P5

Question 1

Alendronic acid (alendronate)

Answer 1

Nitrogen-containing, second generation bisphosphonate

MoA: Inhibit farnesyl pyrophosphate (FPP) synthase. Inhibition of this enzyme in osteoclasts prevents the post-translational farnesylation and geranylgeranylation of small GTPase signalling proteins, such as Rac and Rho. This causes a reduction in osteoclast activity reducing bone resorption and turnover. Furthermore osteoclast survival is also affected, further increasing the ability of the bone to be rebuilt.

Use: Strengthens bone. Used to treat corticosteroid-induced osteoporosis + Paget’s disease, and to prevent osteoporosis in postmenopausal women.

Question 2

Calciferol

Answer 2

Bioactive vitamin D is a steroid hormone required for regulating body levels of Ca2+ and phosphorus, and in mineralization of bone.

MoA: Vitamin D3 is activated by 25-hydroxylation catalysed by the 25-hydroxylase in the liver.

The active form of vitamin D3 (calcitriol) binds to the vitamin D receptor, forms a complex with another intracellular receptor, the retinoid-X receptor, that then function as transcription factors to generally activate gene expression.

Calcitriol increases the serum Ca2+ concentrations.

Question 3

Raloxifene

Answer 3

Selective oestrogen receptor modulator

MoA: Produces oestrogen-like effects on bone + lipid metabolism. Whilst antagonising effects of oestrogen on breast + uterine tissue.

Use: Inhibits proliferation of preosteoclastic cells

Question 4

Codeine

Answer 4

Synthetic opiate agonist

MoA: Opiate receptor agonist in the CNS

Question 5

Clinical difference between morphine and pethidine?

Answer 5

Pethidine has a more rapid onset of action that morphine but has a shorter duration of action

Question 6

Lidocaine

Answer 6

Anaesthetic agent (sodium channel blocker)

MoA: Lidocaine alters signal conduction in neurons by blocking the signal propagation fast voltage gated sodium channels in the neuronal cell membrane. With sufficient blockage the membrane of the postsynaptic neuron will not depolarize and will thus fail to transmit an action potential. This creates the anaesthetic effect by both preventing the initiation of the pain signal, and the prevention of the propagation of that signal to the brain.

Use: Lidocaine is used to treat ventricular tachyarrhythmias associated with Myocardial infarction. Lidocaine depresses ventricular excitability and increases the stimulation threshold of the ventricle during diastole. The sinoatrial node is, however, unaffected.

Question 7

Tramadol

Answer 7

Multi-target analgesic

MoA not clear

Question 8

Arnica montana

Answer 8

Homeopathic therapy used for bruising + trauma (possibly works due to manganese levels)

Question 9

Dobutamine

Answer 9

Beta- 1-adrenergic agonist

Direct-acting inotropic agent

MoA: Via stimulation of 1-adrenergic receptors, with little effect on beta-2 or alpha-adrenergic receptors. This leads to increase myocardial contractility and stroke volume, resulting in increased cardiac output.

Question 10

Isoprenaline

Answer 10

Beta-adrenergic agonist.

Isoproterenol is a relatively selective 2-adrenergic bronchodilator.

MoA: stimulation intracellular adenyl cyclase, elevatation of cAMP levels, therefore the relaxation of bronchial smooth muscle + inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells

Use: Treatment of bronchospasm associated with COPD

Question 11

Salbutamol

Answer 11

Beta-2-adrenergic agonist

MoA: stimulates beta-2-adrenergic receptors –> adenyl cyclase activation –> increases in cAMP concentration –> activation of cAMP-dependent protein kinase A. PKA modulates myosin phosphorylation + lowers intracellular calcium concentrations causing smooth muscle relaxation and bronchodilation

Use: In addition to bronchodilation, salbutamol inhibits the release of bronchoconstriction agents from mast cells, inhibits microvascular leakage, and enhances mucociliary clearance.

Question 12

Norepinephrine

Answer 12

Alpha-adrenergic agonist

MoA: Norepinephrine functions as a peripheral vasoconstrictor by acting on both alpha-1 + alpha-2-adrenergic receptors.

It is also an inotropic stimulator of the heart and dilator of coronary arteries as a result of it’s activity at the beta-adrenergic receptors.

Question 13

Phenoxybenamine

Answer 13

Alpha-adrenergic antagonist

MoA: Phenoxybenzamine blocks the alpha-adrenergic receptors which leads to muscle relaxation + blood vessel dilatation. This widening of the blood vessels results in a lowering of blood pressure

Use: Hypertension treatment + sweating associated with pheochromocytoma

Question 14

Doxazosin

Answer 14

selective inhibitor of the alpha-1-adrenoceptors

Use: Hypertension treatment

Note: Prazosin has replaced doxazosin.

Question 15

Muscarine

Answer 15

Muscarinic cholinergic receptor agonist

MoA: Muscarine binds the muscarinic acetylcholine receptors and so mimics the effects of acetylcholine.

Question 16

Pilocarpine

Answer 16

Muscarinic cholinergic receptor agonist.

MoA: Stimulation of muscarinic receptors leading to contraction of the iris sphincter muscle and ciliary muscle.

Question 17

Atracurium

Answer 17

Atracurium is a non-depolarising skeletal muscle relaxant

Competitive cholinergic receptor antagonist

MoA: Antagonises the neurotransmitter action of ACh by binding competitively w/ cholinergic receptor sites on the motor end-plate í muscle relaxation

Question 18

What can reverse action of atracurium?

Answer 18

Acetylcholinesterase inhibitors such as neostigmine, edrophonium, pyridostigmine

Question 19

Pilocarpine

Answer 19

Glaucoma treatment

Pilocarpine is a slowly hydrolysed muscarinic agonist

Question 20

Botulinum A toxin

Answer 20

Acetylcholine release inhibitor

MoA: By binding pre-synapticly to high-affinity recognition sites on the cholinergic nerve terminals.

Causes a decrease in the release of acetylcholine, causing a neuromuscular blocking effect

Recovery occurs through proximal axonal sprouting and muscle re-innervation by formation of a new neuromuscular junction

Question 21

Cocaine

Answer 21

Noradrenaline reuptake inhibitor/sodium channel blocker.

MoA: Cocaine produces anaesthesia by inhibiting excitation of nerve endings or by blocking conduction in peripheral nerves. This is achieved by reversibly binding to and inactivating sodium channels, which are necessary for the depolarization of nerve cell membranes and subsequent propagation of impulses along the course of the nerve.

Use: Local anaesthetic indicated for the introduction of local (topical) anaesthesia of accessible mucous membranes of the oral, laryngeal + nasal cavities.

Note: Cocaine is the only local anaesthetic with vasoconstrictive properties.
This is a result of its blockade of norepinephrine reuptake in the autonomic nervous system. Cocaine binds differentially to the dopamine, serotonin, and norepinephrine transport proteins and directly prevents the re-uptake of dopamine, serotonin, and norepinephrine into pre-synaptic neurons.

Question 22

Dexamphetamine

Answer 22

Noradrenaline releaser

It is an amphetamine

MoA: Peripheral actions include elevations of systolic + diastolic blood pressures and weak bronchodilator and respiratory stimulant action

Question 23

Dopamine

Answer 23

Dopamine is a precursor to norepinephrine in noradrenergic nerves and is also a neurotransmitter in the central nervous system.

MoA: In the brain, dopamine act as an agonist to the 5 dopamine receptor subtypes (D1, D2, D3, D4, D5) on beta-adrenoceptors and indirectly by causing release of norepinephrine from storage sites in sympathetic nerve endings producing positive chronotropic and inotropic effects on the myocardium, resulting in increased heart rate and cardiac contractility

Question 24

Fuoxetine

Answer 24

Selective serotonin re-uptake inhibitor

Use: Treat depression, bulimia nervosa, premenstrual dysphoric disorder, panic disorder and post-traumatic stress

MoA: Inhibition of the re-uptake or serotonin at the serotonin re-uptake pump of the neuronal membrane, enhancing the actions of serotonin on 5HT1A autoreceptors.

SSRIs bind with significantly less affinity to histamine, acetylcholine, and norepinephrine receptors than tricyclic antidepressant drugs.

Question 25

Imipramine

Answer 25

Catecholamine uptake inhibitor

MoA: Inhibition of the sodium-dependent serotonin transporter + sodium-dependent norepinephrine transporter preventing or reducing the reuptake of norepinephrine and serotonin by nerve cells. This leads to enhanced serotonergic transmission

Use: Imipramine is a tricyclic antidepressant

Question 26

Levodopa

Answer 26

Dopamine replacement therapy

MoA: Levodopa is a natural form of dihydroxyphenylalanine (immediate dopamine precursor)

Use: Replace dopamine lost in parkinson’s disease

Question 27

Nicotine

Answer 27

Nicotinic acetylcholine agonist

It is a highly addictive stimulant

MoA: Is an agonist at nicotinic acetylcholine receptors on autonomic ganglia, the adrenal medulla, neuromuscular junctions and in the brain. Dopamine binding to its receptors is responsible the euphoric and addictive properties of nicotine.

Use: Nicotine inhalers and patches are used to treat smoking withdrawal syndrome.

Question 28

Phenelzine

Answer 28

Monoamine oxidase inhibitor

Use: Antidepressant

Question 29

Pralidoxime

Answer 29

Cholinesterase reactivator

Use: Pralidoxime is an antidote to organophosphate pesticides and chemicals.

Question 30

Sarin

Answer 30

Irreversible cholinesterase inhibitor

It is a nerve agent

Extremely toxic + rapid effect

Question 31

Tropicamide

Answer 31

Muscarinic cholinergic receptor antagonist

MoA: Inhibition of the muscarinic receptor M4 –> this inhibition leads to pupil dilation and relaxation of the lens.

Use: Tropicamide is used to treat mydriasis and cycloplegia.