Drugs List Block 5

Question 1

Alendronic acid (Alendronate)

Answer 1

strengthens bone
used to treatcorticosteroid-induced osteoporosis and Paget’s disease, and osteoporosis in postmenopausal women.
inhibit (FPP) synthase by acting as analogues of isoprenoid diphosphate
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.
in postmenopausal women it increases bone mass

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.
The active form of vitamin D3 (calcitriol) binds to the vitamin D receptor, forms a complex with retinoid-X receptor, that then function as transcription factors to generally activate gene expression.
Calcitriol increases the serum Ca2+ concentrations by:
1) Increasing GI absorption of phosphorus and Ca2+,
2) Increasing osteoclastic resorption, and
3) Increasing distal renal tubular reabsorption of Ca2+.
4) Promote intestinal absorption of calcium

Question 3

Calcitonin/Salcatonin

Answer 3

Calcitonin is produced by the thyroid gland, and is important in the control of the calcium concentration within the blood.
The calcitonin receptor is an example of a GPCR. This activates the cAMP and calcium signalling pathways, leading to the enhance production of vitamin D producing enzymes (25-hydroxyvitamine D-24-hydroxylase), greater calcium retention and enhanced bone density.
Net increase in bone mass and a reduction in plasma calcium levels. In addition to affecting osteoclasts, in also stimulates bone building by osteoblasts.
promotes the renal excretion of calcium, phosphate, sodium, magnesium, and potassium ions by decreasing tubular reabsorption, and so increases jejunal secretion of water, sodium, potassium, and chloride ions.
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Question 4

Hormone replacement therapy

Answer 4

There are different types of HRT, with oestrogen or progesterone alone therapies, or a oestrogen and progesterone combination therapy.
There has been debate over the effects of this therapy in regards to it having a detrimental effect in the patients, by increasing the chances of suffering from either cancer (breast and ovarian), and cardiovascular events.

Question 5

Raloxifene

Answer 5

Raloxifene, produces estrogen-like effects on bone and lipid metabolism, while antagonizing the effects of estrogen on breast and uterine tissue.
Raloxifene in the bone, binds to the estrogen receptors, resulting in reduced bone resorption and increased bone mineral density in postmenopausal women, slowing the rate of bone loss.
This is achieved via activation of transforming growth factor-β3, which is a bone matrix protein with antiosteoclastic properties. In addition Raloxifene can inhibit the proliferation of preosteoclastic cells
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Question 6

Codeine

Answer 6

Codeine is an opiate agonist in the CNS
It conversion to morphine.
mechanism of action is via mediation of opiate receptors are coupled with G-protein receptors, which activate adenylate cyclase and the production of cAMP.
Opioids decrease intracellular cAMP by inhibiting adenylate cyclase.
the release of the nociceptive neurotransmitters substance P, GABA, dopamine, acetylcholine and noradrenaline and the hormones vasopressin, somatostatin, insulin and glucagon is inhibited. Opioids also close N-type voltage-operated calcium channels (OP2)and open calcium-dependent inwardly rectifying potassium channels (OP3 and OP1 receptor agonist). results in hyperpolarization and reduced neuronal excitability.

Question 7

Pethidine

Answer 7

Meperidine is a synthetic opiate agonist recommended for relief of moderate to severe acute pain. The onset of action is more rapid than morphine, but has a shorter duration of action.
kappa-opiate receptor agonist with local anesthetic effects.
Opiate receptors are coupled with G-protein receptors, which activate adenylate cyclase and the production of cAMP.
All same info as codeine

Question 8

Lidocaine

Answer 8

alters signal conduction in neurons by blocking 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.
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 9

Tramadol

Answer 9

Tcentrally-acting analgesic. metabolised to O-desmethyl metabolite (M1). Both the parent molecule and the metabolite are OP3-receptor agonists. Its mechanims of action is not clear but it is thought Tramadol works by
Binding of parent and M1 metabolite to μ-opioid receptors and
Weak inhibition of reuptake of norepinephrine and serotonin in the CNS​

Question 10

Dobutamine

Answer 10

Dobutamine is a direct-acting inotropic agent. Its mechansim of action is mediated via stimulation of b1-adrenergic receptors, with little effect on b 2 or a receptors.
This leads to increase myocardial contractility and stroke volume, resulting in increased cardiac output

Question 11

Isoprenaline

Answer 11

Isoproterenol is a relatively selective b2-adrenergic bronchodilator used for the treatment of bronchospasm associated with COPD.
stimulation intracellular adenyl cyclase, elevatation of cAMP levels, and therefore the relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells.

Question 12

Salbutamol

Answer 12

Salbutamol has two isomers. The R-isomer, levalbuterol, is responsible for bronchodilation while the S-isomer increases bronchial reactivity.
stimulates b2adrenergic receptors, leading to adenyl cyclase activation, increases in cAMP concentration, and therefore activation of cAMP-dependent protein kinase A. PKA modulates myosin phosphorylation and lowers intracellular calcium concentrations causing smooth muscle relaxation and bronchodilation. In addition to bronchodilation, salbutamol inhibits the release of bronchoconstricting agents from mast cells, inhibits microvascular leakage, and enhances mucociliary clearance.

Question 13

Salmeterol

Answer 13

Salmeterol is a long acting b2 adrenoceptor agonist (LABA). Salmeterol’s long, lipophilic side chain binds to exosites near b2receptors in the lungs and bronchiolar smooth muscle allowing the active portion of the molecule to remain at the receptor site, continually binding and releasing. When used regularly inhaled salmeterol decreases the number and severity of asthma attacks. However, it is not for use for relieving an asthma attack that has already started.

Salmeterol’s duration of action lasts approximately 12 hours in comparison to 4-6 hours of salbutamol.

Question 14

Norepherine

Answer 14

Norepinephrine is a precurser of epinephrine secreted by the adrenal medulla. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. Norepinephrine functions as a peripheral vasoconstrictor by acting on both a1 and a2 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 b adrenergic receptors

Question 15

Phenoxybenzamine

Answer 15

Phenoxybenzamine is used to treat hypertension and sweating associated with pheochromocytoma.
blocks the a adrenergic receptors which leads to muscle relaxation, and blood vessel dilatation.
Lowering blood pressure.

Question 16

Doxazosin

Answer 16

Doxazosin is a selective inhibitor of the a1-adrenoceptors and therefore is used to treat hypertension. Doxazosin inhibits the postsynaptic a1 adrenoceptors on vascular smooth muscle, blocking the vasoconstrictor effect of circulating and locally released catecholamines (epinephrine and norepinephrine).

Question 17

Muscarine

Answer 17

Muscarine binds the muscarinic acetylcholine receptors and so mimics the effects of acetylcholine. There are 5 different types of muscarinic receptors; M1 - M5. The M2 and M3 subtypes are present in peripheral autonomic tissues, whilst M1 and M4 subtypes are more abundant in brain and autonomic ganglia. M1, M3 and M5 interact with Gq proteins, whilst M2 and M4 receptors interact with Gi proteins to inhibit adenylyl cyclase. Most agonists for muscarine receptors are not selective for subtypes.

Question 18

Pilocarpine

Answer 18

Pilocarpine is a slowly hydrolyzed muscarinic agonist used in the treatment of glaucoma. Its mechanism of action is the stimulation of muscarinic receptors leading to contraction of the iris sphincter muscle and ciliary muscle.

Question 19

Atracurium

Answer 19

nondepolarizing skeletal muscle relaxant.
antagonizes the neurotransmitter action of acetylcholine by binding competitively with cholinergic receptor sites on the motor end-plate. This leads to muscle relaxation. The duration of neuromuscular block is between 1/3 to ½ of d-tubocurarine, metocurine, and pancuronium at initially equipotent doses. Repeated administration of maintenance doses of Atracurium has no cumulative effect on the duration of neuromuscular block if recovery is allowed to begin prior to repeat dosing.
The action of Atracium is reversed by acetylcholinesterase inhibitors such as neostigmine, edrophonium, and pyridostigmine.

Question 20

Botulinium

Answer 20

Botulinum toxin is produced by Clostridium botulinum, a gram-positive anaerobic bacterium. The clinical syndrome of botulism can occur following ingestion of contaminated food, or from a wound infection. The toxing has 7 types (A, B, C [C1, C2], D, E, F, and G), which are antigenically and serologically distinct but structurally similar. Human botulism is caused mainly by types A, B, E, and (rarely) F.

The mechanism of action of Botulinum toxin is by binding presynaptically to high-affinity recognition sites on the cholinergic nerve terminals. This 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

Cocaine is a local anaesthetic indicated for the introduction of local (topical) anaesthesia of accessible mucous membranes of the oral, laryngeal and nasal cavities. 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.
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. Its effect on dopamine levels is most responsible for the addictive property of cocaine.

Question 22

Dexamphetamine

Answer 22

The exact mechanism of action is not known. Amphetamines are agents with CNS stimulant activity. Peripheral actions include elevations of systolic and diastolic blood pressures and weak bronchodilator and respiratory stimulant action. The mechanism of action is unknown. Its possible mechanisms are

1) Stimulation of the release of norepinephrine from central adrenergic receptors.
2) At higher dosages, it causes dopamine release from the mesocorticolimbic system and the nigrostriatal systems by reversal of the monoamine transporters.
3) Act as a direct agonist on central 5-HT receptors
4) Inhibit monoamine oxidase (MAO).
5) In the periphery cause the release of noradrenaline by acting on the adrenergic nerve terminals and alpha- and beta-receptors.

Question 23

Fluoxetine

Answer 23

Fluoxetine is used to treat depression, bulimia nervosa, premenstrual dysphoric disorder, panic disorder and post-traumatic stress. Fluoxetine is metabolized to norfluoxetine. Its mechanism of action is the inhibition of the reuptake or serotonin at the serotonin reuptake 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 24

Imipramine

Answer 24

Imipramine is a tricyclic antidepressant. The mechanism of action of Imipramine is via inhibiting the sodium-dependent serotonin transporter and sodium-dependent norepinephrine transporter preventing or reducing the reuptake of norepinephrine and serotonin by nerve cells. The slowing of the uptake of these neurotransmitters is thought to contribute to relieving symptoms of depression. In addition imipramine causes down-regulation of cerebral cortical b-adrenergic receptors and sensitization of post-synaptic serotonergic receptors with chronic use. This leads to enhanced serotonergic transmission.
It takes approximately 2 - 4 weeks for antidepressants effects to occur but can be up to 8 weeks.

Question 25

Levodopa

Answer 25

Levodopa is a natural form of dihydroxyphenylalanine. It is therefore an immediate precursor of dopamine. It can be taken orally (alongside a dopamine decarboxylase to reduce metabolism at the gut wall) and can readily cross the blood brain barrier. Within the brain it is taken up by dopaminergic neurons and converted to dopamine. It is used to replace dopamine lost in Parkinson’s disease.

Question 26

Phenelzine

Answer 26

Phenelzine is an antidepressant. Its mechanism of action is not fully determined, but it is believed to irreversibly inhibit monoamine oxidase (MAO). There are two forms of MAO, (A+B). MAO-A is found in cells in the periphery, whilst MAO-B is found extracellularly and predominately in the brain. The two subtypes are different substrates, with MAO-A catalysing the breakdown of serotonin, norepinephrine, epinephrine, dopamine and tyramine, whilst MAO-B acts on phenylethylamine, norepinephrine, epinephrine, dopamine and tyramine. As Phenelzine inhibits MAO, it therefore increases the concentration of free amines, most specifically serotonin and norepinephrine. MAO A inhibition is thought to be more relevant to antidepressant activity as selective MAO B inhibitors (selegiline), have no antidepressant effects.

As with other antidepressants, several weeks of therapy may be required in order to realize it’s full clinical benefit. It is not the first choice ant-depressant therapy available.