biochemistry of emergency drugs

8/3/2019 Biochemistry of Emergency Drugs

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Biochemistry

of EmergencyDrugsMiss Yah Nee LoLecturer

[email protected]

Friday, August 26, 2011



Learning Objectives

•Know the common classes of drugs used in the A&E especially

in Brunei•Be able to describe themechanism of action of

important classes of emergencydrugs

•The basic dosage and infusion

guide of emergency drugs?Friday, August 26, 2011



Accident & Emergencysituations

• List down the common situations or conditions thatcomes into our own A&E department in the RIPASthat you can think of?

• Shortness of breath

• Anaphylactic shock• Cardiovascular problem e.g. heart block,

arrhythymia, etc

• Heart Attack

…




Asthmatic/

COPD




1. Aminophylline

• Bronchodilator

• Compound of the bronchodilatortheophylline with ethylenediaminein 2:1 ratio

• Ethylenediamine improves solubility• Theophylline relaxes bronchialsmooth muscles.

• MOA unclearFriday, August 26, 2011



6

Aminophylline

• contradictions: hypersensitive, avoid bolus dose if patient taking Oral Theophylline

• Adverse Drug Ef ects: Nausea, Vomiting, abdominalpain, diarrhoea, headache, insomnia, dizziness...

• the potentially fatal: Convulsions, cardiacarrthymias, hypotension and sudden death after toorapid IV injecion

•Loading dose: 250 mg (Slow I/V in

15 mins)•Infusion Rate: 20-80 mils/hr

6




2. Salbutamol

•Short acting B2-adrenergicreceptor agonist used for relief of bronchospasm

• racemic mixture with a 1:1 ratioof the isomer, levelbuterol ands-albuterol.

•The tertiary butyl group insulbutamol makes it moreselective for B2-receptors.




3. Magnesium Sulphate

• sterile solution of magnesium sulphateheptahydrate in water for injection

• Electrolyte, anticonvulsants•

Indications:• Seizures of eclampsia• TDP• Hypomagnesaemia• Refractory VF

• Use with caution in renal failure• CNS depressant ef ects 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 ‘fight-or-flight’response of the sympathetic nervoussystem.

• Chemically it is a catecholamine, a

monoamine produced only by theadrenal glands from the a.a.phenylalanine and tyrosine

•

used best for anaphylactic shock

9




10

Doxapram (Dopram)

• Doxapram hydrochloride

• Central Respiratory stimulant

• Stimulates increase in tidal volume and

RR• Stimulates the chemoreceptors in the

carotid arteries which in turn stimulatesthe respiratory centre in the brain

• Thought to stimulate the carotid body byinhibiting certain potassium channels

10




Bradycardia

& Heart

BlockFriday, August 26, 2011



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1. Atropine•

MOA: Anticholinergic agent thatcompetitively blocks the muscarinicreceptors

• Muscarinic receptors found in peripheral

tissues such as the heart, intestines,bronchial muscles, iris and secretory glands.

• abolishes bradycardia and reduces heartblock due to vagal activity

•

Adverse reaction: Dry mouth, Dysphagia,contipation, restlessness, confusion, etc

12




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2. Isoprenaline

• MOA: a beta-1 and beta-2 adrenergic receptoragonist.

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Antiarrythmics




Classes of antiarrythmics

• Class 1- Membrane stabilizers

• Class Ia- lengthen action potential, prolongrepolarization, prolong PR, QRS, QT. e.g.Quinidine, procainamide,disopryamide

• Class 1b- shorten action potential, shortenrepolarisation, shorten QT, raise fibrillationthreshold e.g. lignocaine, mexilitine,phenytoin

•

Class 1c- no ef ect on action potential or onrepolarization, prolongs PR and QRS e.g.flecainide

•

Class II- beta blockers e.g. propanolol

15




Classes of antiarrythmics

•Class III- Potassium channelblockers that prolong durationof action potential e.g.amiodarone, disopryamide

•Class IV- Calcium channel

blockers that have importantef ects on upper and middleparts of the AV node. e.g.

Verapamil

16




17

1. Adenosine (Adenocor)• Purine Nucleoside

• comprise of a molecule of adenineattached to a ribose sugarmolecule via a β-N9 glycosidicbond.

• also acts as a neurotransmitter• when administered I.V., causes

transient heart block in the AVnode

• Via A1 receptor, inhibiting adenylylcyclase, reducing cAMP and socausing cell hyperpolarization byincreasing outward potassium ionflux 15




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2. Lignocaine

•Class 1B antiarrythmic drug

•also act as local anaesthetic.

•

contain amide group in thestructure

•MOA: block the fast voltage

gated sodium (Na+) channels• inhibit sodium influx

• block rise of action potential

• inhibit signal conduction16




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3. Verapamil

•MOA- Calcium ion influxinhibitor

•L-type calcium channel blocker

• relaxation and prevention of coronary artery spasm- dilates

the main coronary arteries andarterioles both in normal andischemic regions. 17




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4. Amiodarone

• Class III antiarrthymic drug

• Blocks sodium channels at rapid pacingfrequencies

• noncompetitive antisymphatetic action

• lengthen cardiac action potential

• negative chronotropic ef ect 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 ef ect

seen with I.V. amiodarone18


Procainamide &



Procainamide &Disopyramide

• Both are Class 1a antiarrythmics

• interfere directly with the depolarization of thecardiac membrane

• Inhibits the fast sodium channels

• Increases the duration of a.p. in cardiac cells

21

Disopyramide

Procainenamide




Propanolol

• A synthetic non selective beta-adrenergicreceptor-blocking agent.

• arrhythmia and thyroid crisis as well ashypertension

• blocks action of the sympathetic nervous system byblocking beta receptors on sympathetic nerves

• highly lipophilic

• undergoes high first pass metabolism by theliver

• 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 sympatheticnervous system by blocking beta

receptors on sympathetic nerves• also reduces force of contraction of the heart 23




Hypertensive

crisis




1.Hydralazine (Apresoline)•

Direct-acting smooth musclerelaxant

• vasodilator primarily inarteries and arterioles.

•

Relaxing vascular smoothmuscle, reduce peripheralresistance, lower bp.

• MOA: increase guanosine

monophosphate (GMP)decreasing action of secondmessenger IP3, limitingrelease 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 areinactive.

• 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




1. Dopamine

• also act as a catecholamine neurotransmitter inthe brain

• intravenous medication acting on sympatheticnervous system

• precursor for noradrenaline and releases it fromintracardiac adrenergic nerve endings.

• in the periphery, dopamine stimulatesprejunctional dopaminergic DA2-receptors

which results in inhibition of NA release andinturns, facilitates vasodilation.

• ef ects like increased heart rate and bloodpressure 28




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 potentiallyreversible heard failure

• acts on the beta1 receptors of the heart toreduce its contractility and cardiac output.

• * Since it does not induce release of NA likeDOPAMINE, it is less prone to inducehypertension 29




3. Noradrenaline

•also a hormone and aneurotransmitter

•

Potent alpha agonist with somebeta-adrenergic properties

•shown to increase MAP in

patients with hypotensionresistant to fluid resuscitation inpatients with septic shock 30




Quiz timeText




Myocardial

Infarction




1. Streptokinase

• Protein secreted by streptococci• Ef ective thrombolysis medication, MI, PE.

• Fibrinolytics

• There are three domains to Streptokinase, denoted α

(residues 1–150), β (residues 151–287), and γ (residues 288–414). Each domain bindsplasminogen, although none can activateplasminogen independently

• Extra streptokinase --> extra plasmin production

--> break down of fibrin --> dissolve clots

• given IV ASAP after onset of MI to dissolve clots inther heart arteries.

• Note the dif erence 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 centersurrounded by 5 tightly bound cyanide ligands and alinear 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 andreduce availibility--> relaxation of smooth muscles--> vessels dilate.

• Good for Heart Failure + Malignant Hypertension 34




Eclampsia

- Magnesium

SulphateFriday, August 26, 2011



Status

Epilepticus




1. Phenytoin

• Chemical structure related tobarbiturates

• Antiepiletic

• Stabilize the inactive state of voltagegated sodium channels

• Suppress abnormal brain activity

seen in seizures ---> by reducingthe electrical conductance amongbrain cells 37


2 Di



2. Diazepam

• Benzodiazepine group• Commonly for anxiety, insomnia, muscle

spasm and of course seizure includingstatus epilepticus, alchohol withdrawal.

• MOA: enhances the ef ect of neurotransmitter GABA by binding to thebenzodiazepine site on the GABA A receptorleading to CNS depression

• GABA A receptor activated ---> increase inchloride ions influx into cell ---> increasedhyperpolarisation --> hard to achieve ationpotential --> reduce in excitation

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