Exam 4 Flashcards
__% of hypertension is uncontrolled
>61%
___% are unaware they have high BP
33%
hypertension= ____BP
>140/90 mmHg
secondary hypertension=
secondary to a specific disorder
essential hypertesion=
and accounts for __% of all cases
no clear identifiable cause
=95% of all cases
RAAS system
RAAS is stimulated by
SNS… B1 receptors
and barroreceptors
aldosterone is synthesised in the___
and fxn is___
adrenal cortex
-increases Na+ re-absorption in collecting duct
vasopressin action=
increases TPR and water retention
Big 4 hypertensive agents
- Diuretics
- Direct vasodialtors
- Sympatholytic agents
- Angiotensin related agents
(5. Combination therapy - most common)
Diuretics used for__
actions____
**first choice for MILD hypertension
- low cost but effective
initially=increase urine volume
delayed= decrease peripheral resistance by increaseing Na+ excretion
Loop diuretics action
=high efficacy
-blocks lots of Na+ readbsorption
= deplete K+ = HYPOKALEMIA
=retain uric acid = gout
loop diuretics list
furosemide
ethacrynic acid
thiazides action
=moderate efficacy
=stop Na+ reabsorption in distal convoluted tubule
=deplete K+ =HYPOKALEMIA
=retain uric acid= gout
thiazides list
hydrochlorothiazide
chlorthalidone
potassium sparing agents action
-reduce Na+/K+ exchange in DCT and CD
= Na+ excretion
= K+ retention
-COUNTERACTS HYPOKALEMIA
diuretic that is first line of treatment =
thiazides
bc they have moderate efficacy
all diuretics have ___ as a side effect
dehydration
Mechanism of Loop Diuretics (draw schematic)
Thiazide mechanism (draw schematic)
____ is the most effective diuretic and is longer acting
chlorthalidone
spironolactone mechanism schematic
=a K+ sparing diuretic
-inhibits Muscarinic Receptor ∴ decreases expresion of Na+/K+ ATPase
=big K+ effects
=small Na+ effects
thiameterine and amiloride mechanism (schematic)
=K+ sparing diuretics
= inhibit K+ channel on apical membrane
=HUGE K+ resprption
=small Na+ excretion
direct acting sympatholytic agetnts lower blood pressure by
- beta blockers
- reduce HR and Force = decreased CO
- reduce renin production - alpha 1 antagonists
- vasodilate (block contraction) = decreased TPR
beta blockers for decreasing BP drugs
propanolol (non-selective)
atenolol (cardioselectve)
nadolol (long-acting)
don’t use ___ in asthmatics
atenolol
indirect acting sympatholytic agents to reduce BP types=
- alpha 2 agonists
- trick nerve into thinking theres lots of NT and stop SNS activity - catecholamine release inhibitors
- inhibit vesiculare release
- can cause CNS side effects (reduced DA)
alpa 1 adrenergic receptor antagonists to control BP drug list
prazosin
terazosin
alpha 2 agonists drug list
clonidine
catecholamine release inhibiors drug list
reseprine
hydralazine
direct vasodilator
oral drug
=selective arterial dilator
Calcium Channel Blockers
vasodilator
oral drug
block Ca+ dependent channels on vascular smooth muscle
CCB mechanism schematic
minoxidil
vasodilator
oral drug
higly effective!
lots of side effects! (excessive hair)
last resort
alpha 1 receptor antagonists will mimic ___ effects
CCBs bc they also block the V-G Na+ channels
sodium nitroprusside
parenteral drug
vasodilator
diazoxide
vasodilator
parenteral drug
highly effective and long acting ∴ not a first choice drug
Nitrates mechanism of action schematic
hydralazine, diaxodine, monoxidil mech. of action schematic
CCB’s can target____ channels
L-type Voltage Dependent Ca2+ channels on cardiac or vascular smooth muscle
Non-cardioactive CCB’s action
-more selective for Ca2+ channels on smooth muscle than in heart ∴ don’t have an effect on heart
= dihydropyridines
non-cardioactive CCB’s drug list
all =dihydropyridines
- amlodipine - long half life
- nifedipine - short half life
short acting dihydropyridines
= increased risk for acute MI
=AVOID
=nifedipine
-only use extended release version if nifedipine
long acting dihydropyridines
- use these for hypertension or angina pectoris
=amlodipine
cardioactive CCB’s action
=equally selective for ca2+ channels on vascular smooth muscle AND in heart
∴ relaxe sm. muscle AND reduce CO
verapamil
diltiazem
cardioactive CCB’s drugs
vasodialtor side effects
- postural (orthostatic) hypotension
- flushing/sweating headache
- reflex tachycardia
- body’s reflex is to set at high BP so barroreceptors (+) increased HR - reflex fluid retention
- juxtaglom. retain Na+ to increase volume
to prevent reflex tachycardia we coadminister ___
beta blocker
to prevent reflex fluid retention with vasodilation we coadminister ___
diuretic drug
beta blockers tha are also vasodilators drug list
=decreas CO AND TPR
carvendilol
nebivolol
carvendilol
mixed beta 1/2 and alpha 1 antagonist
∴decreases CO AND TPR
nebivolol
beta 1 blocker that promotes NO production
∴decreases CO AND TPR
Angiotensin related agents types and general action
- ACE inhibitors
- Angiotensin Recptor Blockers
- Renin Inhibitors
=vasodilate and decrease aldosterone and vasopression ∴ decrease blood volume
ACE Inhibitors action and drug list
= (-) angiotension I to II
captopril
enalapril
ramipril
Angiotensin Receptor Blockers action and list
=inhibit binding of angiotnesin II to AT1
losartan
valsartan
Renin inhibitors action and list
= (-) conversion of angiotensinogen to angiotensin I
aliskiren
captopril
ACE Inhibitor
- not a prodrug
- associated with higher side effect risk
- short half life
enalapril
=ACE Inhibitor
-pro-drug
ramipril
=ACE Inhibitor
-prodrug
*greater cardioprotective
*greater efficacy
∴
**most commonly used**
ACE Inhibitor side effects
=BIG DEAL
- dry cough- inhibit the breakdown of bradykinins by ACE ∴ they accumulate in lungs
- Angioedema - rapid non allergic swelling of skin and mucos -from bradykiin
- Hyperkalemia - reduced Na+/K+ exchange in kidney form reduced aldosterone
- also, TERATOGENIC
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
ARBs drug list
losartan
valsartan
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
AVOID Renin Inhibitors in
patients with type 2 diabetes and kidney disease
- increases incidence of cardiovascular and renal events
Phase 1 hypertension use ___
if phase 2 use__-
phase 1= one drug
phase 2= two drugs
for most hypertensive patients first prescribe
thiazide diuretics
for diabetic patients first prescrib
______ for hypertension
ACE Inhibitors
=protects kideys
for pts with Coronary Heart Disease first prescribe______ for hypertension
Beta Blockers
in African American patients __ = first line
CCBs or thiazides
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
classic angina
occlusion of coronary artery resulting form an anthrosclerotic plaque
- most common
- symptoms occur during exercise/stress
antherosclerosis formation
- LDL penetrates arterial wall
- foam cells
- foam cells shear off and expose tissue
- clotting
- plaque formation
=cholesterol center with platelet/fibrin cap
variant (Printzmetal’s) angina
=spontaneous vasoconstriction of coronary arteries
- genetic origin
- symptoms at rest
- less common
Liproprotiens
HDL= good -small amt of cholesterol
-takes cholesterol back to liver
LDL=bad -lots of cholesterol
VLDL=BAD triglycerides
Lipid metabolism steps
- chylomicrons transport cholesterol and TGY from GI into circulation
- Lipoprotien lipase cleaves TGYs from chylomicrons and realeases ffa, leaving cholesterol to go to liver
- liver makes VLDL
- Lipoprotien lipase breaks down VLDL which go back to liver and are turned into LDL
- LDL binds to LDL recptors on cells =internalization
- HDL is also made in liver = (+) lipoprotien lipase and brings cholesterol back to liver
liver makes its own cholesterol via
HMG Co-A reductase
hypertryiglyceridemas
=increased VLDL
=some risk for CHD adn pacreatitis
hypercholesterolemias
= increased LDL
=high risk for CHD
* most common is = “multifactorial”
-genetic, lifestyle, diet
two basic strategies for treating hyperlipidemia
- decrease lipid entering blood
- low fat diet
- reduce lipoprotien synthesis
- reduce dietary cholesterol absorption - improve clearance of lipid from the blood
- for VLDL - affect lipoprotien lipse
- for LDL - increase LDL receptors
drugs for hypertriglyceridemia
niacin
fibric acid derivatives
drugs for hypercholestrolemia
- bile acid binding sequestrants
- statins
- ezetimibe
- nacin
- combination therapy
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
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)
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
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
statins drug list
low efficacy=:
pravastatin
lovastatin
medium efficacy:
simvastatin
pitavastatin
high efficacy:
atorvastatin (big one)
rosuvastatin
statins side effects
los incidence liver toxicity
momory loss
diabetes risk (not enough to avoid tx.)
myopathy
statin drug interactions
grapefruit juic inhibits metabolism and increases risk for rhabdomyolysis
rhabdomyolysis
-induced by statins
=skeletal muscle cell lysis and dumping contents onto kidney causeing kidey failure and death
ezetimibe
- anticholesterol drug
- inhibits fxn of protien in brush border of GI that would absorb cholesterol in small intestine
∴reduces LDL
enhance study
- reducing LDL may not be affecting coronayr antherosclerotic plaque formation …
maybe statins do other stuff too…
AIM High Study
- added niaspan to a statin
- affected lipid profile as expected BUT didn decrease risk for heart atack
AND increased stroke risk…
PCSK9
Proprotein convertase subtilisin/kexin type 9
-protien that metabolizes LDL-R insead of recycling them
alirocumab
=mooclonal antibody
- inhibits PCSK9
- injected subcutaneously
statin treatment guidelinse from American Heart Association
- pts with CHD
- pts with LDL > 190mg/dL
- diabetics 40-75 with out CHD and LDL < 190mg/dL
- pts w/out diabetes or LDL > 190 mg/dL who have estimated CHD risk >7.5% and 40-75 yrs old
clot formation steps
- adhesion of platelets
- aggregation
- clotting vactors activated by endothelium
= (+) prothrombin -> thrombin
= (+) fibrinogen -> fibrin
- via PAR-1 receptor, thrombin (+) rlease of ADP nd TXA2
- prostacyclin (PGI2) opposes this
- fibrin mesh
antithrombin III
proteas inhibitor in blood that limits coagualtion
-all heparins area verison of this
tissue plasminogen activator (T-PA)
fibrinolytic
limits coagutlaition
-all clot-busters are a version of this
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!
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
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
antithrombotics/antiplatelets general fxn
inhibit platelet fuction
- used for WHITE CLOTS
- dont break down clots, just prevent clots form forming in arteries
thrombolytics/fibrinolytics general fxn
destroy clots after they are formed
-break down fibrin!!
parenteral anti coagulent types
- heparins
- indirectly inhibit thrombin via anti-thrombin III - parenteral direct thrombin inhibitors
- directly inhibit thrombin
oral anti-coagulant types
- warfarin
- oral nonpeptide DTI
- factor Xa inhibitor
heparins
=parenteral anticoagulents
-stimulates ANTITHROMBIN III
= inhibits clotting factor synthesis
types:
- unfractionated heparin
- low molecular weight heparin
- side effect =bleeding and heparin induce thrombocytopenia (immune rxn cuases clots)
unfractionated heparin
combination of low and high molecular weights
=more activity
low molecular weight heparin
less activity
=enoxaparin
warfarin
=oral anticoagulant
- delayed effects, need to use up already exixtant clotting factors
- side effects =bleeding
antidote=vitamin K
warfarin fxn schematic
variation in warfarin enzymes and risks schematic
dabigatran etixilate
=direct thrombin inhibitor
=anticoagulant
=less bleeding risk than warfarin
-no antidote yet
rivaroxaban and apixaban
=factor Xa inhibitors (anticoagulant)
- less bleeding risk than warfarin
- no antidote yet
alteplase
t-PA activator
-often used for strokes
urokinase
- recombinant form of a non t-PA human proteas
- used for acute MI
treating embolic/thrombotic/hemorrhagic stroke
80% of occlusions from
- ebolic = from red thrombi
- thrombotic= from white thrombi
- treat with ALTEPLASE
20% of occlusions from
- hemorrhagic stroke
- DONT GIVE ANTICOAGULANT
anti thrombotic drugs inhibit platelet fxn by interfering with…
- Thromboxane A2
- Adensosine diphosphate (ADP)
- thrombin
thromboxane A2 fxn
=released formplatelets and promotes aggregation and vasocosntriction locally
ADP fxn
released from platelets
binds purinergic receptors on other platelets = (+) aggregation
thrombin fxn
- increases fibirn production
- activates PAR-1 receptor which promotes platelet activation
antiplatelet drugs used for=
- preventing heart attacks/acute MI
- if signs of unstable angina pectoris/during or after heart attack - preventing arterial thrombus of limbs
- preventing thrombotic/ischemic stroke
- preventing percutaneous coronar interventions
schematic of antiplatelet drugs
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
clopridogrel
ADP R eceptor blocker
=a prodrug metabolized by CY2C19
-lots of variation in this enzyme (14%)
plasugrel
ADP (adenosine diphosphate) Receptor Blocker
- a prodrug but metabolized by a less variable CYP enzyme
- stops platelet aggregation
vorapaxar
PAR-1 antagonist
-long half life and no antidote= bleeding concerns ∴ dont use in pt with stroke history
abciximab
tirofiban
=platelet recptor antagonists
=a GPIIb/IIIa antagonist
- parenteral, highly effective drugs
- prevent platelet-fibrin bond
antiplatelet drugs protect against____ as a prophylactic….
heart attack
thrombotic stroke
also at time of heart attack (325mg) to prevent further clotting
aspirin vs. ADP-R blockers
aspirin ADP Blockers
inexpensive expensive
effective more effective
bleeding risk less bleeding risk
more variable effect
asprin, vorapaxar, ADP blockers, and GPIIb/IIIa inhibitors produce _________ effects
ADDITIVE
-maybe more effective but also more dangerous
COX 1
produces TXA2
with inhibition by aspirin=
prevents platelet activation
COX 2
produces prostacyclin (PGI2)
with inhibition by rofecoxib=
platelet activation… CLOT
bleeding risk assessment tests
- APTT (activated partial thromboplastin time ):
for heparin
- PT (prothrombin time)
for warfarin
for surgeries you may ned to induce clotting ∴ we use______
- antifibrinolytic drugs (prevent plasmin)
- hemostatic aids
- anticoagulant antidotes
anticoagulant antidotes
vitamin K- reverses warfarin
protamine sulfates-binds and reverses heparins
angina = imbalance btw__
imbalance between O2 demand and O2 supply
-drugs usually treat oxygen demand
reucing O2 demand of heart by
- decrease HR
- decrease F of contraction
- decrease preload
types of drugs for treating stable angina pectoris
- organic nigrates
- beta blockers
- CCB’s
- Combination therapy
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
CCB’s and variant vs classic angina
CCB’s work better agains variant angina
-in classic angina plaques make vessels unresponsive to relaxation
organic nitrates are used to treat ____ pectoris
classic and variant
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
reflexes reactions to nitrates
- reflex tachycardia
- barroreceptors sense vasodialtion and (+) SNS
∴ coadminister with a BETA BLOCKER
toxic effects of nitrates
- 30% get bad headache (but tolerance develops)
- flushing sweating
- hypotension
NO mechanism schematic
viagra effects schematic
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
rapid termination of ____ can ppt angin pectoris/heart attack
beta blockers
CCBs types and effects towards angina pectoris
- cardioactive and non-cardioactive CCBs
- dilates coronary arteries - cardioactive CCBs only
- decreases HR and F of contraction
CCB uses for angina
- are effective against STABLE CLASSIC angina pectoris
monotherapy= cardioactive CCB
combination with a B-blocker= NON-cardioactie CCB
- FIRST CHOICE for variant (prinzmetal’s) angina
- typically a cardioactive CCB
use ___ for acute MI
urokinase - most effective
-breaks down fibrin
surgical correction of coronary artery disease
- drug-eluting oronayr stents
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
cardiogenic shock =
acute heart failure
frominability of heart to pumb blood
-from MI, arrhythmia valve issues or end stage CHF
drug types to treat cardiogenic shock
- Beta - Receptor agonists (increase HR)
dobutamine
- Phosphodiesterase 3 (PDE3)
milrinone
- Muscarinic receptor antagonists
atropine
chronic congestive heart failure #1 and #2 causes
1=coronary artery disease/MI
left ventricular systolic HF symtoms
pulmonary edema
enlarged heart
fatigue
right ventricular symptoms
pitting edema
fatigue
frank starling mechanism
as preload increses CO decreases
specific therapeutic goals for treating chronic heart failure
- improve contractilit with out increasing HR
- reduce afterload
- reduce preload
drugs for CHF
- ACE inhibitors/Angiotensin-R blockers
- Beta blockers (work but we dont know why)
- diuretics
- vasodialtors (NOT CCBs)
- Cardiac Glycosides (only historical use)
ACE inhibitors and CHF
treat CHF
*** FIRST LINE DRUG FOR CHF with diuretics
- relax arterial sm muscle
- reduce aldosterone producton release
- dilate vens
- reduce trophic changes in myocardium
ACE inhibitors list
(treat CHF)
captopril
enalopril
ramipril
Angiotensin Receptor Blockers
- used for CHF were ACE inhibitors are poorly tolerated
- reduce symptoms AND mortality
ARBs used for CHF list
valsartan
candesartan
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
bisoprolol and metoprolol
cardioselective B-blockers
used for CHR
-weirdly reduce CO
carvedilol
=beta blocker with alph-1 antagonist effects (vasodilator)
-mechanism not clear but it reduces CO, so use with CHF
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
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
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
digoxin and digitoxin mechanism schematic
-used to treat CHF
digitalis glycosides and K+ interactions
-both compete for same spot on Na+/K+ tansporter
∴
hyperkalemia (spironolactone)= LESS digitalis glycoside effects
hypokalemia (hydrochlorothiazide and furosemide)= MORE digitalis glycoside effects
