Pharmacology Flashcards
Digoxin
Class, Use, Property
Cardiac glycoside
Slows HR in atrial fibrillation (-ve chronotrope, +ve inotrope)
Heart failure in patients still symptomatic following diuretics and ACE-Is.
Narrow therapeutic index.
Dobutamine
Class, MOA, Use, Properties
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
Class, Use, Caution
Beta-1 selective beta-blocker
Used to treat angina, post MI, dysrhythmias, CHF, hypertension.
Not safe for asthmatic patients.
Diltiazem + verapamil
Class, Uses
Rate limiting/slowing Ca channel blockers (cardiac + 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
Class, MOA, Uses
ACEI
Reduces preload and afterload.
Used for hypertension, HF, post-MI, diabetic nephropathy, progressive renal insufficiency, high CVD risk.
Losartan
Class, MOA, Uses
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
Class, MOA, Uses, Adverse effects
K channel opener + Organic nitrate that stimulates guanylate cyclase to cause vasodilation.
Used for angina, acute + chronic HF, BP control during anaesthesia.
Adverse effects: hypotension + headache.
Bendrofluazide
AKA, Class, MOA, Uses, Side effects
aka bendroflumethiazide.
Thiazide diuretic.
Inhibit Na + Cl reabsorption in early distal tubule. Increases Na/Cl, K + Mg loss, Ca reabsorption. Moderate increase in urine volume.
Used for HF, hypertension, severe resistant oedema, Nephrogenic DI
Side effect: inhibits insulin secretion (DM)
Spironolactone
Class, MOA, Uses, Side effects
K+ sparing diuretic/aldosterone receptor antagonist.
Acts in DCT. Small increase in urine volume + Na loss.
Used for primary + secondary hyperaldosteronism.
Side effects: gynaecomastia, menstrual disorders, hyperkalaemia.
Amiodarone
Class, MOA, Uses, Side effects
Wide spectrum anti-arrhythmic
Prolongs cardiac action potentials.
Used for supraventricular + ventricular tachyarrhythmias
Adverse effects - accumulation in body (long half life) causes photosensitive skin rashes, hypo-/hyper-thyroidism, pulmonary fibrosis, corneal deposits, Neuro + gastro disturbances. Potent inhibitor of Phenytoin (antiepileptic) metabolism.
Glyceryl trinitrate
Class, MOA, Uses/ administration, prolonged use
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
Class, MOA, Uses
Anti hypertensive vasodilator that also slows/prevents hair loss.
K+ channel opener causing hyperpolarisation.
Doxazosin
Class, Associations, Side effects
Competitive Alpha-1 adrenoceptor blocker -> antihypertensive + coronary vasodilator
Associated with increased rates of CHF by ALLHAT study.
Can induce postural hypotension.
Sumitriptan
Class, MOA, Uses
5HT-1D receptor agonist.
Constricts large arteries + inhibits trigeminal nerve transmission.
Used to treat migraines - contraindicated if have coronary disease.
Streptokinase
Class, MOA, Tolerance, Uses
Thrombolytic
Converts plasminogen to plasmin (natural fibrin protease).
Bacterial product hence tolerance develops after 1st 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.