organic nitrates Nicorandil "Beta blockers" Flashcards
Organic itrates?
Nytroglycerin (glyceryl trinitrate)
Amyl nitrate
Isosorbide Dinitrate
Isosorbide Mononitrate
Pharmacological action of trinitrates?
nitric oxide pathway?
excitation/contraction coupling?
For vascular smooth muscle to contract, a rise in
intracellular calcium concentration must occur
(Excitation/contraction coupling)
isosorbide pathway?
half lives?
administration?
side effects?
tachycardic, hypotensive, dizzy, headache
nitrate tolerace?
Definition:
A decreased therapeutic response to a certain dose
Nitrate Tolerance
May develop in less than 48 hours after the initiation of treatment.
Usually develops following frequent oral dosing or continuous
administration
Can be avoided in most patients if there is a nitrate-free interval of
10-12 hours per day.
Can be reversed within 18 hours of stopping nitrates.
proposed mechanism of tolerance?
Early counter-regulatory responses (pseudotolerance)
Neurohormonal activation of vasoconstrictor signals and
intravascular volume expansion
Long-term treatment (vascular tolerance)
Intrinsic vascular changes, eg, a loss of nitrovasodilatorresponsiveness caused by increased vascular superoxide
production (increased oxidative stress)
nicorandil ation?
actions of nicorandil?
Opens ATP-sensitive potassium channels
(dilates peripheral and coronary resistance arterioles)
Possesses a nitrate moiety
(dilates systemic veins and epicardial coronary arteries)
combined effect of nicorandil?
Increases coronary blood flow reduces pre-load and
afterload
common adr of nicorandil?
less comon ADR;s of nicorandil?>
Risk of gastrointestinal ulceration, including perianal
ulceration. Healthcare professionals should consider
nicorandil treatment as a possible cause in patients who
present with symptoms of gastrointestinal-tract ulceration
beta blockers?
Atenolol (Tenormin)
Bisoprolol fumarate ( Cardicor, Monocor)
Nebivolol (Nebilet)
Propranolol hydrochloride (Inderal)
beta syntehsis
beta receptors?
tissue discributio?
alpha1
– Vascular/genitourinary/intestinal smooth muscle
liver, heart.
alpha2
– Pancreatic islets, platelets, nerve terminals, VSM
beta1
– Heart, juxtaglomerular cells.
beta2
– Vascular/bronchial/genitourinary/gastrointestinal
smooth muscle, skeletal muscle, liver.
beta3
– Adipose tissue
agonist action on adrenoceptors?
β1 receptor stimulation induces:
a positive chronotropic and inotropic effect on the heart
renin release in the kidney
β2 receptor stimulation induces:
smooth muscle relaxation
tremor in skeletal muscle
increased glycogenolysis in the liver/skeletal muscle
β3 receptor stimulation induces:
lipolysis (free fatty acid release)
antagonist action?
use of beta blockers?
Arrhythmias
(inhibit aberrant pacemaker activity)
Angina
Hypertension
Hypertrophic Obstructive Cardiomyopathy
Phaeochromocytoma
Secondary Prevention
guidelines?
beta blockers still used in?
younger women who could gt pregnant
those who cannot take ace inhibi
those who had a heart attack or anigina or heart failure
beta blockers effects?
cardiac?
decrease contraction (ionotropy)
decrease relaxation rate (neggative lusitropy)
decrease heart rate (negative chronotropy
Decrease conduction velocity (negative dromotropy)
Vascular?
Smooth muscle contraction (mild vasocontrction)
heart filure?
Systolic dysfunction (↓ contractility or loss of inotropy) β-blockers treatment counterintuitive? Clinical studies report specific beta-blockers actually improve cardiac function and reduce mortality. Reduce deleterious cardiac remodelling in CHF. Pure β1 blockade (low-dose Bisoprolol) Exact mechanism(s)? Blockade of excessive, chronic sympathetic influences
nebivolol?
β1 selective Nebivolol – dual vasodilator
Nitric oxide-potentiating vasodilatory effect
(via activation of endothelial NO synthase)
Lowers blood pressure by reducing peripheral
vascular resistance
Significantly increases stroke volume with
preservation of cardiac output
metabolic effect of beta blockers?
Reduce free fatty acid levels
Reduce glycogenolysis with consequent
reduction of blood glucose
Inhibit β receptor-mediated renin release
Can mask “warning signs” of hypoglycemia
lipid solubility?
low - bisoprolol atenalol
high - propranalol
intrinsic sympathomimetic activity?
Oxprenolol
Such “partial agonists” may be useful in
individuals exhibiting excessive bradycardia
with sustained beta blocker therapy
