anti anginal Flashcards
(15 cards)
The prevalence of stable angina increases with – and is higher in — than —
pathogenesis of athescrotic plaques:
1- — damage
2- Protective response results in production of
cellular – molecules
3- – and — attached to – surface of endothelial cells
4- migrate through — to — space
5- macrophages take up —-
6- lipid rich – cells
7- fatty — and —
8- plaque — and – fomartion and — artery
age
men
women
endothelial
cellular adhesion
monocyte and t lymphocyte
sticky
arterial wall to sub endothelial space
oxidised LDL cholesterol
foam cells
streak and plaque
rapture , thrombus , bloakcgae
angina symptoms :
Pathophysiology.
Usually associated with the presence of significant — coronary disease (stable disease)
unstable disease associated with —
Clinical presentation
—- discomfort
—-like
may radiate down — or into –
occurs with exertion and — by rest,
obstruction
plaque rapture
retrosternal discomfort
pressure like
arm and into neck
relieved
-Angina occurs when the — supply to the myocardium is insufficient for its needs.
-Cardiac myocytes rely on —.
-If the supply of oxygen falls below a critical value, a sequence of events leading to cell death ensues,
-This is detected clinically by an elevation of circulating — (a biochemical marker of myocardial injury), as well as of cardiac enzymes (e.g. the cardiac isoform of—- ) and changes in the surface ECG.
-The pain has a characteristic distribution in the chest, arm and neck, and is brought on by exertion, cold or excitement.
02
aerobic metabolism
troponin
creatine kinase
Three kinds of angina are recognised clinically:
Stable: - — change in symptoms over previous —
Unstable: - — pattern change typically at —
and Variant: - usually — related, patients develop—
-The treatment goals of angina pectoris are:
improvement in quality of life,
by limiting the number and severity of attacks,
protection against future lethal events, and
measures to lower the burden of risk factors to slow disease progression.
This requires lifestyle modification as well as medical treatment
no change
weeks
abrupt
rest
stress
coronary spasm
stable angina:
—- chest pain on exertion.
Caused by an increased — on the heart
usually caused by fixed narrowing(s) of the coronary arteries by atheroma,
….although, narrowing of the — (‘aortic — ’) can also cause angina by reducing coronary blood flow even in the absence of coronary artery narrowing.
-Symptomatic therapy is directed at reducing cardiac work with
1-organic nitrates,
2-β-adrenoceptor antagonists
3-and/or calcium antagonists,
together with treatment of the underlying atheromatous disease, usually including—lowering drugs such as a Statin
-and prophylaxis against thrombosis with an – drug, such asaspirin
predictable
demand
aortic narrowing aka aortic valve ( stenosis )
lipid
anti platelet
unstable angina:
This is characterised by pain that occurs with less and less exertion, culminating in pain at rest.
The pathology is similar to that involved in — , namely platlet - fibrin — associated with a ruptured atheromatous plaque, but without complete — of the vessel.
Treatment is similar to that for myocardial infarction and includes imaging and consideration of revascularisation procedures.
Antiplatelet drugs (aspirin and/or an ADP antagonist such asclopidogrelorprasugrel) reduce the risk of —- in this setting,
and anticoagulant drugs add to this benefit at the cost of increased risk of — .
Organic nitrates (see later) are used to relieve — pain.
MI
thrombus
occlusion
MI
haemorrhage
ishemic pain
Variant angina, also known asPrinzmetal anginaorvasospastic angina, is a rare type of chest pain that typically occurs at —, often during the night or early morning hours
Unlike stable angina, which is usually triggered by physical exertion or stress, variant angina is caused by a — in the coronary arteries, leading to reduced blood flow to the heart muscle
This is relatively uncommon. It can occur at — and is caused by coronary artery spasm, often in association with atheromatous disease.
Therapy is with coronary artery — (e.g. organic nitrates, calcium antagonists).
rest
temporary spasm
rest
vasodilators
Pharmacological vs Non-Pharmacological Treatments to improve Angina Symptoms:
There are three classes of anti-ischemic drugs commonly used in the management of angina pectoris: —- , —- , — blockers.
Ranolazine(a sodium channel blocker) is a newer addition.
Often, a combination of these agents is used for control of symptoms.
Note: regardless of the acute treatment, long term preventative treatment with — lowering drugs and — agents is initiated in all patients.
Non-Pharmacological treatment: stents, PCI
nitrates
beta blockers
calcium channel
cholesterol
anti platelt
Intact Endothelium regulates coagulation:
Intact endothelial cells
express — & — on their surface
produce inhibitory reagents — & — that prevent platelet activation
Secrete tissue-Plasminogen Activator (tPA)
Heparin coordinates the Anti-Thrombin (aka Anti-Thrombin III; ATIII) pathway
Thrombomodulin coordinates the —
the role of intact endothelium in haemostasis and thrombosis:
1-Synthesize & secretes NO, PGI2 to inhibit platelet activation
2-Synthesize & secrete vasoactive peptides eg —
3- Prevents exposure of platelets to sub-endothelial matrix components such as —
4-Produces heparin to — the coagulation cascade
5- Produce thrombomodulin which, when bound to thrombin, can generate activated —- which degrades – and — .
6-Secretes — and — to degrade formed clots.
heparin and thrombodulin
NO and PGI2
protein c pathway
endothelin
collagen
protein c
FVa and FVIIIa
tPA and urokinase
Nitric oxide (NO) is a soluble gas continuously synthesized from the amino acid — in endothelial cells by the constitutive enzyme — (NOS).
NO has a wide range of biological functions that contributes to the regulation of vascular homeostasis
–> modulation of vascular — tone,
–>regulation of local cell — ,
—> — of the vessel from injurious consequences of platelets activation.
—> — of platelet activation
L-arginine
nitric oxide synthase
dilator
growth
protection
inhibitorn
Organic Nitrates for treatment of Angina:
Nitroglycerin (Glyceryl Trinitrate (GTN)) has been used since 1867in medicineas a potentvasodilatorin the treatment of angina pectorisandchronic heart failure, and, in its extended release forms, it still remains first-line drug therapy for many patients.
-It was previously known that these beneficial effects were due to —- being converted tonitric oxide NO. The enzyme for this conversion was only discovered to be mitochondrialaldehyde dehydrogenase(ALDH2) in 2002.
-Organic nitrates are metabolised with release of NO.
-NO activates — , increasing formation of — , which activates — and leads to a cascade of effects in smooth muscle culminating in dephosphorylation of myosin light chains, sequestration of intracellular Ca2+and consequent relaxation.
nitroglycerin
soluble guanylyl cyclase
cGMP
protein kinase g
Arterial Endothelial Function: Role of Nitric Oxide (NO):
NO activates Guanylate Cyclase
Guanylate Cyclase generates —- a local mediator
cGMP enables smooth muscle — and —
Hypertension, hypercholesterolemia, smoking, diabetes mellitus and heart failure are associated with diminished local synthesis of nitric oxide
Reduced NO leads to:
Enhanced expression of —-attractants
Enhanced expression of adhesion proteins on Endothelial cells-enabling monocyte —
Enhanced — of LDL
Enhanced Platelet —
cGMP
relaxation and vasodilation
chemo
adhesion
oxidisation
activation
Actions of cGMP are terminated by phosphodiesterases:
Phosphodiesterase (PDE) is an enzyme that breaks a phosphodiester bond.
Phosphodiester bonds occur in — (and —)
PDEs regulate the — , — , and — of cyclic nucleotide signaling.
There are 11 human PDE’s
PDE 4, 7 & 8 are specific for cAMP
PDE 5, 6 & 9 are specific for cGMP
PDE 1, 2, 3, 10 & 11 are non-specific
cGMP and cAMP
localisation duration and amplitude
Sublingual (tablets and spray)
Nitroglycerin (GTN), metabolised in liver
Peak concentration in 4 mins, half life of 40 mins
Isosorbide dinitrate – 2-5 minutes
Oral
Isosorbide dinitrate, peak 6 minutes
Half life 2-5 hrs. (mononitrate longer half life*)
Cutaneous
Transdermal patch (GTN)
Intravenous
-Nitrates, usually in the form of a — preparation, are the — therapy for the treatment ofacuteanginal symptoms. Patients should be instructed to use them at the onset of an episode of angina, or for prophylaxis of anginal episodes.
sublingual
1st line
The main adverse effects of nitrates are a direct consequence of their main pharmacological actions, and include — * and a — .
Transient episodes of hypotension - may be exacerbated by —
Excessive use can also result in the formation of — , an oxidation product of haemoglobin that is ineffective as an oxygen carrier
Danger of additive effect with – Inhibitors eg sildenafil (Viagra)
nitrates vs calcium channel blockers:
Most of the anti-ischemic efficacy of nitrates pertains to their ability to decrease myocardial oxygen demand as a result of systemic vasodilatation rather than any activity as a coronary vasodilator. Nitrates do not have a direct effect on cardiac chronotropy or inotropy.
Nitrates also have significant antiplatelet and antithrombotic propertie
postural hypotension and throbbing headaches
alcohol
methaemoglobin
PDE
