Pharmacology Flashcards
Selective HCN chanel blocker
Used in ____
Ivabradine
Angina - decreases HR and increases cardiac efficiency
β agonists eg.s
catecholamines - doputamine (β selective)
adrenaline
noradrenaline
In cardiac arrest adrenaline is given ____
Its effects are ___ (and give receptors)
IV
+ve chrono and iono (β1) peripheral vasoconstriction (α1) dilate coronary arteries (β2)
Dobutamine is given in ____ by ___ route
acute HF eg. post-op/shock
IV
β antagonists eg.s
propranolol (non-selective)
atenolol, bisoprolol, metoprolol (β1 selective)
Effect of β-blockers on HR, force, O2 requirement and exercise tolerance
decrease HR, force (therefore CO), O2 requirement (although non-selective cause coronary vessels to constrict) and exercise tolerance
Uses of β-blockers
AF and SVTs - delay at AVN
Angina - increase diastole = LV perfused
Post-MI
Compensated HF - low dose eg. carvedilol (also α1 antagonist)
adverse effects of β-blockers
bronchospasm
aggravate HF - if rely on sympathetic drive for CO
bradycardia/heart block
hypoglycaemia - glucose release in liver is β2 controlled
fatigue
cold extremities
non-selective competitive muscarinic ACh receptor antagonist eg. and effect
atropine
for bradycardia
increases HR
Drug that blocks NaKATPase on sarcolemma to increase influx of sodium and calcium => increased CICR and contractility
Digoxin
Use for HF with AF
digoxin
Indirectly increases vagal activity and slows SAN and AVN
digoxin
Digoxin toxicity may occur if ____
Unwanted effects=
hypokalaemic (competes w. K for space on NaKATPase) self-repeating tachycardia heart block GI yellow vision
Calcium sensitiser eg.
Mode of action
indication for use
levosimendan
sensitises troponin C for Ca2+ and vasodilation
IV for acute decompensated HF
Inodilator eg.s
Mode of action
Indication for use
milrinone amrinone
inhibit PDE => increase cAMP in cardiac and SM cells => increase contractility and decrease TPR
IV in acute HF
AT1 receptor blockers (ARBs) eg.
losartan, valsartan
ARB and ACEI indications for use
hbp, HF, post-MI, reduce oedema in HF
NOT IN PREGNANCY
Organic Nitrates benefits for angina __
decrease preload - mainly venodilators
decrease afterload (at high dose also = arteriodilators)
dilate coronary collaterals to supply ischaemic area
Organic Nitrates eg.s
Indications
isosorbide mononitrate - PO morning and lunch to stop tolerance
GTN spray / IV if ACS
stable angina, ACS and prinzmetal angina
antagonists of ETa receptor (for endothelin) eg.s
indicated for
bosentan, ambrisentan
pulmonary hypertension
renin inhibitors eg.
alsikiren
NOT WITH ACEI or ARB
ACEI eg.s
effects
side effects
lisinopril, ramipril
less vasoconstriction due to AT2 decrease
more vasodilation due to bradykinin increase
less blood vol due to aldosterone decrease
dry cough
CCB 3 eg.s
verapamil (mostly cardiac CaL channel selective)
amlodipine (mostly SM CaL channel selective)
diltiazem (intermediate selectivity)
effect and method of action of CCBs
block CaL channels => decreased rate and conduction through AVN and force of contraction
CCB preferred for hbp
amlodipine (less effects on heart)
causes arteriole and artery + coronary artery vasodilation
Side effects of CCBs
ankle swelling, hypotension, dizzy, flushing
DONT give verapamil with β-blockers.
DONT GIVE IN HF
K+ channel openers eg.s
mechanism of action
nicorandil - angina (also has NO activity)
minoxidil - last resort for severe hbp
open Katp channels in vascular SM by antagonising ATP that closes them => hyperpolarised + CaL inhibition => relaxation
α1 antagonists eg.
cause
indications for use
prazosin + doxazosin
vasodilation and decreased sympathetic transmission
for benign prostatic hyperplasia and if they also have hbp
Thiazide diuretic eg.
Inhibit ____ in ___
Indications
bendroflumethiazide
inhibit NaCl reabs by blocking NaCl co-transporter in distal tubule
mild HF, hbp, severe resistant oedema (along w. loop)
Loop diuretic eg.
Inhibit ___ in ___
indications
furosemide
NaCl reabs by NaKCl co-transporter blockage in thick ascending loop of Henle
acute pulmonary oedema (IV) chronic HF
Type I antiarrhythmics target-
Phase 0 - Na+ channels
Type I antiarr. classes
a-moderate ass/dis rate = longer refractory period disopyramide
b - rapid ass/dis = prevent prem beats lignocaine
c - slow dis/ass = depress conduction flecainide
Type 2 antiarrhythics
β-blockers - act on depol in SAN and AVN eg. metoprolol
Type 3 antiarrhythmics
K+ channel blockers -prolong AP and increase refractory period eg. amiodarone, sotalol
Type 4 antiarrhythmics
CCBs - slow SAN and AVN conduction and decrease force
eg. verapamil
Drugs that work on atria (rate control of SVT) =
Ic and III eg. flecainide and amiodarone
rate control antiarrhythmics =
β blockers and CCBs
rhythm control antiarrhythmics =
K+ and Na+ blockers
Drugs that work on AVN (rhythm control of SVT) =
adenosine, digoxin, II and IV ie. β-blockers and verapamil
Drugs that work on atria (rate control of SVT) =
Ic and III = flecainide, sotalol/amiodarone
Antiarrhythmics that work on the ventricles =
Ia+b + II
disopyramide, lignocaine, β-blockers
antiarrhythmics that work on atria and ventricles + AV accessory pathways
amiodarone, sotalol (III) and disopyramide (Ia) and flecainide (Ic)
Adenosine (IV) acts on ____ receptors in the ___
Used in ____
A-1 adenosine receptors in the AVN paroxysmal SVTs (atria=140-250bpm) caused by re-entry involving the SA/AVN/atrial tissue
Drug for termination of paroxysmal SVTs (atria=140-250bpm)
Adenosine IV
A-1 adenosine receptors are coupled to ___ > activates ____ > _____ AVN
Gi/o
GIRK
hyperpolarises AVN and so suppresses impulse transduction
Adenosine is used in acute/chronic SVT
acute - is quickly removed
Drug that stimulates vagal activity = slows conduction and increases refractory period in AVN and bundle of His
+ve ionotropic effect
digoxin (IV/PO)
Inhibits the NaKATPase
Treats acute/chronic AF
digoxin
Used for prophylaxis of AF and atrial flutter =
verapamil (PO)
adenosine/verapamil is better for acute AF/ atrial flutter
adenosine
don’t prescribe verapamil with ___
β-blockers (other -ve ionotropic drugs)
Used in ventricular arrythmias post-MI
Ib - lignocaine IV
Ia - procainamide IV
Used to prevent recurrent Ventricular arrhythmias
Ia - disopyramide PO
Prophylaxis for AF (a Na blocker)
Ic - Flecainide
Depress conduction in AVN (control SVT)
Suppress excessive symp drive (prevent VT)
propranolol and atenolol β-blockers
Drug with Ia, II and IV properties used for SVT and VT
amiodarone
Antiarrhythmic used when others have failed and reduces mortality post-MI and in CCF
amiodarone
pulmonary fibrosis, thyroid disorders, photosensitivity and peripheral neuropathy are side effects of
amiodarone
Side effects of diuretics =
hypokalaemia may => arrhythmias
hyperglycaemia
^uric acid => gout
impotence
Thiazides are given in ___
Loops are given in ____
NEITHER IN ____
hbp
CCF
GOUT
cardioselective β-blockers for ___
non-selective for ____
neither in ___ or ___
angina, hbp, CCF
thyrotoxicosis
asthma; short term in HF - fine if start low and increase for medium to long term HF
dihyropyridine CCB used in hbp and angina
may cause ankle swelling
amlodipine
rate limiting CCBs for hbp and angina, AF and SVT
reduce HR and vasodilate
verapamil and (diltiazem - not as much for AF and SVT)
α-blockers for prostatic hypertrophy and hbp
may cause hypotension
doxazosin
for hbp and CCF
good in diabetic neuropathy
bad in renal artery stenosis and gestational hbp
ACEIs
Side effects = dry cough, angioedema, renal dysfunction,
ACEI
Venodilators for acute HF and angina
side effects = tolerance, headaches, hypotension
organic nitrates
Prevent new thrombus in angina, acute MI, CVA/TIA and those at risk of MI/CVA/TIA
antiplatelts eg. aspirin
aspirin sensitivity may induce ___
asthma
Blocks clotting factors 2, 7, 9 and 10
Warfarin PO
Given in DVT, PE, NSTEMI and AF
warfarin PO
Anticoagulant eg.s
warfarin PO
heparin IV
rivaroxaban and dabigatran
fibrinolytic drugs eg.s
alteplase, duteplase, streptokinase, tPA
Contra-ind.s for fibrinolytics
recent haem trauma bleeding tendency (haemophilia) peptic ulcer sever diabetic neuropathy
Used in hypertriglyceridaemia and low HDL
fibrates eg. bezafibrate
Statins block ____
Used in ____
side effects (rare)
HMG CoA reductase
hypercholesteraemia, diabetes, MI, TIA, angina
myopathy, rhabdomyolysis, renal failure
Used to cardiovert SVT and VT if can’t DC cardiovert
amiodarone, flecainide, β-blockers
Used in acute phase of SVT
adenosine
Digoxin toxicity =
nausea, vomiting, yellow vision, bradycardia, heart block, ventricular arrhythmias
gestational hbp sometimes w. fluid retention and proteinurea =
pre-eclampsia
Inhibition of ___ by ___ increases LDL receptor expression and clearance of LDL
HMG CoA-reductase
statins
decreases total chol+LDL by up to 60% + tri. 40%
+HDL increases by 10%
reduce inlam
stabilise atheromatous plaques
statins
Homozygous familial hypercholesterolaemia means you have no ____
and dont respond to ___
LDL receptors
statins
Statins are given ___ at ___ (route and time)
PO night
decrease tri.s 50% + LDL 15%
increase HDL 20%
fibrates
eg. bezafibrate and gemfibrozil
agonise nuclear receptor PPARα + increase transcription of genes including that for LPL
fibrates mechanism of action
fibrates are not to be used in ____
alcoholics
Bile binding resins eg.s
colestyramine, colestipol, colesevelam PO
bile binding resins prevent ___
results in ___
side effects=
enterohepatic (in ileum) recycling of bile
decreased abs of tris and increased LDL expression
GI irritation
Ezetimibe mechanism of action:
Causes a ____ in LDL and ___ in HDL
Not for ___
inhibits NPC1L1 transport protein in duodenal enterocytes decreasing chol. abs.
18% less LDL no change in HDL
NOT in pregnancy
2ndry causes of hyperlipidaemia =
TIID
hypothyroidism
alcoholism
liver disease
If chylomicron levels are elevated then the treatment is ___
none - no elevation in atherosclerotic risk
If LDL levels are high then the treatment is ___
statins w/wo ezetimibe - high atherosclerotic risk
If LDL and VLDL are high the treatment is ___
fibrates, statin (nicotinic acid) high atherosclerotic risk
If βVLDL or VLDL is raised the treatment is ____
fibrates - moderate atherosclerotic risk
If VLDL and chylomicron levels are raised treatment is ___
fibrate, niacin, fish oil and statin - atherosclerotic risk not elevated
Pleiotropic effects of statins
improve endothelial dysfunction increase NO bioavailability anti-oxidant inhibit inflam response stabilise atheromatous plaques
Warfarin blocks ____
stops the formation of the precursors of Factors ___
Vitamin K reductase
2, 7, 9 + 10
Anticoagulants are used to prevent ____ thrombi and emboli
eg. in
venous
DVT, post-op, artificial heart valves, AF
Warfarin is a ____ derivative and has a similar shape to ___
coumarin
Vitamin K
Warfarin has a ____ onset of action within ____
slow
2-3 days
If warfarin is taken factors that increase the risk of haemorrhage =
liver disease (less clotting factors) high metabolism (clotting factors cleared) drugs - NSAIDS, antiplatelets, inhibit liver, inhibit reduction/availability of vit. K
Factors that increase the risk of a thrombus
pregnancy, hypothyroidism, Vit. K consumption, drugs that increase liver metabolism
To reverse warfarin overdose give ___/____
vitamin K/plasma clotting factors
Heparin binds to ____ an endogenous inhibitor of clotting factors and increases its affinity especially for __+___
ATIII (antithrombin3)
Xa and IIa
Heparin must bind to both ATIII and ___ to speed up its degradation.
But only needs to bind to ATIII to speed up breakdown of ___
both = IIa
only ATIII = Xa
Eg.s of LMWHs
Inhibit ___
dalteparin, enoxaparin
Xa
Heparin is given ___/__ (route)
Need a ____ for optimum dosage
Eliminated by ___ order kinetics
Preferred over LMWHs in ____
IV (immediate onset) or S/C (onset after 1hr)
in vitro test
0 order (saturation) kinetics
renal failure
LMWH are given __ (route)
No optimum dosage test needed
eliminated by __
S/C
1st order kinetics ie. only by the kidneys
adverse effects of heparin and LMWHs:
haemorrhage
rare = osteoporosis, hypoaldosteronism, hypersensitivity
If haemorrhage when on heparin give ____ to inactivate it
protamine sulfate
Oral direct inhibitor anticoagulants eg.s
used in ___
dabigatran (IIa)
rivaroxaban (Xa)
hip and knee replacement prophylaxis
INR is monitored in administration of ____
warfarin
Antiplatelet eg.s
Aspirin
Clopidogrel
Tirofiban
Aspirin blocks ___
1) in platelets = _____
2) in endothelial cells = ___
Balances toward antithrombotic as ___ can’t synthesis new COX - take 7-10 days to ____
COX-1
no TXA2
no antithrombotic PGI
platelets - turnover
Drug that blocks P2Y12 receptor on platelets and stops it binding to ADP
Inhibits ___
Clopidogrel
Inhibits conversion of fibrinogen to fibrin
Drug that blocks fibrinogen from binding to GPIIb/IIIa receptor on platelets Given \_\_\_ (route) short term to prevent MI in \_\_\_\_\_
tirofiban IV
unstable angina
Fibrinolytic drugs activate ___ by stimulating ___
plasminogen by stimulating tPA to convert it to plasmin
Effect of plasmin
lyses fibrin to fibrinogen
Fibrinolytics are used in ____
acute MI (if no PCI in 90mins) or stroke rarely: venous thrombosis/PE
recombinant tPA eg.s
route =
more effective against ____ bound plasminogen over ___plasminogen
alteplase duteplase IV (no allergic reaction unlike streptokinase)
fibrin bound>plasma
Sort of antidote to fibrinolytic drugs
tranexamic acid
GTN can come in __/__/___ forms
sublingual pills, spray or patch
If take 1 GTN and doesn’t relieve pain then ____
Phone an ambulance - don’t take another
Gingival hypertrophy, ankle oedema and tachycardia are potential side effects of ___
amlodipine
Side effects of ivabradine =
blurred vision, headaches
Late Na+ channel inhibitor in cardiac myocytes
Used to treat chronic angina
side effects = drug interactions
ranolazine
_____ may mask angina symptoms due to neuropathy
diabetes mellitus
If have claudication do not give _____ as makes it worse
β-blockers
K+ sparing diuretic - aldosterone antagonist for HF
spironolactone
mnemonic for treatment of cardiogenic shock with acute HF
LMNOP Loop diuretic (ferusemide IV) Morphine Nitrate O2 Position - sit up
IABP =
intra-aortic balloon pump
inflates in diastole so coronary arteries fill up
Digoxin is less effective when ____
don’t give with ____ as causes heart block
active (sympathetic activity increases)
amiodarone
Treatment for chronic HF:
oral ferusemide, anti-coag to prevent DVT, stockings, β-blocker, ACEI, spironolactone
DONT give thiazide with warfarin because ___
become HYPERHAEMORRHAGIC
K+ sparing diuretics work on the ___
collecting duct in the kidney
