drugs and their mechanisms of action

Drug Action(s) and notes Uses Covered In …and also

Lithium Manic Depression Hiley 12

Tyrphostins Edwardson 15

Beclonethasone Agonist for cortisol (steroid) receptor Asthma TreatmentEthinyloestradiol Agonist for oestradiol (steroid) receptor Contraception Edwardson 16

Fludrocortisone Agonist for aldosterone (steroid) receptor Edwardson 16Norethisterone Agonist for progesterone (steroid) receptor Contraception Edwardson 16

Lignocaine Edwardson 18 Hiley 37

Bay K 8644 Edwardson 20 Hiley 22

Edwardson 20

Nifedipine Edwardson 20 Hiley 7, 22

Inhibits breakdown of IP (Inositol Phosphate) to I --> prevents Inositol recycling --> no IP3 for PLC to act upon; can produce side effect of diabetes insipidus (see Thiazides)

Edwardson 14

Inhibit receptor tyrosine kinases --> inhibit effects of epidermal growth factor (EGF)

Neoplastic Growth Control (?)

Edwardson 16

Aldosterone deficiencies

Causes Na channel to require more hyperpolarization to reactivate it (by stabilizing inactivated form) - thus increased inactivation; weak base; pH-dependent, use-dependent (only at high rates of stimulation) and voltage dependent; 'fast-in, fast-out'

Local anaesthetic; Class IB antidysrhythmic

Dihydropyridine; acts as agonist for L-type VGCCs (- isomer), but blocker for T-type VGCCs (+ isomer)

Dihydropyridines (Bay K 8644, Nifedipine, Nitrendipine, Nimodepine)

Group of compounds with actions on L-type VGCCs - both agonists and antagonists; "highly lipid-soluble, gain access to channel through lipid phase of membrane"

Heart/smooth muscle targetting (see specific drug)

Dihydropyridine; acts as antagonist for L-type VGCCs; binds preferentially to inactivated channels and so selective for smooth muscle

Angina prevention by peripheral and coronary vasodilation; antihypertensive (see Peripheral Vasodilator Agents)


Glibenclamide See Sulphonylureas Edwardson 22

Verapamil Antagonist for L-type VGCCs in cardiac muscle Edwardson 21 Hiley 22, 38; Barrand 40

Diltiazem Antidysrhythmic Edwardson 22 Hiley 22

Sulphonylureas Edwardson 22Tolbutamide See Sulphonylureas No longer used Edwardson 22

Inhibits ACh release pre-synaptically

Hemicholinium

Vesamicol

β-bungarotoxin Inhibits ACh release pre-synaptically

Decamethonium Blocks CNS nAChRs

Hexamethonium

Nicotine

Non-Insulin Dependent Diabetes Mellitus

Class IV Antidysrhythmic (although has some Class I actions also); used also in treatment of chemotherapy resistance

Antagonist for L-type VGCCs in cardiac muscle; Class: benzothiazepine;

(Tolbutamide, Glibenclamide): Group of compounds that antagonise K(ATP) channel in beta cells of pancreas; induce entry of calcium via depolarisation, causing insulin release

Non Insulin-Dependent Diabetes Mellitus

Botulinum Toxin ("Botox")

Murrell-Lagnado 10

Inhibits uptake of Choline into pre-synaptic nerve terminals, so limiting ACh synthesis

Murrell-Lagnado 10

Blocks ACh transport into vesicles presynaptically

Murrell-Lagnado 10Murrell-Lagnado 10Murrell-Lagnado 11

Post-synaptic channel-pore blocker for nAChR, acts on autonomic ganglia; use-dependent

First effective antihypertensive agent, but no longer used

Murrell-Lagnado 11

Agonist for nAChR; When applied in large quantities, will act as a "depolarising block"

Murrell-Lagnado 11


Trimetaphan

Bethanechol

Carbachol

Metacholine

Pilocarpine

Atropine

Hyoscine

Muscarine

Edrophonium Thorn 5

Neostigmine Thorn 5

Physostigmine

Competitive antagonist for nAChR, acting on autonomic ganglia

Murrell-Lagnado 11

Agonist specific to muscarinic AChRs, resistant to hydrolysis in GI tract --> well absorbed

Murrell-Lagnado 14

Strong agonist for nAChRs, medium-strength for mAChRs

Murrell-Lagnado 14

Strong agonist for mAChRs, weak agonist for nAChRs

Murrell-Lagnado 14

Agonist specific to muscarinic AChRs, naturally occurring alkaloid

Can cross conjunctival membrane easily and therefore used in treatment of glaucoma

Murrell-Lagnado 14

Naturally occurring alkaloid, ANTagonist for muscarinic receptors

Can be used to produce pupillary dilatation (mydriasis)

Murrell-Lagnado 15

Naturally occurring alkaloid, ANTagonist for muscarinic receptors

Murrell-Lagnado 15

Naturally occurring alkaloid, agonist for muscarinic receptors

Murrell-Lagnado 15

Short-acting anticholinesterase (+ve charge --> binds to anionic site); main site of action: NMJ

Diagnosis of Myasthenia Gravis

Murrell-Lagnado 16

Medium-duration anticholinesterase (binds to both active sites in AChE); acts on NMJ

Reversal of competitive neuromuscular block; Myasthenia Gravis treatment

Murrell-Lagnado 16

Medium-duration anticholinesterase (binds to both active sites in AChE); acts on parasympathetic N.S.

Glaucoma treatment (eye drops)

Murrell-Lagnado 16


Pyridostigmine

Dyflos

Ecothiopate Long-duration anticholinesterase

Parathion Long-duration anticholinesterase

Pralidoxime Gibson 10

Carbidopa Inhibits dopa decarboxylase

Methyldopa Hiley 7

α-methyltyrosine

Disulfiram

Reserpine CNS

CNS

Medium-duration anticholinesterase (binds to both active sites in AChE); acts on NMJ

Myasthenia Gravis treatment (longer lasting than Neostigmine)

Murrell-Lagnado 16

Long-duration anticholinesterase, actions can be reversed with pralidoxime; highly toxic

Murrell-Lagnado 17

Glaucoma treatment (eye drops)

Murrell-Lagnado 17

Insectiside, headlice treatment

Murrell-Lagnado 17

Dissociates dyflos (or any organophosphorus anticholinesterase) from cholinesterases

Murrell-Lagnado 17

Reduces peripheral side effects of L-DOPA in Parkinson treatment

Murrell-Lagnado 20

Metabolised to form α-methylnoradrenaline, a "false transmitter" which is less active than noradrenaline on post-synaptic receptors, but more effective on pre-synaptics, inhibiting NT release.

Centrally Acting Antihypertensive

Murrell-Lagnado 20

inhibits tyrosine hydoxylase, blocking NA synthesis

Murrell-Lagnado 20

Inhibits dopamine β-hydroxylase, depleting NA stores

Murrell-Lagnado 21

Binds to catecholamine recognition proteins on surface of vesicles, and thereby blocks accumulation of catecholamines in vesicles; acts both centrally and peripherally

Former antihypertensive, but causes depression so no longer used

Murrell-Lagnado 21

Tricyclic Antidepressants (e.g. imipramine)

Inhibit uptake 1 (neuronal uptake) of catecholamines --> accumulation of NA and 5-HT at receptors, increased sympathetic nerve activity but main effect is on CNS

Murrell-Lagnado 23


Acetylcholine

Amitryptiline See tricyclic antiderpressants CNS

Imipramine See tricyclic antidepressants CNS

Cocaine CNS

Corticosteroids

Entacapone

CNS

Ephedrine

Strong agonist for nicotinic and muscarinic Acetylcholine receptors; rapidly broken down by cholinesterases throughout body

Widespread coverageMurrell-Lagnado 23Murrell-Lagnado 23

Inhibit uptake 1 (neuronal uptake) of catecholamines --> accumulation of NA and 5-HT at receptors, increased sympathetic nerve activity but main effect is on CNS (same actions as tricyclic antidepressants)

Murrell-Lagnado 23

Phenoxybenzamine

Inhibits uptake 2 (non-neuronal uptake) of catecholamines (as do corticosteroids); ANTagonist for α adrenoceptors

Peripheral vascular disease, treatment of phaeochromocytom

Murrell-Lagnado 23, 28

Inhibit uptake 2 (non-neuronal uptake) of catecholamines (as does phenoxylbenzamine)

Murrell-Lagnado 23

Inhibits COMT (which normally breaks down catechomaines (esp. adrenaline) in non-neuronal tissue)

Treatment of Parkinson's Disease

Murrell-Lagnado 23

Sympathomimetic Amines (e.g. amphetamine, tyramine, ephedrine and MDMA ('ecstasy'))

Structurally related to NA, taken up into presynaptic nerve terminals by Uptake 1; competes with NA for uptake into vesicles, and NA is thereby transported into synapse (as well as being broken down by MAO). Some also have direct effects on adr.receptors

Various (see ephedrine)

Murrell-Lagnado 23

See sympathomimetic amines for indirect effects. Acts on β2 adrenoreceptors directly

Nasal decongestant (relaxes bronchial smooth muscle)

Murrell-Lagnado 23


Guanethidine

Bretylium Related to guanethidine

Tyramine

Noradrenaline

Adrenaline More active on β adrenoceptors than α receptors Thorn 2

Isoprenaline Agonist specific to β adrenoceptors

Phenylephrine Agonist specific to α1 receptors

Agonist specific to α2 receptors

Competes with NA for Uptake 1 ('neuronal'), so potentiating exogenously applied catecholamines; displaces NA from vesicle uptake and NA is thereby transported into synapse

Chronic, low-dose usage--> released instead of NA, blocks neurons; large doses--> inhibits exocytosis by inhibiting vesicle fusion)

Murrell-Lagnado 23

Former antihypertensive

Murrell-Lagnado 23

See sympathomimetic amines; found in cheese and red wine, and needs to be eliminated from diet when taking an MAO inhibitor to avoid fatal rises in blood pressure

Murrell-Lagnado 23

More active on α adrenoceptors than β receptors: has very low rates of stimulation on β2 receptors

Murrell-Lagnado 28

Anaphylactic reactions (very powerful vasopressor), acute cardiac failure

Murrell-Lagnado 28

Formerly used in asthma treatment but has tachycardia side effect

Murrell-Lagnado 28Murrell-Lagnado 28

Methylnoradrenaline

Murrell-Lagnado 28


Clonidine Hiley 7

Salbutamol Thorn 5

Dobutamine Hiley 49

Phentolamine ANTagonist for α adrenoceptors Hiley 7

Yohimbine

Prazosin Hiley 7

Propanolol ANTagonist for β receptors ("β-blocker") Hiley 4

Agonist specific to α2 receptors, acts both by inhibiting pre-synaptic NA release and centrally also; sudden withdrawal of drug (e.g. missing single dose) can cause severe "rebound hypertension"

Topical (local) treatment of hypertension (centrally acting antihypertensive (?)); treatment of narcotic withdrawal syndromes

Murrell-Lagnado 28

Agonist specific to β2 receptors, produces bronchorelaxation when inhaled

Aerosolic, acute treatment of asthma

Murrell-Lagnado 28

Agonist specific to β1 receptors; positive inotropic effect during cardiogenic shock

Acute heart failure treatment

Murrell-Lagnado 28

Formerly used as antihypertensive but has tachycardia side effect

Murrell-Lagnado 28

ANTagonist for α2 receptors, naturally occurring alkaloid

Murrell-Lagnado 28

ANTagonist for α1 receptors, causing vasodilatation

Causes relaxation of bladder neck smooth muscle, useful in urinary retention; antihypertensive (see Peripheral Vasodilator Agents)

Murrell-Lagnado 28

Hypertension (formerly), but bronchoconstriction side effects; Class I and Class II antidysrhythmic

Murrell-Lagnado 28


Atenolol Hiley 5

Butoxamine ANTagonist for β2 receptors

Labetolol Hiley 5

Ergotamine Thorn 4

Suramin

Caffeine

Angina treatment Hiley 43

ANTagoinst for β1 receptors ("β-blocker"); does not readily enter brain (used as counter-argument for 'NA theory' of β-blocker action)

Reduces effects of exercise/excitement on heart; antihypertensive; Class II antidysrhythmic


Generalised ANTagonist for all adrenoceptors; 4 stereoisomers: 2 inactive (RS and SS), SR = α-blocker, RR = β-blocker

NOT used as antihypertensive: inactive isomers are not approved (potential for immune reaction), and postural hypotension is problematic

Murrell-Lagnado 28

Partial α adrenoceptor agonist; "ergot alkaloid", partial 5HT-1D receptor agonist, produces vasoconstriction

Acute treatment of migraines

Murrell-Lagnado 28

Lysergic acid diethylamide ("LSD")

Complex range of actions on 5-HT adrenoceptors in CNS

Murrell-Lagnado 28

Attenuates the response of purinergic nerves to ATP

Murrell-Lagnado 30

ANTagonist for A1 (adenosine) receptors, reducing presynaptic inhibition of NT release

Murrell-Lagnado 34

Nitrovasodilators (Glyceryl Trinitrate, Isorbide Dinitrate, Amyl Nitrate)

Produce vasodilation via activation of Guanylate Cyclase in smooth muscle cells; dilate large conducting vessels in the heart, as well as decreasing preload by venous dilation, and decreasing BP by arteriodilation. Tolerance may develop

Murrell-Lagnado 37


See Nitrovasodilators Angina treatment Hiley 43

Isorbide Dinitrate See Nitrovasodilators Angina treatment

Erectile dysfunction Hiley 50

7-nitroindazole

Pindolol Hiley 4 Hiley 44

Sotalol Hiley 5

Carvedilol Hiley 5,39Losartan ANTagonist for A1 angiotensin receptors Antihypertensive Hiley 6

Glyceryl Trinitrate


Amylnitrate ('Poppers')

Release NO, promoting erection and relaxation of the anal sphincter

Murrell-Lagnado 38

Sildenafil ('Viagra')

Prevents breakdown of cGMP by inhibiting PDE5, causing relaxation of smooth muscle and increasing bloodflow -> corpus cavernosum

Murrell-Lagnado 38

L-arginine analogues (L-NMMA, L-NAME, L-NOARG)

Inhibit NOS, but not very selective for different forms of NOS

Murrell-Lagnado 40

Inhibits nNOS, but not eNOS and iNOS: affects binding of arginine to NOS

Murrell-Lagnado 40

N-iminoethyl-L-ornithine

Potent and irreversible inhibitor of iNOS in activated macrophages

Murrell-Lagnado 40

β-blocker (partial agonist) with "intrinisic sympathetic activity"; antihypertensive but has no direct effect on renin-angiotensin system; however, can reduce renin release via 'orthostatic response')

Antihypertensive; Class II antidysrhythmic; angina treatment

ANTagoinst for β1 receptors ("β-blocker"); does not readily enter brain (used as counter-argument for 'NA theory' of β-blocker action)

Antihypertensive; Class II and Class III antidysrhythmic

ANTagonist for β receptors ("β-blocker") but also for α1 receptors, with α1:β potency ratio of 1:10

Antihypertensive; Class II antidysrhythmic; symptomatic heart failure treatment ('myocardial salvage')


Captopril Hiley 6 Hiley 47

Enalapril Hiley 6 Hiley 47

Rilmenadine Hiley 7

Monoxidine Hiley 7

Hiley 7

Nicardipine Hiley 7, 22

Hiley 8

Cromakalim Hiley 8Pinacidil See K+ Channel Openers Hiley 8Diazoxide See K+ Channel Openers; thiazide Hiley 8Minodoxil See K+ Channel Openers Hiley 8

Hydralazine Dilates arterioles: mechanism unknown Hiley 8

ACE inhibitor: decreases BP in 85% of primary hypertensives, but has little effect on patients with normal BP

Antihypertensive; treatment of congestive heart failure

Precursor (prodrug) of enalaprilat, an ACE inhibitor (more potent than captopril); undergoes de-esterification to become enalaprilat

Antihypertensive; treatment of congestive heart failure

More active on Imidazoline 1 (I1) receptors than α2 receptors; few side effects

Centrally acting antihypertensive

More active on Imidazoline 1 (I1) receptors than α2 receptors; few side effects

Centrally acting antihypertensive

Peripheral Vasodilator Agents

Antihypertensives, but only used in conjunction with other antihypertensives: need β-blockers as they tend to cause reflex increase in heart rate, and also not hugely effective alone as they lead to increase in sodium retentionDihydropyridine; L-type calcium channel ANTagonist; bind preferentially to inactivated channels and so selective for smooth muscle

Antihypertensive (see Peripheral Vasodilator Agents)

K+ Channel Openers (KCOs)

Inhibit binding of ATP to K(ATP) channel in vascular smooth muscle, causing it to open (ATP normally causes it to close), leading to increased potassium efflux, relaxing smooth muscle


See K+ Channel Openers: active isomer is levcromakalim



Antihypertensive Hiley 10

Hiley 10Etacrylic acid See Loop diuretics Antihypertensive Hiley 10

Hiley 11

See Thiazides Hiley 11

See Thiazides Hiley 11

Probenecid Treatment of Gout Hiley 13

Allopurinol Treatment of Gout Hiley 13

Loop diuretics (furosemide, etacrylic acid)

Block Na/K/Cl channel in thick ascending Loop of Henle. Side effects: potassium loss may lead to arhythmia/dysrhythmia; competition for organic acid uptake in prox. con. tubule causes decreased uric acid secretion, may be problematic for gout sufferers

Furosemide (a.k.a. Frusemide)

Loop diuretic; derivative of sulphonamides; Secreted into lumen of kidney by organic acid transport process of PCT, blocks Na/K/Cl co-transpoter in Thick ALH, increasing natriuresis and therefore urine flow. Also causes venodilatation

Antihypertensive; venodilatation means beneficial effects in congestive heart failure. See also Loop Diuretics

Thiazides (hydrochlorothiazide, bendroflumethiazide)

Diuretics; block Na/Cl cotransporter in distal convoluted tubule; inhibit dilute urine formation, but not concentrated; also has KCO actions - vasodilator (see Diazoxide); side-effects same as loop diurs. + decreased insulin production

Antihypertensive; can also be used to reduce urine production in diabetes insipidus

HydrochlorothiazideBendroflumethiazide

Uricosuric agent (enhances uric acid secretion); high dose GOOD as block uric acid reabsorption, low dose BAD as block uric acid secretion; Salicylates (e.g. asparin) reduce effectiveness of uricosuric agents

Reduces uric acid production: competitive inhibitor of xanthine oxidase, and metabolised by xanthine oxidase to give Alloxanthine, a non-competitive xanthine oxidase inhibtor


Alloxanthine Treatment of Gout Hiley 13

Spironolactone Hiley 14

Canrenone Hiley 14

Triamterene Hiley 14

Amiloride Hiley 14

Acetazolamide Hiley 15

Product of metabolism of allopurinol by xanthine oxidase; non-competitive inhibitor of xanthine oxidase

Aldosterone ANTagonist; metabolised to Canrenone in the liver; slow-onset, limited by turnover of sodium channels (as it downregulates their transcription)

Potassium-sparing diuretic (treatment of side effects of loop diuretics/thiazides)

Metabolite of Spironolactone; aldosterone ANTagonist (see also Spironolactone)


Epithelial Na Channel (ENaC) blocker, acts on cells of late distal tubule


Epithelial Na Channel (ENaC) blocker, acts on cells of late distal tubule; at higher concentration blocks Na/H exchanger


Carbonic anhydrase inhibitor; prevents reabsorption of H2CO3 in proximal tubule but effects are short-lived; inhibition of HCO3 secretion in eye limits build-up of aqueous humour

First effective diuretic, but now rarely used; instead used in treatment of glaucoma


Hiley 15

Theophylline Hiley 16 Thorn 5

Mibefradil Blocks T-type and L-type VGCCs Hiley 22Nickel (Ni++) Blocks T-type and L-type VGCCs Hiley 22

Quinidine Hiley 37 Barrand 40

Procainamide Hiley 37

Phenytoin Hiley 37

Mexilitine Hiley 37

Flecainide Hiley 37

Encainide Hiley 37

Osmotic Diuretics (Mannitol, Isosorbide)

Freely filtered by glomerulus, but not reabsorbed: lower tubular Na concentration, and so decrease reabsorption. Do not enter brain or the eye. Intravenous administration to promote rapid diuresis

Used when GFR is reduced, to reduce cerebral oedema (and thus intracranial pressure) and intraocular pressure

Non-selective A1/A2 adrenoceptor ANTagonist; as A1 receptor mediates afferent arteriole responses to increased GFR, has weak diuretic action; also phosphodiesterase inhibitor so useful in long-term asthma treatment

Weak diuretic; long-term asthma treatment

Previously used as antihypertensive and antidysrhythmic, but withdrawn due to interfering with drug metabolism -> adverse interactions

Protects against premature re-excitation and repolarisation of VGNaCs

Class IA antidysrhythmic

Protects against premature re-excitation and repolarisation of VGNaCs

Class IA antidysrhythmic

Protects against premature re-excitation and repolarisation of VGNaCs; rapid kinetics

Class IB antidysrhythmic

Protects against premature re-excitation and repolarisation of VGNaCs; rapid kinetics

Class IB antidysrhythmic

Protects against premature re-excitation and repolarisation of VGNaCs; slow-onset/offset

Class IC antidysrhythmic

Protects against premature re-excitation and repolarisation of VGNaCs; slow-onset/offset

Class IC antidysrhythmic


Amiodarone Hiley 38

Streptokinase Hiley 40

Anistreplase Hiley 40

Urokinase (u-PA) Hiley 40

Alteplase Hiley 41

Reteplase Hiley 41

Hiley 41

Tranexamic acid Hiley 41

Heparin Hiley 41

Inhibits repolarising potassium currents, lengthening APD (action potential duration)

Class III antidysrhythmic

Binds to plasminogen, promoting its conversion to the fibrinolytic protease plasmin, but with side effect of systemic thrombolysis

Clot lysis for emergency treatment of myocardial infarct

Streptokinase given in combination with anisoylated plasminogen to restrict systemic thrombolysis


Produced by the kidney and is converted into a two-chain plasminogen activator: synthetic forms include tcu-PA (cultured kidney cells) and scu-PA (recominant form), but no selectivity of fibrin over fibrinogen, so t-PA is normally used instead


Recombinant human tissue plasminogen activator; greater activity to plasminogen specific to fibrin, localising action to circulation, and not allergenic as they are derived from human protein


Recombinant human tissue plasminogen activator with mutations in which three domains including Kringle domain have been deleted


Aminocaproic acid

Lys analogue; reverses fibrinolytic actions of clot-busting drugs in cases of overuseLys analogue; reverses fibrinolytic actions of clot-busting drugs in cases of overuse; less toxic and longer lasting than aminocaprioc acid

Group of mucopolysccharides which activate antithrombin III, which inactivates all serine proteases involved in the blood coagulation cascade

Clot lysis, used in addition to fibrinolytic drugs


Warfarin Hiley 41

Nicorandil Angina treatment Hiley 43

Alprenolol Partial β adrenoceptor agonist Hiley 44

Xamoterol Partial β1 adrenoceptor agonist Hiley 44

Lovastatin Hiley 45

Hiley 46

Cholestyramine Hiley 46

Clofibrate Hiley 46

Inhibits the actions of vitamin K, which is required for the production of factors in the clotting cascade

Clot lysis: oral anticoagulant

Nicotinamide nitrate, which may produce same therapeutic effects as nitrovasodilators, but without producing tolerance - combined nitrovasodilator and potassium channel opener

Attempted use of treating angina without causing side effects of heart failure, but not overly successful...

Attempted use of treating angina without causing side effects of heart failure, but not overly successful…

Inhibits HMG-CoA reductase, which is the rate limiting enzyme for cholesterol synthesis; upregulates hepatic LDL receptors

Hypolipidaemic agent, INCREASES SURVIVAL

Nicotinic Acid (Vitamin B3)

Inhibits triglyceride synthesis/VLDL secretion by liver; increases levels of t-PA, which lowers levels of lipoprotein A

Hypolipidaemic agent, INCREASES SURVIVAL

Ion exchange resin that remains in gut and prevents reuptake of bile acids, thereby limiting cholesterol absorption

Hypolipidaemic agent

Fibric acid derivative: lowers VLDL and LDL, by stimulating lipoprotein lipase

Hypolipidaemic agent


Fish Oil Hiley 46

Hiley 48

Amrinone Hiley 50

Milrinone Hiley 50Rolipram Inhibits PDE4 Hiley 50Zaprinast Inhibits PDE5 Hiley 50

Bosentan Endothelin Anatagonist Hiley 50Thiopentone IV Anaesthetic - see notes General Anaesthesia GA 32Etomidate IV Anaesthetic - see notes General Anaesthesia GA 33

Propofol General Anaesthesia GA 33

Nitrous Oxide General Anaesthesia GA 35

Cyclopropane General Anaesthesia GA 35Halothane Inhalation anaesthetic with middling solubility General Anaesthesia GA 35

Ether General Anaesthesia GA 35

Methoxyfluorane General Anaesthesia GA 35

Stimulates production of PGI3 instead of PGI2 (little change), and TXA3 instead of TXA2 (far less pro-thrombotic), as eicopentanoic acid substitutes for arachidonic acid: reduced risk of thrombosis

Hypotriglyceridaemic agent (not clinically useful); antithrombotic

Cardiac Glycosides (e.g. Ouabain)

Block Na/K countertransporter, causing a shift in the starling curve of the heart (higher CO for given LVEDP); high toxicity, especially when hypokalaemic

Treatment of atrial flutter

Inodilator: inhibits PDE3, inhibiting cGMP breakdown which --> positive inotropic/chronotropic effects

Congestive Heart Failure (doesn't increase survival)

Inodilator: inhibits PDE3, inhibiting cGMP breakdown which --> positive inotropic/chronotropic effects

Congestive Heart Failure (doesn't increase survival)

Congestive Heart Failure Treatment

IV Anaesthetic - see notes; very rapidly metabolised so can be given as constant infusionInhalation anaesthetic with low solubility (so fast on/fast off)Inhalation anaesthetic with low solubility (so fast on/fast off)

Inhalation anaesthetic with high solubility (so slow on/slow off)Inhalation anaesthetic with high solubility (so slow on/slow off)


Anthelmintic Gibson 6Fenbendazole See benzimidazoles Anthelmintic Gibson 6Thiabendazole See benzimidazoles Anthelmintic Gibson 6

Triclabendazol Anthelmintic Gibson 7

Gibson 8

See Proton Ionophores Gibson 8

See Proton Ionophores Gibson 8

Diamphenithide Gibson 8

Clorsulon Anthelmintic Gibson 8

Praziquantrel Gibson 8

Anthelmintic Gibson 10

Benzimidazoles (Fenbendazole, Thiabendazole, Triclabendazole)

Inhibit formation of helminth microtubules, by binding to β-tubulin with high affinity; 250/400x affinity for helminth tubulin compared to mammalian

See benzimidazoles; selective against flukes but ineffective against roundworms

Proton Ionophores (Salicylanides, Substituted Phenols)

Uncouple oxidative phosphorylation (non-selectively cf. mammalian hence low t. index); bind avidly to plasma proteins -> especially blood-sucking helminth-effective; have further action at tegument membrane to lower pH

Anthelmintic, selective to flukes

Salyclanides (Closantrel)


Substituted Phenols (Nitroxynil)


Inhibit glucose metabolism in helminths by increasing malate concentration


Inhibit phospoglycerate kinase/mutase; binds to plasma proteins

Several possible MODAs: increase Ca influx causing paralysis, loss of suction, by acting on β-subunit of Ca channel; may act on CICR; may cause tegument damage leading to immune-mediated response

Anthelmintic, esp. effective against flukes; main drug used against schistosomiasis

Organophosphorus compounds (Dichlorvos)

Anticholinesterase; cause spastic paralysis of helminths allowing for expulsion from host; quite dangerous (low therapeutic index) --> strict attention to dose; Pralidoxime = antidote for recent toxicity






See Helminth Nicotinic Agonists Anthelmintic Gibson 11

See Helminth Nicotinic Agonists Anthelmintic Gibson 11

Cimetidine H2 (Histamine) receptor antagonist Thorn 2

Dimenhydrinate Thorn 2

Loratidine Thorn 2

Carbamates (Aldicarb)

Anticholinesterase; cause spastic paralysis of helminths allowing for expulsion from host; Atropine can be used as antidote

Helminth Nicotinic Agonists

Agonise nAChRs, causing depolarisation, causing spastic paralysis allowing for rapid expulsion; Bell-shaped response due to open-channel blockade; especially potent against GI helmints/lungworms

Imidazothiazoles (Levamisole)

See Helminth Nicotinic Agonists; water-soluble so easy to use; l-isomer of Tetramisole; most potent nic.agonist anthelmintic

Tetrahydropyridines (Pyrantel)

See Helminth Nicotinic Agonists; water-insoluble so minimises side-effects on host (as not readily absorbed by GI tract), needs to be kept away from water/sunlight to avoid isomerisation

Quaternary Ammonium Salts (Bephenium)Pyrimidines (Methyridine)

Treatment of excess stomach acid secretion

H1 (Histamine) receptor antagonist; CAN cross blood-brain barrier

Treatment of motion sickness/allergy

H1 (Histamine) receptor antagonist; DOES NOT cross blood-brain barrier

Treatment of mild atopic asthma/allergy


Mepyramine Thorn 2

Omeprazole Inhibits H+ pump in stomach parietal cells Thorn 2

Terfanidine Thorn 2

Aspirin Thorn 3 Hiley 41

Misoprostol Thorn 3

Celecoxib Thorn 3

Ibuprofen Thorn 3

Paracetemol Thorn 3

Thorn 4

Sumatriptan 5-HT1D agonist, produces vasoconstricion Thorn 4

H1 (Histamine) receptor antagonist; CAN cross blood-brain barrier

Treatment of allegry, used to cause drowsiness as side effect…. Now used as SLEEPING TABLETTreatment of excess stomach acid secretion

H1 (Histamine) receptor antagonist; Blocks K+ Channels in heart (side effect); DOES NOT cross blood-brain barrier Treatment of allergy

NSAID - COX-inhibitor: acts by irreversible acetylation of serine-530; preferentially targets COX-1 over COX-2, so inhbits platelet aggregation (COX-2 endothelial but not found in platelets --> PGI2 sythesis can continue but not TXA2)

Antipyretic, analgesic, anti-inflammatory, anti-clotting

Stable analogue of PGE1, increases mucus secretion etc. of GI tract

Protects stomach from ulceration when using NSAIDs

NSAID - COX-2 inhibitor; side effect of causing heart attacks so now withdrawn

Antipyretic, analgesic, anti-inflammatory

NSAID - COX inhibitor, slightly preferential for COX-1

Antipyretic, analgesic, mildly anti-inflammatory

NSAID - Mechanism of action still unclear, as antipyretic and analgesic effects but NOT anti-inflammatory (may be COX-3 inhibitor)

Antipyretic, analgesic

Dihydroergotamine

Ergot alkaloid - 5-HT1d agonist, produces vasoconstriction

Acute treatment of migrainesAcute treatment of migraines


Valproic Acid Prevents GABA breakdown, increasing [GABA] Thorn 4Ondansetron 5-HT3 antagonist Anti-emetic Thorn 4Granisetron 5-HT3 antagonist Anti-emetic Thorn 4

Alosetron Thorn 4

Cisapride 5-HT4 agonist Thorn 4

Budesonide Thorn 5

Cromolyn Thorn 5

Cortisone Thorn 5

Dexamethasone Thorn 5

Etanercept Thorn 5

Calcineurin Inhibitor Thorn 5

Gold compounds Interferes with neutrophil migration Thorn 5

Ipratropium Thorn 5

Methotrexate Thorn 5 Barrand 27

Prevention of migraines

5-HT3 antagonist, side effect of reducing gut motility

Treatment of irritable bowel syndromeIncreases gut motility

Corticosteroid - agonises glucocorticoid receptor to supress inflammation

Long-term asthma treatment

Mast cell stabiliser - inhibits degranulation (histamine release)



Organ transplant, treatment of myasthenia gravis


Organ transplant, treatment of myasthenia gravis

Resembles TNF-α receptor, so 'mops up' excess TNF-α

Treatment of rheumatoid arthritis

Tacrolimus ('FK506')

Immunosuppression (myasthenia gravis treatment, organ transplant)Treatment of rheumatoid arthritis

Muscarinic AChR antagonist, used to produce bronchorelaxation

Acute treatment of asthma

Inhibits dihydrofolate reductase, inhibiting production of tetrahydrofolate which is required for nucleic acid synthesis; resistance derves from low levels of dihydrofolate reductase

Treatment of rheumatoid arthritis (low dose); cancer treatment (high dose)


Monteleukast Thorn 5

Prednisone Thorn 5 Barrand 25

Salmeterol Thorn 5

Sulphasalazine Modifies lymphocyte behaviour Thorn 5

Zileuton Thorn 5

Ciclosporin Thorn 5Azathioprine Inhibitor of cell proliferation Organ transplant Thorn 5

Inhibitor of cell proliferation Organ transplant Thorn 5Zintevir Inhibits viral attachment to cell surface receptor Antiviral agent Barrand 2

Amantidine Barrand 3

Enfurvitide Antiviral agent (HIV) Barrand 3

Acyclovir Barrand 3

AZT Antiviral agent (HIV) Barrand 3

Leukotriene inhibitor (antagonist for CysLT1 and CysLT2 receptors)


Corticosteroid - agonises glucocorticoid receptor to supress inflammation, inhibits lymphocyte proliferation

Organ transplant, treatment of myasthenia gravis; anticancer agent (used against acute childhood leukaemia)

Long-lasting β2 adrenoceptor agonist, produces bronchorelaxation when inhaled

Long-term asthma treatmentTreatment of rheumatoid arthritis

Leukotriene inhibitor (inhibits actions of 5-lipoxygenase)


Binds to cytosolic protein, cytophilin, to create calcineurin inhibitory compound

Immunosuppression (myasthenia gravis treatment, organ transplant)

Mycophenolate Mofetil

Prevents acidification of endosome after influenza endocytosis, so blocking entry of influenza A

Antiviral agent (Influenza A)

Binds to the 'prehairpin' complex which HIV uses to enter cell in gp120-CD4 interaction, so prevents HIV fusion with cellNucleoside analogue, specific to DNA replication: inhibits nucleic acid synthesis

Antiviral agent (DNA viruses)

Nucleoside analogue, specific to reverse transcriptase: inhibits nucleic acid synthesis; some toxicity to host cells


Tenofovir Antiviral agent Barrand 3

Nevirapine Antiviral agent (HIV) Barrand 3

Saquinavir Antiviral agent Barrand 4

Polymyxins Antibacterial agent Barrand 7

Nigericin Antibacterial agent Barrand 7

Daptomycin Antibacterial agent Barrand 7

Amphotericin B Antifungal agent Barrand 8

Nystatin Antifungal agent Barrand 8

Fluconazole Antifungal agent Barrand 8

Cycloserine Barrand 10

Acyclic nucleoside phosphonate: inhibits nucleic acid synthesisNon-nucleoside reverse transcriptase inhibitor: inhibits nucleic acid synthesisProtease inhibitor: inhibits cleavage of viral proteins (required by virus to produce functional proteins) in final processing of new virions

Group of cyclic peptides - interfere with the cytoplasmic membrane of bacteria; bactericidal; limited use as interfere with mammalian cytoplasmic membrane also

Ionophore antibiotic - interferes with cytoplasmic membrane of bacteria; bactericidal; limited use as interfere with mammalian cytoplasmic membrane alsoLipopeptide, disrupts bacterial membrane function; bactericidal; used in treatment of skin infections by gram positive bacteriaBinds to ergosterol, causing pore formation in the fungal membrane (but poor selectivity against mammalian host; poor solubility)

Binds to ergosterol, causing pore formation in the fungal membrane (but poor selectivity against mammalian host, so too toxic -> only used topically)Inhibits enzymes involved in ergosterol synthesis, altering the fluidity of the membrane, ultimately preventing fungal replication

Inhibit conversion of L-Alanine to D-Alanine; D-Alanine is essential component of bacterial cell wall (peptide side chain) -> inhibits bacterial cell wall synthesis

Antibacterial agent, antitubercular agent


Vancomycin Antibacterial agent Barrand 10

Methicillin Antibacterial agent Barrand 10

Ampicillin Antibacterial agent Barrand 10

Linezolid Antibacterial agent Barrand 13

Tetracyclins Antibacterial agent Barrand 13

Streptomycin Antibacterial agent Barrand 13

Gentamycin Antibacterial agent Barrand 13

Chloramphenicol Antibacterial agent Barrand 13

Ertythromycin Antibacterial agent Barrand 13

Inhibits transglycosylation of peptidoglycan cell wall - inhibits bacterial cell wall synthesis; used if allergic to penicillin

β-lactam; binds PBPs that are important in transpeptidation of bacterial cell wall -> inhibits bacterial cell wall synthesis; resistant to β-lactamase activity, poor access across gram-ve outer membrane; mecA -> low resistance, femA/B/D -> high resistance

β-lactam; binds "penicillin binding proteins" that are important in transpeptidation of bacterial cell wall -> inhibits bacterial cell wall synthesis; resistant to β-lactamase activity, "broad spectrum"Binds the 50S ribosomal subunit and prevents complex formation, thereby inhibiting bacterial protein synthesis

Bind the 30S ribosomal subunit and prevents tRNA interaction during bactrial protein synthesis; only protein synthesis inhibitor that is bacteriocidal rather than bacteiostaticBinds the 30S ribosomal subunit and inhibits peptide bond formationBinds the 30S ribosomal subunit and inhibits peptide bond formationBinds the 50S ribosomal subunit and inhibits peptide bond formation; resistance involves transformation via acetyltransferaseInteracts with the 50S subunit to prevent translocation -> inhibits bacterial protein synthesis


Sulphonamides Barrand 14

Trimethoprim Antibacterial agent Barrand 14

Co-trimoxazole Antibacterial agent Barrand 14Rifampicin Inhibit bacterial RNA polymerase Antibacterial agent Barrand 14

Ciprofloxacin Antibacterial agent Barrand 14

Isoniazid Antitubercular agent Barrand 15Pyrazinamide Antitubercular agent Barrand 15

Pyrimethamine Antimalarial agent Barrand 16

Chloroquine Antimalarial agent Barrand 16

Mefloquine Antimalarial agent Barrand 16

Tamoxifen Anticancer agent Barrand 26

Structural analogues of PABA, and therefore act as 'alternative substrates' for DHPS (DiHydroPteroate Synthase), thereby inhibiting tetrahydrofolic acid synthesis and thereby inhibiting nucleic acid synthesis

Antibacterial agent, antimalarial agent

Competitively inhibits DHFR (DiHydroFolate Reductase), thereby inhibiting tetrahydrofolic acid synthesis and thereby inhibiting nucleic acid synthesisTrimethoprim and sulphamethoxazole given in conjunction; inhibits nucleic acid synthesis

Example of a QUINOLONE -> group of compounds that bind and inactivate DNA gyrase

Prodrug, which during activation affects mycolic acid synthesis -> production of free radicals, to which Mycobacterium tuberculosis is very sensitive (but resistance develops rapidly)

Interfere with nucleic acid synthesis in Plasmodia (malaria) by blocking plasmodial DHFR (DiHydroFolate Reductase)

Inhibits heme polymerase (produced by malaria), thereby interfering with Plasmodium life cycle (but leads to increase in heme concentration which can be toxic, and now has widespread resistance)

Inhibits heme polymerase, thereby interfering with Plasmodium life cycle (but leads to increase in heme concentration which can be toxic, and now has widespread resistance) (?)Anti-estrogen, used in treatment of breast cancer (has a range of agonist and antagonist effects)


Anticancer agent Barrand 26

Leucovorin Anticancer agent Barrand 27

5-fluorouracil Anticancer agent Barrand 28

Cytarabine Anticancer agent Barrand 28Etopocide Topoisomerase II inhibitor Anticancer agent Barrand 30Camptothecins Topoisomerase I inhibitor Anticancer agent Barrand 30

Melphalan Anticancer agent Barrand 32

Anticancer agent Barrand 31

Mitomycin Anticancer agent Barrand 32

Carmustine Anticancer agent Barrand 32

Cisplatin Anticancer agent Barrand 32

Aromatase Inhibitors (e.g. Anastozole)

Inhibit synthesis of estrogens from androgens, so used in treatment of breast cancerSalvages normal tissues from folate depletion when being treated with high doses of methotrexateAntimetabolite - Metabolised to produce 'fraudulent' nucleotide, fDUMP, which inhibits DNA synthesis

Antimetabolite - incorporated (in its phosphorylated form) into DNA/RNA -> main action of inhibiting DNA synthesis; side effects: nausea/vomiting

Nitrogen mustard -> DNA intercalator; but can have side effect of producing secondary mutatiions due to alkylated guanine erroneously pairing with thymine

Cyclophosphamide

Prodrug that upon heptaic conversion is used to produce cytotoxic nitrogen mustard -> has exposed Cl- that is released in neutral/alkaline pH, and reacts with guanines in DNA, so inhibiting DNA replicationCross-link DNA, inhibiting DNA replication; preferential action in hypoxic conditionsNitrosourea - bind guanines at the O6 position, inhibiting DNA replication; can cross blood-brain barrier

Platinum complex, exchanges Cl- for nucleophilic groups to give intercalating agent -> inhibits DNA synthesis; resistance derives from elevated cellular levels of DNA repair enzymes


Doxorubicin Anticancer agent Barrand 34

Mitoxantone Anticancer agent Barrand 34

Vincristine Anticancer agent Barrand 36

Taxol Anticancer agent Barrand 36Imitanib Small molecule kinase inhibitor Anticancer agent Barrand 41

Trastuzumab Anticancer agent Barrand 41Gefitinib Blocks growth receptor autophosphorylation Anticancer agent Barrand 41

Marimastat Anticancer agent Barrand 42Endostatin Endogenous inhibitor of angiogenesis Anticancer agent Barrand 42

Bevacuzimab Anticancer agent Barrand 42

Non-covalently intercalates with DNA, no selectivity of tumour over normal except cells are more rapidly dividing; severe side effect of carditoxicity due to generation of free radicals in cardiac tissue (limited by encapsulation)

Non-covalently intercalates with DNA, no selectivity of tumour over normal except cells are more rapidly dividing; modified version of doxorubicin without cardiotoxic side-effects

Anti-mitotic agent (vinca alkaloid): prevents formation of the mitotic spindle and arrests cell in metaphase; disrupts the balance between microtubule assembly and dissembly

Anti-mitotic agent: prevents formation of the mitotic spindle and arrests cell in metaphase; disrupts the balance between microtubule assembly and dissembly

Humanised monoclonal antibody against the EGF receptor

Matrix metalloproteases inhibitor, limiting metastasis

Blcoks angiogenic proteins secreted by tumour cells -> inhibits angiogenesis

drugs and their mechanisms of action

Documents

plasmodium

peripheral

bacterial

naturally

30s ribosomal

class ib repolarisation

class ia repolarisation

class ic repolarisation