide, bumetanide and torsemide, ethacrynic acid) toxicities/interactions
```
- Metabolic hypokalemic alkalosis
- Ototoxicity
- Hypovolemia
- Efficacy reduced by nonsteroidal anti- inflammatory drugs
- Sulfonamide allergy
54
Thiazide diuretics Hydrochlorothiazide, chlorthalidone (thiazide-like) method of action
- Inhibit Na+/Cl- transporter in distal convoluted tubule
| - Cause moderate diuresis and reduced excretion of calcium
55
Thiazide diuretics Hydrochlorothiazide, chlorthalidone (thiazide-like) toxicities/interactions
- Metabolic hypokalemic alkalosis
- Early hyponatremia
- Increased serum glucose, lipids, uric acid
- Efficacy reduced by nonsteroidal anti-inflammatory drugs
- Sulfonamide allergy
56
K+- sparing diuretics (Spironolactone, eplerenone) method of action
- Steroid inhibitors of cytoplasmic aldosterone receptor in cortical collecting ducts
- Reduce K+ excretion
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K+- sparing diuretics (Spironolactone, eplerenone) toxicities/interactions
- Hyperkalemia
| - Gynecomastia (spironolactone only)
58
K+- sparing diuretics (Amiloride, triamterene) method of action
- Inhibitor of ENaC epithelial sodium channels in cortical collecting duct
- Reduces Na+ reabsorption and K+ excretion
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K+- sparing diuretics (Amiloride, triamterene) toxicities/interactions
- Hyperkalemia
60
Osmotic diuretics (Mannitol) method of action
- Osmotically retains water in tubule by reducing reabsorption in proximal tubule, descending limb of Henle’s loop, and collecting ducts
- In the periphery, mannitol extracts water from cells
61
Osmotic diuretics (Mannitol) toxicities/interactions
- Hyponatremia followed by hypernatremia
| - Headache, nausea, vomiting
62
Angiotensin converting enzyme inhibitor (ACEI) names
- Enalapril
- Captopril
- Ramipril
- Lisinopril
- Benazepril
- Trandolapril
- Others
63
There is sufficient evidence that proves that ACEI and ARB reduce
- Progression of CKD (chronic kidney disease)
64
ACE inhibitors reduce the activity of
- Renin-angiotensin-aldosterone system (RAAS)
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RAAS is activated in response to
- Fall in blood pressure (hypotension) or salt-water
| imbalance of the body
66
Renin
- Released by kidney
- Enzyme that changes angiotensinogen (a protein made in the liver)
to angiotensin I
67
ACE (Angiotensin converting enzyme) converts
- Angiotensin I into angiotensin II
68
The system increases blood pressure by
- Increasing the amount of salt and water the body retains
| - Action of angiotensin as a vasoconstrictor
69
Inhibition of ACE side effects
- Hypotension /dizziness
- Increase serum creatinine/ renal impairment
- Hyperkalemia
70
Inhibition of enzymes other than ACE side effects
- Cough caused by elevated bradykinin level due to ACE inhibition can be a cause of dry cough, angioedema and/or rash, hypotension, and inflammation-related pain
71
Other side effects of ACEI
- Neutropenia, agranulocytosis
- GI: N/V/D
- Impotence
- Taste change
72
Angiotensin II receptor blockers (ARB) names
- Valsartan
- Telmisartan
- Losartan
- Irbesartan
- Olmesartan
- Candersartan
- Others
73
ARBs are AT1-receptor antagonists
- Block the activation of angiotensin II AT1 receptors
74
Blockage of AT1 receptors directly causes
- Vasodilation
- Reduces secretion of vasopressin
- Reduces production and secretion of aldosterone
75
Hepatically metabolized ARBs
- Losartan
- Valsartan
- Irbesartan
- Telmisartan
- Eprosartan
76
Hepatically mixed with renally metabolized ARBs
- Candesartan
- Olmesartan
- Azilsartan
77
Clinical effects of ACEI and ARB
- Relax the efferent arteriole
- Lowers intra-glomerular pressure
- Reduces GFR
78
Advantage of ARB over ACEI
- Doesn’t block type II AgII receptors
- Maintains antiproliferative effect
- Bradykinin is converted to kinin, so no dry cough as side effect
79
Blockage of AT1 receptor side effects
- Hypotension /dizziness
- Increase serum creatinine/ renal impairment
- Hyperkalemia
80
Aliskiren (Tekturna)
- Direct renin inhibitor
| - Taken once a day
81
Aliskiren (Tekturna) method of action
- Renin inhibitor
- Renin is the first enzyme in the RAAS that cleaves angiotensinogen to
angiotensin I
82
Aliskiren (Tekturna) side effects
- Hyperkalemia
- Angioedema
- Low blood pressure
- Cough, diarrhea and headaches
83
Aliskiren (Tekturna) metabolism
- Unchanged in urine and feces
84
Sympathoplegics that act in CNS
- Alpha2-selective agonists (eg, clonidine, methyldopa)
85
Alpha 2-selective agonists (eg, clonidine, methyldopa) cause a decrease in
- Sympathetic outflow by activation of α2 receptors in the CNS
- Both drugs may cause sedation
86
Alpha 2-selective agonist CNS activity
- Readily enter the CNS when given orally
87
Alpha 2-selective agonists reduce blood pressure by
- Reducing cardiac output and vascular resistance
88
Major compensatory response of alpha 2-selective agonists
- Salt retention
89
Sudden discontinuation of clonidine causes
- Rebound hypertension
| - May be severe
90
Methyldopa occasionally causes
- Hematologic immunotoxicity
| - Hemolytic anemia
91
Hemolytic anemia
- Disorder in which red blood cells are destroyed faster than they can be made
92
Adrenoreceptor blockers
- Alpha-1 blockers
| - Beta blockers
93
Alpha1-selective agents (eg, prazosin, doxazosin, terazosin)
- Moderately effective antihypertensive drugs
| - Reduce vascular resistance and venous return
94
Alpha 1 receptor is found in
- Blood vessels
- Sphincters of the GI
- Eye
- Genitourinary (uterus)
95
Nonselective α blockers (phentolamine, phenoxybenzamine) are of no value in
- Chronic hypertension because of excessive reflex tachycardia
96
Alpha 1-selective adrenoceptor blockers cause
- Orthostatic hypotension, especially with the first few doses
- Also relax smooth muscle in the prostate (useful in benign prostatic hyperplasia)
97
Beta blockers are used very heavily in the treatment of
- Hypertension
98
Beta blocker examples
- Propranolol is the prototype
| - Atenolol, metoprolol, and carvedilol are among the most popular
99
Beta blocker effects
- Reduce cardiac output
| - Chronic use may decrease vascular resistance
100
Chronic use of beta blockers may cause a decrease in vascular resistance as a result of
- Reduced angiotensin levels
| - β blockers reduce renin release from the kidney
101
Vasodilators
- Drugs that dilate blood vessels by acting directly on smooth muscle cells
102
Vasodilators act by four major mechanisms
1) Blockade of calcium channels
2) Release of nitric oxide
3) Activation of D1 dopamine receptors through Gs
4) Opening of potassium channels (which leads to hyperpolarization)
103
4 major vasodilators
1) Calcium channel blockers
2) Nitrates, Nitroprusside, hydralazine
3) Fenoldopam
4) Minoxidil, diazoxide
104
Effective vasodilators
- Calcium channel blockers
| - Verapamil and diltiazem also reduce cardiac output in most patients
105
Two types of CCB
- Dihydropyridine (DHP) with nifedipine as the prototype
| - Non-DHP
106
DHP names
- Amlodipine
- Felodipine
- Isradipine
- Nicardipine
- Nifedipine
- Nimodipine
- Nitrendipine
107
DHP mechanism
- High vascular selectivity (reduces SVR and BP)
| - Can lead to reflex cardiac stimulation (tachycardia and increased inotropy)...can offset beneficial effects
108
DHP side effects
- Flushing
- Headache
- Excessive hypotension
- Edema
- Reflex tachycardia
- Long-acting dihydropyridines (e.g., extended release nifedipine, amlodipine) reduce reflex responses
109
Non-DHP names
- Verapamil
| - Diltiazem
110
Verapamil (non-DHP) mechanism
- Selective for the myocardium, less effective as a systemic vasodilator drug
- Indication for treating angina (by reducing myocardial oxygen demand)
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Diltiazem (non-DHP) mechanism
- Intermediate between verapamil and dihydropyridines in its selectivity for vascular calcium channels
- Able to reduce arterial pressure without producing the same degree of reflex tachycardia of dihydropyridines
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Non-DHP side effects
- Bradycardia
- Impaired electrical conduction (e.g., atrioventricular nodal block)
- Depressed contractility
113
Hydralazine and Minoxidil
- Older vasodilators
| - More effect on arterioles than veins
114
Hydralazine
- Acts through the release of nitric oxide from endothelial cells
- Rarely used at high dosage
115
Hydralazine is rarely used at high dosage because of
- Hydralazine-induced lupus erythematosus
| - Reversible upon stopping the drug
116
Minoxidil
- Potassium channel opener that hyperpolarizes and relaxes vascular smooth muscle
117
Minoxidil can cause
- Hirsutism, so it is also available as a topical agent for the treatment of baldness
118
Minoxidil use/mechanism
- Extremely efficacious
- Reserved for severe hypertension
- Diazoxide has the same mechanism of action, but is less preferred because of the high side effects
119
Hydralazine metabolism
- Hepatic
| - DOA = 12h
120
Hydralazine side effects
- Hydralazine-induced Lupus like syndrome
- Blood dyscrasias
- Hypotension
- Peripheral neuritis (pyridozine treatment is needed here)
- Flushing; orthostatic hypotension
121
Minoxidil metabolsim
- Hepatic
| - DOA = 2-5 days
122
Minoxidil side effects
- Fluid retention; sodium/ water retention; weight gain
- Increase serum creatinine and liver enzymes
- US Box warning: pericarditis
- Syncope; sinus tachycardia
- Hypertrichosis
123
Diazoxide (thiazide derivative but lacks diuretic properties) DOA
- Less than 8h
124
Diazoxide side effects
- Hyperosmolar coma
- Hypotension, tachycardia
- Headache
- Pancreatitis
- Hirsutism
- Hyperglycemia
- Sodium retention
- Blood dyscrasias (thrombocytopenia; neutropenia; decrease hematocrit
- Blurred vision
- Gout
125
Parenteral vasodilators used in hypertensive emergencies
- Nitroprusside
- Diazoxide
- Fenoldopam
126
Nitroprusside mechanism
- Releases nitric oxide (from the drug molecule itself) - Increases cyclic guanine monophosphate (cGMP) concentration
- Increases relaxation in vascular smooth muscle
- Dilates arterial resistance vessels more than venous vessels
127
Dopamine D1 receptor activation by fenoldopam causes
- Prompt, marked arteriolar vasodilation
128
Nitroprusside properties
- Brand = Nitropress
- DOA = 10 min
- Short-acting agent
- Light-sensitive
129
Fenoldopam properties
- Brand = Cortopam
- DOA = 1h
- Metabolism = hepatic
130
Nitroprusside and Fenoldopam shared side effects
- Flushing
- Headaches
- Hypotension
- Tachycardia
131
Nitroprusside side effects
- Methemoglobinemia
- Hypothyroidism
- Can release cyanide ions
132
Fenoldopam side effects
- Increase liver enzyme
