Pharmacology Flashcards
what affect does (nor)adrenaline have on HR
increases
what affect does (nor)adrenaline have on contractility
increases
what affect does (nora)adrenaline have on conduction velocity in AV node
increases
what affect does (nora)adrenaline have on duration of systole
decrease
explain the effect of (nora)adrenaline on HR
it increases the slope pacemaker potential (phase 4)
it reduces the threshold for AP initiation
explain the effect of (nora)adrenaline on contractility
it increases phase 2 via enhancing Ca2+ influx
increases sensitisation of contractile proteins to Ca2+
explain the effect of (nora)adrenaline on systole duration
increases uptake of Ca2+ into SR
what does (nora)adrenaline act upon in heart
B1-adrenoceptors in nodal and myocardial cells
what do B1-adrenoceptors do once they are activated by (nora)adrenaline
couple to Gs protein which activates adenylyl cyclase to increase [cAMP]
what does B1-adrenoceptors couple with
Gs protein
what does Gs protein activate
adenylyl cyclase
what does activated adenylyl cause an increase in
[cAMP]
what affect does acetylcholine have on HR
decreases
what affect does acetylcholine have on contractility
decrease
what affect does acetylcholine have on conduction in AV node
decrease
explain the effect of acetylcholine on HR
increases threshold for AP initiation
decreased slope of pacemaker potential via hyperpolarization caused by opening of GIRK channels
explain the effect of acetylcholine on contractility
decrease in phase 2 due to decreased Ca2+ entry
explain the effect of acetylcholine on conduction in AV node
decreased activity of voltage activated Ca2+ channels
hyperpolarization via opening K+ channels
what does acetylcholine act upon
M2-muscarinic cholinoceptors in nodal cells
what does M2-muscarinic cholinoceptors do once activated by acetylcholine
couples to Gi protein which decreases the activity of adenylyl cyclase reducing [cAMP] it also opens GIRK channels causing hyperpolarization of SA node
what do M2-muscarinic cholinoceptors couple to
Gi proteins
what do Gi proteins do once activated by M2-muscarinic cholinoceptors
decrease activity of adenylyl cyclase
open GIRK channels
what does opening on GIRK channels cause (SA node)
hyperpolarization of SA node
what does a decrease in adenylyl cyclase activity result in
decrease in [cAMP]
what is ivabradine
selective blocker of HCN channels
describe the affect of ivabradine on HR
decrease
what is the clinical use of ivabradine
treatment of angina (if uncontrolled with beta blockers and Calcium channel blockers)
chronic HF
describe the mechanism of ivabradine
blocks HCN channels which decreases the slope of pacemaker potential
what do HCN channels do
mediates the “funny current” which modulates the pacemaker potential
what is the full name of HCN channels
cyclic AMP gated HCN channels
explain the process of contraction in cardiac muscle
ventricular AP causes L-type Ca2+ to open during phase 2
this causes a Ca2+ influx into the cytoplasm activating RyR2 on the SR causing Ca2+ to flow out of the SR (this process is called CICR)
Ca2+ binds to troponin C and shifts the tropomyosin out of the actin cleft allowing cross-bridge formation
contraction occurs via the sliding filament mechanism
explain the process of relaxation in cardiac muscle
Ca2+ dissociates from troponin C and leaves the cell in 2 ways:
- via NCX1 (Na+/Ca2+ exchanger)
- returns to the SR via SERCA (Ca2+ATPase of Ca+)
give examples of adrenoceptor agonist
adrenaline
dobutamine
what effects do adrenoceptor agonist have on the heart (5)
increase: force, HR, CO, O2 consumption
decrease: cardiac efficiency
what can long term use of adrenoceptor agonist cause
arrhythmias
what type of adrenoceptor agonist is adrenaline
alpha AND beta agonist
what are the clinical uses of adrenaline
cardiac rest (IV) anaphylactic shock (IM)
what affect does adrenaline have on HR and force, what is it acting on
increases
β1
what affect does adrenaline have on blood vessels, what is it acting on
constricts the skin, mucosal, and abdomen vessels
α1
what affect does adrenaline have on coronary arteries, what is it acting on
dilatation
β2
what type of adrenoceptor agonist is dobutamine
selective beta
what are the clinical uses of dobutamine
acute heart failure (IV)
give examples of β-adrenoceptor antagonists
propranolol, atenolol, bisoprolol, metoprolol
give examples of SELECTIVE β-adrenoceptor antagonists
atenolol, bisoprolol, metoprolol
give examples of NON SELECTIVE β-adrenoceptor antagonists
propranolol
what type of β-adrenoceptor antagonist is propranolol
non selective (β1 and β2)
what type of β-adrenoceptor antagonist is atenolol
selective (β1)
what type of β-adrenoceptor antagonist is bisoprolol
selective (β1)
what type of β-adrenoceptor antagonist is metoprolol
selective (β1)
what affect do β-adrenoceptors have at rest
none
what affect do β-adrenoceptors have during exercise or stress (6)
decreased: HR, force of contraction, CO , maximal exercise tolerance, coronary vessel diameter, myocardial O2 requirement
what are the clinical uses of β-adrenoceptors antagonists (4)
angina, hypertension, arthymias (AF, SVT), heart failure
what are the adverse effects of β-adrenoceptors antagonists
bronchospasms, aggravation of cardiac failure, bradycardia, cold extremities
in what condition are β-adrenoceptors contraindicated
asthma
give an example of muscarinic receptor antagonist
atropine
what are the clinical uses of atropine
bradycardia (1st line)
MI (IV)
anticholinesterase poisoning
what are the affect of muscarinic receptor antagonists
increased HR
give an example of a cardiac glycoside
digoxin
what are the clinical uses of digoxin
acute HR (IV) chronic HR (orally)
what are the side effects of digoxin
heart block/arrhythmias
disturbance of colour vision
vomiting/diarrhoea/nausea
what is the direct action of digoxin
shortens AP and refractory period
what is the indirect action of digoxin
increases vagal activity
what is the mechanism of digoxin
binds to alpha-subunit of Na+/K+ ATPase in competition with K
increases contractility by blocking the sarcolemma ATPase
what is the mechanism of levosimendan
binds to troponin C and densities it to the action of Ca2+
opens K+ channels
what is the affect of levosimendan
increases contractility
what is the affect of digoxin
increases contractility
what is the affect of am- and mil-rinone
increases contractility
what is the mechanism of am- and mil-rinone
inhibits phosphodiesterase (PDE) in cardiac and smooth muscle cells = increase [cAMP]
what is the clinical use of am- and mil-rinone
acute HF (IV)
what is the clinical use of levosimendan
acute decompensated HF (IV)
