Cardiovascular drugs

Question 1

Adrenaline

Answer 1

• Cardiac arrest dose: 1mg 1:10,000 IV
• Anaphylaxis dose: 0.5mg 1:1000 IM (0.3mg for 6-12 years, 0.15mg 6mos - 6 years)
• Mixed alpha and beta adrenoceptor effects
  Effects:
• CVS - beta effects dominate at low doses (increased CO, myocardial oxygen consumption, coronary artery dilatation, may cause fall in peripheral vascular resistance), alpha effects at high / bolus doses (vasoconstriction, increased systemic vascular resistance). May result in arrhythmia
• Resp - potent bronchodilation
• CNS - increases MAC
• Other - increases basal metabolic rate, raises plasma glucose due to glycogenolysis, lipolysis and gluconeogenesis. Raised plasma lactate. Stimulates RAAS. Decreases renal blood flow

Metabolized by mtochondrial MAO and COMT within the liver, kidney and blood to inactive vanillylmandelic acid (VMA) and metadrenaline

Question 2

Noradrenaline

Answer 2

• Mainly acts on alpha1 adrenoceptors, with some beta effects
• Primarily causes peripheral vasoconstriction, increases BP and may cause a reflex bradycardia
• Metabolized by MAO and COMT, with the main metabolite being vanillylmandelic acid (VMA)

Question 3

Dopamine

Answer 3

• Acts on alpha and beta adrenoceptors, as well as D1 and D2 dopamine receptors
• At lower rates beta effects predominate to cause increased contractility, heart rate, cardiac output and coronary blood flow - as well as stimulating the release of noradrenaline
• At higher rates alpha effects predominate to cause increased systemic vascular resistance
• Dilation of mesenteric and renal blood vessels
• Metabolism is via MAO and COMT to inactive compounds

Question 4

Metaraminol

Answer 4

• Has direct and indirect sympathomimetic actions
• Acts mainly via alpha1 adrenoceptors, but also has some beta adrenoceptor activity
• Increases systemic vascular resistance with reflex bradycardia
• Contributes some positive inotropy, however cardiac output may fall due to increased afterload
• Stimulates release of noradrenaline

Question 5

Phenylephrine

Answer 5

• Pure alpha adrenoceptor agonist
• Raises systemic vascular resistance BP, may result in a reflex bradycardia
• Preferred in obstetrics due to more favourable cord gas profile

Question 6

Ephedrine

Answer 6

• Can exist as four isomers, but only L-isomer is active
• Both direct and indirect sympathomimetic actions, also inhibits the actions of MAO on noradrenaline
• Due to its indirect actions it is prone to tachyphylaxis as noradrenaline stores are depleted
• Mixed alpha and beta adrenoceptor agonist
• Increases cardiac output, heart rate, blood pressure, coronary blood flow and myocardial oxygen consumption
• Respiratory stimulant, causes bronchodilation
• Minor metabolism in liver, majority of dose excreted unchanged in urine

Question 7

Dobutamine

Answer 7

• Direct acting synthetic catecholamine derivative of isoprenaline
• Beta1 adrenoceptor effects predominate, but has some beta2 effects
• Used to augment low cardiac output states associated with myocardial infarction, cardiac surgery and cardiogenic shock
• Causes increased contractility, heart rate and myocardial oxygen constumption
• Blood pressure usually increased despite small fall in systemic vascular resistance due to beta2 effect

Question 8

Milrinone

Answer 8

• Bipyridine derivative
• Selective PDE3 inhibitor which prevents the breakdown of cAMP
• Used in short term management of cardiac failure
• Positive inotropy, stroke volume and cardiac output. Reduces peripheral vascular resistance, but little effect on heart rate and blood pressure

Question 9

Atropine

Answer 9

• Racemic mixture, but only l-atropine is active
• Competitive antagonism of acetylcholine at muscarinic receptors
• More effective in treating bradycardia than glycopyrrolate
• Decreases AV conduction time
• Causes bronchodilation, reduces secretions
• Reduces salivation
• Can cross the BBB - therefore may cause central excitation or depression
• Has anti-emetic effects
• Decreases tone and peristalsis in the GI tract and urinary tract > may cause urinary retention
• Mydriasis, increased intraocular pressure

Question 10

Glycopyrrolate

Answer 10

• Competitive antagonism of ACh at muscarinic receptors
• Less effective at treating bradycardias
• Antimuscarinic side effects - dry mouth due to very potent antisialogogue effects, bronchodilation, may cause urinary retention, inhibits sweating
• Cannot cross the BBB due to positive charge of molecule, also causes oral bioavailability <5%

Question 11

Isoprenaline

Answer 11

• Has both beta1 and beta2 adrenergic actions
• Used to treat severe bradycardia associated with AV block or beta blockade
• Increases heart rate, myocardial contractility, automaticity and cardiac output
• Variable effect on BP, can fall due to beta2 effect
• Potent bronchodilation

Question 12

Catecholamine synthesis

Answer 12

Phenylalanine > Tyrosine > L-DOPA > Dopamine > Noradrenaline > Adrenaline

Question 13

Adrenergic receptors

Answer 13