Biochemistry of Emergency Drugs

Miss Yah Nee Lo Lecturer yahneelo@gmail.com

Friday, August 26, 2011

Learning Objectives
Know the common classes of drugs used in the A&E especially in Brunei Be able to describe the mechanism of action of important classes of emergency drugs The basic dosage and infusion guide of emergency drugs?
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Accident & Emergency situations

List down the common situations or conditions that comes into our own A&E department in the RIPAS that you can think of? Shortness of breath Anaphylactic shock Cardiovascular problem e.g. heart block, arrhythymia, etc Heart Attack

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Asthmatic/ COPD
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1. Aminophylline
Bronchodilator Compound of the bronchodilator theophylline with ethylenediamine in 2:1 ratio Ethylenediamine improves solubility Theophylline relaxes bronchial smooth muscles. MOA unclear
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Aminophylline
contradictions: hypersensitive, avoid bolus dose if patient taking Oral Theophylline Adverse Drug Effects: Nausea, Vomiting, abdominal pain, diarrhoea, headache, insomnia, dizziness... the potentially fatal: Convulsions, cardiac arrthymias, hypotension and sudden death after too rapid IV injecion

Loading dose: 250 mg (Slow I/V in 15 mins) Infusion Rate: 20-80 mils/hr
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2. Salbutamol
Short acting B2-adrenergic receptor agonist used for relief of bronchospasm racemic mixture with a 1:1 ratio of the isomer, levelbuterol and s-albuterol. The tertiary butyl group in sulbutamol makes it more selective for B2-receptors.
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3. Magnesium Sulphate
sterile solution of magnesium sulphate heptahydrate in water for injection Electrolyte, anticonvulsants Indications:
Seizures of eclampsia TDP Hypomagnesaemia Refractory VF

Use with caution in renal failure CNS depressant effects may be enhanced in presence of other CNS depressant

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Adrenaline
Sympathomimetic hormone and a neurotransmitter increases heart rate, constricts blood vessels, prepare us for ght-or-ight response of the sympathetic nervous system. Chemically it is a catecholamine, a monoamine produced only by the adrenal glands from the a.a. phenylalanine and tyrosine used best for anaphylactic shock
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Doxapram (Dopram)
Doxapram hydrochloride Central Respiratory stimulant Stimulates increase in tidal volume and RR Stimulates the chemoreceptors in the carotid arteries which in turn stimulates the respiratory centre in the brain Thought to stimulate the carotid body by inhibiting certain potassium channels
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Bradycardia & Heart Block

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1. Atropine
MOA: Anticholinergic agent that competitively blocks the muscarinic receptors Muscarinic receptors found in peripheral tissues such as the heart, intestines, bronchial muscles, iris and secretory glands. abolishes bradycardia and reduces heart block due to vagal activity Adverse reaction: Dry mouth, Dysphagia, contipation, restlessness, confusion, etc
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2. Isoprenaline
MOA: a beta-1 and beta-2 adrenergic receptor agonist.

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Antiarrythmics

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Classes of antiarrythmics
Class 1- Membrane stabilizers Class Ia- lengthen action potential, prolong repolarization, prolong PR, QRS, QT. e.g. Quinidine, procainamide,disopryamide Class 1b- shorten action potential, shorten repolarisation, shorten QT, raise brillation threshold e.g. lignocaine, mexilitine, phenytoin Class 1c- no effect on action potential or on repolarization, prolongs PR and QRS e.g. ecainide
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Class II- beta blockers e.g. propanolol

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Classes of antiarrythmics
Class III- Potassium channel blockers that prolong duration of action potential e.g. amiodarone, disopryamide Class IV- Calcium channel blockers that have important effects on upper and middle parts of the AV node. e.g. Verapamil
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1. Adenosine (Adenocor)
Purine Nucleoside comprise of a molecule of adenine attached to a ribose sugar molecule via a -N9 glycosidic bond. also acts as a neurotransmitter when administered I.V., causes transient heart block in the AV node Via A1 receptor, inhibiting adenylyl cyclase, reducing cAMP and so causing cell hyperpolarization by increasing outward potassium ion ux

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2. Lignocaine
Class 1B antiarrythmic drug also act as local anaesthetic. contain amide group in the structure MOA: block the fast voltage gated sodium (Na+) channels
inhibit sodium inux block rise of action potential inhibit signal conduction
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3. Verapamil
MOA- Calcium ion inux inhibitor L-type calcium channel blocker relaxation and prevention of coronary artery spasm- dilates the main coronary arteries and arterioles both in normal and ischemic regions.
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4. Amiodarone
Class III antiarrthymic drug Blocks sodium channels at rapid pacing frequencies noncompetitive antisymphatetic action lengthen cardiac action potential negative chronotropic effect in nodal tissues blocks myocardial potassium channels --> contributes to slowing of conduction and prolongation of refractoriness in the AV node. hypotension is the most common adverse effect seen with I.V. amiodarone

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Procainamide & Disopyramide

Both are Class 1a antiarrythmics interfere directly with the depolarization of the cardiac membrane Inhibits the fast sodium channels Increases the duration of a.p. in cardiac cells
Disopyramide Procainenamide

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Propanolol
A synthetic non selective beta-adrenergic receptor-blocking agent. arrhythmia and thyroid crisis as well as hypertension
blocks action of the sympathetic nervous system by blocking beta receptors on sympathetic nerves

highly lipophilic undergoes high rst pass metabolism by the liver only about 25% reaches systemic circulation racemic mixture of two enantiomers, R(+) and S (-)
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Metoprolol
Beta-adrenergic blocking agent use also for hypertension, heart pain similar to propanolol. blocks action of the sympathetic nervous system by blocking beta receptors on sympathetic nerves also reduces force of contraction of the heart
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Hypertensive crisis

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1.Hydralazine (Apresoline)
Direct-acting smooth muscle relaxant vasodilator primarily in arteries and arterioles. Relaxing vascular smooth muscle, reduce peripheral resistance, lower bp. MOA: increase guanosine monophosphate (GMP) decreasing action of second messenger IP3, limiting release of calcium from SR of smooth muscle.
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2. Labetalol
mixed alpha/beta adrenergic antagonist acute hypertension and hypertensive crisis has stereoisomers is a racemic mixtures of four isomers. Two of these the (S,S)- and (R,S)-isomers are inactive. the third (S,R)-isomer is a powerful alpha one blocker the fourth (R,R) isomer is a mixed nonselective beta blocker and selective alpha 1 blocker the ratio of alpha:beta block is apporoximately 3:1
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Vasoactive Drugs

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1. Dopamine
also act as a catecholamine neurotransmitter in the brain intravenous medication acting on sympathetic nervous system precursor for noradrenaline and releases it from intracardiac adrenergic nerve endings. in the periphery, dopamine stimulates prejunctional dopaminergic DA2-receptors which results in inhibition of NA release and inturns, facilitates vasodilation. effects like increased heart rate and blood pressure
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2. Dobutamine
Sympathomimetic Drug for treatment of heart failure and cardiogenic shock Direct stimulation of beta-one receptors of the sympathetic nervous system. Clinically used to treat acute but potentially reversible heard failure acts on the beta1 receptors of the heart to reduce its contractility and cardiac output. * Since it does not induce release of NA like DOPAMINE, it is less prone to induce hypertension
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3. Noradrenaline
also a hormone and a neurotransmitter Potent alpha agonist with some beta-adrenergic properties shown to increase MAP in patients with hypotension resistant to uid resuscitation in patients with septic shock
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Quiz time
Text

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Myocardial Infarction

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1. Streptokinase
Protein secreted by streptococci Effective thrombolysis medication, MI, PE. Fibrinolytics There are three domains to Streptokinase, denoted (residues 1150), (residues 151287), and (residues 288414). Each domain binds plasminogen, although none can activate plasminogen independently Extra streptokinase --> extra plasmin production --> break down of brin --> dissolve clots given IV ASAP after onset of MI to dissolve clots in ther heart arteries. Note the difference in dosage for patients coming in for MI or PE
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2. Nitroprusside
Inorganic compound with formula Na2[Fe(CN)5NO]. 2H2O Red Coloured Salt- potent Vasodilator in arterioles (more) and venules. Complex anion with an octahedral ferrous center surrounded by 5 tightly bound cyanide ligands and a linear nitric oxide ligand. Once in the circulation, it break downs to release NO --> activates guanylate cyclase in smooth muscle and increase cGMP --> stimulate Ca2+ to ER and reduce availibility--> relaxation of smooth muscles --> vessels dilate. Good for Heart Failure + Malignant Hypertension

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Eclampsia - Magnesium Sulphate

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Status Epilepticus

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1. Phenytoin
Chemical structure related to barbiturates Antiepiletic Stabilize the inactive state of voltage gated sodium channels Suppress abnormal brain activity seen in seizures ---> by reducing the electrical conductance among brain cells
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2. Diazepam
Benzodiazepine group Commonly for anxiety, insomnia, muscle spasm and of course seizure including status epilepticus, alchohol withdrawal. MOA: enhances the effect of neurotransmitter GABA by binding to the benzodiazepine site on the GABA A receptor leading to CNS depression GABA A receptor activated ---> increase in chloride ions inux into cell ---> increased hyperpolarisation --> hard to achieve ation potential --> reduce in excitation
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