8. CVS drugs

Question 1

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

Answer 1

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)

Question 2

AV nodal conduction agents in WPW

Answer 2

AV nodal conduction, such as adenosine, beta-blockers and calcium channel blockers, are also relatively contraindicated.

Question 3

Aspirin Overdose features
Stim what
Blood gas + K early
Late gas - why
Paeads diff
Urinary ph

Answer 3

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.

Question 4

Aspirin potentiates - + why

Answer 4

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.

Question 5

Adrenaline formulated as

Answer 5

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.

Question 6

C/I to streptokinase

Answer 6

Pregnancy
Bleeding (gut, menstrual)
Recent stroke or surgery
Uncontrolled severe hypertension
GI malignancy, and
Prolonged CPR.
Prolife background diabetic retinopathy

Question 7

LMWH

MOA

Answer 7

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

Question 8

Phentolamine

What is it
How work, where act

Uses

Presented+ Stored

Dosing
onset
duration

reflex

Answer 8

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

Question 9

Amiodarone

What is it
Class

Metab’ism
prot binding
Ite

Inhib by

S/E

Potentiate

Answer 9

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

Question 10

GTN

Metab
Bioavail
VD

Answer 10

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.

Question 11

Sodium nitroprusside

Answer 11

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.

Question 12

Enoximone
MOA

use
se

Answer 12

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.

Question 13

Salmeterol - LABA

15x >potent @ b2
4x< potent @b1

Answer 13

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.

Question 14

Normal SV

SVR

Normal CI

Answer 14

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

Question 15

Verapamil
what is it

How does it work
which leads to what

C/I in what

Answer 15

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

Question 16

Adenosine

Answer 16

AVRT AVNRT

purine nucleoside which blocks the atrioventricular node.

Bronchoconstriction and is competitively inhibited by xanthine derivatives

Vasodilatation with a reduction in blood pressure

Question 17

Antiplatelet

Answer 17

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.

Question 18

Calcium ch antagonists
What channel

Nifedeipine - acts

Veraparmil bio avail

Nimodipine
lip sol v nifed
use

effects on NDMR

Answer 18

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.

Question 19

Phenylephrine
Acting

causes

lasts

Other sites?

Vs ephedrine in obs

Answer 19

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

Question 20

The precursors of adrenaline in order are:

Answer 20

Phenylalanine
Tyrosine
DOPA
Dopamine
Noradrenaline
Adrenaline.

Question 21

Ephedrine
action

uses

Answer 21

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

Question 22

beta-blockers have intrinsic sympathomimetic activity?

Answer 22

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.

Question 23

Torsades treatment

Answer 23

Torsades de pointes is predisposed to by prolonged QT and a magnesium infusion is an appropriate therapy.

Lidocaine C/I

Question 24

Cox inhibitors

Answer 24

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.

Question 25

``` Amiodraone and the thyroid class t1/2 Contains Inhibits Reduces Decrease sensitivity Inhibs release ```

Answer 25

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.

Question 26

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

Answer 26

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.

Question 27

Neostigmine is a Effects include followed by Severe can cause Effect on block - Side effects include HR Lungs Eyes ? cross BBB

Answer 27

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.

Question 28

Aspirin poisoning

Answer 28

``` 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. ```

Question 29

VW class 1

Answer 29

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.

Question 30

VW class 2

Answer 30

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.

Question 31

VW Class 3

Answer 31

Class 3 drugs prolong the duration of the action potential and the relative refractory period

Question 32

VW class 4

Answer 32

Class 4 drugs (calcium channel antagonists) modify the plateau phase in non-pacemaker cells and inhibit the rapid depolarisation (phase 0) of pacemaker cells.

Question 33

QT prolongation a/w Drugs

Answer 33

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.

Question 34

Norad terminated by

Answer 34

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.

Question 35

Clonidine acts where x3 Where are these located saliva sedation?

Answer 35

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.

Question 36

Enoximone Mechanism Effects Metabol S.E

Answer 36

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.

Question 37

Prazosin is a Causes t1/2 PD -

Answer 37

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.

Question 38

Class 1 antiarrhythmic How do they work What is the affect How are they subclassified

Answer 38

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.

Question 39

Dopamine acts where and at what doses Can it cross bbb does it make you feel nauseated

Answer 39

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.

Question 40

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

Answer 40

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).

Question 41

Classify where bp meds act

Answer 41

Centrally acting Clonidine Methyldopa Reserpine Heart Beta blockers ``` Vasculatire Alpha ACei CCV AGII antag Nitrate SNO Diazoxied hydralazine ``` Acting kidney Diuretics Direct renin inhib

Question 42

Hypotensice anaes

Answer 42

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

Question 43

``` Mnemonic for describing drugs CUP A DORSET DAME ```

Answer 43

Chemical Uses Presenation Actionse ``` Dose Onset Route Side fx Everything else Toxic Fx ``` Distrub Absorpti Metab Elim

Question 44

Beta block

Answer 44

``` 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 - intrisic sympathimic act - 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

Question 45

Hypertensice emrgency

Answer 45

HDU Shrt acting GTN SNP Labetolol hyrdalzine

Question 46

SNP What is it What can it be used

Answer 46

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

Question 47

Cyanide toxicity

Answer 47

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

Question 48

Diuretic

Answer 48

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

Question 49

Diuretic use

Answer 49

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 ```

Question 50

Thiazide problems

Answer 50

``` 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

Question 51

Pre op diuretics

Answer 51

Euvolaemic / dehydrate Urea & electrolyte Why taking - optimised

Question 52

Vaughan willims classification

Answer 52

1 - Na 2 Beta block 3 Block K 4 Calcium antag

Question 53

Class 1

Answer 53

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

Question 54

II

Answer 54

Beta blcok block catechol affect b1 Og2 - shortened by adren & norad - increase duration & clow HR Reduce force

Question 55

III

Answer 55

Durg K | Prolong repolirisation & prolong AP & increase refractory - amio bretylilium sotalol

Question 56

IV

Answer 56

Calcium antagonist verapamil Diltaiem | Block L type calciium - slow calcium influx, automaticity rate conduction

Question 57

Limitations VW

Answer 57

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

Question 58

Classify according to uses

Answer 58

SVT - adeno VT - Ligno Both - Amio

Question 59

Supra vent

Answer 59

Tachy arryhtmia Brady - arr SVT / fast afib SVT - adenosin / verapamil Fast Af - Dig amio Brady - atrop / glyco disopyre procain propafenone verapamil

Question 60

Adenosine

Answer 60

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

Question 61

Verapamil

Answer 61

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

Question 62

Afib

Answer 62

Uncoord atrial activity vent rate dep av node tmisson Onsert <48hrs - cardiover dccv, flecanide >48 - dig, bbloq, amido, verapa

Question 63

Digoxin

Answer 63

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

Question 64

Symp dig tox

Answer 64

>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

Question 65

How Rx dig tox

Answer 65

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

Question 66

Amio

Answer 66

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

Question 67

What is an inotrope

Answer 67

Alters force of contract of cardiac muslc withgout changing pre or afterload Psoistive - io ncrease contractilit

Question 68

Positive inotrops

Answer 68

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

Question 69

How does dig act as an Inotrope

Answer 69

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

Question 70

Calcium - when given & why important contractiliy

Answer 70

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

Question 71

Adrenlaine use in practice

Answer 71

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

Question 72

Mechansim action adreanline

Answer 72

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

Question 73

Side effects adrenaline

Answer 73

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

Question 74

Adren v norad

Answer 74

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

Question 75

What Rx for AVRT & AVNRT What can be given if that is contraindicated

Answer 75

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.

Question 76

Metaraminol Main action how achieve this another effect

Answer 76

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.

Question 77

MAOIs + other drugs How do they work - how long enzyme resynth Are they following safe ``` Pethidine Morhpine Fentanyl Metaram Ephdrine Cocaine ketamine Doxapram Naloxone ```

Answer 77

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.

Question 78

nifedipine

Answer 78

rapid onset - great changes to bp | watershed infarcts from use

Question 79

Aminophylline

Answer 79

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

Question 80

SNP and cyanide

Answer 80

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

Question 81

Adrenaline paed dose at diff levels affect what

Answer 81

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

Question 82

Isporenaline what is it

Answer 82

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

Question 83

Various PDE effects and where heart lung

Answer 83

PDE 3 - heart lung liver enox + milrinone ccf - inodiatlor PDE5 - lung plt vsm erect dysfxn + PHTN

Question 84

Protamine lmwh

Answer 84

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

Question 85

Enzyme catecholamine synth

Answer 85

Tyrosine hydroxylase | tyrosine -> DOPA

Question 86

Enz metabolism catechol

Answer 86

comt

Question 87

dopa to norad

Answer 87

dopa a hydroxy

Question 88

dipyridmaole

Answer 88

inhib plt adhesion - inhib adenosin uptake

Question 89

clopi v aspirin gib | action

Answer 89

less gib | acts irrev prevent adp bind recetpor

Question 90

warfain

Answer 90

ihib oxid vit k

Question 91

streptokinase

Answer 91

grp c b haemoltyic strepp

Question 92

heparin

Answer 92

can cause tcytpoaeni win 48hrs | catalyses formation thrombin antithrombin complex

Question 93

Phentolamine | se

Answer 93

Casues nasal congestion - airway instumentaon signifcant bleeding topical vcon - important resp secretions - iv hyoscine to rx

Question 94

Propranolol inhibits what acts - on what

Answer 94

Inhibit hepatic gluc = hypogly compet antag - b1 +b2 brady + bronchocon

Question 95

A2

Answer 95

Clonidine Analgesia + sedation + hypotens (sys >dias) yohimbine

Question 96

A1

Answer 96

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

Question 97

What Rx SVT

Answer 97

Digoxin verapamil adenosine - site action is av node

Question 98

What VT

Answer 98

Disopyramide - act atria vent + accesss path Na channel Lignocaine - ventricles only both use VT

Question 99

Nitrate

Answer 99

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