Cardiovascular and Renal Flashcards
What does PKA phosphorylate in the heart?
SERCA2 and phospholamban
Which heart fibres are fastest?
SAN
What is Wolff-Parkinson-White syndrome?
Abnormal conducting fibres so A>V is too fast
How do inodilators act?
Inhibit PDE (mimic sympathetic stimulation)
How do methylxanthines act?
Non-specific PDE inhibitors and A1 and A2 agonists
What causes phospholamban to inhibit SERCA2?
Sympathetic via B receptors and PKA
Which factors does plasmin cause breakdown of?
II, V, VII
What is glyciproteins IIB/IIIa receptor needed for?
Fibrinogen binding between platelets that causes aggregation
Where does ATIII act and what does it affect?
The brain affecting ADH release
What does adenosine acting on A1 receptors inhibit?
Rise in intracellular cAMP
What does ANP via cGMP inhibit?
Renin release
What are the ATII receptors?
AT1 and AT2
What converts ATII to ATIII?
Brain aminopeptidase A
What converts ATIII to ATIV?
Aminopeptidase-N
Which tubule has peptidases to metabolise bradykinin?
Proximal
Which receptors does the collecting duct have?
Kininogen and bradykinin B2
What converts kininogen to bradykinin?
Killikrein
How do loop diuretics work?
Block Na-K-Cl transport in apical membrane of thick ascending limb
How do thiazide diuretics work?
Block Na-Cl cotransport in cortical thick ascending limb and distal tubule, also some CA inhibition
How do K+-sparing diuretics work?
Block apical Na+ channels OR aldosterone antagonists
How do CA inhibitors work?
Inhibit bicarb reabsorption and decrease H+ availability so there is less to exchange with Na
Which PDE is Ca2+/calmodulin-dependent?
I
Which PDE is cGMP-stimualted?
II
Which PDE is cGMP-specific?
V
Which PDE is cGMP-inhibited?
III
Which PDE is cAMP-specific?
IV
Which inodilator is used for heart failure and which PDE does in inhibit?
Milrinone - type III
Which two drugs inhibit PDE type V?
Dipyridamole and sildenafil
Where is I Ca-L found and what is it for?
Everywhere for plateau phase
Where is I Ca-T found?
Nodal/conductive
Where is I Na-Ca found?
Everywhere
Which Na sites can be glycosylated?
All
Which subunits are linked by a disulphide bridge and are from the same gene?
ALpha2 and delta
Which Ca drugs don’t show use dependence?
DHPs
How many phosphorylation sites do L type Ca2+ channels have?
Two phosphorylation sites on cytoplasmic domain
Where are T type Ca2+ channels found?
Heart conductive tissue
Where are the two DHP binding sites?
S6 and S5-6 loop in domain III and S5-6 loop in domain IV
Where is benzothiazepine binding site?
Outside
What is N type K+ channel inactivation?
Ball and chain
What is C type K+ inactivation?
Residues near the extracellular surface moving
What regulates Kirs?
Phosphorylation, Ca2+ or ATP
Which Gi subunit opens I K-ACh channel?
Beta-gamma
In what conditions do ATP-sensitive Kir channels open?
Low intracellular ATP
What are HCN channels permeable to?
Na and K
What do catecholamines do to RyRs?
Sensitize
What are cells like in ischaemic heart disease?
Partly depolarised and liable to inappropriate action
Which dysrhytmias are class III used for?
Ventricular and re-entrant
Which tissue do class IV antidysrhytmics act on?
Nodal
What causes dilated cardiomyopathy in cats?
Taurine or carnitine deficiency
Which receptors are upregulated when using beta blockers?
Alpha1
Which PDE is it in heart failure
III
How do Ca sensitizers cause peripheral vasodilation?
Inhibit PDEIII
What converts kininogen into bradykinin?
Kallikrein
How do AT2 receptors cause vasodilation?
Use NO which raises cGMP
When is the AT2 receptor present?
Brain and adrenal medulla, fetal development
How do ACE inhibitors affect pre and afterload?
Increase
How do ACE inhibitors affect vascular resistance and blood pressure?
Decrease vascular resistance not blood pressure
How does ANP inhibit renin release?
Via cGMP
How does Angiotensin II inhibit renin release?
IP3 mediated -ve feedback
How does adenosine increase cAMP?
AT1 receptors
What is the structure of angiotensin I?
Decapaptide
What is the structure of angiotensin II?
Octapeptide
How is blood pressure maintained when using an ACE inhibitor?
CO increases
What is angiotensin IV for?
Learning, memory, LTP
Where is AT4 receptor located?
Widely
What is the structure of the AT4 receptor?
Transmembrane, insulin regulated
Where are peptidases which produce bradykinin?
Proximal tubule
Where are the kininogen and bradykinin B2 receptors?
Collecting duct
Where is HCN1 found?
Heart and brain
Where is HCN2 found?
Throughout heart
Where is HCN4 found?
Pacemaker region and Purkinje fibres
Which factors does warfarin inhibit synthesis of?
II, VII, IX, X, C, X, Z
