CVS DRUGS Flashcards
anti-arrhythmics, ANS drugs, CVS drugs
what is lusitrophy?
the ability for cardiac muscle to relax - key to diastole and ensuring adequate filling
positive lusitrophy = good ability to relax
includes how well calcium is removed and hence contractile apparatus relaxes after myocyte depolarisation and contraction
The sympathetic nervous system can enhance lusitropy through β-adrenergic stimulation, which increases the activity of calcium pumps (e.g., SERCA, the sarcoplasmic/endoplasmic reticulum calcium ATPase).
impaired lusitrophy can result in diastolic HF
what is an ionodilator?
An inodilator is a type of drug that has both inotropic and vasodilatory effects
i.e. improves contractility whilst lowering afterload and hence the increase in O2 consumption/ workload of the heart is offset
e.g. milronone, dobutamine and levosimendan
good for HF, cardiogenic shock.
what is an ionotrope?
A drug that increases the force of contraction
work via a variety of mechansism
* B1 receptor
* Glucagon receptor
* phosphodiesterase inhibitors
* increasing sensitivity of contractile units to calcium - levosimendan
* cardiac glycosides
what is a vasopressor
a drug that causes vasoconstriction to improve SVR and MAP.
A1 agonists - NA and adrenaline, metaraminol, phenylephrine, dopamine at high doses. ephredrine indirectly.
V1 receptor - vasopressin
guanylate cyclase and nitric oxide synthase - methylblue inhibits these and hence vasoconstriction.
tell me about the uses of adrenaline
adrenaline is an endogenous catecholamine.
Can be used as a therapeutic drug in cardiogenic shock, anaphylaxis, cardiac arrest for both shockable and non-shockable rhythms and severe bronchospasm as a nebuliser.
It can also be given with local anaesthetic agents to reduce absorption and prolong their action.
how is adrenaline presented? what doses are commonly used?
as a clear colourless solution available in a variety of strengths.
commonly 1 in 1000 and 1 in 10,000
in anaphylaxis in adults 0.5mg IM is given (0.5ml of 1 in 1000)
in cardiac arrest 1mg IV is given
as an infusion (10ml of 1 in 10000)
also comes as a nebuliser solution.
what is the mechanism of action of adrenaline
acts on both B1 and A1 receptors
ionotrophy
chronotrophy
vasopressor
higher affinity for B1 than A1 so vasopressor effects only seen at higher doses.
also on B2 -
* vasodilation of certain vascular beds - blood directed to critical areas.
* bronchodilation
* glucogenolysis, glycolysis - increases glucose production, also causes a lactic acidosis via promoting anaerobic respiration.
what are the pharmacodynamic effects of adrenaline?
respiratory - tachypnoea, bronchodilation
cardiovascular - ionotrophy, chronotrophy, lisotrophy, vasopressor. coronary vasodilation.
CNS - alertness, panic , increases MAC
GI - reduces perfusion to gut, N&V, dry mouth (can lead to gut necrosis)
reanl - reduced blood flow, stimulates renin and water retention
metabolic - glycogenolysis, glycolysis, lactate production.
what are the pharmacokinetic effects of adrenaline?
given IV - 100% BO
hydrophilic - small Vd
COMT and MAO metabolism
renal excretion of metabolites
half life of 3 mins
what additional adrenoceptors do you know?
dopamine receptors
D1 =Gs= invovled in motor function and modulation of extrapyramidal activity. some also located peripherally and cause vasodilation of renal/ splanchnic beds.
D2 = Gi = brain and involved in regulating pituitary hormone output, also basal ganglia and role in parkinsons disease
Tell me about noradrenaline..
endogenous catecholamine
also used exogenously as a drug for vasoconstriction in critically ill.
given as IV infusion through central line
found as clear colourless solution made up to 4mg/50ml. usually runs at 0.5ug/kg/min
acts via A1 receptors predominately to cause vasoconstriction.
therefore pharmacodynamics
- increased SVR and MAP
- reflex bradycardai
- some B1 activity - tachycardia
- respiratory - increased PVR
- GI and renal - reduced blood flow, can lead to AKI, gut necrosis.
no B2 activity and bronchodilation like adrenaline
pharmacokinetics
A- 100% BO
M - MAO and COMT
E - renal excretion of metabolites
t1/2 = 3 mins
what type of molecule is this?
catecholamine
benzene ring
+ amine side group
+ OH groups
this is NA = 3 OH group
adrenaline has a CH3 on end of NH group
dopamine has 2 OH groups
a catecholamine is an endogenous neurohormone of sympathetic NS. involved in fight or flight. derived from tyrosine / phenylalanine
what group of patients should NA be used with caution?
those taking MAO inhibitors
will give an exagerated, prolonged response.
what is the difference between exogenous and endogenous NA?
endogenous - local effects e.g. at the heart - tachycardia
exogenous - widespread effects - vasoconstriction throughout.
what is isoprenaline?
synthetic catecholamine
acts as B1 and B2 agonist
used for bradycardias e.g. AV block
no effect on a1
tell me about metaraminol..
synthetic amine
used for treatment of hypotension, particularly during general anaesthesia or ITU
comes as clear colourless solution in 1ml ampules containing 10mg. diluted in 20ml to give a 0.5mg/ml conc. usually given in 0.5mg boluses or an infusion can be run up to 40ml/hr then should be moving on to NA.
alpha 1 agonist
vasoconstriction - increased SVR and PVR
reflex bradycardia
tell me about phenylephrine
synthetic alpha 1 agonist
used for management of hypotension, particularly in maternity, ITU and threate. also used as a nasal decongestant.
dose - 10mg diluted in 100ml of saline. given as 50-100ug bolus. or infusion.
vasoconstriction - increase SVR, PVR and reflex bradycardia
metabolised by MAO in liver.
What Alpha 2 agonists do you know
clonidine and dexmedetomidine
work pre-synapticaly inhibiting release of NA from neurons.
effects are hypotension, analgesia and sedation
can be used IV or as an adjunct to neuraxial blocks.
CLonidine
does also have effect at A1 but more potent at A2. however this means that paradoxical hypetension can be seen.
also rebound HTN when stopped
**dexmedetomidine **
more selective for A2
less side effects
easier to titrate because shorter half life
what B2 agonists do you know…
short fast acting = salbutamol, terbutaline
long acting = salmeterol
tell me about salbutamol
B2 agonist
commonly used in asthma and COPD, bronchospasm.
but also has a role in hyperkalaemia
can be found as an inhaler, nebuliser solution, IV preparation and as tablets.
it causes bronchodilation via B2 -Gs - PKA and phosphorylation of MLCK which inhibits it.
however also causes
- tachycardia, tremor, hypotension, hypokalaemia, high glucose and lactic acidosis
what alpha antagonists do you know?
alpha 1 antagonist
- doxazocin - reduces BP and helps with BPH and urinary symptoms
- tamsulosin - more selective to prostate
- labetolol - used for HTN e.g. in theatre
- phentolamine - HTN emergencies pheochromocytoma
- phenoxybenzamine - pheochromocytoma long term
alpha 2 antagonist
- Yohimbine - rarely used.
- phentolamine
- phenoxybenzamine
what non selective alpha blockers do you know?
- phentolamine
- competitive non selective alpha blocker
- a1 more than A2
- used in pheochromocytoma in emergency
- phenoxybenzamine
- longer acting non selective a blocker
- a1 more than a2
- used for pheochromocytoma pre-op
how do B blockers cause hypotension?
MAP = CO x SVR
CO = HR x SV
B blockers - reduce ionotrophy and chronotrophy hence CO
also can dilate some vascular beds.
block renin release and hence fluid retention
tell me about labetolol…
combined alpha 1 and b1 antagonist
result in slower HR and vasodilation
used in HTN associated with pregnancy, and ITU and anaesthesia.
tell me about aminophylline
non selective phosphodiesterase inhibitor.
increases cAMP and hence PKA
works as bronchodilator in asthma but also an ionotrope in cardiogenic shock
usually give a loading dose and then maintainance dose. ensuring levels are closely monitored due to its narrow therapeutic index.
pharmacodynamics
- bronchodilation
- ionotropy, tachycardia, vasodilation
- neurologicallly - can reduce seizure threshold
pharmacokinetics
- IV or PO - good BO
- CYP450 metabolism
- 0 order kinetics in toxic dose
- narrow therapeutic index - hence needs HDU for infusion.
do you know any PDE III selective inhibitors?
milronone and enoximone
these act only on myocardium and vascular smooth muscle.
hence increase ionotrophy and used in cardiogenic shock.
tell me about ephedrine..
indirect sympathomimetic
works via promoting vesicles of NA to be released
used commonly in threatre for hypotension treatment.
comes in 30mg in 10ml vials - given as 2-3ml bolus’s
also comes as tablets and nasal drops.
overall effects include
- positive ionotrophy and chronotrophy
- vasopressor
- bronchodilation
tachyphylaxis is seen - once NA stores are exhausted.
which drugs act on the parasympathetic NS?
the parasympathetic NS acts via muscarinic receptors = M1 to M5
drugs can either act as agonist or antagonists to these
agonist
* pilocarpine - used for glaucoma
antagonists - structurally related to Ach
- atropine - bradycardia,
- glycopyrolate -bradycardia, secretion
- hyoscine - buscopan, secretions
- ipratropium - asthma.
some drugs can act indirectly
e.g. acetylcholinesterase inhibitors - neostigmine
e.g. affect ACh release - botilinum toxin, Mg, Gentamicin
compare the structure of atropine and glycopyrolate, what significance does this have?
both have an amine group
atropine is a tertiary amine i.e. not charged
glyco is a quarternary amine and charged
therefore atropine can cross BBB and have central efects. - sedative and delirium in elderly.
what are the effects of antagonising parasympathetic NS e.g. atropine , glycopyrolate
respiratory
- bronchodilation
- reduced secretions
cardio
- tachycardia
GI
- reduced peristasis - constipation
CNS
- restlessness, agitation, delirium , sedation
opthalmic
- pupil dilation - avoid in glaucoma
tell me about atropine..
mAChR antagonist
tertiary amine
used for bradycardia, part of ALS
IV preparation - clear colourless solution, 1ml ampules containing 0.6mg. usually given as 0.2-0.6mg.
pharmacodynamics
- block parasymp
- do by system.
pharamacokinetics
- crosses BBB and placenta
tell me about glycopyrolate
mAChR antagonist
quarternary amine
used for bradycardia and to reduce secretions e..g paliative care, slower onset than atropine
IV preparation - clear colourless solution, 1ml ampules containing 200ug. can give 200-400micrograms
pharmacodynamics
- block parasymp
- do by system.
pharamacokinetics
- doesnt crosses BBB and placenta
what are the uses of hyoscine?
mAChR antagonist
used in N&V, dizziness, antispasmodic, premed as it causes sedation and amnesia.
2 forms - one can cross BBB and one cant e.g. hyoscine butylbromide cant this is buscopan. hydrobromide can.
what is meant by a sympathomimetic and sympatholytic
sympathomimetic - drugs that stimulate adrenoreceptors and hence mimic effects of sympathetic NS. May be endogenous or synthetic catecholamines or synthetic non catecholamines.
sympatholytic - block adrenoceptors and block effects of Symp NS
tell me about dobutamine
synthetic directly acting catecholamine
B1 and B2 receptors
ionodilator - B1 chrono and ionotrophy, B2 - some vasodilation but BP mostly maintained
good for cardiogenic shock. also used in the stress test instead of exercise
has a very short half life because of its rapid metabolism by COMT - therefore given as an infusion
how are anti-hypertensive agents classified?
can be classed according to site of action
blood vessels
* nitrates, CaCB (amlodipine), a1 blocker (doxazocin)
heart
* B blockers - indirect can reduce MAP by reducing CO.
RAAS:
* ACE inhibitors
* ARBs
kindeys
* diuretics
centrally acting
* a2 = clonidine , dexmedetomidine, methyldopa
how do nitrates work to reduce BP? give examples of drugs in this class..
Glyceryl trinitrate, isosobide mononitrate, sodium nitroprusside
arterial and venous dilation
reduce afterload and SVR. therefore reduces MAP.
also reduced preload - hence CO - hence MAP
MAP = CO x SVR
GTN - acute angina releif
long acting nitrates = isosorbide mononitrate = prophylaxis for angina
sodium nitroprusside - HTN crisis
how do ACEi reduce BP
promote diuresis…
less ATII and so less ADH and aldosterone release and hence less Na reabsorption.
reduces blood volume
hence preload –> CO –> MAP
also less ATII normally vasoconstriction therefore ACEi inhibit this.
which anti HTN can be used in pregnancy?
labetolol
methyldopa
nifedipine
can you categorise stages of HTN..
stage 1 BP more than 140/90mmHg or at home 135/85
stage 2 - 160/100, 150/95
stage 3 - 180 systolic or 120 diastolic .
how is HTN managed?
stage 4 is add in others e.g. spironolactone, alpha blocker.
what are the side effects of nitrates?
hypotension
headache
flushing
constipation
tolerance
what are the contraindications of nitrates?
HOCM
severe AS
what groups of CaCB do you know?
non-dihydropyridine CCB (class I)
* mostly act by blocking SAN/AVN and lowering HR
* verapamil
dihydropyridine CCB (clas II)
* work on vascular smooth muscle
* e.g. amlodipine , nifedipine
* HTN, raynauds, cerebral vasospasm
class III - diltiazem
- works on both peripheral and cardiac
both work via blocking Ca entry via L type Ca channels.
tell me about sodium nitroprusside..
inorganic nitrate
used in HTN emergenceies
brown powder that needs reconstituiting in dextrose
donates NO in vivo
main problem is it degrades in sunlight so needs opaque giving sets and produces cyanide ions
both arterio and venodilation - reduced SVR/ MAP and preload
tell me about cyanide toxicity?
cyanide is a toxic inorganic molecule
c triple bond N
it can cause histocytic hypoxia
binds to ETC carrier molecules and blocks their action hence blocks oxidative phosphorylation
leads to metabolic acidosis
tell me about ACEi?
Often first line medication for HTN
Also used for their cardiac remodelling potential and so used after MIs
block conversion of ATI to ATI and therefore work as a diuretic and vasodilator to reduce BP
common side effects include
* low BP/ orthostatic hypotension
* high K
* dry cough
* precipitation of AKI
* angioedma
e..g. ramipril, enalopril, lisinopril
how might intraoperative HTN be managed?
reversible cause..
* treat pain
* treat hypercapnoea
* reduce ET cuff pressure if high
indirect
* anaesthetic agent - inhalation or propofol
* opioids
* MgSO4
direct:
* labetolol - 5 to 10mg IV increments/ infusion
* hydralazine
* GTN infusion
what should intraop BP target be?
MAP 65 in most people
due to autoregulation of CPP occuring between 50-150mmHg
may be higher in chronic HTN, cerebrovascular disease etc.
too low - may not perfuse vital organs such as the brain
too high - can result increased bleeding intraopertively
what level of BP can surgery continue?
elective in community - less than 160/100 mmHg
on the day - less than 180 / 110 mmHg
what are ganglion blockers?
no longer used
block nAChR sympathetic ganglia and result in hypotension.
tell me about hydralazine?
anti HTN medication
often used in treatment of pre-eclampsia
works via inhibition of guanyl cyclase and thus causes vasodilation. - reduces SVR. also thought to interfere with IP3 pathway and reduces intracellular calcium
can be given IV or orally
long term it is associared with SLE
what routes can clonidine be given?
IV or oral or as adjunct in neuroaxial anaesthesia.
effects of clonidine..
hypotension
sedation
analgesia
reduces MAC, paradoxical HTN, rebound HTN, antiemetic, anxiolysis
what role does MgSO4 have in HTN?
inorganic ionic molecule
with many uses -
* analgesia
* hypotension
* prolongs NMBA
* antiarrhyhmic - torsades, AF
* bronchodilator - asthma management 2nd line
* reduces seizure activity
* 1st line for pre-eclampsia and eclampsia
presented as 50% MgSo4 in 2,5,10ml ampoules which requires dilution.
usually give 2-4g IV
it works via antagonism of calcium hence reduces neuronal transmission and relaxes smooth muscles.
where is the body is Mg found?
most abundant intracellular cation after K
found in soft tissue and muscle and bone
physiological effects of Mg?
CVS system
* vasodilation - hypotension
* antiarrhythmic
CNS
* reduces excitability - increases seizure threshol
* hypoMg - causes vasospasm
respiratory
* bronhcodilation - via relaxing smooth muscle.
MSK
* hyporeflexia, muscle weakness
other
* inhibits catecholamine release
* inhibits platelets
describe effect of Mg toxicity..
mild more than 4mM = nausea, hyporeflexia , slurred speach
moderate - 4 to 10 = muscle weakness, resp depression, bradycardia
severe- more than 10 = cardiac arrest
how does Mg work as an analgesic?
effective intro op adjunct for analgesia
thought to be via comp and non-comp NMDA anatagonism preventing transmission in spinal cord
what electrolyte abnormality is associated with hypoMg?
hypo K
should replace Mg before replacing K
as Mg deficiency exagerates renal K excretion and impairs Na/K ATPase
compare and constract ARBs to ACEi…
both drugs act on RAAS
ACEi = block ACE and conversion of ATI I to II. therefore reduce amounts of ATII and downstream effects - aldosterone production, vasoconstriction, ADH secretion
ARB - block the ATII receptor. and thus also reduce effects but not levels of ATII
side effect profile slightly different
ACEi promote bradykinin production and thus dry cough and angioemdma is more common
ARB have a better side effect profile
both can still cause hypotension, hyperkalaemai.
both can be used in HF, post MI and HTN. usually ACEi first line and ARBs if they arent tolerated
how do potasium channel activators act as anti-HTNs?
nicorandil is an example
used as prophylaxis in angina and HF
activates ATP sensitive K channels within heart and arterioles. promotes hyperpolarisation, closing VG ca channels
thus vasodilation, reduces AP duration.
what is pheochromocytoma and how is it managed?
tumour of chromaffin cells
exagerrated sympathetic response
thus intermittent - HTN, tachycardia, sweating, flushing.
treated with sympatholytics - alpha and beta blockade
need to block alpha before beta receptors.
otherwise will have very high afterload that the heart can’t deal with after B blockade. plus blocking B2 as well and reduced vasodilation, worsens BP.
e.g. doxazocin and bisoprolol
stepwise management of angina…
B blockers/ Ca CB
B blockers plus type 2 CCB
long acting nitrate
pottasium channel activator (nicorandil)
acute management of MI
Morphine
oxygen - titrated
nitrates - GTN spray
Aspirin - 300mg
definitive - PCI or fibrinolysis (PCI if it can be made within 120 mins of diagnosis, otherwise fibrinolysis)
after PCI / stenting - Dual antiplatelet - asprin + clopi for for 6months - 1 yrs. then aspirin only.
what are the contraindications to fibrinolysis?
absolute
* previous intracranial bleed
* ischaemic stroke within 6 months
* recent major trauama/ surgery
* GI bleed in last month
* known bleeding disorder
* aortic dissection
relative
* recent TIA
* oral anticoags
* refractory HTN
* active peptic ulcer
* I.E
* advanced liver disease
how do statins work?
block HMG CoA reductase
prevent cholesterol synthesis
how can anti-arrhythmic agents be classified?
Vaughn william classification - traditionally
class I = VG Na blockers, all reduce phase 0 of AP.
* 1a = increase refractory period + AP - quinidine, procainamide
* 1b= decrease refractory P + AP - lidocaine, phenytoin
* 1c = no effect on RP + AP - flecainide
class 2 = B blockers - atenolol, bisoprolol
class 3 = K channel blockers - amiodarone, sotolol
class 4 = Ca CB - verapamil, diltiazam
what are the limitations to vaughn williams classification?
many anti-arrhyhmics drugs dont fit into this classification e..g digoxin , MgSO4, adenosine
some fit into multiple categories e.g. sotolol
other than Vaughn william classification, is there any other methods to classify anti-arrhythmics
by indication
SVT - adenosine, digoxin, B blockers, verapamil
VT - lidocaine, phenytoin
both - amiodarone, flecainide
by molecular targer
- ion channels - flecaindide, lidocaine, amiodarone
- pumps/carriers - digoxin
- receptors - B blockers, adenosine
which part of cardiac AP do the different types of antiarhythmics effects..
draw cardiac AP
class I a - increase RF and AP and reduce phase 0
class Ib - decrease RF and AP and reduce phase 0
class Ic - minimal affect AP/RF , reduce phase o
class II - reduce funny current, slow automaticity , prolong AP duration
Class III - reduce phase 3, prolong AP and refractory
class IV - reduce automaticity, slow phase 0 of pacemaker, prolong AP and refractory
how do different class I anti-arrhyhmics differ in binding to VG Na channels?
1a - intermediate dissociation
1b - fast dissociation, weak block
1c - slow dissociation, strong block
what are the side effects of class I agents?
LAST
* neuro - lip tingling, tinnitus, agitiation, tremor, seizure. excitatory at first. then inhibitory - drowsiness, apnoea, coma
* cardiac - low BP, low HR, arrhythmias (torsade)
which B blockers are classed as selective and non-selective?
SELECTIVE to B1 = BEAM
bisoprolol, esmolol, atenolol, metoprolol
non selective
e.g. labetolol to alpha 1 as well
e.g. propanolol - b1 and b2
what are the side effects of CaCB?
flushing, bradycardia, constipation, ankle oedema , reduced contractility - caution in HF
tell me about amiodarone
class III antiarhythmic agent workss via blocking VG K channels and hence acts at phase 4 of the cardiac AP
used predominately in ventricular arrhtyhmias
given as IV or oral preparation. usually requires a loading dose in an emergency due to very long half life.
e.g. 300mg loading dose given in acute setting IV followed by 900mg over 24 hours. - via central line
pharmacodynamics
* useful effects - prolongs AP and RF , good at blocking accessory pathways e.g. for WPW.
* however
* can increase QTand precipitate torsades, lower HR and BP
* resp - pneumonitis + fibrosis
* liver - hepatitis, cirrhosis
* thyroid - hyper/hypothyroid
* CNS - peripheral neruopathy, corneal deposits
* skin - photosensitivity and slate grey skin
should do baseline TFTs, CXR, LFTs, UEs before use
pharamcokinetics
* oral - 50% BO
* high PB - displaces gixonix, DOACs, CCB etc
* long half life - 50 days hence loading dose
* hepatic metabolism
* biliary, skin secretion.
tell me about digoxin, including toxicity
digoxin is a cardiac glycoside
it blocks the NA/K ATPase
and acts as an anti-arrhythmic agent and a ionotrope and hence mostly used for HF and AF
it is given either orally or IV. levels need to be closely monitored due to its narrow therapeutic range and toxicity outside of this.
pharmacodynamics
- can cause arrhythmias, nausea, vomitting, visual distrubances (green) in toxic doses
pharmacokinetics
- IV or oral
- large vd
- renal excretion unchanged
toxicity can be treated with digibind - monoclonal Ab
supportive - electrolyte corrections, phenytoin to treat arrhythmias
what is the significance of WPW with AF?
WPW is a congenital condition whereby there is an accessory pathway between A and V.
hence can get antidromic and orthodromic conductions loops - down AVN and up accessory path - can lead to re-entry tachycardias.
in those with AF - there is increased risk of SVT
if the AVN is blocked via adenosine, digoxin, CaCB it will encourage rapid transmission of impulses down accessory pathway and may allow for AF to cause VT or VF.
should use amiodarone in these patients
what is brugada syndrome?
abnormal cardiac channels
promote VF and sudden cardiac death
pre-op considerations - check and correct electrolytes, avoid LA agents
treat VF/VT with defibrilation
what are the indications for B blockers
used both in the acute setting and primary care..
can be divided by system
CVS:
* AF, angia, post MI, HTN
endocrine:
* pheochromocytoma
* hyperthyroid
CNS:
* anxiety
* glaucoma
* migrane propjylaxis
* essential tremor
systemic effects of B blockers..
by system
work via blocking B1 and B2 receptors depending on selectivity
heart -
negative chronotrophy = bradycardia (SAN and AVN
negative ionotrophy = reduced contractility hence CO and hence hypotension
increase SVR - due to B2 normally causes vasodilation - hence reduced coronary blood flow
lungs
beta 2 - bronchospasm
RAAS
- block renin production
neuro
- fatigue , nightmares
metabolic
- reduce glycolysis, gluconeogensis
ocular
- reduced ocular pressure
which B blockers can be given IV?
atenolol - 2.5mg
metoprolol - 5mg
labetolol - 5mg
esmolol - 10mg
what is the mechanism behind digoxin toxicity?
inhibits the Na⁺/K⁺-ATPase, leading to:
Severe intracellular calcium overload.
Cellular membrane instability and increased automaticity, which can cause life-threatening arrhythmias.
how is digoxin toxicity managed?
discontinue
supportive care
correct electrolytes
digibind
haemodialysis is not used unless for renal failure and hyperkalaemia
