Pharmacology Flashcards
Adrenaline activates B2 adrenoceptors in the heart to cause increased heart rate. True/False?
False
Acts on B1 adrenoceptors
Which muscarinic receptor does ACh act on in the heart to cause decreased heart rate?
M2 receptors
What does adenylyl cyclase do?
Increases production of cAMP
Which channels, when blocked, decrease the slope of the SA node action potential?
HCN channels
Name a drug that is a selective blocker of HCN channels and for what heart condition it is mainly used
Ivabradine
Used for angina
Sympathetic stimulation decreases AV nodal delay. True/False?
True
Sympathetic stimulation causes increased automaticity. What is this?
Increased tendency for non-nodal regions to acquire spontaneous conduction activity
Sympathetic stimulation causes a decrease in the duration of systole. True/False?
True
What factors increase venous return?
Increased skeletal muscle activity
Adrenergic effects on blood vessels
Increased depth + frequency of respiration
What is the function of ryanodine receptors with regards to calcium action + action potentials?
Enable release of Ca++ from sarcoplasmic reticulum through the process of calcium-induced calcium release
What is the function of SERCA with regards to calcium action + action potentials?
Removes Ca++ from the cytoplasm to bring about relaxation
What happens when phosphalamban is phosphorylated with regards to calcium action + action potentials?
This increases Ca++ storage in the SR and also activates SERCA to promote relaxation
What happens when troponin I is phosphorylated with regards to calcium action + action potentials?
Decreases affinity of troponin C for calcium, thus accelerating relaxation
Name a B1 agonist drug used sometimes in heart failure
Dobutamine
Propranolol is a selective B2 receptor antagonist. True/False?
False
It is non-selective
Name a selective B1 antagonist drug
Atenolol
Metoprolol
Give some clinical uses of B-blockers
Arrhythmias
Hypertension
Angina
Heart failure (low-dose)
Give some adverse effects of B-blockers
Aggravate asthma Aggravate heart failure Cold extremities Bradycardia Fatigue
Which class of drug is atropine?
Non-selective muscarinic antagonist
Name the main clinical use of atropine
Reverse bradycardia modestly
What are the dangers of digoxin?
It has a low therapeutic ratio and is thus toxic, especially in hypokalaemia
Can cause heart block
What is an indirect effect of digoxin?
Slows AV node conduction to increase refractory period
What does Levosimendan do?
Binds to troponin C to increase its affinity for Ca++
In the smooth muscle cell, calcium binds with _____, which undergoes a conformation change. The __-__ complex then interacts with _____ to activate it. The active ____ then phosphorylates ___-__ which, when phosphorylated, ultimately causes contraction.
In the smooth muscle cell, calcium binds with calmodulin, which undergoes a conformation change. The Ca-CaM complex then interacts with MLCK to activate it. The active MLCK then phosphorylates myosin-LC which, when phosphorylated, ultimately causes contraction.
In the endothelial cell, Ca-CaM complex activates ___ which binds _-____ and __ to form NO, which rapidly diffuses into the smooth muscle cell (to ultimately cause relaxation).
In the endothelial cell, Ca-CaM complex activates eNOS which binds l-arginine and O2 to form NO, which rapidly diffuses into the smooth muscle cell (to ultimately cause relaxation).
In the smooth muscle cell, NO does 2 things:
1] activates ___ ____ which synthesises cGMP from ___. cGMP activates protein kinase _ which ultimately causes relaxation.
2] keeps Ca-dependent _ channel open, allowing _ to efflux, leaving _ve charge in the cell which causes membrane potential to ______ so we get relaxation.
In the smooth muscle cell, NO does 2 things:
1] activates guanylate cyclase which synthesises cGMP from GTP. cGMP activates protein kinase A which ultimately causes relaxation.
2] keeps Ca-dependent K channel open, allowing K to efflux, leaving -ve charge in the cell which causes membrane potential to hyperpolarise so we get relaxation.
How do organic nitrates (GTN) work in the smooth muscle cell?
Combines with SH groups to liberate NO, which then acts like endogenous NO in signalling pathways
Nitrates cause arteriolar dilation at low doses. True/False?
False
Mainly cause venorelaxation, but can cause arteriolar dilation at high doses
How do nitrates help in angina?
Decrease preload + afterload
Improve perfusion to ischaemic zone (dilates collateral vessels)
Name 2 examples of organic nitrates used clinically
GTN tablet/spray
Isosorbide mononitrate
Why is it important to have nitrate-low periods?
Repeated use can develop tolerance and reduce efficacy
Endothelin-1 causes vasodilation. True/False?
False
Causes vasoconstriction
Which substances cause upregulation of endothelin production?
Adrenaline
Angiotensin II
ADH
Which substances cause downregulation of endothelin production?
Nitric oxide
ANP
Name antagonists of the endothelin-1 receptor used in treating pulmonary hypertension
Bosentan
Ambrisentan
Name a renin inhibitor
Aliskiren
Renin inhibitors (aliskiren) can be used in conjunction with an ARB or ACEi. True/False?
False
What are the effects of ACE?
Converts AT I to AT II
Inactivates bradykinin
Name an ACEi used in Tayside
Lisinopril
Name an ARB used in Tayside
Losartan
What are the main differences between ACEi and ARBs?
ARBs do not inhibit bradykinin and do not produce dry cough
How do calcium antagonists work?
Prevent opening of Ca channels to limit intracellular Ca++ to reduce heart rate and force of contraction
Verapamil is selective for cardiac L-type channels. True/False?
True
Amlodipine is selective for which L-type channels?
Smooth muscle L-type channels
Amlodipine is preferred to verapamil - why?
Minimises unwanted effects on cardiac muscle, e.g. heart block
Why is verapamil useful in arrhythmias?
Slows conduction of AV node, can help reduce AF
K+ channel openers act primarily on arterial smooth muscle. True/False?
True
Name two K+ channel opener drugs
Minoxidil
Nicorandil
Name two alpha blockers
Prazosin
Doxazosin
What is the main/overall action of diuretics?
Increase Na, Cl and water excretion
Indirectly relax vasculature
What is the undesirable effect of diuretics?
Loss of K+
Name a thiazide diuretic and conditions it is used in
Bendroflumethazide
Mild heart failure, hypertension
Name a loop diuretic and conditions it is used in
Furosemide
Chronic heart failure, acute pulmonary oedema
What are some side effects of diuretics?
Hypokalaemia
Arrhythmias
Gout
Impotence
What is the main side effect of dihydropyridine Ca antagonists?
Ankle oedema
Name conditions in which amlodipine can be used
Hypertension
Angina
In addition to hypertension and angina, verapamil can be used for what?
SVT arrhythmias (AF, VT) but NOT alongside B blockers
ACEi and ARBs are safe in pregnancy. True/False?
False
NEVER use in pregnancy