8. CVS drugs Flashcards
Digoxin
Where effects - nerve
Inhibits what
which leads to what
How is it exceted
what effect does this have
Toxicity increase with what
Avoided in what condition
signs of tx effect
bioavail
Vd
Side effects
Cardiac glycoside
used afib/flutter
Indirect effects via vagus nerve
Inhib Na/K ATPase incr sodium = displace calcium, + inotropic effect.
to cellular sodium overload and an increase in sarcoplasmic calcium content mediated by a Na/Ca exchanger. This increase in cellular calcium result in an increase in myocardial contractility.
Acetylcholine @ cardiac muscarinic receptors = prolongation - effective refractory
SA node
AV node
bundle of His.
Fifty per cent to 70% of digoxin is excreted unchanged in the urine and doses need to be altered in renal failure.
Toxicity is increased in hypokalaemia, hypomagnesaemia and hypernatraemia.
WPW - acclerate access path
Prolonged PR interval, ST segment depression, T wave flattening and shortened QT are therapeutic, not toxic ECG signs.
Po - 70%
Prot bind 20%
5-10 L/Kg.
10% hep met
70% excr unchanged
Junctional bradycardia
Ventricular bigeminy, and
Second/third degree heart blocks.
Phenytoin can b used to rx dig tox (vent tachyarryh)
AV nodal conduction agents in WPW
AV nodal conduction, such as adenosine, beta-blockers and calcium channel blockers, are also relatively contraindicated.
Aspirin Overdose features Stim what Blood gas + K early Late gas - why Paeads diff Urinary ph
Aspirin (salicylates) directly stimulate the respiratory centre causing an initial respiratory alkalosis.
The excretion of bicarbonate, potassium and water is increased which results in hypokalaemia (not hyperkalaemia), dehydration and eventually a metabolic acidosis.
The metabolic acidosis occurs later and is due to uncoupling of oxidative phosphorylation, increased fat metabolism and inhibition of the tricarboxylic acid cycle.
The metabolic acidosis tends to occur more rapidly and more commonly in children under the age of 12.
The urinary pH in aspirin overdosage is initially alkaline and then becomes acidic.
Aspirin potentiates - + why
Warfarin and sulphonamides are highly bound to plasma proteins and aspirin displaces them which increases their unbound proportion and potentiates their effect.
Asprin can cause hypoglycaemia by potentiating the effect of chlorpropamide.
Diazepam and the tetracyclines are unaffected by aspirin.
Adrenaline formulated as
Epinephrine is formulated as 1 ml of 1 in 1000 solution (1 mg) or 10 ml of 1 in 10,000 solution (1 mg).
1 in 1000 = 1g in 1000 ml of solution (1 g = 1000 mg).
Local anaesthetic agents and glucose containing solutions are expressed as a percentage.
A 1% solution is 1 g per 100 ml solution or 1000 mg per 100 ml solution.
10 ml of a 1% solution contains 100 mg of solute.
C/I to streptokinase
Pregnancy Bleeding (gut, menstrual) Recent stroke or surgery Uncontrolled severe hypertension GI malignancy, and Prolonged CPR. Prolife background diabetic retinopathy
LMWH
MOA
Bind to antithrombin = complex -> inactivates Xa
More readily v UFH
- shorter chain less likely bind Antithrombin & thrombin
Fewer chains pentasachh bind site vs UFH 15 vs 33%
Use >4 days UFH > risk HITTS
> bind w/ PF4
Excreted in urine & part hepatic metab
Monitoring in
Phentolamine
What is it
How work, where act
Uses
Presented+ Stored
Dosing
onset
duration
reflex
Non spec alpha antag
direct SM relax
A1 + A2 rec
Use
HTN crisis
clonidine w/drawl
hypotensive anaes
5mg/ml sol
Store 4’C
0.5-5mg bolus / infusion
Onset 2min
duration bolus 10-15 min
Drop in bp ~~ reflex tachy
Amiodarone
What is it
Class
Metab’ism
prot binding
Ite
Inhib by
S/E
Potentiate
benzofuran derivative
Class III antiarrhythmic
prolongs AP & refractory - block K slows phase 3, may prolong QT
Used for VT SVT WPW
Highly protein bound
bioavailability of amiodarone variable
22% to 95%.
Prot bind - 99% - long t 1/2
Amiodarone is extensively metabolised in the liver, and can affect the metabolism of numerous other drugs.
The major metabolite of amiodarone is desethylamiodarone (DEA), which also has antiarrhythmic properties.
grapefruit juice, elevated amiodarone.
37.3% i lt use = accumulation of iodine. Thyroid disorder
Corneal microdeposits reversible
Pneumonitis
hepatitis
Neurological - tremor, ataxia, periph neurop, sleep
Amiodarone inhibits the metabolism of warfarin and so potentiates the anticoagulant effect.
1st line pharm CV - new onset AF
flecanidei if no struct hd
Toxicity related to dose
GTN
Metab
Bioavail
VD
High 1st past metab
- 90% of a dose of GTN is metabolised in the liver by glutathione organic nitrate reductase.
There is also an insignificant amount of metabolism in the intestinal mucosa.
Bioavailability is 38% after sublingual and 1% for oral administration.
GTN is well absorbed by the gastrointestinal tract and is not known to cause gastric irritation.
The volume of distribution GTN is relatively high at 2.1 to 4.5 L/kg.
Sodium nitroprusside
organic nitrate that produces nitric oxide PROdrug
NO, 5 CN- ions and methaemoglobin.
↑cyclic guanosine monophosphate (cGMP), which in turn decreases intracellular calcium levels causing relaxation of smooth muscle and vasodilation
Act GC - Relax SM
Venous and arterial vasodilatation
SE:
Cyanide toxicity:
5 cyanide moieties for every nitric oxide moiety, so cyanide toxicity and a metabolic acidosis
Tachyphylaxis & mix ven Po2 elevated
coronary steal of blood
Atten HPV - Drop PaO2
Platelet aggregation - >16mg infusion
Decreased renin release - overshoot when d/c
It is presented as a reddish-brown powder and requires reconstitution with dextrose to a straw-coloured solution. Exposure to sunlight causes a dark brown or blue discolouration due to the liberation of cyanide ions that are responsible for its toxic effects.
Tachyphylaxis can occur but the mechanism is unclear.
Enoximone
MOA
use
se
Enoximone is a competitive and selective inhibitor of type III isoenzyme of phopshpodiesterase.
Consequenrtly, it casues increased intracellular cAMP - with vasodilatation and inotropic effects.
It is used in cardiac failure.
Side effects include arrhthymias, deranged LFTs and thrombocytopenia.
Salmeterol - LABA
15x >potent @ b2
4x< potent @b1
Salmeterol is a long acting beta-2 receptor agonist, which has a structure similar to salbutamol.
It has a long onset time and so is unsuitable for treating acute asthma.
It is fifteen times more potent than salbutamol at the beta-2 receptor and four times less potent at the beta-1 receptor.
equipotent to isoprenaline as a bronchodilator
Tachyphylaxis to the unwanted side effects commonly occurs, but not to bronchodilation.
Salmeterol has been shown to protect against bronchoconstriction caused by histamine, methacholine and exercise, and may have some degree of anti-inflammatory activity in addition to its bronchodilator role.
Salmeterol has a slower onset of action than other ß2 agonists but its duration of action is up to 12 hours (longer than salbutamol) so that twice daily dosing is sufficient to control the symptoms of mild asthma.
Salmeterol is rapidly absorbed from the lung and is rapidly eliminated with a plasma half life of between two to eight hours. It is extensively metabolised.
The action of salmeterol can be competitively reversed by ß2-antagonists, but when the antagonist is removed, the muscle relaxant activity returns without further dosing with salmeterol, suggesting that it may be permanently anchored near the ß2-receptor site.
Normal SV
SVR
Normal CI
CO/HR x 1000 60 – 100 ml/beat
80 x (MAP – RAP)/CO 800 – 1200 dynes · sec/cm5
Cardiac Index (CI) CO/BSA 2.5 – 4.0 l/min/m2
Verapamil
what is it
How does it work
which leads to what
C/I in what
Calcium antagonist , antiarrhythmic
Prolongs A-V nodal refractoriness
depresses amplitude, velocity of depolarisation and conduction in depressed atrial fibres.
Interrupts re-entrant pathways and slows the ventricular rate.
Depression of SAN activity paradoxically, using verapamil in the aberrant conduction associated with WPW may speed up AF and produce VF.
Not useful in VT.VF
Adenosine
AVRT AVNRT
purine nucleoside which blocks the atrioventricular node.
Bronchoconstriction and is competitively inhibited by xanthine derivatives
Vasodilatation with a reduction in blood pressure
Antiplatelet
Clopidogrel inhibits platelet aggregation through inhibition of the adenosine diphosphate (ADP) receptors on the platelets.
Aspirin has a similar function but mediated through inhibition of cyclo-oxygenase.
Calcium ch antagonists
What channel
Nifedeipine - acts
Veraparmil bio avail
Nimodipine
lip sol v nifed
use
effects on NDMR
L type channel
Nifedipine acts by reducing coronary and peripheral arterial tones, reducing peripheral resistance and may cause a reflex tachycardia.
Verapamil is well absorbed but has a high first-pass metabolism. Its oral bioavailability is only 20%.
Nimodipine is a more lipid-soluble analogue of nifedipine and is used in the treatment after subarachnoid haemorrhage to reduce cerebral vasospasm.
All calcium channel antagonists can potentiate the effects of non-depolarising muscle relaxants.
Phenylephrine
Acting
causes
lasts
Other sites?
Vs ephedrine in obs
direct acting sympathomimetic.
Alpha-adrenergic
vasoconstriction, rise in blood pressure and reflex bradycardia.
lasts for five to 10 minutes
Intramuscular or subcutaneous administration has a slower onset but effects last for up to one hour.
a better umbilical cord gas profile when used in obstetrics compared with ephedrine
The precursors of adrenaline in order are:
Phenylalanine Tyrosine DOPA Dopamine Noradrenaline Adrenaline.
Ephedrine
action
uses
Ephedrine has both direct and indirect actions on alpha- and beta-adrenergic receptors. It also inhibits monoamine oxidase (MAO) and may interact with other MAO inhibitors, precipitating a hypertensive crisis.
Ephedrine is commonly used to treat hypotension but other indications include nasal congestion, nocturnal enuresis and narcolepsy and it can be given orally or intramuscularly.
Alpha + beta
beta-blockers have intrinsic sympathomimetic activity?
beta-blockers have intrinsic sympathomimetic activity?
Labetolol
Pindolol
Not Atenolol
Esmolol
Metop
Beta-blockers that are partial agonists may have agonistic activity leading to sympathomimetic effects when the endogenous catecholamine levels are low but act as antagonists when levels are high.
Torsades treatment
Torsades de pointes is predisposed to by prolonged QT and a magnesium infusion is an appropriate therapy.
Lidocaine C/I
Cox inhibitors
Aspirin like most NSAIDs acts through inhibition of cyclo-oxygenase.
Rofecoxib is a selective COX-II inhibitor and is used specifically as it is not associated with the inhibition of COX-I responsible for the production of mucosal protection in the stomach.
Clopidogrel is an ADP receptor antagonist and responsible for inhibtion of platelet aggregation through this route.
Amiodraone and the thyroid class t1/2 Contains Inhibits Reduces Decrease sensitivity Inhibs release
Amiodarone is a class III antiarrhythmic drug that acts by prolonging the cardiac action potential and refractory period.
It has a half life of over four weeks and prolonged administration may result in numerous side effects including interference with thyroid function causing hyper- or hypothyroidism.
Amiodarone contains iodine and inhibits thyroid hormone synthesis and reduces the peripheral conversion of thyroxine (T4) to tri-iodothyronine (T3).
It also decreases the sensitivity of the pituitary to T4 and T3, and inhibits the release of thyroid stimulating hormone.
Atropine
- derivative
Act on what
What type of molecule is it
how does this affect its crossing of bbb
Elderly increased risk off
which symptoms include
Initial affect on HR odd time
d.t
Atropine and its derivative ipratropium bromide (Atrovent) are bronchodilators, due to competitive inhibition of bronchial muscarinic receptors. Atropine is a tertiary amine (that is, uncharged) and it crosses the blood brain barrier readily.
Central anticholinergic syndrome is seen, particularly in the elderly and the symptoms include
Agitation Hallucination Drowsiness Somnolence Amnesia Dysarthria and Ataxia (although the stimulatory effects are more common with atropine).
An initial bradycardia may occasionally follow atropine administration. It is most likely to occcur if administered by I.M or S.C routes. It causes a transient inhibition of presynaptic M1 receptors before the M2 in the sino atrial node are inhibited.
Atropine is a competitive muscarinic antagonist (not non-competitive), although there may be nicotinic effects at very high doses, this remains competitive antagonism.
Neostigmine is a
Effects include
followed by
Severe can cause
Effect on block -
Side effects include
HR
Lungs
Eyes
? cross BBB
Neostigmine is a quaternary ammonium anticholinesterase compound.
The nicotinic effects include initial skeletal muscle fasciculations (involuntary irregular, violent muscle contractions) followed by the inability to repolarize cell membranes resulting in weakness and paralysis. Severe reactions can lead to ventilatory failure and death secondary to a cholinergic crisis.
It has no effect on phase I block caused by suxamethonium but it does transiently antagonise phase II block.
Bradycardia is the predominant effect on heart rate leading to a decrease in cardiac output.
It causes bronchospasm and constriction of the pupillary sphincter muscle leading to miosis (not mydriasis).
Neostigmine does not cross the blood brain barrier due to the quaternary ammonium group rendering it lipid insoluble.
Aspirin poisoning
Hyperventilation Nausea and vomiting Hypoglycaemia (particularly in children), hyperglycaemia has also been reported Acute renal failure (rare) Rhabdomyolysis GI perforation Hypotension Tinnitus and Hearing loss.
VW class 1
Class 1 drugs (membrane stabilisers) inhibit the rapid influx of sodium ions responsible for phase 0 of the action potential, and reduce the rate of phase 4 depolarisation in pacemaker cells. They are further divided into three sub-groups: 1a, 1b and 1c.
VW class 2
Class 2 drugs (beta adrenoreceptor antagonists) antagonise the effects of increased sympathetic tone on the heart by depressing (reducing the slope of) phase 4 depolarisation, decreasing the maximum rate of depolarisation (phase 0), and prolonging the duration of the action potential.
VW Class 3
Class 3 drugs prolong the duration of the action potential and the relative refractory period
VW class 4
Class 4 drugs (calcium channel antagonists) modify the plateau phase in non-pacemaker cells and inhibit the rapid depolarisation (phase 0) of pacemaker cells.
QT prolongation
a/w
Drugs
QT prolongation is seen with a QT interval above 0.45 ms on the ECG, and may lead to torsades de pointes.
It is associated with:
Hypokalaemia
Hypocalcaemia
Hypothermia, and
Hypomagnesaemia (although hypermagnesaemia can also prolong QRS complex and by default QT interval)
It is also seen with drug therapies such as:
Tricyclic antidepressants Major tranquilisers Amiodarone Antihistamines Erythromycin, and Ciprofloxacin.
It is not associated with Digoxin, Gentamicin, or Atropine.
Norad terminated by
80% active re-uptake by postganglionic nerve terminals for reuse.
The remaining 20% is metabolised by catechol-O methyltransferase (COMT) and monoamine oxidase (MAO).
The initial enzymatic action is deamination (MAO) and methylation (COMT) rather than decarboxylation.
Clonidine
acts where
x3
Where are these located
saliva
sedation?
Agonist - central acting a2-
Agonist for imidazoline (I1) receptors
Dopamine antagonist.
Locus ceruleus BS
noradrenergic outpuT
control of blood pressure.
Sympathetic stimulation reduces salivary flow.
Clonidine and the superselective alpha-2 adrenoreceptor agonist (dexmedetomidine) produce sedation, have nociceptive actions and can reduce the MAC of the volatile anaesthetic agents.
Clonidine is known to improve the efficacy of the non-steroidal anti-inflammatory drugs and has anti-nociceptive activity at a spinal level.
Clonidine acts through a secondary neurone system which reduces the effects of dopamine receptor stimulation.
Enoximone
Mechanism
Effects
Metabol
S.E
Enoximone is a phosphodiesterase inhibitor and acts through selective and competitive inhibition of the type III isoenzyme.
It is a vasodilator and produces increased cardiac output. It is used in the treatment of severe cardiac failure and typically these patients are hypotensive.
It is administered IV through infusion with an onset of action between 2 - 5 minutes.
It is hepatically metabolised.
Side effects include
Arrhythmias
Deranged liver function tests
Thrombocytopenia.
Prazosin is a
Causes
t1/2
PD -
selective alpha1 adrenergic blocker.
It produces a fall in blood pressure that is generally unaccompanied by any significant rise in heart rate or fall in cardiac output.
Its half life is approximately three hours.
It is extensively plasma bound and excreted primarily through bile and faeces.
Class 1 antiarrhythmic
How do they work
What is the affect
How are they subclassified
Class 1 antiarrhythmic agents block phase 0 of the cardiac action potential by reversibly blocking the Na+ channel; so called “membrane stabilisers”.
They all inhibit the influx of sodium via voltage-gated channels and slow the maximum rate of phase 0 depolarisation, are negatively inotropic and slow conduction velocity.
The sub-classes of the type I antiarrhythmic agents having different effects on the refractory period and length of action potential:
Class Ia (quinidine, procainamide and disopyramide) - Increase the refractory period.
Class Ib (lidocaine, phenytoin and bretylium) - Shorten the action potential and reduce the refractory period.
Class Ic (flecainide and propafenone) - Have minimal effect on action potential duration and the refractory period.
Dopamine acts where and at what doses
Can it cross bbb
does it make you feel nauseated
opamine acts predominately at
The dopamine receptors at low dose (1-5 mcg/kg/min)
Beta adrenoceptors at intermediate doses (5-10 mcg/kg/min) and
Alpha receptors at high doses (10-15 mcg/kg/min).
Its use does not affect the progression to renal failure, although urinary output is often increased by its use.
It has marked emetogenic effects (not antiemetic) by the action at the chemoreceptor trigger zone, which is outside the blood brain barrier.
However, L-dopa does cross the blood brain barrier and is therefore used in the treatment of Parkinson’s disease.
Disopyramide
What class of antiaryhtmic
How does it work
what phase do they effect
Which causes
Also affect where
Cause what type of block
Absorption
Half life
Excretion
Inotropy
Side effects
Disopyramide is a group Ia antidysrhythmic drug (together with quinidine and procainamide) that has membrane stabilising properties.
It acts by blocking (open) voltage-dependent sodium channels.
The dominant electrophysiological properties of group Ia drugs are related to their ability to block the rapid influx of sodium ions during phase 0 depolarisation of the cardiac action potential. This effect causes a decreased level of membrane responsiveness and slowed conduction of cardiac impulses.
These drugs also decrease the rate of spontaneous phase 4 deploarisation, resulting in reduced automaticity.
Group Ia drugs also induce a bi-directional block and thus interrupt re-entry.
Approximately 90% of an oral dose is absorbed and the elimination half life is 8 - 12 hours. About 50% is excreted unchanged by the kidney, so a prolonged elimination half life is seen in the presence of renal dysfunction.
Disopyramide has a negative inotropic action and may cause hypotension and aggravate heart failure.
It also has marked anticholinergic side effects that include a dry mouth, blurred vision and occasionally urinary retention (not dry cough).
Classify where bp meds act
Centrally acting
Clonidine
Methyldopa
Reserpine
Heart
Beta blockers
Vasculatire Alpha ACei CCV AGII antag Nitrate SNO Diazoxied hydralazine
Acting kidney
Diuretics
Direct renin inhib
Hypotensice anaes
Delib induced - prevent blood loss
hale enderby
Bleeding - restric vision
Middle ear
ENT
Neuro
Head up
Hypotension induced - increasing concetration
opiates
alfent / remi
IV agent - short act
esmolol -b
lavetolol a b
Nitrate - gtn & SNP
defined by starting bp
~80
Elderly - insufficiency
Insufficiency
Mnemonic for describing drugs CUP A DORSET DAME
Chemical
Uses
Presenation
Actionse
Dose Onset Route Side fx Everything else Toxic Fx
Distrub
Absorpti
Metab
Elim
Beta block
Uses Angina HTN CCF Arryhtma Hyperthryodi glucome anxiety migrane prop second prevent - Mi
Beta - hyerptensice reponse laryngoscpy
hypotensice aneaes
Htn/ arryhtmia
Antag @ beta adrenrigc
Non select B1 B2 tilolo sotlaol
Selctive - b 1
Atenolol
meotp
some embrane stab - sotalol
Neg inotropy & chronotrp - red work & bp
PO
Some IV - atenolol alvetol esmolol
S e - brady
worse ccf
worsen WORSEN pVD
Cold extrem
Bspams - asthmatic
Tireness
nightmare sleep dist
Diambete - reduce glyocnelolsys & insluin relase - blut hypogly response
not use w/ Calcium chan antag -> neg ino - verap dilt - prof hypoenti brady conduction
Hypertensice emrgency
HDU
Shrt acting
GTN
SNP Labetolol hyrdalzine
SNP
What is it
What can it be used
Inorganic
Htn emergency - hypertnsion dissect aneurysm & hypotensive anestheise
Red brown powder - brown glass ampule - 5% dex
Prod NO = GC & Inc CGMP = relax VSM
Action cvs
Vaso venidilat - = red bp
Red LVedp & o2 demand
Compesn tachy - contractily unaffcet
resp = HPV imparied
Fall PaO2
Reuces Gi motility
Dose 0.1-0.8 ug/kg.m
higher - risk cyanide tox
Onset rapid - seconds 0 iv
Problems
Untable - soln protect light
opaque syringes & giving set
Comnpens tachy - ischame in susecpt
Rebound htn on stop
Rise ICP
worse v/q matching - cns & resp affect
Cyanide posong - incrase high dose infusin
SNP metab - cyanide ion
normall meatb liver - overwmelm can acum - tox
small Vd .2l/kg
short t/12
elim 1 ug kg min
Cyanide toxicity
Non sepc - dizzi, headache confuson
tachynpeoic/ apenoc
ABG - decrease av diff - met acidos - reaise lact
ABC
Chelating
dicoblat edate - combine cyanbide - non harm inert comp
sodium nitrite - hb to met hb - ctyanide -> cyanethm
Sodium thio
cyanide -> thiocynate water sol
Diuretic
Increase diuereis - incrase rate urine production kidney
Firstly Osmotic - mannitol urea glucose - PCT - freely filt, non reabs osmotic
Carbonic anhydrazse - aceto
Inhib car an - lumial membrane - prox tube - red bicar - weak duit
Loop
furse bumet
na k 2 c; - thick asc loh
THaizde bendo na cl co tport early dct
K spare diuretic
Distal conv & collect tube - spirnolacte - aldo antag
Amiloride - inhb na k pump red Na entry
Other
canthins - caffeine & aminiohl - red sodim eccr
dopa - increase rbf & na reab
Water ehtanol - hib vao secr
demo cylcin - block bas on dct & cd
Diuretic use
Hypetrrson
thiaxide- elder
Acut & chornic mx ccf
Fruse APO - rrapid onset - venodilat
Acute & CRF - fluid over
bridge to dial
Mannitol - reduce IVP
Spirnolactone - conns syndrone
ascite liver dis
Acetazol - glauc Altit sick Manage met alk Thiazide - form calcium renal calculi
Thiazide problems
commonly used Hypo K N Uricaemia Mag Cl - alkoslis
Hyper gly & chol
used caution diatb gout
Exacr - hep rean impar impotence
Rashe/ tycpto
lt use - homocsty - atheroscleror risk
Pre op diuretics
Euvolaemic / dehydrate
Urea & electrolyte
Why taking - optimised
Vaughan willims classification
1 - Na
2 Beta block
3 Block K
4 Calcium antag
Class 1
non nodal - charact fast depol
act like La
affect phase 4 - reduce rate sponmt depol, spont autmoac
Ia - prolong refractor muscle - quinide
Ib - hsorten refractor period - lido pheny
Ixc - no effect refractor - flecanidie
II
Beta blcok block catechol affect b1
Og2 - shortened by adren & norad - increase duration & clow HR
Reduce force
III
Durg K
Prolong repolirisation & prolong AP & increase refractory - amio bretylilium sotalol
IV
Calcium antagonist verapamil Diltaiem
Block L type calciium - slow calcium influx, automaticity rate conduction
Limitations VW
Severe lim
New drugs - dont fit class
Exclude potenaite sites action
for ex dig & adeno -
Sotalol I II III - not clear anti arryh
Multiple mech actions
Drugs act diff healt/ disease
Classify according to uses
SVT - adeno
VT - Ligno
Both - Amio
Supra vent
Tachy arryhtmia
Brady - arr
SVT / fast afib
SVT - adenosin / verapamil
Fast Af - Dig amio
Brady - atrop / glyco
disopyre
procain
propafenone
verapamil
Adenosine
Natural purine necloside
Colourless sln vial room temp
3 6 12mg 1-2 min iveterval untl effect
Term SVT, ID underlyng rhythm - transient slow hr
A1 adnno recepot SA / AV node
Open K channel - snes o ach bind mus rec
Opening = hyperpol myocardium
voltage sens ca open less freq - reduce rate fire SA & slow condction av node
Flush chest dyupnoea bspasm
ci ashmatic - cik sinus 2 3rd hblock
half life 8 -19 deamin - rbc short action
Verapamil
Calcium channel antag
40-240mg tbas
2.5mg ml iv
up to 480mg daily
used svt - afib/ flutter
prophylaxis angina
also used htn / angina
Prvent ca influx voltage L type calcium sa av node
Red ca influc - plateau phase cardic Ap
Reduce automaticy reduce rtate conduction
cor art dilatation
S/e dizzy flush nause 2nd 3rd block
IV - lv fail wpw - vt vf
brady combi w/ other av slower
Increase serum dig
Potent grapefruit
Complet abs high 1st past po 25%
90% prote bound - metab liver / excret kid elim 3-7hrs liver eznym saturated increase dose intervale
Afib
Uncoord atrial activity vent rate dep av node tmisson
Onsert <48hrs - cardiover dccv, flecanide
>48 - dig, bbloq, amido, verapa
Digoxin
Cardiac glycoside - extract digitalis lanata - flxglove
tablet / iv
Load dose 1-1.5mg in diver over 24
daily dose 1205-500ug -
Therap rang 1-2ug/L
Uses rx . prevent afib/flutter / heart failure
Direct & Indirect
Direct - Na K ATPase - receptor in cell membrane
inc Na & dec K
Na 00 exchange va - increase intra cell ca - pos intortop
Dec intracell K - reduce automactiy slow av condctuin
indrei - enhance rel ach - cardiac musc recpt - prolong refactory av node his
red rate contract - better vor flow - vent fill increase co
Siode - narrow range - easily
Card arrhy conducton deffect
junctio brady, bigeminy , block
prec hypok, hper Ca alt phj
anorex n// v h dirarr
headahce rosines conf vis dist
gyno rashses
Level increase amio erhyty captol
decrease pheny metocpl antacide
unpred abso po bioab >70%
filt glomerules -
secrete unchagne by filtration & active tublar section
elim red renal impo
Symp dig tox
> 2/5
nv diarrho malaise conf
impare colour vision -eary
Signs - cardiac arryht
ecg prolong pr heart block twi st depression - reverse tick
may occur not indciator
How Rx dig tox
ABC approach to rx - admin
electrolyte - correct hyperkalaemia - feature rx
hypo - worsen also rx
atropine / pacing
ven arryhtma - lid pheny
> 20ug - dig spec antibody frag
igG frag bind dig > affin than receptor - retrm action
remove kidney
anayphlyxis on rexop
Amio
Benzofuran & class III
table soln inf (5% dex)
Admin load dose 5mg.kg 1 hour
15mg/kg over 24
starting oral dose is 200mg tds
reduce 200mg od
SVT VT WPW
block K channel - slow rate repol - increase fduration ap & refractory
What is an inotrope
Alters force of contract of cardiac muslc withgout changing pre or afterload
Psoistive - io ncrease contractilit
Positive inotrops
1 - increase intracellular calcium
Ca Ion, drugs increase cardiac cAMP - adreno agonist
PDEi & glucagon
Drgs affect Na K ATPase - dig
II
Increase sens of actomyosin to calcium - eg levosimndan
III
Metabolic or endocrine - eg triiodothyonine T3
Commonly used - Class I
adreno agonist
Adnrealine, noradpine, dopa
Dopexamine dobutaime isoprenlie salbutamol
How does dig act as an Inotrope
Na/K sarcolemmal membrane - increase intra cell Na
Na pump by Na Ca exchcnaghe pump - high na grad
Increase Na decrease grad - less Na pump cell in & Less Ca pumped out in return
_. increase intracell Ca
Any positive inotropic somwehat offset by activation PSns
Calcium - when given & why important contractiliy
Ion calcium low
Antag hyperCa & mypermg
Ion ca - myosite contract
enters voltage gate Ca in sarcolemma in reponse to depolirsation - increase sarc ca - more Ca rel from retciulu -
Resting myocytes tropomysin overlay myosin binding on acting - prevent cross linkage
If ca avaul bind trop C conform change in tripmysin complex - allow myson acces to bing on acting - contract
Ca gluc 10% - antag hyperK - less elemnatin ca
9mg in 10ml
27mg in 10ml 10% ca cl
Adrenlaine use in practice
Cardiac arrest 1mg - 2-3 min
10ug .kg paed arrest
Anapyhlacis 100ug iv 0.3-0.5mg im
Infusion - inotrop crti care
.01-.3ug kg min
Neb adrean - severe asthma, airway oedema
Added to La - 1 200000
serves - prolong action, decreases bleeding, marker iv injection
reduces systemic uptake - increase lido 3->7
not bupiv
Mechansim action adreanline
Nat catechol
Secrete by adrenal medulla - sympathetic stim
A1 B1 B2
Adrenocept GPCR - increase Ca influx A - Gq = stim phospholipase C ITP, Dag
B - Gs - stim AC -> CAMP from atp
CAMP - activ pro kin A
Low dose infsuions - stim B2 = sm releax bronch, uterus, gi, glycogenoyslis
Mid rang - B1 - inotropy & chrontropy
0.03-0.2 ug kg min stim b1
Inotro, chrono, contract, automaticy SA AV & ventricular cell
Renin release & loplysis in adipost
High dose 0.2-0.3ug kg min - stim a - Vaso & veno con
SVR - Pre & Afterload
Side effects adrenaline
CV
Myocard O2 deamnd - ischamei suscpetible
Tachy,, vent arryhtmia - prob / halothane
down reg b uf longer 24h tachphylaxis
Gi - high dose splanch vcon, - ishamceia & bact tlocatiob
Metab - glycgonolysis, gluconeo & lipolsysi
hperlgy all patient req slide scale - lactic acidosos
Adren v norad
Both nat occur catechol secr adren medulla response to sympathetic stim
Secret great amount by adrenaline grand
norad functions as NT at synapses in sns
Norad - vasopresson in crit care / maint map in vasoldiated states
Septic shock
Adren - arerests anyphlyaxis, nebulised upper airway obstruction, inotrop la addtivie
Both clear colourless solution in glass vial
Adren 1 in 1000 in 1 10000
minmi jet r100ml of 1 10000
norad 4mg dil 1/ w50ml conc 80ugml
both atct adrenorecptor
adren low dose - stim b, high a
Norad a with some b1
Dose range norad 0.01-4ug kg min
adnrealine different doses depending on circumstance
Both quick onset & offset - plasma t 1/2 2 min
Norad - central line -
Aden iv im sv neb
infsuion -cv
CV effect - increase o2 demande
norad - reflex brady
systolic bnp increase
adren contin 24 hours down reg
Aren bdial - norad no effect aiwray calibrew
pulmonary vconstic
Both - splanchic vcon
Renal perfusion oimproved with increase bp
Adren - great metab effects - increase BMR, glyocog, gluconeo, lipysis - hyperglyace lactic acidosos
Both similar metab - COMT tfrease in liver & MAO in adregnic neurones - to inacitve meab
What Rx for AVRT & AVNRT
What can be given if that is contraindicated
Regular narrow complex tachycardias include:
Sinus tachycardia
AV nodal re-entry tachycardias (AVNRT)
AV re-entry tachycardia (ANRT)
Atrial flutter with regular AV conduction.
Vagal manoeuvres and adenosine will terminate most AVNRT and AVRT arrhythmias.
Verapamil 2.5-5 mg intravenously can be considered if adenosine is contraindicated.
Beta-blockers and digoxin are indicated in narrow complex irregular tachycardias.
Amiodarone is not a first-line anti-arrhythmic for AVNRT or AVRT.
Metaraminol
Main action
how achieve this
another effect
Metaraminol acts through peripheral vasoconstriction by acting as a pure alpha-1 adrenergic receptor agonist,).
Its effect is thought to be associated with the inhibition of adenyl cyclase which leads to an inhibition of the production of cAMP. Another effect of metaraminol is that it releases norepinephrine from its storage sites indirectly.
MAOIs + other drugs
How do they work - how long enzyme resynth
Are they following safe
Pethidine Morhpine Fentanyl Metaram Ephdrine Cocaine ketamine Doxapram Naloxone
Monoamine oxidase inhibitors (MAOIs) irreversibly antagonise the enzyme monoamine oxidase (MAO), which takes three weeks to resynthesise.
They can interact with numerous drugs administered during the course of an anaesthetic, especially opioid analgesics (pethidine). It is therefore traditional to stop taking MAOIs at least three weeks preoperatively, but this interval may be insufficient for the levels of MAO to return to normal, and may expose the patient to the risk of worsening depression.
Sympathomimetic drugs acting indirectly via the release of catecholamines may produce an exaggerated hypertensive response, for example, metaraminol and ephedrine.
Catecholamines and drugs increasing catecholamine concentrations should be avoided, for example, cocaine, ketamine and pancuronium.
Morphine may be the opioid of choice, although fentanyl has been safely used despite its being related to pethidine.
Naloxone is safe to be used but doxapram is considered unsafe.
nifedipine
rapid onset - great changes to bp
watershed infarcts from use
Aminophylline
Non selective PDEI - inhib all 5
Prevent tubular Na reabs - diuretic
metab cyp450
phenytoin induces - increased elim
Reduces seizure threshold
blocks adenosine - inhibiting mast cell degran
SNP and cyanide
Toxicity >8ug/ml
commoner hypothermic
SOdIUM THIOSULFATE INCREASE CYANIDe to thiocyanate - most excrete urine - decrease cyanide ions
Allow accum thocyanate harmful
can interfere w/ thyroid fxn
Cyanide ion tox = inactivat cyto oxidase
impair o2 util = increase mix venous o2 sat
Adrenaline
paed dose
at diff levels affect what
Paed dose
.1mk/kg 1:10000
Low dose - b effect predom
decrease tpr, increase insulin
high dose - a predom - vasocon - decrease insulin
metab excrete VMA
When use halo dose 100ug/30min avoid arryth
Isporenaline
what is it
Synthetic non spec B adren agonist
B1 = gs ac camop - pka increase ca
b1= post chrono + inotropic + dromotropic
promotes lipolsyis
increased ADH
Increase amylase secretion
Various PDE effects and where
heart
lung
PDE 3 - heart lung liver
enox + milrinone
ccf - inodiatlor
PDE5 - lung plt vsm
erect dysfxn + PHTN
Protamine
lmwh
fully reverse heparing at 1mg / 100iu heparin
doesnt fully reverse LMWH - adocated bleeding
LMWH - increased affinity xa - decreasef vwf
monit xa not rec - doesnt predict risk bleed
aptt unaltered
Enzyme catecholamine synth
Tyrosine hydroxylase
tyrosine -> DOPA
Enz metabolism catechol
comt
dopa to norad
dopa a hydroxy
dipyridmaole
inhib plt adhesion - inhib adenosin uptake
clopi v aspirin gib
action
less gib
acts irrev prevent adp bind recetpor
warfain
ihib oxid vit k
streptokinase
grp c b haemoltyic strepp
heparin
can cause tcytpoaeni win 48hrs
catalyses formation thrombin antithrombin complex
Phentolamine
se
Casues nasal congestion - airway instumentaon signifcant bleeding
topical vcon - important
resp secretions - iv hyoscine to rx
Propranolol
inhibits what
acts - on what
Inhibit hepatic gluc = hypogly
compet antag - b1 +b2
brady + bronchocon
A2
Clonidine
Analgesia + sedation + hypotens (sys >dias)
yohimbine
A1
Prazosin - highly selective
hypotens + bladder sphincter relax
Phenoxybenzamine
long acting NON SELECTIVE but more a1 than a2
Metaraminol
synthetic amine
a1 agonist
with some beta activity
What Rx SVT
Digoxin
verapamil
adenosine
- site action is av node
What VT
Disopyramide - act atria vent + accesss path
Na channel
Lignocaine - ventricles only
both use VT
Nitrate
Induced hypotension - pred to venodilation
tolerance - depletion VSM sulphylhydryl groups
ISMN 100% bioavail
lack first pass metab
Nitite rel NO metab oxid iron in oxyhb
isosorb dintire - hepatic metab confer effect
is2mon is5