Pharmacology Flashcards
Actions of adenosine as a drug, and effects (heart)
Binds to A1 receptors in SAN and AVN
Suppresses pacemaker current in SAN
Suppresses Ca2+ entry in AVN blocking fast current travelling through AVN
Used to treat supraventricular tachycardia (fast SAN and AVN rhythm)
Side effects of adenosine as a drug (heart)
Potent vasodilator, so causes flushing and headache due to systemic arterial hypotension
Class of drugs that adenosine is in (heart)
Anti-dysrhythmic
What are the effects of adrenaline on:
Liver?
Muscle?
Adipose tissue?
Liver
- PKA phosphorylating/deactivating acetyl CoA carboxylase in FA biosynthesis, therefore inhibiting FA biosynthesis
- stimulating oxidation because acetyl CoA makes malonyl CoA which inhibits CPT1, so CPT1 is uninhibited
Muscle and liver
- PKA stimulates phosphorylates/stimulates glycogen phosphorylase, stimulating glycogen mobilisation
- PKA inhibits protein phosphatase 1 which activates glycogen synthase by dephosphorylating, again stimulating glycogen mobilisation
Adipocytes
– PKA phosphorylating/activating hormone sensitive lipase (HSL) to mobilise more TAGs
Which adrenoreceptor(s) are found in: Heart Blood vessels Bronchi G.I Tract Liver Eye Skeletal muscle Adipose tissue
And effects
Heart - B1 - inotropic and chronotropic increase
Most blood vessels - A1 - smooth muscle constriction
Skeletal muscle blood vessels - A1 and B2 - smooth muscle constriction and relaxation respectively
Bronchi - A1 and B2 - smooth muscle constriction and relaxation respectively
G.I. Tract - A1 and B1 - relaxation and lowered motility
Liver - A1 and B2 - glycogenolysis and gluconeogenesis
Eye - A1 - Pupil dilation
Skeletal muscle - B2 - tremor
Adipocytes - B3 - lipolysis (brown fat = thermogenesis)
Rank NA, Adr and Isoprenaline effects on alpha and beta receptors in order of potency
Alpha = NA > Adr > Isoprenaline (minimal) Beta = Isoprenaline > Adrenaline > NA (minimal)
How can there be B2 and A1 in the same tissue if they have the same agonist but different actions?
Adrenaline has lower potency on B2 than A1
Effects determined thus by concentration of adrenaline and also proportion of B2/A1 in tissue
Synthesis of catecholamines pathway
Phenylalanine –> Tyrosine [phenylalanine hydroxylase]
Tyrosine –> L-Dopa [tyrosine hydroxylase]
L-Dopa – > Dopamine [L-aromatic amino acid decarboxylase]
Dopamine –> Noradrenaline [dopamine beta-hydroxylase]
Noradrenaline –> Adrenaline [PNMT]
Tetrodotoxin effects
Incredibly potent fast VGNaC blocker, causing paralysis of voluntary muscles and loss of sensation by inhibiting action potentials
Botulinum toxin mechanism of action
Neuromuscular blocking drug (secreted by anaerobic bacteria C. Botulinum)
Cleaves and inactivates SNARE protein complex prevent fusion of ACh vesicles with the presynaptic membrane
Prevents neuromuscular transmission, causing paralysis
Aspirin effects
Prostaglandin/thromboxane synthesis inhibitor
Non-dissociated form crosses cell membrane and inhibits cyclooxygenase 1 & 2 (Cox-1&2)
Cox-1&2 important for converting arachidonic acid to prostaglandins/thromboxanes, which are mediators of inflammation, pain, and platelet aggregation
What is a cardiac glycoside?
Why do they have a low therapeutic index?
How is this issue dealt with?
Inotropic drugs
Can cause rhythmic disturbances, especially in hypokalaemia
Thus, they are often administered with anti arrhythmic drugs
What are ouabain and digoxin?
What are their mechanisms of action?
Cardiac glycosides, thus positive inotropes
Thought to inhibit Na/K and thus NCX antiporter (which is powered by the Na gradient set up by the Na/K pump)
This raises intracellular calcium, increasing force of contraction
