HTN Flashcards
Aging in HTN
decreased CO + increased peripheral resistance
Preganglionic neurons
primary neurotransmitter is acetylcholine
Postganglionic neurons
PNS: primary is acetylcholine
SNS:
primary: norepinephrine
sweat glands: acetylcholine
adrenal medulla: epinephrine
renal: dopamine
PSNS
cholinergic receptors
acetylcholine: endogenous
muscarinic: exogenous
nicotinic: exogenous
SNS
adrenergic receptors
norepinephrine: endogenous
epinephrine: endogenous
Alpha 1
vasoconstriction
pupillary dilation
ejaculation
gi inhibition
Alpha 2
vasoconstriction
inhibit NE release
decrease CV
Beta 1
cardiac stimulation
secretion of renin
Beta 2
bronchodilation
uterine relaxation
gi inhibition
vasodilation
Baroreceptor reflex
Decrease in BP:
-activates sympathetic fibers
-increase in HR by b1 receptors
-vasoconstriction by alpha 1
-inhibits vagus
-result: increased BP
Increase in BP:
-inhibits sympathetic fibers
-decreased HR
-activates vagus
-result: decrease in BP
Targets for antihypertensive drugs
Heart: reduce CO by both PSNS and SNS
Decrease resistance of arterioles and veins
Kidneys: reduce fluids and blood volume
Where are Alpha 1 receptors located?
vascular smooth muscle, genitourinary smooth muscle, intestinal smooth muscle, heart, liver
Where are Alpha 2 receptors located?
CNS
Where are Beta 1 receptors located?
cardiac muscle and CNS
Alpha-1 antagonists
Prazosin: 3 hrs
Terazosin: 12 hrs
Doxazosin: 12 hrs
Alpha 1 antagonists structure
Quinazoline ring allowing for alpha 1 specificity
Piperazine ring and acyl moiety allowing for PK activity
Alpha 1 antagonists effect
Produce peripheral vasodilation without causing reflex tachycardia or increased CO–> decreased TPR
Alpha 1 antagonists indications
HTN, BPH, and Raynaud’s disease
Alpha 2 agonists
Inhibits the release of NE causing reduced CO from the brain
results in decreased HR, contractibility, renin release, vasoconstriction
Clonidine (Alpha 2 agonist)
Imidazole drug
Contains a dichlorophenol ring that decreases the pka from 13.6 to 8.0
This creates much less charge in this compound allowing for CNS access
HTN, ADHD
oral, IV, transdermal
Side effects: hypotension, sedation, dry mouth
Guanfacine/Guanabenz (alpha 2 agonist)
Open-ring imidazoline ring
Contains a 2-atom bridge to the guanidine group allowing a decrease of pka to that the drug is mostly un-ionized and allows for CNS access
contain dichlorophenol ring
HTN, ADHD
oral
Methyldopa and Methyldopate (alpha 2 agonist)
Methyldopa is a prodrug that contains a Zwitterion ion between the amine and carboxylic group on the molecule allowing for less charge and easy access across BBB into CNS
Converted to alpha-methylnorepinephrine
Methyldopate contains a positive amine group on the molecule that interacts with chloride ion forming salt that is very water soluble
HTN (during pregnancy)
Methyldopa is oral and Methyldopate is IV
Beta blockers
effect: decrease cardiac output and inhibits the release of renin
structure: aryloxypropanolamine: aromatic ring + bulky R group
Propranolol
non-selective beta receptor antagonist
lipophilic due to large bulky group
AVOID IN PT WITH ASTHMA
Decrease CO and HR, reduce renin release, increase VLDL, inhibits lipolysis, inhibit glycogenolysis, increase bronchial airway resistance
HTN, angina, cardiac arrhythmias, migraine, stage fright, CHF
Nadolol
non-selective beta receptor antagonist
Less lipophilic than propranolol
mostly excreted unchanged in the urine
oral
hypertension, angina, migraine
Timolol
Thiadiazole nucleus with morpholine ring
Route of administration: oral, eye drops
glaucoma HTN, agina, migraine
Pindolol
non-selective beta receptor antagonist
“Intrinsic sympathomimetic activity”–> partial activation and blockage–> partial agonist
reduced ability to cause bradycardia
oral
HTN, angina, migraine
Carteolol
nonselective beta receptor antagonist
“Intrinsic sympathomimetic activity”–> partial activation and blockage–> partial agonist
reduced ability to cause bradycardia
oral, eye drops
HTN, glaucoma
Metoprolol/Bisoprolol
Beta 1 receptor antagonist
Contains a para-substituted phenyl derivative
Contains only 1 aromatic ring–> less bulky
Moderate lipophilicity–>1/2 life: 3-4 hours
First pass metabolism
Oral, IV
Atenolol
Beta 1 receptor antagonist
contains a para-substituted phenyl derivative
low lipophilicity–>water soluble–>half life: 6-9 hours–> long lasting
oral, IV
HTN, angina
Esmolol
Beta 1 receptor antagonist
contains a para substituted phenyl derivative
contains ester group on the substitution–>rapid hydrolysis by esterases–>half life: 9 minutes–> short acting
IV
supraventricular tachycardia, a-fib, HTN (surgery)
Nebivolol
3rd generation
beta 1 receptor antagonist
low lipid solubility
vasodilation due to NO production
HTN
Labetalol
Nonselective beta receptor antagonist + alpha 1 receptor antagonist
1R, 1’R isomer is beta blocking activity
1S, 1’R is alpha 1 blocking activity
Beta blocking activity prevents tachycardia associated with alpha 1 antagonists
oral, IV
HTN, hypertensive emergency
Carvedilol
Nonselective beta receptor antagonist + alpha 1 receptor antagonist
both enantiomers are alpha 1 antagonist
only S enantiomer is beta antagonist
oral
HTN, CHF
Beta blocker side effects
bradycardia
AV block
sedation
mask hypoglycemia symptoms
withdrawal
Beta blocker contraindications
asthma
COPD
CHF
TAPER DOSE WHEN D/C
Dopamine receptor agonist
Fenoldopam
severe HTN
avoid in glaucoma due to increase in IOP
maintains/increases renal perfusion while lowering blood pressure
