Exam 4 Flashcards
(174 cards)
1
Q
__% of hypertension is uncontrolled
A
>61%
2
Q
___% are unaware they have high BP
A
33%
3
Q
hypertension= ____BP
A
>140/90 mmHg
4
Q
secondary hypertension=
A
secondary to a specific disorder
5
Q
essential hypertesion=
and accounts for __% of all cases
A
no clear identifiable cause
=95% of all cases
6
Q
RAAS system
A
7
Q
RAAS is stimulated by
A
SNS… B1 receptors
and barroreceptors
8
Q
aldosterone is synthesised in the___
and fxn is___
A
adrenal cortex
-increases Na+ re-absorption in collecting duct
9
Q
vasopressin action=
A
increases TPR and water retention
10
Q
Big 4 hypertensive agents
A
- Diuretics
- Direct vasodialtors
- Sympatholytic agents
- Angiotensin related agents
(5. Combination therapy - most common)
11
Q
Diuretics used for__
actions____
A
**first choice for MILD hypertension
- low cost but effective
initially=increase urine volume
delayed= decrease peripheral resistance by increaseing Na+ excretion
12
Q
Loop diuretics action
A
=high efficacy
-blocks lots of Na+ readbsorption
= deplete K+ = HYPOKALEMIA
=retain uric acid = gout
13
Q
loop diuretics list
A
furosemide
ethacrynic acid
14
Q
thiazides action
A
=moderate efficacy
=stop Na+ reabsorption in distal convoluted tubule
=deplete K+ =HYPOKALEMIA
=retain uric acid= gout
15
Q
thiazides list
A
hydrochlorothiazide
chlorthalidone
16
Q
potassium sparing agents action
A
-reduce Na+/K+ exchange in DCT and CD
= Na+ excretion
= K+ retention
-COUNTERACTS HYPOKALEMIA
17
Q
diuretic that is first line of treatment =
A
thiazides
bc they have moderate efficacy
18
Q
all diuretics have ___ as a side effect
A
dehydration
19
Q
Mechanism of Loop Diuretics (draw schematic)
A
20
Q
Thiazide mechanism (draw schematic)
A
21
Q
____ is the most effective diuretic and is longer acting
A
chlorthalidone
22
Q
spironolactone mechanism schematic
A
=a K+ sparing diuretic
-inhibits Muscarinic Receptor ∴ decreases expresion of Na+/K+ ATPase
=big K+ effects
=small Na+ effects
23
Q
thiameterine and amiloride mechanism (schematic)
A
=K+ sparing diuretics
= inhibit K+ channel on apical membrane
=HUGE K+ resprption
=small Na+ excretion
24
Q
direct acting sympatholytic agetnts lower blood pressure by
A
- beta blockers
- reduce HR and Force = decreased CO
- reduce renin production - alpha 1 antagonists
- vasodilate (block contraction) = decreased TPR
25
beta blockers for decreasing BP drugs
propanolol (non-selective)
atenolol (cardioselectve)
nadolol (long-acting)
26
don't use ___ in asthmatics
atenolol
27
indirect acting sympatholytic agents to reduce BP types=
1. alpha 2 agonists
- trick nerve into thinking theres lots of NT and stop SNS activity
2. catecholamine release inhibitors
- inhibit vesiculare release
- can cause CNS side effects (reduced DA)
28
alpa 1 adrenergic receptor antagonists to control BP drug list
prazosin
terazosin
29
alpha 2 agonists drug list
clonidine
30
catecholamine release inhibiors drug list
reseprine
31
hydralazine
direct vasodilator
oral drug
=selective arterial dilator
32
Calcium Channel Blockers
vasodilator
oral drug
block Ca+ dependent channels on vascular smooth muscle
33
CCB mechanism schematic
34
minoxidil
vasodilator
oral drug
higly effective!
lots of side effects! (excessive hair)
last resort
35
alpha 1 receptor antagonists will mimic ___ effects
CCBs bc they also block the V-G Na+ channels
36
sodium nitroprusside
parenteral drug
vasodilator
37
diazoxide
vasodilator
parenteral drug
highly effective and long acting ∴ not a first choice drug
38
Nitrates mechanism of action schematic
39
hydralazine, diaxodine, monoxidil mech. of action schematic
40
CCB's can target\_\_\_\_ channels
L-type Voltage Dependent Ca2+ channels on cardiac or vascular smooth muscle
41
Non-cardioactive CCB's action
-more selective for Ca2+ channels on smooth muscle than in heart ∴ don't have an effect on heart
= dihydropyridines
42
non-cardioactive CCB's drug list
all =dihydropyridines
1. amlodipine - long half life
2. nifedipine - short half life
43
short acting dihydropyridines
= increased risk for acute MI
=AVOID
=nifedipine
-only use extended release version if nifedipine
44
long acting dihydropyridines
- use these for hypertension or angina pectoris
=amlodipine
45
cardioactive CCB's action
=equally selective for ca2+ channels on vascular smooth muscle AND in heart
∴ relaxe sm. muscle AND reduce CO
46
verapamil
diltiazem
cardioactive CCB's drugs
47
vasodialtor side effects
1. postural (orthostatic) hypotension
2. flushing/sweating headache
3. reflex tachycardia
- body's reflex is to set at high BP so barroreceptors (+) increased HR
4. reflex fluid retention
- juxtaglom. retain Na+ to increase volume
48
to prevent reflex tachycardia we coadminister \_\_\_
beta blocker
49
to prevent reflex fluid retention with vasodilation we coadminister \_\_\_
diuretic drug
50
beta blockers tha are also vasodilators drug list
=decreas CO AND TPR
carvendilol
nebivolol
51
carvendilol
mixed beta 1/2 and alpha 1 antagonist
∴decreases CO AND TPR
52
nebivolol
beta 1 blocker that promotes NO production
∴decreases CO AND TPR
53
Angiotensin related agents types and general action
1. ACE inhibitors
2. Angiotensin Recptor Blockers
3. Renin Inhibitors
=vasodilate and decrease aldosterone and vasopression ∴ decrease blood volume
54
ACE Inhibitors action and drug list
= (-) angiotension I to II
captopril
enalapril
ramipril
55
Angiotensin Receptor Blockers action and list
=inhibit binding of angiotnesin II to AT1
losartan
valsartan
56
Renin inhibitors action and list
= (-) conversion of angiotensinogen to angiotensin I
aliskiren
57
captopril
ACE Inhibitor
- not a prodrug
- associated with higher side effect risk
- short half life
58
enalapril
=ACE Inhibitor
-pro-drug
59
ramipril
=ACE Inhibitor
-prodrug
\*greater cardioprotective
\*greater efficacy
∴
\*\*most commonly used\*\*
60
ACE Inhibitor side effects
=BIG DEAL
## Footnote
1. dry cough- inhibit the breakdown of bradykinins by ACE ∴ they accumulate in lungs
2. Angioedema - rapid non allergic swelling of skin and mucos -from bradykiin
3. Hyperkalemia - reduced Na+/K+ exchange in kidney form reduced aldosterone
- also, TERATOGENIC
61
Angiotensin Receptor Blockers effects and side effects
=competitive antagonist at AT1 Receptors
=some AT2 receptor antagonist
=avoid side effects mediated by interactions with other receptors
side effects = hyperkalemia and are teratogenic
62
ARBs drug list
losartan
valsartan
63
Renin Inhibitor action, side effects, and normal usage
=(-) conversion of angiotensin 1 -\> 2
- same side effects as ARBs (hyperkalemia and teratogenicity)
- idea is to reduce compensatory increase in renin caused by ARB and ACE inhibitors
64
AVOID Renin Inhibitors in
patients with type 2 diabetes and kidney disease
- increases incidence of cardiovascular and renal events
65
Phase 1 hypertension use \_\_\_
if phase 2 use\_\_-
phase 1= one drug
phase 2= two drugs
66
for most hypertensive patients first prescribe
thiazide diuretics
67
for diabetic patients first prescrib
\_\_\_\_\_\_ for hypertension
ACE Inhibitors
=protects kideys
68
for pts with Coronary Heart Disease first prescribe\_\_\_\_\_\_ for hypertension
Beta Blockers
69
in African American patients __ = first line
CCBs or thiazides
70
NIH Sprint Study
- under 60yrs start tx with BP of 140/90
- older than 60 start tx with BP of 150/90
- adults 50yrs or older should maintain systolic \<120 mmHg
71
classic angina
occlusion of coronary artery resulting form an anthrosclerotic plaque
- most common
- symptoms occur during exercise/stress
72
antherosclerosis formation
1. LDL penetrates arterial wall
2. foam cells
3. foam cells shear off and expose tissue
4. clotting
5. plaque formation
=cholesterol center with platelet/fibrin cap
73
variant (Printzmetal's) angina
=spontaneous vasoconstriction of coronary arteries
- genetic origin
- symptoms at rest
- less common
74
Liproprotiens
HDL= good -small amt of cholesterol
-takes cholesterol back to liver
LDL=bad -lots of cholesterol
VLDL=BAD triglycerides
75
Lipid metabolism steps
1. chylomicrons transport cholesterol and TGY from GI into circulation
2. Lipoprotien lipase cleaves TGYs from chylomicrons and realeases ffa, leaving cholesterol to go to liver
3. liver makes VLDL
4. Lipoprotien lipase breaks down VLDL which go back to liver and are turned into LDL
5. LDL binds to LDL recptors on cells =internalization
6. HDL is also made in liver = (+) lipoprotien lipase and brings cholesterol back to liver
76
liver makes its own cholesterol via
HMG Co-A reductase
77
hypertryiglyceridemas
=increased VLDL
=some risk for CHD adn pacreatitis
78
hypercholesterolemias
= increased LDL
=high risk for CHD
\* most common is = "multifactorial"
-genetic, lifestyle, diet
79
two basic strategies for treating hyperlipidemia
1. decrease lipid entering blood
- low fat diet
- reduce lipoprotien synthesis
- reduce dietary cholesterol absorption
2. improve clearance of lipid from the blood
- for VLDL - affect lipoprotien lipse
- for LDL - increase LDL receptors
80
drugs for hypertriglyceridemia
niacin
fibric acid derivatives
81
drugs for hypercholestrolemia
- bile acid binding sequestrants
- statins
- ezetimibe
- nacin
- combination therapy
82
Niacin
treats hypertriglyceridemia
- decreases circulating VLDL
1. inhibits VLDL synthesis in liver
2. stimulates breakdown of VLDL by lipoptotien lipase
=net decrease in LDL
=most effective at increasing HDl
-side effects = tachyfalaxis and flushing
83
gemfibrozil
treats hypertriglyceridemia
=fibric acid derivative
- most effective at reducing VLDL , but minimal effects on LDL and HDL
1. inhibits VLDL synthesis
2. stimulates breakdown of VLDL to LDL via lipoprotien lipase - (offsets the reduction of LDL)
84
colesevelam
=bile acid sequestrant
=treates hypercholestrealemia
-reduces LDL and increases HDL
\*second line of tx after statins
- take orally, and bind to bile acids in stomach ∴ we need to make more
- lower cholestrol= upregulation of LDL-R in liver
side effects - reduced folic acid absorption and GI probs
85
Statins action
HMG-Co A Reductase Inhibitors
- treat hypercholestrolemia
- inhibit cholestrol synthes = upregulation of LDL-R
∴ increast removal of LDL fro blood
- 60% decrease in cardiovascular events
- 17% decrease in strokes
86
statins drug list
low efficacy=:
pravastatin
lovastatin
medium efficacy:
simvastatin
pitavastatin
high efficacy:
**atorvastatin (big one)**
rosuvastatin
87
statins side effects
los incidence liver toxicity
momory loss
diabetes risk (not enough to avoid tx.)
myopathy
88
statin drug interactions
grapefruit juic inhibits metabolism and increases risk for rhabdomyolysis
89
rhabdomyolysis
-induced by statins
=skeletal muscle cell lysis and dumping contents onto kidney causeing kidey failure and death
90
ezetimibe
- anticholesterol drug
- inhibits fxn of protien in brush border of GI that would absorb cholesterol in small intestine
∴reduces LDL
91
enhance study
- reducing LDL may not be affecting coronayr antherosclerotic plaque formation ...
maybe statins do other stuff too...
92
AIM High Study
- added niaspan to a statin
- affected lipid profile as expected BUT didn decrease risk for heart atack
AND increased stroke risk...
93
PCSK9
Proprotein convertase subtilisin/kexin type 9
-protien that metabolizes LDL-R insead of recycling them
94
alirocumab
=mooclonal antibody
- inhibits PCSK9
- injected subcutaneously
95
statin treatment guidelinse from American Heart Association
1. pts with CHD
2. pts with LDL \> 190mg/dL
3. diabetics 40-75 with out CHD and LDL \< 190mg/dL
4. pts w/out diabetes or LDL \> 190 mg/dL who have estimated CHD risk \>7.5% and 40-75 yrs old
96
clot formation steps
1. adhesion of platelets
2. aggregation
3. clotting vactors activated by endothelium
= (+) prothrombin -\> thrombin
= (+) fibrinogen -\> fibrin
4. via PAR-1 receptor, thrombin (+) rlease of ADP nd TXA2
5. prostacyclin (PGI2) opposes this
6. fibrin mesh
97
98
antithrombin III
proteas inhibitor in blood that limits coagualtion
-all heparins area verison of this
99
tissue plasminogen activator (T-PA)
fibrinolytic
limits coagutlaition
-all clot-busters are a version of this
100
white thromubs
forms in high pressure arteries
- small amounts of fibrin
- mostly platelets
∴want to use an antiplatelet drug
- causes local ischemia from artery occlusion
- if in coronary arteries =MI PECTORIS!
101
red thrombus
- form in low pressure veins and in the heart
- have platelets AND buly fibrin tails
∴want to use an anti-coagulant drug
- DVT fibrin cap breaks off =PULMONARY EMBOLI
- or cardiogenic emboli = EMBOLIC STROKE
102
anti-coagulant basic function
regulate the fuction and sythesis of clotting factors
- use with RED THROMBI
- prevent clots form forming in venous system and heart
103
antithrombotics/antiplatelets general fxn
inhibit platelet fuction
- used for WHITE CLOTS
- dont break down clots, just prevent clots form forming in arteries
104
thrombolytics/fibrinolytics general fxn
destroy clots after they are formed
-break down fibrin!!
105
parenteral anti coagulent types
1. heparins
- indirectly inhibit thrombin via anti-thrombin III
2. parenteral direct thrombin inhibitors
- directly inhibit thrombin
106
oral anti-coagulant types
1. warfarin
2. oral nonpeptide DTI
3. factor Xa inhibitor
107
heparins
=parenteral anticoagulents
## Footnote
-stimulates ANTITHROMBIN III
= inhibits clotting factor synthesis
types:
1. unfractionated heparin
2. low molecular weight heparin
- side effect =bleeding and heparin induce thrombocytopenia (immune rxn cuases clots)
108
unfractionated heparin
combination of low and high molecular weights
=more activity
109
low molecular weight heparin
less activity
=enoxaparin
110
warfarin
=oral anticoagulant
- delayed effects, need to use up already exixtant clotting factors
- side effects =bleeding
antidote=vitamin K
111
warfarin fxn schematic
112
variation in warfarin enzymes and risks schematic
113
dabigatran etixilate
=direct thrombin inhibitor
=anticoagulant
=less bleeding risk than warfarin
-no antidote yet
114
rivaroxaban and apixaban
=factor Xa inhibitors (anticoagulant)
- less bleeding risk than warfarin
- no antidote yet
115
alteplase
t-PA activator
-often used for strokes
116
urokinase
- recombinant form of a non t-PA human proteas
- used for acute MI
117
treating embolic/thrombotic/hemorrhagic stroke
80% of occlusions from
1. ebolic = from red thrombi
2. thrombotic= from white thrombi
- treat with **ALTEPLASE**
20% of occlusions from
- hemorrhagic stroke
- DONT GIVE ANTICOAGULANT
118
anti thrombotic drugs inhibit platelet fxn by interfering with...
1. Thromboxane A2
2. Adensosine diphosphate (ADP)
3. thrombin
119
thromboxane A2 fxn
=released formplatelets and promotes aggregation and vasocosntriction locally
120
ADP fxn
released from platelets
binds purinergic receptors on other platelets = (+) aggregation
121
thrombin fxn
- increases fibirn production
- activates PAR-1 receptor which promotes platelet activation
122
antiplatelet drugs used for=
1. preventing heart attacks/acute MI
- if signs of unstable angina pectoris/during or after heart attack
2. preventing arterial thrombus of limbs
3. preventing thrombotic/ischemic stroke
4. preventing percutaneous coronar interventions
123
schematic of antiplatelet drugs
124
aspin functionn
inhibits COX 1\> COX 2
∴decreased TXA2 production
∴inhibits platelet aggregation
HAS THESE EFFECTS AT LOW DOSES (because of covalent acetylation of COX)
do not exceede **325mg**
125
clopridogrel
ADP R eceptor blocker
=a prodrug metabolized by CY2C19
-lots of variation in this enzyme (14%)
126
plasugrel
ADP (adenosine diphosphate) Receptor Blocker
- a prodrug but metabolized by a less variable CYP enzyme
- stops platelet aggregation
127
vorapaxar
PAR-1 antagonist
-long half life and no antidote= bleeding concerns ∴ dont use in pt with stroke history
128
abciximab
tirofiban
=platelet recptor antagonists
=a **GPIIb/IIIa** antagonist
- parenteral, highly effective drugs
- prevent platelet-fibrin bond
129
antiplatelet drugs protect against\_\_\_\_ as a prophylactic....
heart attack
thrombotic stroke
also at time of heart attack (325mg) to prevent further clotting
130
aspirin vs. ADP-R blockers
**aspirin ADP Blockers**
inexpensive expensive
effective more effective
bleeding risk less bleeding risk
more variable effect
131
asprin, vorapaxar, ADP blockers, and GPIIb/IIIa inhibitors produce _________ effects
ADDITIVE
-maybe more effective but also more dangerous
132
COX 1
produces TXA2
with inhibition by aspirin=
prevents platelet activation
133
COX 2
produces prostacyclin (PGI2)
with inhibition by rofecoxib=
platelet activation... CLOT
134
bleeding risk assessment tests
1. APTT (activated partial thromboplastin time ):
for heparin
2. PT (prothrombin time)
for warfarin
135
for surgeries you may ned to induce clotting ∴ we use\_\_\_\_\_\_
1. antifibrinolytic drugs (prevent plasmin)
2. hemostatic aids
3. anticoagulant antidotes
136
anticoagulant antidotes
vitamin K- reverses warfarin
protamine sulfates-binds and reverses heparins
137
angina = imbalance btw\_\_
imbalance between **O2 demand** and **O2 supply**
**-**drugs usually treat oxygen demand
138
reucing O2 demand of heart by
1. decrease HR
2. decrease F of contraction
3. decrease preload
139
types of drugs for treating stable angina pectoris
1. organic nigrates
2. beta blockers
3. CCB's
4. Combination therapy
140
vasodilators for angina pectoris
- targeting venous system= reducing preload
- targeting coronary a. = increasing delivery of blood to myocardium
(dilating arteries is NOT beneficial bc it diverts blood away from coronary arteries)
∴ we use **CCB's** and **Nitrates**
141
CCB's and variant vs classic angina
CCB's work better agains variant angina
-in classic angina plaques make vessels unresponsive to relaxation
142
organic nitrates are used to treat ____ pectoris
classic and variant
143
nitroglycerine
isosorbide di- and mono- nitrate
=organic nitrates
=dlate veins and coronary arteries
nitroglycerine -give sublingually or transdermally
isosorbidine di-/mono-nitrate - give orally
TOLERANCE
144
reflexes reactions to nitrates
- reflex tachycardia
- barroreceptors sense vasodialtion and (+) SNS
∴ coadminister with a **BETA BLOCKER**
145
toxic effects of nitrates
- 30% get bad headache (but tolerance develops)
- flushing sweating
- hypotension
146
NO mechanism schematic
147
viagra effects schematic
148
beta blockers and angina pectoris use
ONLY FOR CLASSIC ANGINA PECTORIS WITH **CCB or NITRATE**!!
- for CCB's ONLY use **amlodipin** or **nifedipine** (only relax vascular sm. muscle)
- NOT verapamil bc they also relax coronary vessels
1. decreases HR
2. decreases F of contraction
- good for stress/exercise tolerance
**-may cause vasopsam in prinzmetal's angina**
149
rapid termination of ____ can ppt angin pectoris/heart attack
beta blockers
150
CCBs types and effects towards angina pectoris
1. cardioactive and non-cardioactive CCBs
- dilates coronary arteries
2. cardioactive CCBs only
- decreases HR and F of contraction
151
CCB uses for angina
1. are effective against STABLE CLASSIC angina pectoris
monotherapy= cardioactive CCB
combination with a B-blocker= NON-cardioactie CCB
2. FIRST CHOICE for variant (prinzmetal's) angina
- typically a cardioactive CCB
152
use ___ for acute MI
urokinase - most effective
-breaks down fibrin
153
surgical correction of coronary artery disease
- drug-eluting oronayr stents
154
overview:
drugs to treat stable angina:
drugs to treat unstable angina:
drugs to treat acute MI:
**stable angina**
beta blockers
nitrates
CCBs
**unstable angina**
anti-platelet drugs
**acute MI**
fibrinolytics
155
cardiogenic shock =
acute heart failure
frominability of heart to pumb blood
-from MI, arrhythmia valve issues or end stage CHF
156
drug types to treat cardiogenic shock
1. Beta - Receptor agonists (increase HR)
dobutamine
2. Phosphodiesterase 3 (PDE3)
milrinone
3. Muscarinic receptor antagonists
atropine
157
chronic congestive heart failure #1 and #2 causes
#1=coronary artery disease/MI
#2= hypertension -\> hypertrophy
158
left ventricular systolic HF symtoms
pulmonary edema
enlarged heart
fatigue
159
right ventricular symptoms
pitting edema
fatigue
160
frank starling mechanism
as preload increses CO decreases
161
specific therapeutic goals for treating chronic heart failure
1. improve contractilit with out increasing HR
2. reduce afterload
3. reduce preload
162
drugs for CHF
1. ACE inhibitors/Angiotensin-R blockers
2. Beta blockers (work but we dont know why)
3. diuretics
4. vasodialtors (NOT CCBs)
5. Cardiac Glycosides (only historical use)
163
ACE inhibitors and CHF
treat CHF
\*\*\* FIRST LINE DRUG FOR CHF with diuretics
1. relax arterial sm muscle
2. reduce aldosterone producton release
3. dilate vens
4. reduce trophic changes in myocardium
164
ACE inhibitors list
(treat CHF)
captopril
enalopril
ramipril
165
Angiotensin Receptor Blockers
- used for CHF were ACE inhibitors are poorly tolerated
- reduce symptoms AND mortality
166
ARBs used for CHF list
valsartan
candesartan
167
Beta Blockers and CHR
- actually reduce cardiac output but improve survival
- in combinaton with **ACE inhibitor and ARB!**
- we dont kno why
only use bisoprolol, carvedilol and metoprolol
-initiate at slow doses
168
bisoprolol and metoprolol
cardioselective B-blockers
used for CHR
-weirdly reduce CO
169
carvedilol
=beta blocker with alph-1 antagonist effects (vasodilator)
-mechanism not clear but it reduces CO, so use with CHF
170
diuretics and CHD
\*\* FIRST LINE OF TX for CHD (with ACE inhibitors)
-actions: reduce Na+ reabsorption in nephron =decreased blood volume
includes thiazides, loob diuretics and K+ sparing drugs
∴reduce edema and preload
171
vasodilators and CHF
NOT a first line of treatment
venous dilators =nitrates
∴decrease preload
arteriole dilators = hydralazine
∴ decrease afterload
**DO NOT USE CCBS** FOR CHF PATIENTS!!
it will reduce CO
172
cardiac glycosides
- used to be a first line of treatment for CHF
- increase CO by increasing mycoardial contractility
- can't switch to ACE inhibitors without deteriorating condition
- can cause more arrythmias bc it messes with membrane electronics
- very small therepeutic window
=digoxin and digitoxin
173
digoxin and digitoxin mechanism schematic
-used to treat CHF
174
digitalis glycosides and K+ interactions
-both compete for same spot on Na+/K+ tansporter
∴
**hyper**kalemia (spironolactone)= LESS digitalis glycoside effects
**hypo**kalemia (hydrochlorothiazide and furosemide)= MORE digitalis glycoside effects
