Pharmacology Flashcards
what activates adenylyl cyclase
coupling through Gs protein
Sympathetic
what does coupling through Gi cause
- decreases activity of of adenylate cyclase and reduces [cAMP]
- opens potassium channels to cause hyperpolarization of SA node
parasympathetic
what is the inward current/funny current
current activated by hyper polarisation and cAMP
carried by sodium
what does blockage of the HCN channel cause
decrease in the slope of the pacemaker potential and reduces HR
what do hormones that increase cAMP also do
increase HR
how does sympathetic stimulation increase contractility
increases phase 2 cardiac AP
enhanced Ca++ entry
increases sensitivity of contractile protein to Ca++
how does sympathetic stimulation decrease duration of systole
increased uptake of Ca2+ into the SR
how does parasympathetic stimulation decrease contractility
decrease phase 2 cardiac AP
decreased Ca++ entry
how does parasympathetic stimulation decrease conduction in AV node
decreased activity of voltage-dependent Ca2+ channels and hyperpolarization via opening of K+ channels
what is located in the t-tuble membrane
voltage-gated L-type Ca channels (DHP receptors)
what does calcium activate and what occurs
the myofilaments and contraction occurs
how is Ca removed from the cytoplasm
SERCA
when is isoprenaline used
as a treatment for bradycardia
what does isoprenaline cause
bigger calcium ‘transients’
bigger and faster twitches
what is the function of voltage gated calcium channel
trigger’ calcium plateau phase of action potential
how is voltage gated calcium channels gated
phosphorylated by protein kinase A
increases trigger calcium
increases Ca induced Ca release
what is the function of ryanodine receptors and how is it regulated
Ca-induced Ca release from SR
Regulated by protein kinase A
what is the function of troponin
regulates actin/myosin interaction using calcium
what phosphorylates troponin and how does the affect it
protein kinase A
reduces its affinity for Ca - accelerates relaxation
how do hormones increases FOC
increase cAMP and activate PKA
increase Ca influx and release
how do hormones shorten the contractile cycle
increase cAMP and activate PKA
increase Ca reuptake
what are the effects of beta-adrenoceptor agonist
↑ Force, rate, CO, O2 consumption
↓ cardiac efficiency
what are side effects of beta-adrenoceptor agonist
arrhythmias
when is adrenaline used
cardiac arrest
anaphylactic shock
drug selective for beta1-adrenoceptors and when is it used
Dobutamine
acute heart failure
what is a non-selective beta blocker
propranolol
what are beta-adrenoceptor antagonist
beta-blockers
what are selective beta 1 blockers
atenolol
what does Digoxin do
increases contractility of the heart by blocking the SARCOLEMMA Na/K ATPase
what happens in the presence of digoxin
Na+/K+ATPase blocked
↑storage of Ca2+ in SR
what is the effect of digoxin on action potentials
shortens AP and refractory period in myocytes - useful in HF coupled with AF
side effects of digoxin
heart block
dysrhytmias
what are examples of inotropes
digoxin, levosimendan
what channels does calcium enter through
L-type Ca2+ channel
GPCR coupled to Gq/11
what is the steps to contraction
1 - Ca2+ enters the cell 2 - binds with Calmodulin 3 - Ca-CaM binds with MLCK 4 - active MLCK causes myosin-LC to phosphorylate 5 - contraction
what is the steps to relaxation
1 - cGMP binds with Myosin-LC-phosphatase
2 - myosin-LC-phosphatase becomes active
3 - dephosphorylates myosin-LC
4 - relaxation
what are side effects of organic nitrates
headaches
hypotension
collapse
which organic nitrate is resistant to first-pass metabolism
isosorbide mononitrate
what is the receptor for endothelin-1
ETa receptor
renin inhibitor
aliskiren
what do ACEi cause
venous dilatation (↓preload) arteriolar dilatation (↓afterload and ↓TPR) decreasing BP and cardiac load
ACEi increases contractility - true or false
false
has no affect on contractility
when does ACEi especially cause hypotension
in combination with diuretics
when should ARB and ACEi not be used
Pregnancy
Bilateral renal artery stenosis
what do beta 1 blockers do
decrease myocardial oxygen requirement
decreases duration of diastole
how do beta blockers help restore normal BP
reduce CO
reduce renin release
what do calcium antagonist interact with and where are they
L-type calcium channels
in the heart and smooth
what are the three main types of calcium antagonist
amlodipine, verapamil, diltiazem
what is an immediate selective calcium antagonist
diltiazem
when are calcium channel blockers used
Hypertension
Angina
Dysrhythmias
alpha blockers
prazosin
doxazosin
what is the pathway of platelet reactions following endothelial damage
1 - endothelial damage 2 - adhesion, activation and aggregation of platelets 3 - secretion and synthesis of mediators 4 - further aggregation of platelets 5 - fibrin clot
what are the mediators excreted by platelets
ADP
TXA2
5-HT
what factors cause further aggregation of platelets
Thrombin (IIa)
Fibrinogen
what is the pathway of blood coagulation following endothelial damage
1 - endothelial damage
2 - VIIa, XIIa, XIa cause conversion of X to Xa
3 - Xa causes conversion of Prothrombin (II) to Thrombin (II)
4 - Thrombin causes conversion of fibrinogen to fibrin
5 - fibrin clot
what are the clotting factors
Prothrombin (II), VII, IX and X
what are the serine proteases
Thrombin (IIa), VIIa, IXa and Xa
what are the stages of conversion by Vit K reductase
1 - vitamin K oxidised form - epoxide
2 - vitamin K - quinone
3 - vitamin K reduced form - hydroquinone
what does warfarin do
competes with vit K for binding to vit K reducatse preventing conversion of epoxide to hydroquinone
what factors does warfarin render inactive
II, VII, IX and X
what is an inhibitor of coagulation
Antithrombin III
what does Heparin do
bind to ATIII increasing its affinity for Xa and IIa to increase rate of inactivation
Heparin must bind to both AT III and IIa to inhibit IIa - true or falee
true
Heparin needs to bind to AT III and Xa to inhibit Xa - true of false
false
only needs to bind to ATIII
what does LMWH inhibit
factor Xa
still works as Xa upstream
side effects of heparin and LMWH
haemorrhage
osteoporosis
hypoaldosteronism
orally active inhibitors
dabigatran etexilate - inhibitts thrombin
rivaroxaban - inhibits Xa
what is the mechanism of action of aspirin
irreversibly blocks COX preventing TXA2 synthesis and production of prostaglandin I2
what is the mechanism of clopidogrel
Links to P2Y12 receptor
when is tirofiban given
IV to prevent MI in patients with unstable angina
what causes plasminogen to convert to plasmin
endogenous tissue plasminogen activator
what is the role of plasmin
converts fibrin to fibrin fragments
leading to clot lysis
what are Alteplase and duteplase
recombinant tissue plasminogen activator (rt-PA)
how can the risk of haemorrhage from fibrinolytic be controlled
tranexamin acid
inhibits plasminogen activation
what should a CCB never be given in
Heart Failure
what is given to treat valvular AF
warfarin
why should organic nitrates not be stored in a clear bottle
as they are photosensitive and are rendered useless
what are side effects of statins
muscle aches
side effects of nicorandil
mouth ulcers
what is a potassium sparing diuretic
Triamterene
Spironolactone
Eplerenone
side effects of digoxin
elderly patients with renal impairment can get toxicity Digoxin Toxicity Nausea, vomiting Yellow vision Bradycardia, Heart Block Ventricular Arrhythmias
what does spironolactone block
aldosterone
what are anti anginal drugs
Beta Blockers
Calcium Antagonists
Nitrates
Nicorandil
what are diuretic side effects
hypokalaemia (tired + arrhytmias)
hyperglycaemia (diabetes)
increase uric acid (gout)
impotence
when are cardioselective beta blockers used
angina, hypertension, heart failure
when is nonselective beta blockers used
thyrotoxicosis/hyperthyroidism
what are the two types of CCB
Dihydropyridines - Amlodipine
Rate limiting calcium antagonist - verapamil, diltiazem
what do alpha blockers do and when are they used
Block α adrenoceptors to cause vasodilatation
Hypertension, prostatic hypertrophy
side effects of alpha blocker
postural hypotension
what are SE of anti platelet agents
Haemorrhage
Peptic ulcer
Aspirin sensitivity in Asthma
when are fibrinolytic drugs not to be used
recent haemorrhage trauma bleeding tendencies severe diabetic retinopathy peptic ulcer
what is used to treat Supraventricular Arrhythmias in acute phase
Adenosine
what is used to treat Ventricular/Supraventricular Arrhythmias
Amiodarone
Beta Blockers
Flecainide
what are the side effects of anti-arrhythmic drugs
phototoxicity
pulmonary fibrosis
thyroid abnormalities (hypo or hyper)
