Exam 2 lecture 4 Flashcards
What is resting pulse pressure
SBP-DDBP
Resting pulse pressure markers
> 40 is unhealthy
60 is a risk factor for heart disease
Are age and genders a factor for HTN
yes
Who has lower SBP when younger
women
who has higher SBP when older
women
What happens to BP as we age
Increases
Age and sex affect on BP
Women have lower SBP at a younger age, higher when older, Old people have higher BP
parameters for HTN
Cardiac output (CO) lowers as we age
Peripheral resistance- increases as we age
Two classifications of HTN
primary and secondary
difference between primary and secondary HTN
primary is more common (90 percent)
risk factors for HTN
FH
age
diabetes
obesity
diet
lack of exercise
alcohol
biggest cause of secondary HTN
CKD
what are some causes of secondary HTN
ABCDE
aldosterone
Bad kidney
cushings
drugs
endocrine disorders
How interrelated are HTN and DM
Lifestyles that lead to HTN also lead to diabetes
strategies for lowering of risk of HTN for elevated BP (120-129/<80)
Non-pcol, reassess in 3-6 months
strategies for lowering of risk of HTN for stage 1 (130-139/80-89)
If ASCVD<10 non pcol, reassess in 3-6 months
If ASCVD > or = 10 pcol and non col, reassess in 1 month
strategies for lowering of risk of HTN for stage 2 (140-149/90+)
pcol and nonpcol, reassess in 3-6 months if goals are met
LSM to reduce BP
-Lose 10 kg (will reduce 5-20 mm hg)
-adopt DASH (dietary approach to stop HTN) (8-14 mm hg)
-Increased physical activity (4-9 mm hg)
Na decrease (2-8 mm hg)
moderate alc consumption (2-3 mm hg)
effect of single drug therapy 8-14
in HTN, weightloss and DASH is considered comparable to pills
Yes
Race with most HTN
non hispanic blacks
How do we calculate BP
BP= CO x TPR
cardiac output
toral peripheral resistance
how to calculate CO
SV x HR
stroke volume x heart rate
what is SV determined by (Stroke volume)
-Cardiac contractility
-venous return to heart
-resistance the left ventricle must overcome to eject blood into aorta
how is contractility affected by catecholamines?
Increased catecholamines lead to increased contractility (so increased stroke volume)
neurotransmitter types in ANS
Parasympathetic, sympathetic
parasympathetic neurotransmitter
Ach
Sympathetic neurotransmitter
Norepinephrine, epinephrine
What are the two adrenoceptors for norepinephrine and epinephrine
Alpha (a1 and a2)
Beta (b1, b2, b3)
for a1, B and a2, name what GPCR they are coupled with
a1- Gq
B- Gs
a2- Gi
A1 functions (innervated or no)
-vasoconstriction (INNERVATED)
-pupilary dilation
-ejaculation
-Gi inhibition
A2 functions (innervated or no)
-Vasoconstriction (uninnervated)
-Prejunctional NE inhibition
-lower CV SNS input in CNS
B1 functions (innervated or no)
-Cardiac stimulation (innervated)
-renin secretion
B2 functions (innervated or no)
-Cardiac stimuation (uninnervated)
-bronchodilation
-Uterine relaxation
Vasodilation (uninnervated)
which adrenoceptors does Epinephrine bind more? Which ones does norepinephrine bind more?
Epinephrine- B» A
Norepinephrine- A1, A2, B1
What is the only structural difference between epinephrine and norepinephrine
epinephrine has an extra methyl group
In general which adrenoceptor is on cardiac and which one is on BV
B is cardiac (cardiac stimulation), A is on BV (vasoconstriction)
For AV node name the receptor, SNS and PSNS response
B1 receptor
SNS- increase conduction
PSNS- decrease conduction
For myocardium, name the receptor, SNS, and PSNS response
B1 receptor
SNS- increase contraction force
PSNS- decrease contraction force
for veins, name receptor and SNS and PSNS function
Receptors- A1, B2
sympathetic constriction/dilation
no PSNS
For arteries, name receptor, SNS and PSNS function
Receptor- A1
sympathetic- constriction
no PSNS
Which one does SNS and PSNS control?? Which one does only SNS control?
a) vessels
b) HR
Vessels controlled by SNS
HR controlled by both
What is the tissue distribution of adrenoceptors for
a)cardiac
b)skeletal muscle
c)Vascular smooth muscle
d)Liver
cardiac- B1 and B2, mostly B1
skeletal muscle- B1 and B2, mostly B2
vascular smooth muscle- A1 and B2- most;y A1
Liver- B2
what are the two types of baroreceptors
Carotid and aortic
What does the baroreceptor do?
Detects BP
How does Baroreceptor react when BP lowers
-Decrease in BP activates SNS that feedback and innervate the heart (B1)
-Causes rise in HR (reflex tachycardia)
-innervated BV (a1 receptors) result in vasoconstriction
-inhibits vagus (PSNS)
- net increase in BP
How does Baroreceptor react when there is a rise in BP
-inhibits SNS
-activates vagus (PSNS)
-leads to reflex brady cardia (lowering of HR)
Which adrenoceptors do epinephrine, norepinephrine and isoproterenol act on more? where do they usually function?
Norepinephrine- A1>B1 (mainly BV)
Epinephrine- B1 and B2> A1 (mainly heart function)
Isoproterenol- B1 and B2
How to easily recognize B blocker drugs by name?
B agonist drugs?
B agonist- nol
B blocket- lol
How do Norepinephrine, epinephrine and isoproterenol affect BP regulation?
Norepinephrine- Has direct A1 effect, has a strong vasoconstriction effect
epinephrine- affects B1, B2 and A effects, net increase in HR. no effect on BP
isoproterenol- leads to net dilation due to action on B, leads to lower BP
Strongest B1 agonist
isoproterenol
How does epinepherine affect BP? why?
No BP change, this is due to B1 and B2 canceling each other out
Isoproterenol effect on BP
B2 effect is stronger than B1 effect, reduced BP is seen
What are the 4 classes of antihypertensives
Diuretics
Sympatholytics
vasodilators
Renin angiotensin-aldosterone system antagonist
What are the 3 types of diuretics used as antihypertensives
Thiazide
K sparring
Loop diuretics
How do diuretics lower BP for HTN
decrease circulating volume
What are the sympatholytic drug classes for antihypertension
B-blockers
Combined a and b blockers
central a2- agonist
peripheral a-1 agonist
How does each sympatholytic act as an antihypertension medication
- B blockers- lower HR, contractility and renin secretion
- Combined a and B blockers- same as B blockers, plus vascular SM relaxation
-central a2 agonist- decrease sympathetic tone
-peripheral a1 agonist- vascular SM relaxation
Name the vasodilator drugs used to lower BP
Ca channel blockers
Direct vasodilators
How do Vasodilator drugs lower BP
Ca channel blockers and direct vasodilators Lower vascular resistance
how do renin angiotensin-aldosterone system antagonists lower BP
lower vascular resistance
lower Na retention
Which antihypertensive meds can be used in HF
diuretics, B blockers ACE inhibitors, angiotension II receptor blocker, aldosterone antagonist
Which antihypertensive drugs can be used post MI
B blockers, ACE inhibitors, ANG II blockers, aldosterone antagonists
Which antihypertensive is indicated in diabetes
ACE inhibitor
ANG II blocker
Ca 2+ blocker
tissue distribution of a receptor? function in BV
vascular smooth muscle.
mediates vsoconstriction
Name a-antagonist drugs. Hlaf life arrange
-osins
Perazosin, Terazosin, Doxazosin
(shortest- perazosin 3h, longest doxazosin, 20hrs)
structure of A- antagonist
know for exam
has piperazine and quinazoline
indication for a-antagonist drugs, how are they named
-osins
indicated for HTN and BPH
MOA of a-agonist?
stop A- receptor binding and acts as a vasodilator
Compare a-antagonsits and non-selective antagonsits (phentolamine)
alpha antagonists Produce vasodilation without causing a lot of reflex tachycardia
What is an issue seen when taking a-selective blockers? what other condition can a-selective blockers be used for?
1st dose phenomenon- orthostatic HTN, with 1st dose
also used for reynauds phenomenon
Which drug has less tachycardia, prazosin or phentolamine
prazosin
Name A-2 agonist drugs
clonidine
methykdopa
guanabenz
guanfacine
Brimonidine
How does A2 affect sympathetic output from brain? can A1 do this? why? how does it affect BP
A2 lowers sympathetic output from brain and lowers BP. A1 can not do this because it does not cross BB.
how does A2 agonist lower SNS
inhibition of NE release
how does a-agonists inhibition of NE release affect specific parts of SNS?
Lower HR
lower contractility
lower renin
lower vasoconstriction
how to recognize clonidine structurally?
is an imidazoline drug with two Cls.
Clonidine MOA
The two Cls withdraw electrons and reduce PKA from 13 to 8.
it goes into brain and activates A2 receptor
indications ofnclonidine
HTN, ADHD, glaucome
which a2 agonist drug has the shortest and longest half life
Guanabenz has shortest
clonidine and guanfacine are the longest
how to recognize guabenz and guanfacine
open ring imidazoline
Which a2 agonist is a prodrug
methyldopa
what is the active form of methyldopa
methylnorepineohrine
MOA of methyldopa to methylepinephrine
Methyldopate
(catalyzed by esterase)
methyldopa
(catalyzed by aromatic amino decarbpxylase)
methyldopamine
(catalyzed by dopamine)
methylnorepinephrine
Which A2 agonist is safe for pregnant women
Methyldopa
how do B blockers reduce BP
reduce CO, inhibit renin secretion
B blocker structure
know (aryloxypropanolamines
How to recognize B blocker drugs
all en in -olol
RECOGNIZE STRUCTURE
Name the non-selective B blockers
Propanolol
Nadolol
timolol
pindolol
carteolol
which teo non selective B blockers have intrinsic sympathomimetic activity(ISA) (partial agonists)
Pindolol
carteolol
what use do ISA B blocker drugs have?
less likely to cause bradycardia
Name selective B blockers
Metorpolol
Atenolol
Esmolol
main difference in structure between selective and non selective B blocker
Selective have para substituent on aromatic group
shortest acting B blocker? why is it the shortest acting? when is it used?
Esmolol.
It is easily hydrolized by esterase
only used for surgery
Which non selective B blocker has more hydrophilicity
Atenolol
name the 3rd gen B1 blocker
Nebivolol
How is the 3rd gen drug nebivolol mechanistically different in how it acts
vasodilation function is due to nitric oxide production
It is B1 selective
side effects of B blockers
Bradycardia, AV blocks, sedation
contraindications of B blockers
Asthma, COPD, Type IV HF
difference in action between propanolol, and Metoprolol, atenolol, esmolol
propanolol- 1st gen- non selective B1 and B2,
metoprolol, atenolol, esmolol- 2nd gen, selective B1
mixed action adrenergic blocker drugs
Labetalol
Carvedilol
Important info when DX b blockers
Always taper doses down.
which receptor does Labetalol work on
A1 antagonism and non selective B1 and B2 antagonism
Which receptor does carvedilol work on?
A1 antagonism and non selective B1 and B2 antagonism
Name a dopamine receptor agonist
fenoldopam.
MOA of fenoldopam
Does not activate alpha or Beta receptors, it is an agonist for dopamine 1 receptor
when is fenoldopam useful? when should we not use it?
Useful in pts with renal impairments
Do not use in pts with glaucoma
fenoldopam is used for
SEVERE htn
