CVS Drugs 31 to 40
List the classes of drugs used for the management of AF in the emergency department.
Ca-channel blockers Cardiac glycosides Class 1c antiarrhythmics Class 3 antiarrythmics
Pass: 3 of 5
Describe the pharmacodynamics of sotalol:
Non-selective beta blocker, Class II
Prolongs plateau phase Class III
Pass: Need class II + III
List the main side effects.
Pro-arrthymic- Esp prolongation of QT and
Asthma, AV blockade
Pass: Prolonged QT + 1 other
What drug interactions with Sotalol prolong the QT?
Prompt: What other interactions can occur with sotalol?
Drugs which prolong QT– phenothiazines, Macrolides, eg erythromycin, quinolones
antidepressants,- Increased risk of Torsades
Drugs which cause hypokalaemia hypomagnesaemia increase risk of Torsades
Myocardial depressant drugs- increased LVF
Calcium channel blockers, class 1a antiarrythmics, may increase refractory time and contraction
Pass: 2 examples
Describe the mechanisms by which drugs interact with Warfarin.
Prompts: Please describe pharmacokinetic interactions. Please describe pharmacodynamic interactions.
PK – Enz inhibition (majority), Enz induction,
altered, plasma protein binding, altered abs
PD — Synergism (impaired haemostasis)
Competitive antagonism (clotting factor
Pass: Must get one example of PK and PD
Give some examples of drugs that increase the INR.
Increased INR: aspirin, heparin, corticosteroids
metronidazole, fluconazole, trimethoprim- sulfamethoxazole, third generation
cephalosporins, macrolides, amiodarone, SSRIs, tramadol
Give some examples of drugs that decrease the INR.
Decreased INR: Vit K, diuretics, barbiturates, phenytoin, carbamazepine, rifampicin, diclox, azathioprim
Pass: Must give at least 1 example of each
What are the indications for use of Adenosine?
Conversion of paroxysmal SVT to sinus rhythm
How does it work?
Activation of inward rectifier K+ currents and inhibition of calcium currents. Leads to marked hyperpolarisation and suppression of calcium-dependent APs. Effect is direct inhibition of AV nodal conduction and increase in AV node RP.
This interrupts re-entry pathway thru AV node.
Notes: AV node conduction interruption
How do the specific pharmacokinetic properties of adenosine influence the method of administration?
Very rapid metabolism by adenosine deaminase in red cells and vessels walls = very short elimination t1/2 (<10s) and duration of action
(-30s). Must be given by rapid intravenous bolusing. If initial dose ineffective then subsequent dose should be increased (no accumulation occurs).
Describe the mechanism of action of tissue plasminogen activator (tPA)?
Activates plasminogen to form plasmin, resulting in fibrin digestion. Preferentially activates plasminogen bound to fibrin by several hundred fold therefore is considered clot specific. Short half life therefore heparin is essential adjunct.
What are the clinical uses of tPA?
Prompt: Are there are any other time-critical indications?
AMI, unstable PE, acute ischaemic stroke, severe
DVT, intra arterial peripheral limbs
First 3 to pass
What are the complications of tPA?
Haemorrhage. Physiological hemostatic thrombi at site of vascular injury eg GIH, or systemic lytic state resulting from formation of plasmin, producing fibrinogenolysis and destruction of other coagulation factors esp V and VIII.
Pass: Must give more than one site
What is the mechanism of action of atropine?
A reversible muscarinic antagonist
Binds to the muscarinic receptor, preventing the release of inositol trisphosphate (IP3) and the inhibition of adenyl cyclase which are caused by the muscarinic agonists.
Bold to pass
Describe the organ effects of atropine.
CNS: Decreased tremor in Parkinson’s Disease, delirium
EYE: Mydriasis and cycloplegia
LUNG: Bronchodilation and decreased secretions
GIT: Increased salivary secretion, decreased gastric secretion acid,
pepsin and mucin, decreased gastric emptying, increased Gut
GUT: relaxes ureteric and bladder wall smooth muscle and slows voiding; decreased sweating.
3/6 organ effects to pass
Describe the mechanism of action of heparin?
Binds to endothelial cell surfaces and plasma proteins and its activity depends on antithrombin
Heparin binds to antithrombin, causes a conformational change in the inhibitor, exposing its active site for more rapid interaction with proteases. Heparin acts as a co factor for the antithrombin-proteases reaction Antithrombin inhibits proteases espec thrombin 2a, 9a, 10a by forming stable complexes with them and the presence of heparin accelerates this reaction 1000x
The binding of AT Ill and unfractionated heparin t degradation of both factor Xa and thrombin
Pass: Binds to AT III
How is heparin reversed?
Prompt: is there a specific antidote?
Stop the drug
Administer antagonist protamine (100 units heparin-1mg protamine) which binds heparin to form a complex devoid of anticoag activity
Excess protamine anticoag effect
What are the potential adverse effects of heparin?
Prompt: Are you aware of any less common but serious idiosyncratic effects?
Bleeding (elderly women, renal failure more prone)
TCP (1-4%), rare pregnancy, lower rates in paediatrics. Mortality relates to thrombosis Allergy
‘1` hair loss
Accelerates the clearing of post prandial lipaemia by causing release of lipoprotein lipase from tissues
Long term: osteoporosis, spontaneous fracture, mineralocorticoid deficiency
What are the principle effects of adenosine on cardiac conduction?
1 Inhibits AV nodal conduction (increased PR interval)
2 Increases AV nodal refractory period
3 These effects are a result of enhanced K conduction and inhibition of cAMP-induced calcium influx resulting in hyperpolarisation and suppression of calcium-dependent action potentials
Pass: 1 and 2
How do the unusual pharmacokinetics of adenosine influence its use in therapeutics?
- Rapidly metabolised in the blood with a elimination half-life of less than 10 seconds
- Only suitable for IV use
- Must be given by rapid bolusing to achieve therapeutic effects_
- Repeat doses must be escalated
- Will not be effective for supraventricular tachyarrhymthias caused by adenosine-blockers such as theophylline
Must know 1,2,3 to pass
What is the mechanism of action of captopril?
- Angiotensin converting enzyme inhibitor
- Stops conversion of Angiotensin Ito Angiotensin II
- Angiotensin II is potent vasoconstrictor Angiotensin II also increases aldosterone secretion
- Increased salt and water rentention
- ACE (kininase II) also metabolises Bradykinin into its inactive form
- Increase in bradykinin causes vasodilation, decreased PVR and therefore decreased BP
What are the potential adverse effects of captopril?
- Profound hypotension
- ARF esp with renal artery stenosis
- Hyper K+
- Cough, Wheeze
- Fetal abnormalities
- Renal failure
- Increased malformations
- Increased fetal death
Pass: must get 4
Describe the effects of an intravenous adrenaline infusion on the CARDIOVASCULAR system.
Prompt: How does the effect of adrenaline on the cardiovascular system vary with the plasma adrenaline concentration?
1. Predictable physiological effects from a combination of alpha and beta stimulation, i.e.:
— Increased cardiac output (chronotropy + inotropy)
— (low dose: beta > alpha): vasodilation with widened pulse pressure
— (higher doses: alpha > beta): vasoconstriction with narrowing of pulse pressure
Must know all to pass (except difference between high dose and low dose rates)
What are the potential side-effects or complications of an adrenaline infusion?
1. GENERAL- Anxiety, tremor, nausea, vomiting, pallor
2. HEART & CIRCULATION- Palpitations and/or arrhythmias, myocardial ischaemia, hypertension
3. METABOLIC (beta effect) – hyperglycaemia, metabolic (lactic) acidosis, hypokalaemia
Must get 2 & 3 to pass
How does the effect of adrenaline differ from noradrenaline?
Prompt: What are the differences in receptor effects of these two agents?
1. Noradrenaline peripheral alpha effect-vasoconstriction
2. Adrenaline mixed peripheral alpha and beta as above
3. Noradrenaline lesser cardiac effect
4. Slightly different side-effect profile (metabolic effects due predominantly to beta receptor activation)
Describe the mechanisms for drug interactions with warfarin and give examples.
Prompts: Please describe a pharmacokinetic interaction with warfarin. Please describe a pharmacodynamic interaction. What drugs could increase the INR? What drugs could decrease the INR?
PK – enz inhibition (majority), Enz induction, altered
plasma protein binding, altered abs (cholestyramine p 157)
PD – bioavailability of Vit K, influencing Vit K dependant clotting factors, drugs affecting haemostasis (1 eg)
Pass: Must get bold items