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Jamie Manuell Year 2 Pharmacology & Therapeutics.

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Presentation on theme: "Jamie Manuell Year 2 Pharmacology & Therapeutics."— Presentation transcript:

1 Jamie Manuell Year 2 Pharmacology & Therapeutics

2 Drugs and the Autonomic Nervous System

3 Cholinomimetics Directly Acting

4 acetylcholine Class Directly acting cholinomimetic MOA Neurotransmitter. Acts on muscarinic or nicotinic receptors. in Autonomic NS Indications Side Effects Other

5 Bethanecol Class Directly acting cholinomimetic Parasympathomimetic MOA Choline ester, selective for muscarinic receptors, then M 3. Not acted on by acetylcholinesterase so long lasting. They increase detrussor muscle contraction, by stimulating post synaptic receptors Indications Gut and Bladder stimulation postoperatively Side effects Bronchoconstriction / secretion, salivation Other

6 Pilocarpine Class Directly acting cholinomimetics, i.e. muscarinic agonist MOA Alkaloid, selective for muscarinic receptors. Causes constriction of the constrictor pupillae muscles of the iris, allowing aqueous humour to drain into trabecular meshwork. Indications Given to treat glaucoma (by causing pupil constriction and therefore aiding drainage) Side Effects Eye irritation, headache and browache, blurred vision, hypersalivation, may exacerbate asthma. Other Not with acute iritis, anterior uvetis

7 Cholinomimetics Indirectly Acting

8 Neostigmine Class Intermediate lasting Anticholinesterase MOA Inhibits acetylcholinesterase by addition of a Carbamyl group to the enzyme and so increases the amount of ACh in the synaptic cleft. Indications Used IV to reverse the effects of non depolarising blockers. Shows some selectivity for the NMJ Side Effects Other Despite selectivity, atropine is sometimes co-administered to block muscarinic effects of the drug.

9 Physostigmine Class Intermediate acting anticholinesterase. MOA Inhibit AChE so increasing amount of ACh in the synaptic cleft. Shows selectivity for the postganglionic parasympathetic junction. Indications Used to constrict the pupil, and contract the ciliary muscle in glaucoma. Side Effects Initial excitation, followed by depression, followed by respiratory depression and unconsciousness. Other Tertiary amine, so can cross the blood/brain barrier. Central effects can be combated by atropine.

10 Ecothiapate Class Long lasting anticholinesterase. Organophosphorous compound. MOA Irreversible inhibitor of AChE, so increasing ACh duration of action in synaptic cleft. Inhibit enzyme by phosphorylation. Enhance muscarinic activity. Moderate dose affects all autonomic ganglia, high doses causes depolarising block at ganglia. Indications Treatment of glaucoma Side Effects Bradycardia, breathing problems, depolarizing neuromuscular block, central effects, and possible death form peripheral nerve demyelination. Other Phosphorylated enzyme is stable, so new enzymes have to be produced to regain function.

11 Cholinoceptor Antagonists Muscarinic Antagonists

12 Atropine Class Non selective Muscarinic cholinoceptor Antagonist MOA Bind to receptor, but has no intrinsic activity, effect therefor depends on previous level of supplied tone by the agonist. Indications Reduces gastrointestinal motility, cardiac arrest, prevent salivation, bronchial secretions, protect heart from arrhythmias, particularly those caused by neuromuscular blockers. Side Effects Dry mouth and skin, raised body temperature, dilatation of pupil, relaxation of ciliary msucle (no accomodation) urinary retention, irritability and hyperactivity Other Different tissues have different levels of responsiveness. Salivary, sweat, bronchial>parietal cells production of gastric acid. Treat poisoning with anticholinesterase drugs The one from the belladonna alkaloids, found in deadly nightshade.

13 Class Muscarinic Receptor Antagonist, antiemetic MOA Binds to receptor making it inaccessible for ACh to activate receptor. Emetic actions in vest. Nuclei, NTS, vomiting centre, to block VCs activation. Indications Used to prevent bronchial secretions and salivations.protect heart from arrhythmias, particularly those caused by neuromuscular blockers. Prevention of motion sickness, parkinsons disease. Side Effects Dry mouth and skin, raised body temperature, dilatation of pupil, relaxation of ciliary msucle (no accomodation) urinary retention, irritability and hyperactivity. Drowsiness, slow gut movement. Other Different tissues have different levels of responsiveness. Salivary, sweat, bronchial>parietal cells production of gastric acid. Hyoscine (Scopoloamine)

14 Tropicamide Class Non-selective Muscarinic cholinoceptor Antagonist MOA Indications Motion sickness, to dilate the pupil to view the retina. Side Effects Low exocrine secretions, initial drop in HR followed by tachycardia. Initial excitation, then depression, amnesia, tranquility, OD – Coma, respiratory depression, death Other

15 Ipratropium Bromide Class Muscarinic Receptor Antagonist, parasympatholytic MOA Inhaled, blocks action of acetylcholine. Indications Used in bronchodilation. For asthma and obstructive airways disease. Side Effects Systemic effects of blocking muscarinic cholinoceptors. Other

16 Cholinoceptor Antagonists Nicotinic Antagonists

17 Trimetapham Class Short lasting Nicotinic cholinoceptor Antagonist (also known as ganglion blockade) MOA Blocks transmission at all autonomic ganglia (parasympathetic and sympathetic). Indications Used clinically to provide 2-3 minutes of hypotension in surgery Side Effects Drop BP, Impaired postural reflexes, reduced renin secretion, decreased GI motility, impotence, impaired bladder emptying, inhibition of all glands, dilated pupils, poor eye reflex, far vision. Other They Do Not block transmission at nicotinic receptors in the skeletal NMJ. Actions depend on the prevailing autonomic tone to the target organ.

18 Hexamethonium Class Nicotinic Receptor Antagonist MOA Blocks transmission at all autonomic ganglia (parasympathetic and sympathetic). Indications No longer used clinically Side Effects Drop BP, Impaired postural reflexes, reduced renin secretion, decreased GI motility, impotence, impaired bladder emptying, inhibition of all glands, dilated pupils, poor eye reflex, far vision. Other

19 Non Depolarising Neuromuscular Blockers

20 Tubocurarine Class Non depolarising Neuromuscular Blockers Competitive MOA Competitive neuromuscular blocking drug, bind to the nicAChR but dont activate it, therefore cause neuromuscular block % must be blocked for its actions to take place. Indications Surgery to stop reflexes. Side Effects Partial ganglion block, mild histamine release, rare hypersensitivity Other

21 Atracurium Class Non-depolarising Neuromuscular blockers MOA Like tubocurarine, but with shorter duration of action. Competitive neuromuscular blocking drug, bind to the nicAChR but dont activate it, therefore cause neuromuscular block % must be blocked for its actions to take place. Indications preventing reflexes in surgery Side Effects Reduction in BP, bronchospasm, tachycardia and apnoea. Other

22 Depolarising Neuromuscular Blockers

23 Suxamethonium Class Depolarising neuromuscular blockers, causing phase 1 block. MOA Binding to and exciting postsynaptic nAChR, but for a long period of time (mins vs ms for ACh). Eventually, APs can no longer be produced because voltage sensitive Na channels have been inactivated – get flaccid paralysis. Indications Only one used clinically because of its rapid onset and short duration of action (4 minutes) Side Effects Initial spasms, resulting in postoperative muscle pain. Muscarinic receptor activation resulting in bradycardia. (prevented by administering atropine). Potassium release from muscle giving elevated potassium levels. Other Some people with funny AChE may suffer NMB for hours. In myasthenia gravis dont do anything because already have v few receptors on end plate.

24 Adrenoceptor Agonists Directly Acting

25 Adrenaline Class Non selective α&β adrenoceptor agonist MOA Binds to and excites the α&β adrenoceptors, giving its actions. Indications Acute anaphylactic reactions – inhibits mediators of immune response. Cardiac stimulant in heart block, prolongs action of local anaesthetics (vasoconstrictor). Maintain bp during spinal anaesthesia. Decrease blood flow for use in glaucoma. Side Effects Tachycardia, arrhythmia, hypertension, cerebral haemorrhage, pulmonary oedema, low mucus secretions, tremor due to skeletal muscle effects. Other

26 Salbutamol Class Β2 selective Adrenoceptor Agonist MOA Stimulates B2 receptors in the SM of the lungs and bronchi, inhibits the release of bronchoconstrictor substances from mast cells. Relative resistance to MAO and COMT Indications Ventolin (asthma inhaler), uterine relaxation (if premature labour) Side Effects Arrhythmias, tachycardia, vasodilation Other Given by aerosol so limited systemic effects.

27 Dobutamine Class Positive Chronotrope, Beta 1 adrenoceptor agonist MOA β1 adrenoreceptors are linked to adenyl cyclase and their activation leads to increased cAMP levels, which leads to and increase in intracellular calcium and so to an increased cardiac force of contraction. Indications CCF, all shocks, cardiomyopathy, cardiac surgery. Side Effects Tachycardia and hypertension Other Not to be given to tachyarrhythmic patients.

28 Isoprenaline Class Non selective beta Adrenoceptor Agonist MOA Simple agonist Indications Treatment of heart block, Side Effects Reflex tachycardia, dysrhythmias. Other Less susceptible to uptake 1 and MAO than adrenaline.

29 Phenylephrine Class Selective for a1 receptors MOA Simple agonist (Relatively resistant to COMT but not MAO) Indications Nasal decongestant (Drops/PO) Myadriatic (Eye Drops) Vasoconstrictor (IV) Side Effects Hypertension Other

30 Clonidine Class Alpha 2 selective Adrenoceptor Agonist. MOA Reduces sympathetic tone via central brainstem action within baroreceptor pathway, to reduce sympathetic outflow. Indications Hypertension and migraine. Side Effects Drowsiness, hypotension Other

31 Ephedrine Class Indirectly acting Adrenoceptor Agonist. (promote NA release) MOA Taken in by uptake 1 and displace NA from the vesicles. Also inhibit MAO, so displaced NA can continue to have a sympathetic effect. Potentiate actions of NA. Indications When you need more sympathomimetic. Useful in restoring blood pressure and tissue perfusion in cases of shock. Decongestant (vasoconstriction of nasal BVs) Side Effects Tachycardia, arrhythmias, dry mouth, cold extremities, anxiety… other α & β stimulation issues. Other Watch out for neglecting ither things such as kidney.

32 Adrenoceptor agonists Indirectly Acting

33 Cocaine Class Sympathetic enhancer MOA Strongly inhibits the reuptake of catecholamines at NAergic neurons and thus strongly enhances sympathetic activity. Indications Abuse. Occaisionally used as a topical anaesthetic by ear, nose and throat specialists. Side Effects Toxic psychosis, cardiac arrhythmias, hypertension, and stroke. Psychological dependence, but no real physical dependence. Chronically produces paranoid psychosis, vasoconstriction, tissue anoxia at sites of injection, damage to fetal brain. Withdrawl causes a in motor performance, restorable on provision of the drug.

34 Tyramine Class Weak agonist Monoamine compound derived from the amino acid Tyrosine MOA Tyramine competes with catecholamines for uptake 1, displaces NA from storage vesicles into cytosol, this leaks into the synapse and stimulates postsynaptic adrenoceptors, also competes for sites on MAO Indications Found in the diet (Cheeses) Side Effects When MAO is inhibited (Antidepressants – Phenelzine) indigestion of food containing tyramine may result in a hypertensive crisis (Cheese Reaction)

35 Adrenoceptor Antagonist

36 Propranolol Class Non selective beta adrenoceptor antagonist. Anxiolytics. MOA Acts by antagonism at β- adrenoceptors so that excessive catecholamine release does not produce the usual sympathetic responses. Indications Hypertension, angina, arrhythmias, good at alleviating signs of sympathetic arousal, such as palpitations, tremor, sweating and diarrhoea. Also useful in socially anxious people or musicians with stage fright. Side Effects Bradycardia, heart failure, bronchospasm, peripheral vasoconstriction Other Not in people with asthma or heart failure.

37 Class Negative chronotrope and inotropes, beta blocker, beta 1 selective MOA Competitive antagonist for beta 1 adrenoceptor so reduces sympathetic innervation of the heart. Lowers tachycardia and force of contraction. Indications Given after MI, hypertension, prophylaxis, anti-arrhythmia, thyrotoxicosis, glaucoma and anxiety Side Effects Bronchospasm, bradycardia, heart block, hypotension Other At high doses loses selectivity, so caution for asthmatics. Not in bradycardia, hypotension, AV block, and CCF Atenolol

38 Labetalol Class Alpha/beta blocker Adrenoceptor antagonist MOA Lowers BP by a reduction of peripheral resistance. This is via blockade of α1 in blood vessels and β1 effects on neurotransmitter renin release. No change in HR or CO Indications Hypertension Side Effects Postural hypotension Other

39 Phentolamine Class Non selective α antagonist. MOA Causes vasodilation and a fall in BP due to blockade of α1/2 receptors. Indications hypertension Side Effects Increased GI motility, so diarrhoea a common problem. Other Blockade o f α receptors tend to increase noradrenaline release (enhances the reflex tachycardia seen with any bp lowering agent)

40 Doxazosin Class α 1 adrenoceptor antagonist. MOA Cause inhibition of α 1 adrenoceptor mediated vasoconstriction, so reducingPVR and venous pressure. Also lower LDL, VLDL, and TGA, and increase HDL, reducing risk of CAD Indications Hypertension, (esp with CCF), prostate hyperplasia (reduced bladder and prostate resistance) and CAD. Side Effects Postural hypotension, dizziness, headache and fatigue, weakness palpitations, and nausea. Other

41 False Transmitters

42 Methyldopa Class False transmitter, antihypertensive agent MOA Taken up by NAergic neurons, where decarboxylated and hydroxylated to form α methyl NA. Not metabolised by MAO, so shunts NA from synaptic vesicles. Release as NA but less active that NA on post α1 receptors, so less vasoconstriction, and more active on presynaptic α2 receptor. Stimulates vasopressor centre to inhibit sympathetic outflow. Indications Renal blood flow well maintained so a good hypertensive in patients with renal insufficiency. Good in pregnancy as has no adverse effects on foetus. Side Effects Dry mouth, sedation, postural hypotension, male sexual dysfunction, liver looks like hepatitis. Orthostatic hypotension. Other

43 Drugs and the Heart & Vasculature

44 Positive Chronotropes

45 Digoxin Class Positive Chronotrope (cardiac glycoside) MOA These act by inhibiting the membrane Na+/K+ ATPase pump. This raises intracellular Na, decreasing Na gradient, meaning less Ca is pumped out in the Ca/Na exchanger. Ca levels increase, and so does force of contraction. Stimulation of vagus shorten atrial AP. They decrease HR, and reduce AV conductance for use in arrhythmias. Indications Heart failure and superventricular arrhythmias. Side Effects At high doses they raise Sym stimulation causing arrhythmias and heart block. Nausea, vomitting, visual disturbances, ab pain, diarrhoea. Other Contraindications are heart block and hypokalaemia. Narrow therapeutic window. In toxicity, potassium supps and anti- arrhythmics given.

46 Dobutamine Class Positive Chronotrope, Beta 1 adrenoceptor agonist MOA β1 adrenoreceptors are linked to adenyl cyclase and their activation leads to increased cAMP levels, which leads to and increase in intracellular calcium and so to an increased cardiac force of contraction. Indications CCF, all shocks, cardiomyopathy, cardiac surgery. Side Effects Tachycardia and hypertension Other Not to be given to tachyarrhythmic patients.

47 Milrinone Class Positive chronotrope, Phosphodiesterase II inhibitor MOA Phosphodiesterase is responsible for the degradation of cAMP. Inhibiting this raises cAMP levels, so contractility and vasodilation Indications Severe acute heart failure, resistant to other drugs. Side Effects Nausea, vomiting, arrhythmias, liver dysfunction, abdo pain, hypersensitivity. Other Developed to get around adverse effects with cardiac glycosides.

48 Negative Chrono and Inotropes

49 Class Negative chronotrope and inotropes, beta blocker, beta 1 selective MOA Competitive antagonist for beta 1 adrenoceptor so reduces sympathetic innervation of the heart. Lowers tachycardia and force of contraction. Indications Given after MI, hypertension, prophylaxis, anti-arrhythmia, thyrotoxicosis, glaucoma and anxiety Side Effects Bronchospasm, bradycardia, heart block, hypotension Other At high doses loses selectivity, so caution for asthmatics. Not in bradycardia, hypotension, AV block, and CCF Atenolol

50 Diltiazem Class Negative chronotrope and inotrope, rate limiting calcium channel blocker MOA These bind to and inhibit opening of the L-type calcium channels. This causes arterial vasodilation, so reducing cardiac workload. Has –ve chronotropic and inotropic effects Indications Indications are prophylaxis and treatment of angina and hypertension. Verapamil and diltiazem are given for supraventricular arrhythmias Side Effects can cause flushing, headaches, hypotension, ankle swelling, CCF, heart block, constipation Other Not to be given to patients in cardiogenic shock, severe heart failure, those taking beta-blockers, and severe bradycardia.

51 Verapamil Class Negative chronotropes and inotrope, Rate limiting calcium channel blockers MOA These bind to and inhibit opening of the L-type calcium channels. This causes arterial vasodilation, so reducing cardiac workload. Has –ve chronotropic and inotropic effects Indications Indications are prophylaxis and treatment of angina and hypertension. Verapamil and diltiazem are given for supraventricular arrhythmias Side Effects can cause flushing, headaches, hypotension, ankle swelling, CCF, heart block, constipation Other Not to be given to patients in cardiogenic shock, severe heart failure, those taking beta-blockers, and severe bradycardia.

52 Drugs reducing Preload & Afterload

53 Ramipril / Enalapril Class Ace Inhibitor to reduce preload and afterload MOA These work by preventing angiotensin I to Angiotensin II, meaning that the ATI receptors in the arterioles and in the adrenal cortex are not triggered, resulting in increased water and sodium excretion in the kidney Indications Indications are in CVD, such as hypertension, post MI, Diabetic neuropathy, Progressive renal insufficiency, patients at high risk of CVD. Side Effects Adverse effects are hypotension, dry cough and angioedema. Other Not in pregnancy, renovascular disease, aortic stenosis

54 Captopril Class Ace inhibitor MOA These work by preventing angiotensin I to Angiotensin II, meaning that the ATI receptors in the aterioles and in the adrenal cortex are not triggered, resulting in increased water and sodium excretion in the kidney Indications Indications are in CVD, such as hypertension, post MI, Diabetic neuropathy & nephropathy, Progressive renal insufficiency, patients at high risk of CVD. Side Effects Adverse effects are hypotension, dry cough and angioedema. Other Not in pregnancy, renovascular disease, aortic stenosis

55 Losartan Class Angiotensin receptor blocker MOA Cause inhibition at the angitensin II receptor, resulting in vasodilation with reduction in PVR. Indications Hypertension Side Effects Cough, orthostatic hypotension, dizzyness, headache, fatigue, hyperkalaemia and rash. Other Contraindications in breastfeeding, pregnancy. Caution in renal artery stenosis and aortic stenosis.

56 Nicorandil Class Organic nitrate (reducing preload and afterload). Potassium channel activator MOA Activates potassium channels of vascular SM. Potassium flows out of the cells causing hyperpolarisation. This inhibits the influx of calcium, so inhibits contraction – hence vasodilation. Indications Prophylaxis of angina Side Effects Headache, cutaneous vasodilation, nausea and vomiting Other Cardiogenic shock, left ventricular failure, hypotension.

57 Bendrafluazide Class Thiazide diuretic MOA These act on the early distal tubule. They inhibit the Na/Cl cotransporter in the luminal membrane. They increase secretion of K and protons into the collecting ducts, but decrease Ca excretion. Indications Hypertension, oedema 2ndary to CCF, liver disease, or nephrotic syndrome. Sometimes for prophylaxis of calcium containing renal stones. Side Effects Hypokalaemia, hyperuricaemia, hyponatraemia, hypercalcaemia, and metabolic acidosis. Other Shouldnt be used in those taking cardiac glycosides, or diabetes mellitus (as may cause hyperglycaemia). Or in hypokalaemia, hyponatraemia, or hypercalcaemia.

58 Spironalactone Class Aldosterone antagonist. MOA Inhibits the sodium retaining effects of aldosterone. Indications It is useful in heart failure and resistant cases of hypertension. Side Effects Can cause hyperkalaemia due to sodium retention, and steroid like side effects like gynaecomastia, menstrual disorders, and testicular atrophy. Other Due to +ve feedback, more aldosterone may be produced, increasing unwanted side effects. Doesnt prevent aldosterone production.

59 Drugs to control or correct Dysrhythmias

60 Amiodarone Class Wide spectrum anti-arrhythmic, potassium channel blockers. MOA These are potassium channel blockers which prolong cardiac action potential duration, and the refractory period. It also blocks sodium and calcium channels, and blocks β and α adrenoceptors. Indications For ventricular and supraventricular arrhythmias. Side Effects Can cause arrhythmias, thyroid dysfunction, liver damage, pulmonary disorders, photosensitivity and neuropathy. Other Not to be given to those with AV block, sinus bradycardia, or thyroid dysfunction

61 Diltiazem Class Negative chronotrope and inotrope, rate limiting calcium channel blocker MOA These bind to and inhibit opening of the L-type calcium channels. This causes arterial vasodilation, so reducing cardiac workload. Has –ve chronotropic and inotropic effects Indications Indications are prophylaxis and treatment of angina and hypertension. Verapamil and diltiazem are given for supraventricular arrhythmias Side Effects can cause flushing, headaches, hypotension, ankle swelling, CCF, heart block, constipation Other Not to be given to patients in cardiogenic shock, severe heart failure, those taking beta-blockers, and severe bradycardia.

62 Verapamil Class Negative chronotropes and inotrope, Rate limiting calcium channel blockers MOA These bind to and inhibit opening of the L-type calcium channels. This causes arterial vasodilation, so reducing cardiac workload. Has –ve chronotropic and inotropic effects Indications Indications are prophylaxis and treatment of angina and hypertension. Verapamil and diltiazem are given for supraventricular arrhythmias Side Effects can cause flushing, headaches, hypotension, ankle swelling, CCF, heart block, constipation Other Not to be given to patients in cardiogenic shock, severe heart failure, those taking beta-blockers, and severe bradycardia.

63 Digoxin Class Positive Chronotrope (cardiac glycoside) MOA These act by inhibiting the membrane Na+/K+ ATPase pump. This raises intracellular Na, decreasing Na gradient, meaning less Ca is pumped out in the Ca/Na exchanger. Ca levels increase, and so does force of contraction. Stimulation of vagus shorten atrial AP. They decrease HR, and reduce AV conductance for use in arrhythmias. Indications Heart failure and superventricular arrhythmias. Side Effects At high doses they raise Sym stimulation causing arrhythmias and heart block. Nausea, vomitting, visual disturbances, ab pain, diarrhoea. Other Contraindications are heart block and hypokalaemia. Narrow therapeutic window. In toxicity, potassium supps and anti- arrhythmics given.

64 Class Negative chronotrope and inotropes, beta blocker, beta 1 selective MOA Competitive antagonist for beta 1 adrenoceptor so reduces sympathetic innervation of the heart. Lowers tachycardia and force of contraction. Indications Given after MI, hypertension, prophylaxis, anti-arrhythmia, thyrotoxicosis, glaucoma and anxiety Side Effects Bronchospasm, bradycardia, heart block, hypotension Other At high doses loses selectivity, so caution for asthmatics. Not in bradycardia, hypotension, AV block, and CCF Atenolol

65 Coronary Vasodilators

66 Diltiazem Class Negative chronotrope and inotrope, rate limiting calcium channel blocker MOA These bind to and inhibit opening of the L-type calcium channels. This causes arterial vasodilation, so reducing cardiac workload. Has –ve chronotropic and inotropic effects Indications Indications are prophylaxis and treatment of angina and hypertension. Verapamil and diltiazem are given for supraventricular arrhythmias Side Effects can cause flushing, headaches, hypotension, ankle swelling, CCF, heart block, constipation Other Not to be given to patients in cardiogenic shock, severe heart failure, those taking beta-blockers, and severe bradycardia.

67 Verapamil Class Negative chronotropes and inotrope, Rate limiting calcium channel blockers MOA These bind to and inhibit opening of the L-type calcium channels. This causes arterial vasodilation, so reducing cardiac workload. Has –ve chronotropic and inotropic effects Indications Indications are prophylaxis and treatment of angina and hypertension. Verapamil and diltiazem are given for supraventricular arrhythmias Side Effects can cause flushing, headaches, hypotension, ankle swelling, CCF, heart block, constipation Other Not to be given to patients in cardiogenic shock, severe heart failure, those taking beta-blockers, and severe bradycardia.

68 Glyceryl Trinitrate Class Organic Nitrates MOA Release NO which activates Guanylate cyclase causing more cGMP and more Ca storage in the SR, hence Venodilation which reduces preload and therefore SV and CO, also coronary vessel vaso-d Indications Angina Side Effects Venodilation causes Postural hypotension, dizziness, syncope and reflex tachy. Arterial dilation causes throbbing headaches and flushing Other

69 Minoxidil Class K+ channel opener MOA Potent vasodilator acting on arteries and arterioles by opening potassium channels in SM and causing hyperpolarisation. Indications Used in hypertension control in pregnancy Side Effects In the absence of β blockade it causes reflex tachycardia. Other

70 Doxazosin Class α 1 adrenoceptor antagonist. MOA Cause inhibition of α 1 adrenoceptor mediated vasoconstriction, so reducingPVR and venous pressure. Also lower LDL, VLDL, and TGA, and increase HDL, reducing risk of CAD Indications Hypertension, (esp with CCF), prostate hyperplasia (reduced bladder and prostate resistance) and CAD. Side Effects Postural hypotension, dizziness, headache and fatigue, weakness palpitations, and nausea. Other

71 Vasoconstrictors

72 Sumitriptan Class Agonist at 5HT 1D receptors MOA Causes vasoconstriction at some large arteries and inhibits trigeminal nerve transmission, Indications Used to treat migraine attacks Side Effects Sensation of tingling, heat, chest tightness Other Contraindicated in patients with CAD as it causes coronary vasoconstriction, hepatic impairment, pregnancy and breastfeeding.

73 Anti-Thrombotic & Anticoagulants

74 Thrombolytics (Fibrinolytics)

75 Streptokinase Class Tissue plasminogen activator MOA This forms a complex with and activates plasminogen into plasmin, a fibrinolytic enzyme Indications Life threatening venous thrombosis, pulmonary embolism, arterial thromboembolism, and acute MI. Side Effects Nausea, vomiting and bleeding. Derived form streptococcus, therefore antigenic. Repeated administration could result in anaphylaxis. Other Not for use in recent haemorrhage, trauma, surgery or any form of Cerebrovascular disease.

76 Alteplase Class Tissue type plasminogen activator MOA Binds with and activates plasminogen into plasmin, which breaks down fibrin in a clot. Indications Useful as a fibrinolytic if the antigenic streptokinase has already been administered once, as it is non antigenic. MI, Pulmonary embolism Side Effects Nausea, vomiting, and bleeding Other Same as streptokinase, ie any patient who has recently suffered a trauma likely to have required clot formation.

77 Anticoagulants

78 Warfarin Class Vitamin K antagonist MOA Vitamin K is vital in the post transcriptional γ-carboxylation of glutamic acid residues of prothrombin (factor II) and clotting factors VII, IX, and X by the liver. This stops clotting cascade Indications Warfarin can be used in treatment of DVT and pulmonary embolism, prophylaxis of embolisation in atrial fibrillation and rheumatic disease and in patients with prosthetic heart valves Side Effects haemorrhage Other Warfarin only affects new factors so takes 72 hrs to take effect. Should not be used in Cerebral thrombosis, peripheral arterial occlusion, peptic ulcers, hypertension, pregnancy

79 Heparin Class Anticoagulant MOA Heparins work by activating antithrombin III, which inactivates thrombin and factor X. It also inhibits platelet aggregation Indications Heparin and LMWH given in thrombosis and pulmonary embolism, MI, prophylaxis against PO DVT and pulmonary embolism in high risk patients. Side Effects haemorrhage Other Action is immediate so can be used in emergency. Should not be used in haemophilia, thrombocytopenia, or peptic ulcers.

80 Anti-Platelet Drugs

81 Aspirin Class Cyclo-oxygennase inhibitor.acetylates the active site. MOA This inhibits the COX enzymes, which in turn inhibit production of thromboxane A2, preventing platelet aggregation. Also inhibits PGE2, making it an analgesic. COX-2 is proinflammatory. Indications In overdose can uncouple oxidative phosphorylation, causing metabolic acidosis. Side Effects Stomach ulcers, bronchoconstriction. Arachidonic acid either forms PGs with COX, or Leukotrienes with lipoxygenase. LT4 is a powerful bronchoconstrictor, more produced if COX inhibited. Asthmatics vulnerable. Reduced creatinine clearance, possible nephritis. Bad because effects COX fold more than COX-2. Other Effects vary according to dose. Asthmatics cant take them. Aspirin also displaces wafarin from plasma causing bleeding, as warfarin normally 5% unbound.

82 Clopidigrel Class Anti platelet aggregation drug. MOA Clopidogrel inhibits activation of the IIb/IIIa receptor on the surface of platelets, required for aggregation to occur. Indications Used if patient truly allergic to aspirin. Secondary prevention of CVD. Side Effects Haemorrhage, ab discomfort, nausea and vomiting. Other

83 Abciximab Class Glycoprotein IIb/IIIa inhibitor MOA It is an antibody fragment antagonist of the glycoprotein IIb/IIIa receptor on platelets. This prevents aggregation. Indications Used if problems with other ones. Ischaemic cardiac complications in open heart surgery. Short term prevention of MI in unstable angina. Side Effects Haeorrhage, nausea, vomiting hypotension. Other Single administration because it is antigenic, potential anaphylaxis if second administration

84 Statins

85 Simvastatin Class HMG-CoA Reductase Inhibitor MOA Catalyses the enzyme that is the rate limiting step in Cholesterol synthesis in the Liver, the fall in circulating Cholesterol then causes up regulation of LDL receptors on hepatocytes cell surfaces, also reduces circulating VLDLs and TGs Indications Hyperlipidaemia Side Effects GI upsets CNS effects (Dizziness, blurred vision, headache) Cause of abnormal LFTs Myalgia if used with Fimbrates Other Stabilizes atherosclerotic plaques and reduces inflammatory cell migration into plaques

86 NSAIDS

87 Aspirin Class Cyclo-oxygennase inhibitor.acetylates the active site. MOA This inhibits the COX enzymes, which in turn inhibit production of thromboxane A2, preventing platelet aggregation. Also inhibits PGE2, making it an analgesic. COX-2 is proinflammatory. Indications In overdose can uncouple oxidative phosphorylation, causing metabolic acidosis. Side Effects Stomach ulcers, bronchoconstriction. Arachidonic acid either forms PGs with COX, or Leukotrienes with lipoxygenase. LT4 is a powerful bronchoconstrictor, more produced if COX inhibited. Asthmatics vulnerable. Reduced creatinine clearance, possible nephritis. Bad because effects COX fold more than COX-2. Other Effects vary according to dose. Asthmatics cant take them. Aspirin also displaces wafarin from plasma causing bleeding, as warfarin normally 5% unbound.

88 Ibuprofen Class NSAID, COX-2 antagonist MOA Works as a competitive substrate for the COX-2 enzyme, preventing the arachidonic acid conversion by COX-2 into prostaglandins, and prostacyclins. Indications Mainly for high risk GI patients who would get stomach ulcers from Aspirin. Drug of choice for inflammatory joint disease Side Effects Very few Other

89 Celecoxib Class This is a selective COX-2 inhibitor MOA Selective but expensive COX-2 inhibitor. Used for high risk GI as no COX-1 side effects. Also less effect on nephrotoxicity. Indications High risk GI anti-inflammatory Side Effects Other Contraindicated in Inflammatory bowel disease.

90 Diuretics

91 Mannitol Class An osmotic diuretic. MOA Freely filtered at the glomerulus, but only partially reabsorbed. Means that water leaves tubule under osmosis, and more sodium is excreted, and there is less free reabsorption of water. Indications Raised intracranial and intrtaocular pressure. Side Effects Chills and Fever Other Contraindicated in congestive cardiac failure, and pulmonary oedema.

92 Acetazolamide Class Carbonic anhydrase inhibitor. Weak diuretics MOA Acts in the proximal tubule to prevent the usual removal of Na + and HCO 3 -, water follows. Prescence of Na + in the distal tubule also increases excretion of K +. Indications Not normally used as diuretics but of value in the treatment of glaucoma. Side Effects Loss of carbonate can result in metabolic acidosis. Other

93 Frusemide Class Loop diuretic – powerful diuretic MOA Act on thick ascending segment of the L of H. Inhibit the Na+, K+, 2Cl- cotransporter in the luminal membrane. This dilutes the medullary interstitium and reduces the concentrating power in the collecting duct. delivery of Na to distal tubule activates Na/K exchanger. Gives urine, excretion of Na, K, Cl, Ca, Mg Indications Acute pulmonary oedema, oedema due to heart failure, liver disease, renal disease, hypercalcaemia, hyperkalaemia, Acute renal failure Side Effects Metabolic acidosis, hypokalaemia, loss of Ca, Mg, hypovolaemia, hypotension, nausea, deafness, allergies. Other

94 Bendrofluazide Class Thiazide MOA Inhibition of Na and Cl reabsorption in the early distal tubule. solute reabsorption of water, volume, Na, K, Cl, and Mg. Reduced loss of Ca. Also vasodilation and insulin production due to opening of K channels. Indications Congestive Heart failure, hypertension, Idiopathic hypercalcaemia, nephrogenic diabetes insipidus Side Effects Hypokalaemia, alkalosis, hypperglycaemia, uric acid retention (gout). Allergies, hyponatraemia. Other

95 Spironalactone Class Aldosterone antagonists, potassium sparing diuretic. MOA This is a competitive antagonist at aldosterone receptors, Na reabsorption, and potassium and proton secretion. Mild diuresis, excretion of 2-3% of Na. Indications Heart failure and resistant cases of hypertension Side Effects Hyperkalaemia due to sodium retention, and steroid like effects like gynaecomastia, menstrual disorders, and testicular atrophy. Other

96 Amiloride Class Potassium sparing diuretic, Sodium Channel Blocker, distal tubule MOA These block sodium reabsorption by the principal cells, thus reducing the potential difference across the cell, and potassium secretion Indications With K losing diuretics to prevent K loss. Primary and secondary hyperkalaemia. Side Effects Better tolerated than spironalactone. Hyperkalaemia, hyponatraemia, GI disturbances. Other

97 Anti-Emetics

98 Promethazine (Remember Promet-h-azine) Class Anti-emetic (phenothiazine derivative) H1>M>D2 MOA Acts as a competitive antagonist at histaminergic (H1), cholinergic (M), and dopaminergic receptors. (Mostly H1). It acts centrally (Labyrinth, NTS, vomiting centre) to block activation of the vomiting centre. Indications Motion sickness (prophylaxis), labyrinth disorders (ie Menieres disease), morning sickness, pre and post operatively. Sedative and anti muscarinic actions are also useful. Side Effects Dizziness, fatigue, Tinnitus, sedation, Excitation in excess, convulsions, Antimuscarinic side effects. Other

99 Metoclopramide (Remember metoclopromi-d-e) Class Anti-emetic. Receptor antagonist. D2>>H1>>M MOA Acts on D2 receptors, especially centrally at the central trigger Zone. Acts in the GI tract in SM motility, in Gastric emptying. Indications Nausea and vomiting associated with uraemia, radiation sickness, GI disorders, Cancer chemotherapy like cisplatin. Side Effects Drowsiness, dizziness, anxiety, extrapyramidal reactions, no anti- psychotic reactions unlike other D antagonists. Other Competes with other drugs. Adsorption and effectiveness of digoxin is. Accelerate GI may cause nutrient deficiency.

100 Class Muscarinic Receptor Antagonist, antiemetic MOA Binds to receptor making it inaccessible for ACh to activate receptor. Emetic actions in vest. Nuclei, NTS, vomiting centre, to block VCs activation. Indications Used to prevent bronchial secretions and salivations.protect heart from arrhythmias, particularly those caused by neuromuscular blockers. Prevention of motion sickness, parkinsons disease. Side Effects Dry mouth and skin, raised body temperature, dilatation of pupil, relaxation of ciliary msucle (no accomodation) urinary retention, irritability and hyperactivity. Drowsiness, slow gut movement. Other Different tissues have different levels of responsiveness. Salivary, sweat, bronchial>parietal cells production of gastric acid. Hyoscine (Scopolamine)

101 Ondansetron (Remember ondan-s-etron) Class Anti emetic, 5HT 3 (Serotonin) receptor antagonist. MOA Blocks 5HT 3 receptors in visceral afferents and central trigger zone Indications Anti emetic in chemotherapy induced vomiting, especially cisplatin. Radiotherapy induced sickness, PO nausea and vomiting. Side Effects Headache, sensation of flushing and warmth, increased large bowel transit time (constipation) due to 5HT 3 receptor block. Other

102 Drugs used for Gastric & Duodenal Ulcers

103 Antimicrobials

104 Metronidazole Class Antiprotozoal and antibacterial against anaerobic bacteria. Antibiotic to eliminate helicobacter pylori – bactericidal. MOA Metabolised to an intermediate that inhibits bacterial DNA synthesis and degrades existing DNA. Selective because intermediate form is not produced in mammalian cells. Indications Helicobacter pylori eradication in peptic ulcer sufferers. Side Effects Mild headache and GI disturbance. ADRs with alcohol Other Not to pregnant women

105 Amoxycillin Class Broad spectrum Penicillin antibiotic. MOA Inihibit bacterial wall synthesis. They bind to penicillin binding proteins. This results in inhibition of peptide crosslinking within the cell wall, and indirect activation of autolytic enzymes, resultant lysis. Indications Broad spectrum so loads of applications. Used in eradication of helicobacter pylori in peptic ulceration. Side Effects Specific and safe but possible hypersensitivity reactions inc. rashes and anaphylaxis. Diarrhoea common, neurotoxicity at CSF levels. Other Not for known hypersensitivity sufferers. Resistance can be due to microbial production of a β- lactamase enzyme which breaks the β-lactam ring of penicillins.

106 Clarithromycin Class Macrolide. Bactericidal/bacteriostatic. MOA They bind to the bacterial ribosome, preventing the translocation movement of the ribosome along mRNA. Inhibits translocation of bacterial tRNA. Indications Good against gram +ve bacteria and spirochaetes. Haemophilus influenzae, mycobacterium avium cellulare, and helicobacter pylori. Side Effects GI disturbance Other Resistance due to alteration of binding site of ribosome.

107 Inhibitors of Gastric Acid Secretion

108 Omeprazole Class Proton pump inhibitor in Peptic ulceration. MOA Prodrug converted in acidic pH to sulphonamide, which binds covalently to the suphydryl groups on H + /K + ATPase responsible for gastric acid secretion. Inihibit acid secretion by >90%. Is a weak base so attracted to acidic areas like cannaliculi of parietal cells. Prevents widespread actions. Indications Peptic ulceration, reflux oesophagitis, H 2 receptor antagonist resistant patients. Side Effects GI upset, nausea, headaches. Potential gastric atrophy Other

109 Cimetidine ranitidine Class H 2 receptor antagonists. MOA Block actions of histamine on parietal cells Indications First line treatment of GORD and peptic ulcer disease. Side Effects Dizziness, fatigue, gynaecomastia, and rash Other Less effective than PPIs at healing ulcers (60% in acid secretion). Inhibits p450 enzymes, so not to be administered with warfarin, phenytoin, and theophylline.

110 Cytoprotective Drugs

111 Sucralfate Class Polymer containing aluminium hydroxide and sucrose octa- sulphate. Cytoprotective drugs. MOA It acquires a strong negaitve charge in acidic environment. Binds to +ve proteins forming a protective gel over the ulcer, not allowing peptins or acids to damage. mucus, PGs and HCO 3 -, helicobacter pylori. Indications Peptic ulcer. Side Effects Can cause constipation and may absorption of many other drugs (ie antibiotics) through stomach wall. Other

112 Bizmuth chelate Class Polymer structure as with sucralfate MOA Forms protective gel over ulcer Indications Peptic ulcer disease Side Effects Constipation, absorption of other drugs through wall. Other

113 Misoprostol Class PGE 1 analogue MOA Mimics actions of PGE 1 which stimulates mucus secretions in the gastroduadenal lining. Indications Peptic ulcer disease Side Effects Diarrhoea, uterine contractions, ab cramps. Other May be co prescribed with NSAIDs to counteract their anti PG effect chronically and prevent peptic ulcers.

114 Drugs for Inflammatory Bowel Disease

115 Glucocorticoids

116 Hydrocortisone Class Natural glucocorticoid with some mineralocorticoid actions. MOA Move into cells where they activate glucocorticoid receptors. These receptors are translocated to the DNA where they cause transcription of corticosteriod responsive genes. These have diverse effects on target tissues. See prednisolone. Can also turn off genes (reduced antigen presentation, reduced production of adhesion molecules, COX, NO, cytokines such as IL-1 and TNFα) Indications IBD (crohns, Ulcerative colitis), Anti-inflammatory, immunosuppression Side Effects Cushing like appearance. See separate slide. Adrenal suppression and atrophy. Other Withdraw slowly to avoid adrenal insufficiency crisis. Normal markers of infection suppressed so must be aware.

117 prednisolone Class Synthetic glucocorticoid. Anti- inflammatory, immunosuppressant. MOA These induce lipocortin which inhibits the conversion of membrane phosphilipid to arachidonic acid by phospholipase A 2. Leukotrienes and prostanoids are therefore not produced, suppressing inflammation and chemotaxis of immune agents. Indications IBD (crohns, UC) Side Effects As for hydrocortisone. Other

118 Budesonide Class Synthetic glucocorticoid. Anti- inflammatory, immunosuppressant. MOA Budesonide in comparison with prednisolone has been associated with fewer bone density losses and unlike other corticosteroids has little influence on the hypothalamic- pituitary-adrenal axis which also limit the need of tapering before discontinuation. Overall, it has a lower incidence of systemic manifestations than similar medications. Indications IBD (crohns, UC) Side Effects As for hydrocortisone. Other

119 Aminosalicylates

120 Sulfasalazine Class Aminosalicylate MOA Broken down in the gut to 5-ASA. These scavenge free radicals. Fewer anti-inflammatory actions and no immunosuppressive ones. AI actions are inflammatory cytokine production, PG and LT, leukocyte infiltration. Activated by gut flora from moiety. Indications Maintain remission and prevent relapse of inflammatory bowel conditions Side Effects Sulfaphrindine (non active part of sulfasalazine) reaponsible for Nausea, vomiting, headache and rashes., hypospermia, anorexia Other Not to people with renal impairment, or salicylate intolerance

121 Mesalazine Class Aminosalicylate (5-ASA) MOA Same as sulfasalazine, but without nasty side effects. Indications Inflammatory bowel syndrome. Side Effects Few, no sulfapyridine to worry about. Other

122 Immunosupressants

123 Azothioprine Class Immunosuppressive MOA Activated by gut flora to 6 metcaptopurine, a purine analogue, interferes with DNA synthesis. Inihibits cell replication, cell and antibody mediated immune reponses, lymphocyte proliferation, mononuclear cell infiltration, synthesis of antibodies. Indications Inflammatory bowel syndrome. Used to maintain remission in CD Side Effects Other More effective than other immunosuppressives so can get away with fewer GCs. Not good in gout treatment because it is metabolised by Xanthine Oxidase (target of gout treatment).

124 Anti-TNFα

125 Imfliximab Class MOA Crohns is a type 1 autoimmune response. TNF-α plays an important role in pathogenesis. Anti reduces activation of anti- TNFα receptors in the gut. Promotes apoptosis of activated T- cells. Indications Inflammatory bowel disease and other Th1 mediated AI diseases Side Effects incidence of extra pulmonary TB. Worsening of heart failure, can be immunogenic, specialist use. Other 1 IV every 8 weeks

126 Drugs used in Respiratory Disease

127 Salbutamol Class Β2 selective Adrenoceptor Agonist MOA Stimulates B2 receptors in the SM of the lungs and bronchi, inhibits the release of bronchoconstrictor substances from mast cells. Relative resistance to MAO and COMT Indications Ventolin (asthma inhaler), uterine relaxation (if premature labour) Side Effects Arrhythmias, tachycardia, vasodilation Other Given by aerosol so limited systemic effects.

128 salmeterol Class β-2 receptor agonist MOA Stmiulation of β 2 receptors in the airway SM leads to rise in intracellular cAMP levels and SM relaxation. Also prevent mast cell activation. This has potent β 2 effects but limited β 1 actions, so fewer cardiac side effects. Indications Alone to treat mild asthma and bronchospasm, but more often with corticosteroids Side Effects Fine tremor, tachycardia and hypokalaemia after high doses. Other Not in hyperthyroidism, CVD, arrhythmias.

129 aminophylline Class Phosphodiesterase inhibitor MOA Acts by raising the cAMP levels (which relaxes SM), by inhibiting phosphodiesterase, the enzyme responsible for converting cAMP to AMP. Aminophylline is the IV xanthine used in severe asthma attacks. Indications Status asthmaticus Side Effects Nausea, vomiting, tremor, insomnia, and tachycardia. Other Not often used because PDE exists everywhere in the body, cAMP is very common. Not for use in CVD, hypertension, hepatic impairment, have many drug interactions.

130 Ipratropium Bromide Class Muscarinic Receptor Antagonist, parasympatholytic MOA Inhaled, blocks action of acetylcholine. Indications Used in bronchodilation. For asthma and obstructive airways disease. Side Effects Systemic effects of blocking muscarinic cholinoceptors. Other

131 Drugs of Abuse

132 Opiates

133 Morphine Class Strong opioid analgesic MOA Acts on opiate receptors. These exist in the dorsal horn relay neurones, descending inhibitory NA fibres from the brainstem, and descending seratonergic fibres from the brainstem, all of which block sensory information from travelling in the dorsal column, leading to analgesia. Indications Drug of choice for severe pain in terminal care. Side Effects Drowsiness and sedation – initial excitement followed by sedation and coma (in OD). in sensitivity of resp centre to CO 2 leading to shallow and slow respiration, tolerance and dependence, suppression of cough (antitussive), vomiting due to CTZ stimulation, pupillary constriction due to stimulation of parasympathetic 3 rd CN nucleus, hypotension and CO, due to reduced hypothalamic sympathetic outflow. Bronchospasm, flushing and arteriolar dilation due to histamine release.

134 Heroin (dimorphine) Class Opioid drug of abuse, sometimes analgesic MOA Acts on opioid receptors. Twice as potent as morphine owing to its greater penetration of the BBB, metabolised to morphine in the body. Indications Severe pain, post operative, MI and acute pulmonary oedema. Not used as much as morphine due to added euphoria and dependence. Side Effects Causes less nausea and hypotension than morphine, but more euphoria. Other

135 codeine Class Weak opioid analgesic MOA Acts on opioid receptors. Only 1/12 analgesic potency of morphine. Indications Mild to moderate pain, Anti- tussive and anti diarrhoeal effects (taking advantage of side effects). Side Effects Nausea and constipation Other

136 methadone Class Long acting opioid analgesic. MOA Acts on opioid receptors. Withdrawl symptoms are more prolonged but less intense than withdrawl from heroin. Indications Weaning opioid addicts from their addiction Side Effects As opioid general ADRs, but not too marked. Other

137 Opiate Receptor Antagonists

138 Naloxone Class Opiate receptor antagonist MOA Acts as a competitive inhibitor at opiate receptors. Indications Used in heroin or other opioid overdose IV, along with respiratory support. Side Effects Other

139 Reuptake Inhibitors

140 Cocaine Class Sympathetic enhancer MOA Strongly inhibits the reuptake of catecholamines at NAergic neurons and thus strongly enhances sympathetic activity. Indications Abuse. Occaisionally used as a topical anaesthetic by ear, nose and throat specialists. Side Effects Toxic psychosis, cardiac arrhythmias, hypertension, and stroke. Psychological dependence, but no real physical dependence. Chronically produces paranoid psychosis, vasoconstriction, tissue anoxia at sites of injection, damage to fetal brain. Withdrawl causes a in motor performance, restorable on provision of the drug.

141 MethyleneDio xyMethAmpet amine (ecstasy) Class Serotonin (5-hydroxytryptamine) reuptake inhibitor MOA Release of monoamines, inhibition of monoamine uptake. Especially acts on serotonergic neurons, potentiating 5-HT. Indications Drug of abuse Side Effects Stimulant and hallucinogenic properties, euphoria, arousal, and perceptual disturbances are common. Feelings of euphoric empathy so that social barriers are reduced. Withdrawl like amphetamines. Toxicity results in hyperthermia, exhaustion, dehydration. Seratonergic neurodegeneration chronically.

142 Alcohol

143 Ethanol Class Alcohol MOA Acts as a volatile anaesthetic agent producing general CNS depression. Cellular mechanisms involve inhibiting calcium entry, and so reducing NT release, as well as potentiation of GABA transmission. Indications Antidote to methanol poisoning. Side Effects Physical and psychological dependence occur. Withdrawl hangover. Late stage involves delirium, tremor, hallucinations, and confusion. Acute toxicity causes ataxia, nystagmus, coma, resp. depression, and death. Chronically causes neurodegeneration (worsened by vit deficiency), dementia, liver damage, pancreatitis, and accompanying depression. vasopressin secretion causing diuresis and delayed parturition at term due to inhibitory effects at the hypothalamus. Action at ant. Pit. Causes ACTH production leading to adrenal steroid production. This leads to feminisation in males. Helped by enhanced testosterone inactivation in the liver.

144 Ethanol Aversion Therapy

145 Disulfiram Class MOA Inhibits action of Acetaldehyde dehydrogenase and so inhibits conversion of Acetaldehyde to Acetic acid Indications Ethanol aversion therapy Wanted Side Effects flushing of the skin, accelerated heart rate, shortness of breath, nausea, vomiting, throbbing headache, visual disturbance, mental confusion, postural fainting and circulatory collapse Other

146 Antimicrobial Drugs

147 Drugs which interfere with the synthesis / action of Folate

148 Sulfamethoxazole Class Sulfonamide – anti folate MOA Folate necessary to make DNA. Man has uptake processes, bacteria have to produce theirs, and need p- aminobenzoic acid. Sulfonamide is an analogue of this, meaning it isnt produced, so bacteria cant replicate. Bacterostatic, then host system can erradicate infection. Indications Not used much except in co- trimoxazole. Side Effects Nausea &vomiting, headache, mental depression. Potential severe: hepatitis, hypersensitivity, bone marrow suppression. Other Widespread resistance to these drugs.

149 Trimethoprim Class Folate antagonist. MOA Inhibits Dihydrofolate reductase, an enzyme which is more sensitive in bacteria to interference. DNA is stopped from replicating. Indications Urinary and respiratory tract infections. Side Effects Nausea & vomiting, skin rashes, hypersensitivity Other

150 Co-trimoxazole Class Folate buggerer – sequential blockade. (actually trimethoprim and sulfamethoxazole) MOA Trimethoprim blocks dihydrofolate reductase in bacteria, blocking cell replication. Sulfamethoxazole affects folate synthesis (earlier in same pathway). They potentiate one another, meaning that1/10 th the dose is needed. Indications Infections with pneumocystis carinii, which causes pneumonia in AIDS patients. Used in high doses. Side Effects Combination of effects from trimethoprim and sulfamethoxazole. Other

151 Drugs which interfere with the synthesis of Peptidoglycan

152 Penicillins Class β-lactam antibiotics. Cell wall targetting MOA Has a thiazolidine ring linked to a β-lactam ring. Prevents transpeptidisation. Antibiotic bonds to normal peptidoglycan which then cant join with others to form a lattice. Bacterium open to osmotic pressures so lyses. Indications Do not cross BBB. Side Effects Hypersensitivity (antigenic), skin rashes and fever but can be anaphylactic shock. Can also interfere with gut flora causing GI disturbance. Other Amidaze and β-lactamases can destroy the anti-biotic, normal defence mechanism. Using a β- lactamase inhibitor (clavulanic acid) normally gets round this problem. Other resistance stems from impermeability of the outer membrane, and modified penicillin binding sites.

153 cefotaxime Class Cephalosporin. Peptidoglycan targetting. MOA Like penicillins targets the peptidoglycan synthesis. Can combine two or more synergistically which target different binding sites to efficiency. Indications Meningitis due to G-ve intestinal bacteria Side Effects Hypersensitivity as seen in penicillins. Nephrotoxicity, alcohol intolerance, diarrhoea. Other Nearly all gram –ve bacteria possess β-lactamase, very effective against cephalosporins.

154 Drugs which affect Bacterial Protein Synthesis

155 tetracyclin Class Broad spectrum antibiotics MOA Inhibit bacterial protein synthesis. Actively transported into bacteria where they interfere with protein synthesis. Competes with tRNA for the binding site, doesnt kill, just stops growth. Indications Side Effects Form an insoluble complex with metal ions, so work best without food. GI disturbances common, because chelate calcium can stain teeth and lead to bone deformities. Some (doxycycline) produce sensitivity to sunlight. Other Resistance based around tetracyclines being transported out of the cell, but also on alterations of the target, the bacterial ribosome.

156 chloramphenicol Class Broad spectrum ribosome binding. MOA Inhibits protein synthesis by reversibly binding to the 50S subunit of the ribosome and inhibiting transpeptidation (formation of peptide bonds). Both bactericidal and bacteriostatic Indications Broad spectrum. V. toxix so reserved for life threatening infections such as typhoid fever and meningitis. Side Effects Depression of the bone marrow leading to pancytopenia. Not in babies because inadequate excretion can result in grey baby syndrome (40% mortality). Other Not to pregnant women or neonates. Resistance due to choloramphenicol acetyl- transferase, plasmid mediated so resistance easily transferred

157 gentamicin Class Aminoglycosides MOA Inhibit bacterial protein synthesis by binding to the 30S subunit of the ribosome, causing an alteration in codon:anticodon recognition. mRNA is read wrong, so faulty proteins produced. Transported in by O 2 dependent active transport which chloramphenicol can block. Indications Streptococcus lysteria or pseudomonas. Mostly gram-ve, some +ve. Polar so not absorbed – IV or IM. Not cross BBB. [Tissue] can become toxic. Side Effects Ototoxicity – destruction of cells in the vestibular and cochlear regions. Damage to kidney tubules (so cant be excreted – viscious circle) Other Not good anaerobically. Enhanced by cell wall disrupting agents. Resistance due to conformational binding changes, failure of penetration, or inactivation by microbial enzymes.

158 Anti-Mycobacterial Agents

159 isoniazid Class Antimycobacterial agent. MOA Passes freely into mammalian cells and inhibits synthesis of mycolic acids, important constituents of the cell wall peculiar to mycobacteria. Indications Mycobacterium (leprosy and tuberculosis). After phagocytosis, both can survive inside the macrophage. Side Effects Rare skin eruptions, fever, GI disturbances. Other

160 rifampicin Class Antimycobacterial agent MOA Binds to and inhibits DNA- dependent RNA polymerase in prokaryotic but not eukaryotic cells. One of best anti-tuberculosis agents known. Active against most gram +ve and some gram-ve. Indications Antimycobacterium, mostly tuberculosis. Side Effects Rare side effects including skin eruptions, fever and GI disturbances. Other

161 pyrazinamide Class Anti-mycobacterial. Related to nicotinamide MOA Inactive at neutral pH but active in acidic pH. Effective once agent has been phagocytosed, as acidic in phagolysosomes. Involves metabolism of drug inside bacterium to produce a toxic product, pyrazinoic acid. Indications Anti-mycobacterial (tuberculosis, leprosy Side Effects Hepatotoxicity, and raised plasma urate levels can lead to arthralgia and gout. Other Resistance can be rapid.

162 Antifungal Agents

163 nystatin Class Polyene macrolide MOA Acts by forming a transmembrane ion channel in fungal cells, affecting permeability and transport functions. Not absorbed so used in GI tract or on skin. Affects fungi and some protozoa, mild mammalian effects, not at all to bacteria. Selective due to ergosterol rather than cholesterol in mammal membranes. Indications skin or GI infections. Side Effects Rare. Some GI disturbance in high dose, v. rare rash. Other

164 miconazole Class Broad spectrum anti mycotic of the azole group. MOA Azoles block the synthesis of ergosterol by interating with the enzyme needed to convert lanosterol to ergosterol. This alters the fluidity of the membrane which interferes with action of membrane associated enzymes. Also prevents the transformation of yeast cells into hyphae, the invasive and pathogenic form of the parasite. Indications Orally for GI, IV for systemic fungal infections Side Effects Rare, some GI disturbance, also pruritus, blood dyscrasias. Other

165 Anti-Viral Agents

166 acyclovir Class Nucleic acid synthesis inhibitor. A guanosine derivative. MOA Acyclovir is converted to the monophosphate form by thymidine kinase – the viruss own kinase is more effective at converting it than the host cells own kinase, and then converted to the active triphosphate. Therefore it is only activated in infected cells. It is used as a guanine substitute, which prevents DNA synthesis. Indications Herpes simplex virus Side Effects Minimal. Local inflammation around injection site if extravasion occurs (alkaline solution so irritant). Renal dysfunction reported. Nausea and headache. Other Resistance due to changes in viral genes coding for thymidine kinase or DNA polymerase, and acyclovir resistant form have caused pneumonia and encephalitis in immunocompromised patients.

167 Zidovudine (AZT) Class Analogue of thymidine, reverse transcriptase inhibitor. MOA Active inhibitor of reverse transcriptase. Phosphorylated to the triphosphate form, where it competes with cellular triphosphates, essential for formation of proviral DNA by viral reverse transcriptase (viral RNA dependent DNA polymerase). It is incorporated into the growing DNA strand which results in chain termination. Indications In retroviruses such as HIV virus. Reduces risk of transmission from mothers, reduces chance of opportunistic infection, HIV associated dementia etc. Side Effects Anaemia and neutropenia, abnormalities of liver function and myopathy, GI disturbances, confusion, anxiety, depression, rash. Other Mammal α-DNA polymerase is resistant but mitochondrial γ-DNA polymerase is susceptible. Resistance is due to changing a.a. in the viral reverse transcriptase, so it is a constantly moving target.. Also phosphoylation of zidovudine to its active form, in viral load, and increased virulence of the pathogen.

168 Anxiolytics

169 Diazepam Class Benzodiazepine (long acting, 32hrs) MOA Benzodiazepines potentiate the action of GABA by binding to a site on GABA A receptors, increasing their affinity for GABA. This results in an increased opening fluctuations of these ligand gated Cl - channels, thus increasing the inhibitory effects on postsynaptic firing. Indications Short term relief of severe anxiety and severe insomnia, preoperative sedation, status epilepticus, and acute alcohol withdrawl. Side Effects Drowsiness, ataxia, reduced psychomotor performance, dependence after 4-6 weeks. If taken in combination with alcohol, fatal respiratory depression can result. OD treated with flumazenil Other Not be given to people with bronchopulmonary disease, and have combination effects with other depressants such as alcohol, barbiturates, and antihistamines.

170 oxazepam Class Benzodiazepine (short acting, 8hrs) MOA Acts to potentiate effects of GABA, by binding to GABA A receptors and increasing their affinity for GABA, therefore increasing the frequency with which Cl- is allowed into the cell and the inhibitory effect on the postsynaptic cell. Indications Short term relief of severe anxiety and insomnia, preop sedation, statuss epilepticus, and acute alcohol withdrawl. Side Effects Drowsiness, ataxia, and psychomotor performance are seen. Dependence develops after 4-6 weeks, fatal respiratory depression if taken in combination with alcohol (or other CNS depressants) Other

171 Buspirone Class Anxiolytic, Azapirones, act on 5- HT (serotonergic) receptors MOA In the raphe nucleus, dendrites of the serotonergic neurones have autoreceptors (5-HT 1A )which the firing of 5-HT neurons. Azapirones act as partial agonists at these receptors. Indications Short term relief of general anxiety disorder. Side Effects Nervousness, dizziness, headache and light headedness. Does not cause sedation or cognitive impairment, doesnt potentiate alcohol, and only has a minimal risk of dependence. Other Not in epileptics. Effects evolve over 1-3 weeks.

172 Sedatives / Hypnotics

173 Temazepam Class Short lasting benzodiazepine MOA Potentiates the effects of GABA by binding to a site on GABA A receptors, their affinity for GABA, amount of Cl- entering the cell and so inhibiting the firing of the neurone. Indications Given in short term relief of severe anxiety and insomnia, preop sedation, status epilepticus, and acute alcohol withdrawl. Side Effects Drowsiness, ataxia, and psychomotor performance are seen. Dependence develops after 4-6 weeks, fatal respiratory depression if taken in combination with alcohol (or other CNS depressants) Other

174 amobarbital Class barbiturates MOA These prolong the time Cl- channels are opened at GABA receptors whereas benzodiazepines the firing frequency. Indications Sedation, reduction of anxiety. Not used now Side Effects More depressant than benzodiazepines as they Cl- conductance directly, decreasing the neurones sensitivity to excitatory transmitters. Other

175 Chloral hydrate Class Hypnotic MOA Chloral hydrate is metabolised to trichloroethanol, which I an effective hypnotic. Cheap but no advantage over newer benzodiazepines. Indications Previously popular hypnotic for children, but worse than benzodiazepines and children shoudnt be sedated anyway. Side Effects Gastric irritation Other

176 Anticonvulsants

177 Phenytoin Class Sodium channel inhibitors, anti epileptic / arrhythmic. MOA Bind preferentially to the closed Na + channels, preventing them from opening, and so preventing depolarisation. In a seizure, the number of channels susceptible to blockade is higher, meaning that normal transmission is relatively unaffected. Indications Seizures, except absence seizures Side Effects Dosage effects: Affect cerebellovestibular system, leading to ataxia, blurred vision, and hyperactivity. Acute toxicity leads to sedation and confusion. Non dosage effects: collagen effects such as gum hypertrophy, coarsening of facial features, allergic reactions (rash, hepatitis, lymphadenopathy), haematological effects (megaloblastic anaemia), hirsutism, teratogenic effects (congenital malformations) Other This drug is liver saturable – will build up in system until effects become marked suddenly, like beer. Fosphenytoin is a water soluble pro- drug.

178 Carbamazepine Class Na + channel blockers MOA Inhibits fast Na + channels involved in neuronal excitation. Prevents excessive depolarisation Indications Seizure suppression Side Effects Limited to NS – ataxia, nystagmus, dysarthia, vertigo, and sedation. Other

179 Sodium valproate Class anticonvulsant MOA Like phenytoin causes use dependent block of voltage gated Na+ channels. Also Inhibit GABA metabolism by GABA transaminase Indications All forms of epilepsy Side Effects GI upset, liver failure. Other Hepatic toxicity exacerbated when used with other anti-convulsants. First line for many types of seizure syndromes.

180 vigbatrin Class Anti convulsant MOA Inhibit GABA metabolism by irreversible inhibition of GABA transaminase. Indications Tough epilepsy Side Effects Drowsiness, dizziness, depression, and visual hallucinations Other Side effect of hallucinations, so not in people with history of psychosis. New drug used in conjunction with other therapies.

181 Lamotrigine Class Anti epileptic MOA Acts by effect on sodium channels, and inhibiting release of excitatory amino acids. Indications Monotherapy and treatment of partial and generalised tonic clonic seizures. Neuralgic pain (nerve root pain) (by stabilising neurones involved, limiting activation) Side Effects Rashes, fever, malaise, drowsiness, hepatic dysfunction Other Not in hepatic impairment

182 Anaesthetics

183 Local Anaesthetics

184 Cocaine (Ester) Class Local anaesthetic MOA Blocks Na+ channels. Also prevents the uptake of NA at the synapse. Indications Ear, nose and throat surgeons Side Effects Does not cause CNS depression like the other local anaesthetics because it causes euphoria through long lasting chatecolamine action. Other

185 Procaine Class Local anaestheic. MOA Basically a synthetic derivative of cocaine. Causes sodium channel block Indications Seldom used because of its CNS side effects Side Effects Causes CNS depression the worst out of all the local anaesthetics. Resp depression, myocardial depression and vasodilation, visual disturbances and twitching. Other

186 Lidocaine (lignocaine) Class Local anaesthetic Amide MOA Indications Widely used in all applications, EMLA Side Effects Caused by leaking into the circultion. Restlessness, tremor, confusion, agitation, CNS depression. Other

187 Bupivicaine Class Local anaesthetic MOA Slow onset, long lasting local anaesthetic, with moderate tissue penetration. Indications Epidural and spinal anaesthesia Side Effects Systemic problems as with the others. Other

188 General Anaesthetics

189 Nitrous Oxide Class Inhalational GA MOA Blockade of NMDA type Glutamate receptors Indications Rapid control of depth of anaesthesia Side Effects Other

190 Halothane & Enflurane Class Inhalational GA MOA Potentiate GABAa receptor (and Glycine receptors in the spinal cord to educe reflexes), inhibition of nicotinic Ach receptors & facilitate TREK (backround leak of Potassium due to channel opening leading to reduced neuronal activity) Indications Side Effects Other

191 Propofol & Etomidate Class IV GA MOA Potetiates the action of GABAa receptors, most effective when Beta subunits of the GABAa receptor complex predominate, anaesthesia from depression of Thalamocortical neurones and influence on the reticular activating system, amnesia from depression of the synaptic transmission at the Hippocampus and Amygdala Indications Side Effects Other

192 Usual GA Cocktails Loss of Consciousness (Induction by IV GA – Propofol) Supression of Reflexes (Maintainance with Enflurane) Analgesia (Fentanyl) Muscle Relaxation (Suxamethonium) Amnesia (Midazolam – BDZ)

193 Anti-Parkinsonian Drugs

194 L-dopa Class Exogenous precursor to Dopamine MOA Allows the remaining (30% or lower) DA-ergic neurones to function by having more of a reservoir of DA to use Indications Treats rigidity & tremor Start with low dose of the drug and increase dose until maximum benefit without side effects Effectiveness of L-DOPA declines with time! Side Effects Acute (N&V, Hypotension and a Schizophrenic like syndrome) Chronic (Dyskinesias and On/Off fluctuations) Other To prevent N&V formulations of L-DOPA have been created with a peripheral DOPA decarboxylase inhibitor Sinamet (+ Carbidopa) Madopar (+Benserazide)

195 bromocriptine Class DA 2 receptor agonist. MOA Simple Agonist, no need of functioning DA-ergic neurones as in L-DOPA therapy Indications Acromegaly,, Benign breast tumour relief, Acromegaly, Parkinsons, prolactinoma Side Effects Nausea, vomiting, ab cramps, psychomotor excitation, dyskinesias, postural hypotension, vasospasm in fingers and toes Other Caution in Raynauds disease where vasospasm in fingers and toes happens already.

196 Deprenyl (Selegiline) Class Selective for MAO-B, predominates in dopaminergic areas of CNS. Actions are without peripheral side effects of none- selective MAO-Is MOA Increases available DA Indications Can be given alone in the early stages of the disease. Or in combination with L-DOPA, reduce the dose of L-DOPA by % Side Effects Side effects are rare - hypotension, nausea/vomiting, confusion and agitation. Other

197 Entacapone Class Peripheral and CNS COMT inhibitor MOA CNS - Prevents breakdown of dopamine in the brain Peripheral - COMT in the periphery converts L-DOPA to 3-0-methyl-DOPA (3-0MD). 3- OMD and L-DOPA compete for same transport system into the brain. COMT inhibitors stop 3-OMD formation thus increasing the bioavailability of L-DOPA, Thus more L-DOPA converted to dopamine in the CNS. Reduce L-DOPA dosage! Indications Side Effects Other

198 Neuroleptic Drugs

199 chlorpromazine Class Typical antipsychotic MOA CNS Antagonist against D2, Ach and H Indications Acute and Chronic Psychoses, Schizophrenia and the manic phase in Bipolar disorder Side Effects Less incidence of extra pyramidal disorders in contrast to the more potent neuroleptics (Haloperidol) most SE from the drugs Anti Ach activity (sedation, dry mouth, constipation, urinary retention) Other

200 haloperidol Class Typical antipsychotic MOA CNS Strong Antagonist against D2 (and to a lesser extent Ach & H) Indications Schizophrenia Side Effects Extrapyramidal symptoms like acute dyskinesias (Too much Ach), Tardive Dyskinesia (Upregulation of DA receptors), Parkinsonian like syndrome and possible increase in Prolactin levels Other Can be used as an anti emetic

201 sulpiride Class Selective CNS D2 receptor Antagonist MOA Simple antagonist Indications Schizophrenia Side Effects Extrapyramidal symptoms like acute dyskinesias (Too much Ach), Tardive Dyskinesia (Upregulation of DA receptors), Parkinsonian like syndrome and definite increase in Prolactin levels (Breast Cancer?) Other

202 clozapine Class Atypical antipsychotic MOA CNS Antagonist against D2, Ach, H & 5HT (Hence Atypical) Indications Schizophrenia Side Effects Agranulocytosis and myocarditis it may rarely lower seizure threshold, cause leukopenia, cause hepatic dysfunction, weight gain and be associated with type II diabetes. More common side effects are predominantly anticholinergic in nature, with dry mouth, sedation and constipation Other

203 Cytotoxic Drugs

204 cyclophosphamide Class Alkylating agent MOA Highly reactive molecules that bind irreversibly to cell macromolecules causing intra and inter chain cross links (Notably DNA / RNA) binding sites N7 of G, N1 & N3 of A and N3 of C Indications Chemotherapy (& immunosupression at lower doses) Side Effects General toxic side effects Myelosupression Impaired wound healing Depression of Growth Sterility Teratogenicity Loss of Hair N&V Other

205 methotrexate Class Antimetabolite MOA Folate antagonist and so reduces the synthesis of Purine nucleotides (Reduction of the enzyme DHFR) Indications Chemotherapy (& immunosupression at lower doses) Side Effects General toxic side effects Myelosupression Impaired wound healing Depression of Growth Sterility Teratogenicity Loss of Hair N&V Other

206 Azathioprine Class Antimetabolite MOA Purine analogue, inhibit Purine synthesis and is incorperated into DNA itself Indications Chemotherapy (& immunosupression at lower doses) Side Effects General toxic side effects Myelosupression Impaired wound healing Depression of Growth Sterility Teratogenicity Loss of Hair N&V Other

207 bleomycin Class Cytotoxic Antibiotic MOA Causes fragmentation of DNA chains and can act on non dividing cells. Bleomycin is a metal chelating glycopeptide antibiotic which uses Iron ions to create ROS which then cause DNA damage Indications Chemotherapy Side Effects General toxic side effects Myelosupression Impaired wound healing Depression of Growth Sterility Teratogenicity Loss of Hair N&V Other

208 doxorubicin Class Cytotoxic Antibiotic MOA Topoisomerase II inhibitor and in such creates DNA strand breaks Indications Chemotherapy Side Effects General toxic side effects Myelosupression Impaired wound healing Depression of Growth Sterility Teratogenicity Loss of Hair N&V Other

209 vincristine Class Vinca Alkaloid MOA Spindle Poisons and exert there actions by binding to tubulin causing depolymerisation of microtubules and therefore producing metaphase arrest Indications Chemothrapy Side Effects General toxic side effects Myelosupression Impaired wound healing Depression of Growth Sterility Teratogenicity Loss of Hair N&V Other

210 etoposide Class Podophyllotoxin MOA Topoisomerase II inhibitor, prevents DNA replication and causes strand breaks Indications Chemotherapy Side Effects General toxic side effects Myelosupression Impaired wound healing Depression of Growth Sterility Teratogenicity Loss of Hair N&V Other

211 procarbazine Class Miscellaneous anticancer drug (MAO-I) MOA Inhibition of incorporation of Thymidine and adenine into DNA Indications Chemotherapy Side Effects General toxic side effects Myelosupression Impaired wound healing Depression of Growth Sterility Teratogenicity Loss of Hair N&V Other

212 cisplatin Class Miscellaneous anticancer drug (Platinum Compound) MOA After dissociation of a Cl- from the drug this generates a reactive complex that cross links between G units in DNA (Similar to alkylating agents) Indications Chemotherapy Side Effects General toxic side effects Myelosupression Impaired wound healing Depression of Growth Sterility Teratogenicity Loss of Hair N&V (WORST SIDE EFFECT!) Other

213 goserelin Class GnRH agonists. MOA Blocks oestrogen production, constant bombardment of the adenohypophesis with the GnRH agonist causes down regulation of the GnRH receptors Indications Breast cancer in pre menopausal women. Side Effects Other Can also block oestrogen actions using enzymatic inhibition, or just inhibit the actions of oestrogen within the tumour cell.

214 Drugs for Endocrine Disorders

215 tamoxifen Class Estradiol analogue – anti- oestrogen MOA Works by acting as a competitive inhibitor at the ER on the breast cell tumours. This stops the effect and holds the cell at the G 1 phase. Indications Endocrine treatment of choice for postmenopausal women Side Effects Other

216 Ferrous sulphate Class Oral iron compound MOA Ingested and solves iron deficiency Indications Iron deficiency anaemia Side Effects none Other

217 cabergoline Class DA 2 receptor agonist with some DA 1 actions. MOA Indications Hyperprolactinaemia. Not as good as bromocriptine but side effects are less pronounced and it is longer lasting. Side Effects Other Mutual antagonists with anti- psychotics. Sympathomimetic toxicity is increased. Exacerbates effects of alcohol.

218 Octreotide Class Somatostatin analogue MOA Imitates actions of somatostatin by inhibiting production of Growth hormone. Indications Acromegaly – short term treatment before pituitary surgery. Side Effects Other

219 Ethinyloestradiol & medroxyprogesterone Class TSH & LH replacement therapy MOA Replaces actions of progesterone and oestrogen. Indications Hormone replacement in cases where gonadotrophins are no longer produced in pan hypopituitarism Side Effects Other

220 Terlipressin Class V 1 receptor agonist. MOA Acts at V 1 receptors as an agonist casuing an increase in IP3/DAG and so causing vasoconstriction, platelet aggregation, hepatic glycogenolysis, vWF and Factor VIII, ACTH and so cortisol. Indications Stopping bleeding from oesophageal varices, prolongs the actions of local anaesthetics. Side Effects Other

221 Desmopressin Class V 2 receptor agonist MOA Imitates actions of vasopressin in the distal collecting duct as an anti diuretic Indications Given in central diabetes insipidus. Has no effect with nephrogenic diabetes. Thiazides used for nephrogenic diabetes insipidus. Side Effects Other

222 Lithium & dimethylchlor otetracycline Class Inhibitors of vasopressin action on the distal tubule MOA Prevents anti-diuretic actions of excessive vasopressin Indications Excessive vasopressin production. Side Effects Other

223 Levothyroxine Class Thyroxine analogue MOA Acts to raise metabolism in tissues – replacing T 4 Indications hypothyroidism Side Effects Other

224 Liothyronine Class T 3 analogue – tri-iodothyronine MOA Replacement of T 3. binds to intracellular receptor where I tis transported to the DNA and causes transcription of tissue specific DNA regulated effects, ie raising BMR, sesnsitising tissue to sympathetic stimuli etc. Indications Hypothyroidism. At birth to prevent cretinism Side Effects Other

225 Protirelin Class Thyrotrophin releasing hormone analogue MOA Stimulates release of thyroxine from the thyroid gland Indications Used in stimulation tests of the thyroid to test function. Side Effects Other

226 Metformin Class Insulin sensitiser (Biguanide) MOA Requires endogenous insulin production. Works by decreasing glucose output by the liver and increasing its uptake by liver and peripheral cells. Indications Type 2 Diabetes mellitus in fat people whose diet control hasnt worked properly Side Effects Lactic acidosis, vitamin B 12 absorption. Nausea and vomiting, headache, anorexia. Other Not in renal insufficiency or hepatic impairment.

227 Glibenclamide Class Sulphonurea MOA These block ATP dependent potassium channels in the membranes of the pancreatic β cells, causing depolarisation, calcium influx, and insulin release. Indications Type II Diabetes Mellitus where there is still β cell activity in the pancreas Side Effects Potential hypoglycaemia in people with renal or hepatic insufficiency. Other Contraindications in people with ketoacidosis

228 Rosiglitazone Class Thiazolidinediones. Insulin sensitisers MOA Work by reducing peripheral insulin resistance, leading to a reduction in plasma glucose Indications Uncontrolled Type II DM Side Effects Weight Gain, potential liver failure. Other Must only be used in combination with a sulphonylarea or metformin.

229 Acarbose Class α glucosidase inhibitor MOA Inibits the breakdown of oligosaccharides (starch and sucrose), therefore delays CHO absorption. This reduces the – CHO peaks a bit like metformin. Indications Useful in the obese diabetic patient. Side Effects GI gas Other Not in pregnancy, breastfeeding, bowel problems.

230 carbimazole Class Thiourylenes – also includes propylthiouracil MOA Blocks thyroperoxidase which is responsible for the production of thyroglobulin and T 3 & T 4 synthesis. May also antibody production in Graves disease and the conversion of T 4 to T 3 in peripheral tissues. Indications Hyperthyroidism Side Effects Hypothyroidism Other

231 Iodide Class Anion inhibitor MOA Inhibit the conversion of T 4 to T 3, of organification and of hormone secretion. They also reduce the size and vascularity of the gland Indications Hyperthyroidism Side Effects Allergic responses Other

232 Radioiodine Class Anti hyperthyroid MOA Selectively taken up by the thyroid gland where it has very local cytotoxic effects due to β particles. The γ particles pass straight out. Can destroy the over producing thyroid follicular cells. Indications Low dose test of thyroid function, high dose, hyperthyroidism or thyroid tumours. Side Effects Not in children or pregnancy Other

233 Miscellaneous Drug Information

234 SYMPathetic α1α1 located postsynaptically, Their activation causes SM contraction (except in non sphincter GI), glycogenolysis in the liver, and potassium release from the liver & salivary glands. G- protein linked, & by increase in 2 nd messengers. α2α2 Located most pre, but post on hepatocytes, platelets and BV SM. Activation of pre inhibits NA release and provides end product negative feedback. Activation of post causes BV constriction & platelet aggregation. G-protein linked & by decrease in 2 nd messengers. β1β1 Mostly postsynaptic in the heart, platelets and non sphincter GI. Activation causes rise in rate and force of contraction of the heart, relaxation of GI, platelet aggregation, rise in NA, lipolysis in Fat, amylase secretion from salivary glands. G-protein and rise in 2 nd messenger cAMP. β2β2 Located post, SM relaxation, glycogenolysis in liver, inhibition of histamine from mast cells, tremor in skeletal muscle. G-protein and and increase in cAMP.

235 Parasympathetic M1M1 Neuroparietal normally found in the CNS, peripheral neurons, and gastric parietal cells. Effects are excitatory, depolarizing membranes through a decrease in K conductance. Activation causes central excitation and gastric acid secretion, transduction through G-proteins and Increase in 2 nd messengers. M2M2 Neurocardiac are found in the heart and on peripheral neurons. Effects are inhibitory raising K conductance(

236 Multiple drug therapies Helicobacter pylori Metronidazole/amoxycillin, clarithromycin, Omeprazole Tuberculosis1 st phase of 2 months: isoniazid, rifampicin, pyrazinamide (+ethambutol if resistant) 2 nd phase of 4 months: Isoniazid and rifampicin

237 Histamine H1H1 Histamine in hypersensitivity reaction. Capillary and venous dilation (systemic hypotension vascular permeability (oedema) Contraction of SM (bronchial and GI contraction) mucus secretion by goblet cells H2H2 Regulation of gastric acid secretion. -H 2 receptors respond to histamine secreted from enterochromaffin like cells that are adjacent to the parietal cells. -Negative feedback if on mast cells and basophils. -Increases vasopermeability & dilation and stimulates exocrine glands. H3H3 Neurotransmission. Not sure what. Possible presynaptic inhibition of NT release in the CNS and autonomic NS? Role in pain perception?

238 Vasopressin Receptors V1V1 Vascular smooth muscle (prevention of blood loss from oesophageal varices), non vascular smooth muscle, anterior pituitary, Liver, platelets (Stimulation of factor VIII and von Willbrandt factor), Brain and CNS V2V2 Kidney (distal collecting duct), CNS

239 Glucocorticoid SE osteoporosis osteoclast activity, osteoblast activity Gastric ulceration PG production in stomach (lipocortin arachidonic acid.) Suppression of HPA-ve feedback on pit. & hypothalamus hypertensionNa + Cl -, water retention; adrenoceptors hence response. infectionImmunosupression Skin thinning connective tissue, tissue turnover and repair Muscle wasting & buffalo hump storage of glucose in muscle, leads to an in fat deposition. Cataracts & glaucoma


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