Pharmacology Flashcards
Digoxin
Cardiac glycoside used to slow HR in atrial fibrillation (-ve chronotrope, +ve inotrope) and for heart failure in patients still symptomatic following diuretics and ACE-Is. Narrow therapeutic index.
Dobutamine
Directly acting adrenoceptor agonist - beta 1 selective. Stimulates cardiac contraction without major effect on HR (+ve inotrope). Treats heart block, half-life 2mins (rapid metabolism by COMT), lacks isoprenaline’s reflex tachycardia.
Atenolol
Beta-1 selective beta-blocker used to treat angina, post MI, dysrhythmias, CHF, hypertension. Not safe for asthmatic patients.
Diltiazem + verapamil
Rate limiting/slowing Ca channel blockers (cardiac and smooth muscle actions). -ve inotropic effect Verapamil > Diltiazem. Ca be used to control/correct dysrhythmias. Verapamil is a Phenylalkaylamine, Diltiazem is a Benzothiazepine. Can double Carbamezepine levels (anti-convulsant/mood stabiliser).
Enalapril + captopril
ACEI - reduces preload and afterload. Used for hypertension, HF, post-MI, diabetic nephropathy, progressive renal insufficiency, high CVD risk.
Losartan
Angiotensin II receptor blocker (ARB/AIIA). Antagonist of AT1 receptors. Hypertension as alternative to ACEIs with less side effects, CHF in patients who cannot tolerate ACEIs.
Nicorandil
K channel opener and Organic nitrate that stimulates guanylate cyclase to cause vasodilation. Used for angina, acute and chronic HF, BP control during anaesthesia. Adverse effects - hypotension and headache.
Bendrofluazide
aka bendroflumethiazide. Thiazide diuretic. Inhibit Na and Cl reabsorption in early distal tubule. Increases Na/Cl, K and Mg loss, Ca reabsorption. Moderate increase in urine volume. Used for HF, hypertension, severe resistant oedema, idiopathic hypercalciuria, nephrogenic diabetes insipidus. Side effect - inhibits insulin secretion (DM)
Spironolactone
Potassium sparing diuretic/aldosterone receptor antagonist. Acts in the distal convoluted tubule. Small increase in urine volume and Na loss. Used for primary and secondary hyperaldosteronism. Side effects - gynaecomastia, menstrual disorders, hyperkalaemia.
Amiodarone
Side effects it causes
Wide spectrum anti-arrhythmic used for supraventricular and ventricular tachyarrhythmias. Prolongs cardiac action potentials. Adverse effects - accumulation in body (long half life) causes photosensitive skin rashes, hypo-/hyper-thyroidism, pulmonary fibrosis, corneal deposits, Neuro and gastro disturbances. Potent inhibitor of Phenytoin (antiepileptic) metabolism.
Glyceryl trinitrate
Organic nitrate that releases NO into smooth muscle causing vasodilation. Often given sublingually for rapid relief of angina - short half life ~5mins. Via transdermal patch gives longer action. Prolonged use associated with tolerance.
Minoxidil
Anti hypertensive vasodilator that also slows/prevents hair loss. Potassium channel opener causing hyperpolarisation.
Doxazosin
Competitive Alpha-1 adrenoceptor blocker -> antihypertensive and coronary vasodilator but associated with increased rates of CHF by ALLHAT study. Can induce postural hypotension.
Sumitriptan
5HT-1D receptor agonist. Constricts large arteries and inhibits trigeminal nerve transmission. Used to treat migraines - contraindicated if have coronary disease.
Streptokinase
Thrombolytic - converts plasminogen to plasmin (natural fibrin protease). Bacterial product hence tolerance develops after first admin. Used in the treatment of MI.
Alteplase
Thrombolytic - converts plasminogen to plasmin (natural fibrin protease). Recombinant plasmin activator. Used in the treatment of acute MI and ischaemic stroke. Must be given within 12 hrs symptom onset.
Warfarin
Anticoagulant - Vitamin K antagonist. Long delay of onset (~5days) narrow therapeutic window, unpredictable pharmacokinetics and numerous drug interactions. Protein binding interactions most clinically significant with warfarin. Phenytoin (antiepileptic) increases clearance.
Heparin
Anticoagulant - activates Antithrombin-III (LMWHs also inhibit factor Xa). Short half life ~1hr, LMWHs longer.
Aspirin
Antiplatelet activator - irreversible non-specific cyclo-oxygenase inhibitor (but binds COX-1 more avidly) - prevents platelet production of thromboxane A2. At higher doses also inhibits endothelial COX preventing production of protective prostacyclin PGI2 (COX-2). Major side effects - gastric irritation + ulceration, bronchospasm in asthmatic (pseudoallergy), prolonged bleeding times, nephrotoxicity. Can displace other drugs from albumin increasing their free conc. Preferentially absorbed in stomach (acid pH) but majority in gut.Analgaesic - inhibiting prostanoid (PG) synthesis prevents sensitisation of nociceptors thus increases threshold for pain.
Clopidogrel
Antiplatelet activator - ADP/P2Y receptor antagonist.
Abciximab
Antiplatelet activator - Glycoprotein IIb/IIIa receptor antagonist. GPIIb/IIIa receptor plays important role in platelet aggregation. Used for treatment of thrombotic disorders.
Simvastatin
HMG-CoA reductase inhibitor. Lipid lowering drug. Used to treat dyslipidemia and to prevent CVD. Grapefruit juice inhibits cytochrome P450 thus inhibits metabolism. Side effects - rhabdomyolysis.
Ibuprofen
Typical non-selective NSAID. Inhibits COX reversibly. Has anti-inflammatory, analgesic and anti-pyretic actions.
Celecoxib
Selective COX-2 inhibitor. Get fewer ulcers than with non-selective NSAIDs. Increased risk to CVS however - MIs
Mannitol
Osmotic diuretic - inert, filtered but not reabsorbed, decreases water reabsorption. Clinically used to prevent acute renal failure, decrease intra-cranial and ocular pressures. Side effects - increases ECF volume, hyponatraemia.
Acetazolamide
Carbonic anhydrase inhibitor - acts on the proximal tubule to prevent reabsorption of HCO3 and Na. Weak diuretic. Clinical used for renal stones, metabolic alkalosis and to decrease intra-ocular pressure. Unwanted - K loss and met. acidosis
Frusemide
Aka furosemide - Loop diuretic. Blocks the Na/Cl/K transport in the ascending limb of loop of Henle. Decreases the osmolarity of the medullary interstitium hence reduced concentrating power of collecting duct. Leads to a large increase in urine volume, Na, Cl, K, Ca and Mg loss. Clinical uses - oedema, moderate hypertension, hypercalcaemia, hyperkalaemia. Unwanted effects - hypovolaemia, hypotension, metabolic alkalosis (K loss)
Amiloride
Potassium sparing diuretic - aldosterone-sensitive Na channel inhibitor. Prevents Na reabsorption from the early distal tubule - increases Na and uric acid loss but H retention. Small increase in urine volume. Clinical uses - combine with K losing diuretics. Unwanted effects, hyperkalaemia, metabolic acidosis.
Promethazine
Anti-emetic. Competitive antagonist at histaminergic (H1), cholinergic (M), and dopaminergic receptors (D2). Acts centrally (labyrinth, NTS, VC) to block activation of vomiting centre. Used to treat/prevent - motion sickness, labyrinth disorders (Meniere’s), hyperemesis gravidarium, pre- and post-operatively. Unwanted effects - dizziness, tinnitus, fatigue, sedation, excitation in excess, convulsions, anti-muscarinic effects.
Metoclopramide
Anti-emetic, dopamine receptor antagonist (D2). Acts centrally CTZ and in GIT (increases gastric motility and emptying). Care must be taken with bioavailability of co-admin oral drugs. Uses - uraemia, radiation sickness, GIT disorders, chemotherapy. Side-effects - drowsiness, dizziness, anxiety, extrapyramidal reactions (children), hyperprolactinaemia, galactorrhoea, menstrual disorders. Note - no anti-psychotic actions.
Hyoscine
Anti-emetic, muscarinic receptor antagonist. Acts centrally esp in vestibular nuclei, NTS, VC to block VC activation. Uses - prevent motion sickness (little effect once nausea established), pre-op medication (sedation). Side-effects - drowsiness, dry mouth, cycloplegia, mydriasis, constipation (at higher doses)
Ondansetron
Anti-emetic, 5HT3 receptor antagonist. Blocks visceral afferent transmission and CTZ. Uses - preventing chemotherapy induced vomiting, radiation sickness, post-op nausea. Side effects - headache, flushing sensation, increased large bowel transit time (constipation).
Metronidazole
Antibiotic active against anaerobic bacteria and Protozoa. Used against H. pylori as part of triple therapy with clarithromycin and a PPI. Interferes with alcohol metabolism.
Amoxycillin
Broad spectrum beta-lactam antibiotic useful against sensitive bacteria. Used against H. pylori as part of triple therapy along with clarithromycin and a PPI, depending on pattern of local resistance.
Clarithromycin
Macrolide antibiotic - inhibits translocation of bacterial tRNA. Used against H. pylori as part of triple therapy along with a PPI and either metronidazole or amoxycillin. Can also be used with a H2 receptor antagonist and bismuth.
Omeprazole
Proton pump inhibitor. Irreversible inhibitor of H/K ATPase. Inhibits basal and stimulated gastric acid secretion from parietal cells by >90% Uses - component of triple therapy against H. pylori, peptic ulcers resistant to H2 antagonists, reflux Oesophagitis, with NSAIDs to limit gastric side effects.
Cimetidine + ranitidine
Histamine type 2 receptor antagonists - inhibit gastric acid secretion by ~60%. Relapses likely after withdrawing treatment. Cimetidine inhibits CYP 450 and hence can decrease metabolism of other substances.
Sucralfate
Cytoprotective drug - polymer containing aluminium hydroxide and sucrose octasulphate. Forms gel-like complex in stomach that coats and protects gastric ulcer. May cause constipation and reduce absorbance of other drugs.
Bismuth chelate
Cytoprotective drug sometime used in triple therapy.
Misoprostol
Cytoprotective drug - stable prostaglandin analogue that mimics the action of locally produced prostaglandins to maintain the gastroduodenal mucosal barrier. May be co-prescribed with chronic NSAIDs use. Side effects - diarrhoea, abdominal cramps, uterine contraction (do not use in pregnancy!)
Prednisolone + Fluticasone
Glucocorticoid. Powerful anti-inflammatory and immunosuppressive. Used for symptomatic treatment of active IBD and to prevent relapse. Drug of choice to induce remission of Crohn’s but declining use for Ulcertive colitis. Chronic systemic use associated with Cushing Syndrome.
Budesonide
Glucocorticoid that is degraded locally, limiting its systemic effects. Powerful anti-inflammatory and immunosuppressive. Given topically for Crohn’s disease and associated with less side effects that prednisolone.
Sulfasalazine + mesalazine (5-ASA)
Aminosalicylates - anti-inflammatory but not immunosuppressive. Used to treat active ulcerative colitis and maintain remission. Ineffective in treating active Crohn’s disease but may help maintain surgically-induced remission. Topical delivery, pH-dependent capsules or slow release microspheres used to control site of absorption. Superior to topical steroids for inducing Ulcerative colitis remission.
Azathioprine
Immunosuppressant used to maintain remission for both UC and CD. Can be used to induce CD remission. Prodrug activated by gut flora to 6-mercaptopurine which interferes with purine biosynthesis, DNA synthesis and cell replication. Side effects - bone marrow suppression. Metabolised by xanthine oxidase - allopurinol inhibits this hence leads to accumulation -> blood disorders.
Ipratropium Bromide
Muscarinic receptor antagonist (anticholinergic) used in asthma/obstructive airway disease to dilate the airways.
Salbutamol
Aka ventolin. Directly acting sympathomimetic / beta-2-adrenergic receptor agonist. Synthetic catecholamine derivative with relative resistance to MAO and COMT. Used to treat asthma (relax bronchial smooth muscle and inhibit release of bronco constrictor substances from mast cells) and to prevent premature labour (i.v.) Side effects - reflex tachycardia, tremor, hyperthyroidism and diabetes.
Morphine
Opiate (alkaloid derived from poppy). Tertiary nitrogen = analgesia. Poor lipid solubility. Metabolised by liver to morphine-6 glucuronide (more potent analgesic) and excreted in urine. Pharmaco effects - analgesia, euphoria, sedation, respiratory depression, cough suppression, nausea and vomiting, pupillary constriction, constipation, histamine release -> bronchoconstriction and hypotension.
Heroin
Aka diamorphine is essentially a prodrug rapid converted to morphine and 6-monoacetylmorphine. Has greater lipid solubility than morphine thus crosses the blood brain barrier more rapidly when injected i.v. More likely to cause dependence than i.v. Morphine.
Codeine
More readily absorbed by oral route than morphine, but has ~20% analgesic properties. 5-10% converted by demethylation to morphine (analgesic effects). Causes little or no euphoria and rarely addictive, however same degree of resp depression (seldom problem however). Causes constipation and has marked anti-tussive effect.
Methadone
Orally active and pharmacologically similar to morphine but considerably longer duration of action - half life > 24 hrs as very lipophilic (dissolves in fat, slowly releases to periphery). Less physical withdrawal symptoms than morphine but same psychological dependence. Used to treat heroin addiction.
Naloxone
Opiate receptor antagonist. Produces rapid reversal of effects of morphine and other opioids. Often given to treat respiratory depression from opioid overdoes. Rapidly metabolised, effect only last 2-4hrs thus often need repeated dosing.
Cocaine
CNS stimulant and local anaesthetic (ester). Local anaesthetic effects by blocking Na channels. Cocaine HCl - intranasal or I.v. Crack/Freebase - inhalation. Short half life euphoria. Also has less potent effects on NA (inhibits reuptake 1 into presynaptic terminal) and 5HT transporters. Causes vasoconstriction, decreased cerebral blood flow and inflammation in walls of brain vessels. Increases risk of MI (vasoconstriction, increased HR, increased platelet activation)
Cannabis
Herbal cannabis contains over 400 compounds including over 60 cannabinoids. Most potent psychoactive agent - delta-9-THC. Orally undergoes extensive first pass met, delayed onset but prolonged. Metabolised by liver into more potent form. 25% excretion into urine, 65% into gut from which reabsorbed, prolonging effect. Slowly accumulates in poorly perfused fatty tissues. Poor correlation between plasma conc and degree of intoxication. Neural receptors CB1, immune CB2. Endogenous agonist - anandamide. Pharmacodynamics - psychosis, schizophrenia, increased food intake, memory loss, psychomotor performance, immunosuppressant, tachycardia/vasodilation, reddening of conjunctivae.
Nicotine
A particulate in cigarette smoke - rapid absorption from small airways / alveoli. Half life 2-3hrs extensive liver metabolism to cotinine. Low dose - symp activation increases HR and BP. Higher doses - binds to nicotinic AChR -> ganglionic stimulation, catecholamine release from adrenals. Very high dose - ganglion blockade. Increases firing rate on Da VTA neurons -> euphoria. Increases coagulation, coronary and peripheral vasoconstriction, increases LDL, decreases HDL -> CVD. Increases metabolic rate, decreases appetite. Protective for Alzheimer’s and PD?
Ethanol
20% absorbed from stomach, 80% from rest of gut. Speed of onset proportional to rate of gastric emptying. 85% metabolised in liver to acetaldehyde 75% by alcohol dehydrogenase, 25% mixed function oxidase (can be upregulated). 15% metabolised in gut by alcohol dehydrogenase. Low pharmacological potency, little selectivity. CNS depressant, impairs sensory and motor function. CVS - cutaneous vasodilation. Diuresis due to decreased ADH. Chronic effects - dementia, ataxia, Wernicke-Korsakoff syndrome, liver damage. Increased ACTH, decreased testosterone.
Disulfiram
Inhibitor of aldehyde dehydrogenase leads to accumulation of acetaldehyde. Used to discourage recovering alcoholics from drinking (no effect without alcohol)
Co-trimoxazole
Anti microbial combination of sulphamethazole and trimethoprim. Trimethoprim inhibits tetrahydrofolate reductase in bacteria (part of essential thymidylate synthesis from folate pathway). Sulphamethazole inhibits folate synthesis, potentiating effect of trimethoprim x10. Used for infections with pneumocystis carinii which causes pneumonia in AIDS patients.Resistance due to production of other DHF reductases that are I effected by the antibiotic OR hyper produce DHF reductase
Cefotaxime
(Beta lactam) Cephalosporin. Interferes with peptidoglycan synthesis. Widespread resistance (beta-lactamase). Paraenteral route of admin. Widely distributed, crosses BBB - bacterial meningitis.
Tetracyclin
Broad-spectrum gram+ve/-ve. Affects protein synthesis. Actively transported into bacteria, competes with tRNA for A binding site. Bacteriostatic, not bactericidal. Widespread resistance - energy dependent efflux mechanism and/or mutations in ribosome structure. Oral or paraenteral. Irregular absorption from GIT - chelate metal irons forming non-absorbable complex. Excreted via bile and kidney. Not to be given to children, pregnant women or nursing mothers (chelates calcium).
Chloramphenicol
Binds to 50S ribosomal subunit inhibiting transpeptidation hence protein synthesis. Wide spectrum bacteriostatic gram+ve/-ve. Resistance due to chloramphenicol acetyl-transferase - plasmid mediated (can be reduced by fluorine mod.) Oral admin, rapidly absorbed. 10% excreted unchanged in urine, rest metabolised by liver. Rare side effect, depression of bone marrow - pancytopenia. Can result in grey baby syndrome in new-borne if inadequate inactivation / excretion. Can block oxygen-dependant active transport system which transports aminoglycosides.
Gentamicin
Aminoglycoside. Binds to 30S ribosomal subunit - alters codon:anticodon recognition -> production of defective bacterial proteins (does not explain rapid lethality) Penetration through cell membrane dependent on oxygen-dependent active transport system (chloramphenicol can block). Bactericidal, effect enhanced by cell wall synthesis interferers. Resistance - inactivation by microbial enzymes, failure of penetration (overcome by penicillin/vancomycin), ribosomal mutations. Effective against aerobic gram -ve, some gram +ve. Combine with penicillin to use against Strep, Listeria, Pseudomonas. Not orally available, i.m./i.v. Do not cross BBB. Excretion via glomerular filtration entirely. Side effects - ototoxicity, nephrotoxicity.
Isoniazid
Anti-Mycobacterial. Static on resting, can kill dividing. Effective against intracellular bacteria (passes into cells). Inhibits synthesis of cell wall components. Orally available, wide distribution, penetrates well into necrotic tuberculous lesion. Metabolism varies in individuals - slow acetylators better response. Used against TB.
Rifampacin
Binds to and inhibits DNA-dependent RNA polymerase in prokaryotic cells. One of the most effect anti TB agents known. Can kill intracellular bacteria. Orally available, widely distributed, excreted urine and bile, progressive deacetylation. Side effect, skin eruptions, fever, GI tract disturbances.
Pyrazinamide
Anti-myobacterial. Inactive at neutral pH, active at acidic. Effective in intracellular acidic phagolysosome. Orally available, wide distribution, excretion by glomerular filtration. Side effects, arthralgia, GIT disturbances, malaise, fever. Part of first phase ~2months against TB (along with Rifampacin and isoniazid)
Nystatin and amphotericin
Anti fungal. Polyene macrolide - no absorption from mucous membranes or skin - used for fungal infections of the skin and GIT. Binds ergosterol in fungal cell membrane and interferes with permeability and transport functions by forming a pore. Unwanted effects - nausea and vomiting with high oral dose, rash.
Fluconazole
Anti fungal. Azole group of synthetic antimycotic agents - broad spectrum. Blocks synthesis of ergosterol, altering fluidity of cell membrane and action of membrane associated enzymes thus inhibits replication. Inhibits transformation of candidal yeast cells into hyphae (invasive pathogenic form). i.v. Infusion for systemic infection, orally for GIT infection.
Acyclovir
Antiviral - Guanosine derivative with high specificity for herpes simplex. Converted to monophosphate by thymidine kinase (viral form much more effective) mono form then converted to triphosphate by host cell kinases - thus only adequately activated in infected cells. Activated form inhibits viral DNA-polymerase, terminating chain reaction. Resistance if changes in viral thymidine kinase or DNA polymerase. Oral, i.v. and topical delivery. i.v. side effects - local inflammation, renal dysfunction, nausea and headache.
Zidovudine
Aka Azidothymidine (AZT) analogue of thymidine - active inhibitor of reverse transcriptase. Phosphorylated by cellular kinases. Incorporation into growing viral DNA strand results in chain termination. Gamma DNA polymerase in host cell mitochondrion sensitive to AZT. Orally available or i.v. Enter cells by passive diffusion unlike other nucleotides. Given to AIDS patients - reduces opportunistic infections, stabilises weight, reverses thrombocytopenia, stabilises dementia and reduces viral load. Reduces risk of transmission from mother to foetus by 66%. Given to people accidentally exposed to HIV. Common side effects - anaemia, neutropenia. Resistance - response wanes with long term use. Mutations in viral reverse transcriptase.
Diazepam
Aka valium. Long-acting benzodiazepine. Anti-convulsant, spasmolytic, anxiolytic. Acts at GABA-A receptors. Bind plasma proteins strongly and highly lipid soluble -> wide distribution. Wide margin of safety, does NOT induce liver enzymes. Side effects - sedation, tissue tolerance, dependence.
Oxazepam
Short-acting benzodiazepine. Sedative/hypnotic. Slower to reach peak plasma conc than other benzos. Metabolite of diazepam. Acts at GABA-A receptors. Bind plasma proteins strongly and highly lipid soluble -> wide distribution. Wide margin of safety, does NOT induce liver enzymes. Side effects - tolerance, dependence.
Amobarbital
Barbiturate. Non-selective CNS depressant. Sedative / hypnotic (severe intractable insomnia) Low safety margin, depresses respiration, overdose lethal. Enzyme inducer, tolerance, dependence.
Chloral hydrate
Sedative/hypnotic. Converted by liver to trichloroethanol. Unknown MOA. Wide margin of safety, ok to use in children and elderly.
Buspirone
Anxiolytic. 5HT-1A agonist. Slow onset of action (days/weeks), few side effects.
Temazepam
Sedative/hypnotic. Short-acting benzodiazepine. Metabolised to oxazepam.
Phenytoin
Anticonvulsant. Blocks v-gated Na channels. Used for partial and secondary generalised seizures and status epilepticus. Complex pharmacokinetics - oxidation->hydroxylation->conjugation->renal excretion. Saturable kinetics. P450 inducer. Amiodarone and isoniazid both potent inhibitors of its metabolism. Aspirin and valproate displace protein binding.
Carbamazepine
Anticonvulsant. Blocks v-gated Na channels. Used against partial and secondary generalised seizures. Auto-induction. Macrolide antibiotics inhibit metabolism.
Sodium valproate
Anticonvulsant. Unclear MOA - enhances GABA. Use - partial or generalised seizures - wide spectrum. Potent inhibitor of hepatic enzymes.
Vigabatrin
Anticonvulsant. Relatively short half life, few interactions. Major side effect - visual field defects. Rarely used except for infantile spasms.
Lamotrigine
Anticonvulsant - blocks v-gated Na channels. Uses - partial and generalised seizures - wide spectrum. Long half life, mostly metabolised by conjugation. Usually well tolerated, rash (sometimes severe). No effect on hepatic enzymes.
Lidocaine
Local anaesthetic (amide). Good mucous membrane absorption, metabolism by hepatic N-dealkylation. 2h plasma half life. Side effects - Paradoxical CNS stimulation, restlessness, confusion, tremor. Myocardial depression, vasodilation, decreased BP. May be used to treat ventricular arrhythmias.
Nitrous oxide
Gaseous general anaesthetic. Blocks NMDA glutamate receptors thus alters synaptic function. Also blocks nACh receptors, 5-HT3 receptor and Kainate receptor.
Halothane and Enflurane
Gaseous general anaesthetic. Alters synaptic function by potentiating GABA-A receptor function (and glycine receptors). Less potent than i.v. and show no subunit selectivity. Also inhibit nACh receptors (amnesia & analgesia) and facilitate TREK (background leak) K channel opening, reducing neuronal excitability (reflex suppression).
Propofol and etomidate
I.v. general anaesthetics. Potentiate GABA-A receptor function - more effective when beta-subunits predominate. Suppress reflexes and cause amnesia (alpha-5). Propofol often used to induce LOC.
L-DOPA
Anti-parkinsonian drug. Treats hypokinesia, rigidity & tremor. Effects decrease with time, causes dyskinesias and on-off oscilations. Precursor to dopamine. 95% administered L-DOPA metabolised in the periphery -> Nausea and vomiting, thus combine with peripheral DOPA decarboxylase inhibitor.
Bromocriptine and pergoline
Dopamine D2 receptor agonist. Ergot derivative. Longer duration of action that L-DOPA - smoother & more sustained response. Independent of DA neurons. Less incidence of dyskinesias. Can use with L-DOPA.
Carbidopa and benserazide
Peripheral DOPA decarboxylase inhibitor - used in conjunction with L-DOPA to reduce side effects.
Domperidone
Peripheral dopamine antagonist given with L-DOPA to prevent nausea.
Entacapone and tolcapone
Peripheral COMT inhibitor. Increases the bioavailability of L-DOPA allowing reduction in dose by preventing convention to 3-OMD that competes for transport into the brain.
Clozapine
Neuroleptic - most effective schizophrenia drug. Dopamine antagonist. Relatively none selective between D1 and D2 receptors - high affinity for D4. Treat +ve but not -ve symptoms. Take weeks to work. also a 5HT-2a antagonist
Deprenyl
Aka selegiline. Selective MOA-B inhibitor (CNS) no peripheral side-effects. Can be given alone in early stage disease or in combination with L-DOPA. Rare side effects - hypotension, nausea/vomiting, confusion and agitation.
Chlorpromazine
Neuroleptic - anti-schizophrenic. 1st generation Dopamine antagonist.
Haloperidol
Neuroleptic - anti-schizophrenic. Very potent (50 times more than chlorpromazine) Dopamine antagonist.
Risperidone
Anti-schizophrenic. Treats mania, aggressive behaviour, acute and chronic psychosis. Very potent 5-HT 2a and D2 receptor antagonist. Side effects are more extra pyramidal symptoms and hyperprolactinaemia than other anti- psychotics
Cyclophosphamide
Cytotoxic drug in treatment of breast cancer- bifunctional alkylation agent (nitrogen mustard). Covalently bonds with nucleophiles - main target Guanine N7. Causes intra- and inter-chain cross links, thus interferes with transcription and replication.
Methotrexate
Antimetabolite Cytotoxic drug - folate antagonist hence interferes with thymidylate synthesis. Blocks DNA synthesis.
Bleomycin
I.V. Cytotoxic antibiotic. Directly interacts with DNA. Metal-chelating glycopeptide that degrades DNA - active against non-dividing cells.
Doxorubicin
Cytotoxic antibiotic. Directly interacts with DNA to inhibit DNA and RNA synthesis.
Vincristine and vinblastine
Cytotoxic plant vinca alkaloid. Causes cell cycle block at G2. Binds tubulin inhibiting microtubule polymerisation hence spindle formation.
Etoposide
Cytotoxic plant alkaloid podophyllotoxin. Inhibitor of topoisomerase type II enzyme thus causing cell death
Procarbazine
Miscellaneous cytotoxic drug. Inhibits DNA and RNA synthesis and interferes with mitosis at interphase. Activated by cytochrome P450 and MOA to alkylate DNA.
Cisplatin and carbaplatin
Miscellaneous cytotoxic drug (platinum compound). Alkylating compounds that Interact with DNA causing guanine intrastrand cross-links.
Acetylcholine
Released at all autonomic ganglia and by postganglionic parasympathetic neurons and motor neurons. Synthesised from acetyl CoA and Choline by choline acetyltransferase. Degraded by acetylcholinesterase in the synaptic cleft. Only choline reuptaken.
Pilocarpine
Directly acting non-selective cholinomimetic / muscarinic agonist (alkaloid). Good lipid solubility, half life ~3-4 hrs. Used as local treatment for glaucoma. Side effects - hypotension, respiratory distress.
Bethanecol
Directly acting cholinomimetic / muscarinic agonist (choline ester). Minor modification of ACh - M3 AChR selective. Resistant to degradation, half life ~ 3-4 hrs, orally active, limiting CNS access. Main use - assist bladder emptying and enhance gastric motility. Side effects - bradycardia, hypotension, respiratory difficulty.
Neostigmine
Indirectly acting cholinomimetic - reversible anticholinesterase. Donates carbamyl group to enzyme, blocking active site. Removed by slow hydrolysis thus increases duration of ACh activity in synapse.
Physostigmine
Indirectly acting cholinomimetic - reversible non-polar anticholinesterase (can cross BBB). Primarily acts at postganglionic parasympathetic synapse (half life ~ 30 mins). Used to treat glaucoma and atropine poisoning, particularly in children. Low dose CNS effects - excitation, convulsions. High dose - unconsciousness, respiratory depression, death.
Ecothiopate
Indirectly acting cholinomimetic - irreversible anticholinesterase (Organophosphate). Rapidly reacts with enzyme blocking active site - stable and resistant to hydrolysis (days). Used in treatment of glaucoma - prolonged duration of action. Side effects - bradycardia, hypotension, respiratory difficulty.
Atropine
Muscarinic receptor antagonist. CNS effects - agitation. Used to alter heart rate if post MI bradycardia.
Tropicamide
Muscarinic receptor antagonist. Used to examine the retina.
Trimetaphan
Nicotinic receptor antagonist / ganglion blocking drug. Use-dependent block. Hypotension, pupil dilation, bronchodilation, bladder dysfunction, decreased GIT tone, decreased sections. Clinically used to induce hypotension during surgery as short-acting.
Hexamethonium
Nicotinic receptor antagonist. Use-dependent block. First anti-hypertensive.
Tubocurarine
Non-depolarising (competitive nAChR antagonist) neuromuscular blocker. Naturally occurring quaternary ammonium alkaloid. Causes flaccid paralysis - graded block = different proportions of fibres blocked. Does not affect consciousness or pain sensation. Always require respiration assistance. Used to reflex skeletal muscle for surgery and permit artificial ventilation. Action can be reversed by anticholinesterases. I.V. admin, not metabolised, does not cross BBB.
Atracurium
Non-depolarising (competitive nAChR antagonist) neuromuscular blocker.
Suxamethonium
Depolarising (nAChR agonist) neuromuscular blocker. Causes muscle relaxation.
Adrenaline
Directly acting adrenoceptor agonist, selective for beta over alpha (noradrenaline selective for alpha over beta). Used in allergic reaction and anaphylactic shock - blocks release of hypotensive and bronchoconstrictor mediators. Used in COPD, chronic bronchitis, emphysema and asthma emergencies. Used to increase heart rate and force of contraction in acute management of heart block. Used to maintain BP with spinal anaesthesia, and to prolong duration of local anaesthetics (vasoconstrictor properties). May also be used to decrease aqueous humour production (glaucoma)
Phenylephrine
Directly acting adrenoceptor agonist - alpha 1 selective. More resistant to COMT but not MAO than adrenaline. Clinically used as a vasoconstrictor (i.v. or topically to reduce superficial bleeding) or as a pupil dilator (eye drops). Also used as a nasal decongestant.
Clonidine
Directly acting adrenoceptor - alpha 2 selective (presynaptic auto-inhibitory receptors). Used to treat hypertension and migraine (oral or i.v.). Reduces sympathetic tone by inhibiting NA release and by acting centrally within baroreceptor pathway to reduce sympathetic outflow.
Tyramine
“the cheese reaction” a dietary amino acid (cheese, red wine, soy sauce) that acts as a ‘false’ transmitter. No problem unless on MOA inhibitors -> hypertensive crisis!
Isoprenaline
Directly acting adrenoceptor agonist - non-selective beta agonist. Less susceptible to uptake 1 (reuptake) and MAO than adrenaline - half life ~2hrs. Clinically used to treat heart block (cardiogenic shock, acute HF, MI). Not used to treat asthma due to unwanted reflex tachycardia and dysrhthmias)
Labetalol
Duel acting beta-1 and alpha-1 antagonist. Lowers BP by reducing peripheral resistance. No long term change in HR or CO.
Phentolamine
Non-selective alpha-antagonist. Causes vasodilation and fall in BP due to alpha-1 blockade. Alpha-2 blockade increases NA release and enhances reflex tachycardia. Increases GIT motility hence diarrhoea! No longer clinically used.
Prazosin
Highly selective alpha 1 antagonist. Causes vasodilation and dramatic fall in blood pressure. Less tachycardia than non-selective antagonists (no increase in NA). Postural hypotension is troublesome. Causes modest decrease in LDL and increase in HDL cholesterol.
Propranolol
Non-selective beta-adrenoceptor antagonist. Little effect at rest but reduces the effect of exercise or stress on HR, CO and BP. Side effects - bronchoconstriction, cardiac failure, hypoglycaemia, fatigue, cold extremities, bad dreams.
Aliskirin
Renin inhibitor, blocks cleavage of angiotensinogen by renin
Ecstasy
Induces ADH secretion, can be fatal because of speed of secretion and amount of water drunk
Octreotide
Somatastatin analogue, used to treat neuroendocrine tumours
Methyldopa
Anti-hypertensive. False transmitter. Taken up by noradrenergic neurons, decarboxylated and hydroxylated to form false transmitter, alpha-methyl-noradrenaline. Not broken down my MAO so tend to accumulate in neurons, displacing NA from synaptic vesicles. Less active on alpha-1 receptors when released, more active on alpha-2 -> autoinhibitory feedback. Renal blood flow is well maintained. Side effects - dry mouth, sedation, postural hypotension, male sexual dysfunction.
Alpha 1 receptors
Cause vasoconstriction, and relaxation of the GI tract
Alpha 2 receptors
Inhibition of transmitter release, contraction of vasculature smooth muscle, CBS actions
Beta 1
Increased rate and force, relaxation of GI Tracy
Terlipressin
Vasopressin analogue, maintains hepatic blood flow whilst decreasing portal pressure. Used to treat portal hypertension.
Metoprolol
Beta1 selective beta blocker that decreases myocardial oxygen demand by decreasing HR, diastolic BP and contractility
Timolol
Non selective beta blocker used to treat glaucoma
Fluvastatin
Increases LDL receptor in the liver which decreases circulating LDL and triglycerides, and increases HDL
Beta 2
Bronchodilation, vasodilation, relaxation of visceral smooth muscle, hepatic gluconolysis
Ezetimibe
Inhibits cholesterol reabsorption by being absorbed then activated by glucuronidation. This then inhibits CETP which clears HDL so HDL levels are markedly increased (adverse side effects)
Fibrates
Work via the peroxisome proliferator activated receptor (PPAR) alpha which activates glitazones in the liver leading to decreased fatty acids and triglycerides
Nabilone and dronabinol
Synthetic delta-9 THC which suppress emesis and stimulate appetite. Sativex (another CB receptor agonist) is used to treat MS
St. John’s wort
An over the counter treatment for depression with an unknown mechanism of action believed to involve inhibition of 5-HT. also a cytochrome P450 inducer therefore having many adverse drug effects
Quetiapine
Indicated for treatment of schizophrenia, mania and psychosis. Very potent antagonist of H1 receptors. Fewer EPS than other antipsychotics
Aripiprazole
Treats mania, schizophrenia and controls agitation. Partial agonist of D2 and 5-HT 1a so no more efficacious than other anti-psychotics
Gemcitabine
A cytotoxic anti-metabolite that, inhibits ribonucleotide reductase, DNA polymerase and incorporates into DNA causing chain termination
5 flurouracil
A cytotoxic antimetabolite pyramidine analogue
Docetaxil and paclitaxel
Cytotoxic taxanes that prevent micro tubule assembly
Ciproflaxin
A quinolone, inhibits DNA gyrase and topoisomerase IV
Vancomycin
Peptidoglycan synthesis inhibitor that binds to alanine residues on the pentapeptide.
Bacitracin
Inhibits peptidoglycan transportation by inhibiting bactoprenol regeneration
Erythromycin
Macrolide antibiotic, Inhibit bacterial ribosomes. Mainly active against gram positives but some activity against negatives. Clarithromycin is a more effective macrolide. Resistance has arisen due to spontaneous mutations mainly in genes encoding 23s ribosomes
Penicillin
Inhibits transpeptidases (bacteriocidal) but high resistance and limited spectrum of diseases. Has subsequently been proceeded by flucloxacillian, temocillin, ampicillin and amoxicillin which have greater resistance to beta lactamases
Enfluvirtide and maraviroc
Bind to HIV GP41 transmembrane glycoprotein and ccr5 chemo line receptor respectively
Efavirenz
Non-nucleoside reverse transcriptase inhibitor that requires no phosphorylation for activation
Raltegravir
HIV integrase inhibitor
Saquinovir and fosamprenavir
First and second generation HIV protease inhibitors preventing the cleavage of Gag proteins into structural proteins
Levetiracetam
Anti-convulsant, mechanism of action is unclear but binds specific vesicles protein
Amitriptyline
Disease modifying drug used for treatment of cluster headaches
Thionamides
Inhibition of thyroid hormone synthesis to treat hyperthyroidism. Inhibits TPO and Dio1
