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.
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 is HTN managed?
stage 4 is add in others e.g. spironolactone, alpha blocker.
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.
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
