3. ATROPINE
• antimuscarinic agent / ‘parasympatholytic’ agents - reduce the activity of the PNS
• Synthetic tertiary amine
• MOA : Act as competitive antagonists of acetylcholine (ach) at muscarinic acetylcholine receptors (mACHr)
• located in
- post-ganglionic target tissues innervated by the parasympathetic nervous system
- in the sympathetically innervated sweat glands.
4. ATROPINE
USES
• Premed to decrease secretions
• Treatment of symptomatic bradycardia (0.5 mg IV every 3 to 5 minutes,
max 3mg)
• Treatment of organophosphate poisoning
• METABOLISM AND EXCRETION
• Hepatic metabolism • excreted in urine
5. EFFECTS
• Tachycardia • Effect last 2–3 hours • May precipitate arrhythmias by
decreasing AV conduction time
CVS
• Bronchodilation • ↑RR
RS
• Crosses BBB causing central anticholinergic syndrome
• Antiemetic
• Antiparkinsonian effects
CNS
• Antisialagogue
• ↓Tone lower oesophageal sphincter
GI
• Inhibits sweating may cause hyperpyrexia in children
METABOLIC
• Dry mouth
• Urinary retention • Blurred vision
ANTIMUSCARINIC
11. EFFECT
• Increase systemic vascular resistance and blood
pressure and may result in a reflex bradycardia,
all of which results in a drop in cardiac output.
It is not arrhythmogenic.
Cardiovascular
• Blood low falls in a manner similar to that
demonstrated by noradrenaline.
Renal
• use as a nasal decongestant and mydriatic
agent.
Others
12. PHENYLEPHRINE
How to use
• Peripheral line
• Dilute into 100ml NS – 100mcg/ml
• Infusion dose: 0.1-10mcg/kg/min
• Bolus: 50 to 100 mcg
METABOLISM AND EXCRETION
• Hepatic metabolism by monoamine oxidase
13. EPHEDRINE
• Synthetic non catecholamine agonist at α, β1, and
β2 receptors with both direct and indirect actions
• MOA : Indirect sypathomimetic, i.e. causes release of
noradrenaline from nerve terminals • Direct stimulation of
α and β receptors • Inhibits monoamine oxidase
• USES : Hypotension • Nasal decongestant • Nocturnal
enuresis
• DOSE : Oral: 30 mg t.d.s. • IV: given as boluses of 3 mg,
titrate to effect
14. EFFECTS
• ↑ HR • ↑ CO • ↑ BP • ↑ Coronary artery blood flow • ↑ Myocardial O2
consumption
CVS
• Bronchodilation •
RS
• ↓ Renal blood flow • ↓ GFR
Renal
• Caution with MAOIs can precipitate hypertensive crisis NB Tachyphylaxis occurs
as noradrenaline stores are depleted. Usually seen after ～30 mg given
Others
16. ADRENALINE
• α and β adrenoreceptor agonist
• Effects are mediated by stimulation of adenylyl cyclase increase in
CAMP
Alpha 1 increase SVR increase BP
Beta 1 increase HR CO
Beta 2 bronchodilation, reduce mast cell release
17. ADRENALINE
Pharmacokinetics
• Administration : IV /IM
• Elimination : degraded by conjugation with glucuronic and sulphuric acids and excreted in
the urine. Smaller part oxidised by amine oxidase and inactivated by o-methyl-transferase
Dose
• Infusion dose : 0.01-1.5 mcg/kg/min
• Single strength: 3mg in 50cc (0.06mg/ml)
• Double strength: 6mg in 50cc (0.12mg/ml)
19. EPINEPHRINE
USES
• Severe septic shock
Added as 2nd vasoactive agent when noradrenaline dose > 15-20mcg/min does not achieve the
target
• ACLS
1mg 3-5min push IV
• Anaphylaxis
Administered adrenaline in boluses of 0.05-0.1mg. If no response, administered infusion adrenaline
at 0.1mcg/kg/min.
Adrenaline is preferred as it reverses peripheral vasodilation and reduces oedema
• Viral croup
• Asthma
Use 1:1000 solution and (if required) make up to a total of 5ml using normal saline prior to
administration
• Used locally to decrease the spread of LA and to reduce surgical blood loss
20. NORADRENALINE
• Direct and indirect α1 agonist, some small action at β receptors
Uses
• Vasoactive agent of choice
• Sepsis
• Cardiogenic shock
• Neurogenic shock
Dose
• Infusion dose : 0.01-1.5 mcg/kg/min
• Infusion (1 vial 4mg/4ml)
• Single strength: dilute 1 vial in 50ml (0.08mg/ml)
• Double strength: dilute 2 vials in 50ml (0.16mg/ml)
21. EFFECTS
S/E
• NE vasoconstricts the pulmonary, renal and mesenteric circulation, infusion must be
monitored to prevent injury to vital organs.
• Prolonged infusion can cause ischaemia in the fingers because of marked peripheral
vasoconstriction
• ↑BP and SVR (CO may ↓) • Peripheral vasoconstriction
• ↑ Myocardial O2 consumption • Coronary artery
vasodilation
• ↑ Pulmonary vascular resistance
CVS
• ↓Renal blood flow • ↓Splanchnic blood flow
GI
22. NORADRENALINE
METABOLISM AND EXCRETION
• Exogenous noradrenaline metabolised by:
• • Mitochondrial monoamine oxidase (in liver, brain and kidney)
• • Cytoplasmic COMT
• Excreted in urine, main product is VMA (3-methoxy, 4-hydroxymandelic acid)
• Endogenous noradrenaline metabolised by:
• Uptake 1: active uptake back in to nerve terminals where reused, or metabolised by MAO
• Uptake 2: diffusion away from the nerve and metabolised by COMT to VMA, or
normetadrenaline
24. REFERENCES
• The Primary FRCA Structured Oral Examination Study Guide 2. Second Edition. Kate
McCombe and Lara Wijayasiri
• Pharmacology for Anaesthesia and Intensive Care. Fourth Edition. T.E Peck, S.A Hill
Notas do Editor
Tolerance: larger doses required to produce the same effect.
Pharmacokinetic clearance: increased drug clearance induced by repeat doses
Pharmacodynamic tolerance: changes in receptor number or function due to exposure to the drug
Physiological tolerance: homeostatic adaptation of unrelated systems to compensate for drug effect
Behavioural tolerance: learned compensation for the effect of the drug which diminishes its effects.
Tachyphylaxis: a rapid decrease in response to repeated doses over a short time period
Not dose-dependent (i.e. giving a larger dose of the drug may not restore the maximum effect)
Rate-sensitive (i.e. requires frequent dosing)
After a relatively short period of withholding the drug, its effect is restored (i.e tachyphylaxis resolves rapidly)
