Drugs Flashcards
Analgesic NNTs (number needed to treat to reduce pain by 50%)
- Paracetamol 1g + Ibuprofen 400mg = 1.5
- Diclofenac 100mg = 1.8
- Paracetamol 1g + Codeine 60mg = 2.2
- Ibuprofen 400mg = 2.5
- Morphine 10mg IM = 2.9
- Paracetamol 1g = 3.5
- Tramadol 100mg = 4.8
- Codeine 60mg = 16.7
Analgesics
- Simple analgesics/anti-inflammatories (COX-2 induced with tissue damage where it synthesises prostacyclin/prostaglandins/thromboxane in the vascular endothelium)
– Aspirin - irreversible COX-1 inhibition
– NSAIDs (PO/TOP/PR/IV) - COX-1/2 inhibition
– Coxibs (PO/IV) - COX-2 inhibition
– Paracetamol - COX-3 (CNS) - Local anaesthetics - pass through cell membrane and become ionised, bind to sidum channel and prevent conduction of Na and therefore generation of AP
- Opioids - activate mu opioid receptors (Gi)
- Tramadol - opioid with complicated mechanism of action - acts on all opioid receptors, inhibits 5HT reuptake, inhibits NA reuptake, NMDA receptor antagonist
- Steroids - anti-inflammatory
- Clonidine
- Antidepressants
– TCAs - competitively inhibit reuptake of NA and 5HT, NMDA antagonism
– SNRIs - Anticonvulsants - gabapentinoids - inhibit alpha-2-delta subunit on voltage gated calcium channels in the CNS –> inhibit neurotransmitter release, may have some NMDA receptor activity
- TRPV1 agonists - capsaicin - regression of C fibres
- NMDA antagonists - ketamine - non competitive antagonist of NMDA and glutamate receptors in the CNS, Na channel inhibition, reduce presynaptic glutamate release
- Cannabinoids - nabilone - act on CB1+CB2 receptors
- Inhalational analgesia - entonox, methoxyflurane
Antacids
- Non particulate antacids - chemical neutralisation - sodium citrate - base reacts with gastric acid to produce salt and water
- Particulate antacids - chemical neutralisation - Na/CaCO3/AlOH/MgOH carbonate/salts - base reacts with gastric acid to produce salt and water
- Raft forming - alginates
- Protective barrier - sucralfate
- Acid reducers
– H2 blockers - competitive antagonism of the H2 receptor, which decreases cAMP, decreases intracellular Ca++ and decreases action of H+/K+ ATPase
– Proton pump inhibitors - irreversible antagonism of the parietal H+/K+ ATPase
Anti-Arrhythmics
- Ia - procainamide, quinidine, disopyramide
– block fast sodium channels, reduces rate of rise of phase 0, raises the threshold potential, increase refractory period and AP - Ib - lignocaine, phenytoin, mexilitine
– block fast sodium channels, reduces rate of rise of phase 0 of the action potential, decreases refractory period - Ic - flecainide
– block fast sodium channels, reduces rate of rise of phase 0, don’t affect refractory period - II - beta blockade (competitive blockade of beta-adrenoreceptors)
– selective B1 antagonism - bisoprolol, esmolol, atenolol, metoprolol
– non selective B1 and B2 antagonism - propranolol, sotalol, timolol
– non selective B and A antagonism - carvedilol, labetalol - III - amiodarone
– block potassium channels, inhibiting slow outward current and slowing repolarisation
– B blocker like activity on SA and AV nodes - decreasing automaticity and slowing nodal conduction
– Ca channel blocker-like activity on L-type calcium channels, decreasing slow inward Ca current, increasing depolarisation time and decreasing nodal conduction
– a-blocker-like activity, decreasing SVR - IV - block calcium channels - verapamil
Digoxin - cardiac glycoside -
– Direct - inhibits Na+/K+ ATPase –> increased intracellular Na, decreasing activity of Na/Ca pump, increased intracellular Ca increases inotropy, decreased K results in prolonged refractory period of the AV node and bundle of His
– Indirect - parasympathomimetic effects by increasing ACh release at cardiac muscarinic receptors (sensitisation of baroreceptors and increased vagal ouput from the nucleus of tractus solitarius) –> slows AV node conduction and ventricular response
Adenosine
– acts via A1 adenosine receptors in the SA and AV node –> open K+ channels causing hyperpolarisation and a reduction in Ca current –> blockade of AV nodal conduction
Magnesium
– inhibits ACh release at the NMJ
– acts as a cofactor in multiple enzyme systems
– important in production of ATP, DNA, RNA
Anti-cholinergic Drugs
- Natural alkaloids e.g. atropine, hyoscine hydrobromide
- Semi-synthetic derivatives e.g. ipratropium, tiotropium
- Synthetic
— mydriatics
— antisecretory-antispasmodics
—— quaternary - glycopyrrolate
—— tertiary vesicoselective - oxybutynin, tolterodine
—— tertiary anti-Parkinsonian - procyclidine
Anti-Emetics
- Histamine receptor (H1) antagonists e.g. cyclizine
– act at vestibular nuclei, NTS and vomiting centre
– competitive H1 antagonist and anticholinergice at M1, M2, M3
— side effects - anticholinergic - sedation, dry mouth, urinary retention, blurred vision, restless, hallucinations - Muscarinic receptor (M3) antagonists e.g. hyoscine
– act at CTZ, vestibular nuclei, higher cortex centres, efferent nerves, vomiting centre and NTS - Dopaminergic receptor (D2) antagonists
– act at CTZ, NTS and vomiting centre
– phenothiazines e.g. prochloperazine, chlorpromazine
— side effects - sedation, extrapyramidal reactions, NMS. Jaundice, skin sensitisation, haematological abnormalities in chronic use. Other S/Es through anticholinergic, antinoradrenergc and antihistamine actions.
– butyrophenones e.g. droperidol
– central D2 blockade and post-synaptic GABA antagonism
— side effects - extrapyramidal reactions, apprehension, restlessness, nightmares. Not with QT prolonging drugs or CYP 3A4 inhibitors
– benzamides e.g. metoclopramide
– central D2 antagonism, prokinetic activity via muscarinic agonism in the GI tract, peripheral D2 antagonism
— side effects - extrapyramidal reactions particularly oculogyric crisis, tardive dyskinesia, agitation, NMS. Hypotension, tachycardias after IV injection - 5HT3 antagonists e.g. ondansetron
– act at visceral afferents, CTZ, NTS and vomiting centre
– central and peripheral antagonism of 5HT3 receptors, reducing input to the vomiting centre
— side effects - headache, sensation of warmth/flushing, visual disturbance, occasional cardiac arrhythmias, constipation with chronic use - NK1 antagonists e.g. aprepitant
– act at vestibular nuclei, visceral afferents, CTZ, NTS and vomiting centre
— specifically used with cisplatin chemotherapy - Corticosteroids e.g. dexamethasone
— mechanism uncertain, possible reduced release of arachidonic acid, reduced turnover of 5HT or decreased permeability of BBB.
— side effects - rectal/perineal warmth if give awake, impaired glucose tolerance and risk of hyperglycaemia and associated wound healing and thrombotic issues, psychotic/delusional reactions - Cannabinoids e.g. nabilone
— side effects - dysphoria, hallucinations - Propofol
- Benzodiazepines
Anti-Epileptics
- Potentiation of GABA activity
— GABA agonist - benzodiazepines, barbiturates
— Inhibit breakdown of GABA - vigabatrin
— Inhibit GABA reuptake - tiagabine - Modulate sodium flux
— Sodium channel blockade - valproate, phenytoin, lamotrigine, carbamazepine
— Calcium channel blockade - gabapentin, levetiracetam - Antagonism of glutamate - topiramate
Anti-hypertensive Drugs
Based on location of action
* Heart - beta blockers
* Blood vessels
— direct vasodilators - SNP, GTN
— indirect vasodilators - Calcium, alpha blockers, K+ activators, Mg
* Kidney
— diuretics - thiazides
— RASS - rampiril
* CNS
— central - clonidine, methyldopa
— ganglion blocker - trimetaphan
Based on mechanism of action
* Targetting RASS
— ACE-I
— ARBs
— Direct renin antagonists
— Neprilysin inhibitor
* Adrenoceptor antagonists
— Beta-blockers
— Alpha-blockers
* Calcium channel blockers
* Diuretics
* Vasodilators e.g. hydralazine, minoxidil
* Centrally acting agents e.g. clonidine, methyldopa
* Ganglion block e.g. trimetaphan
Anti-Muscarinic Drugs
By indication:
* Premedication - hyoscine
* Bradycardia treatment - atropine
* Anti-sialogogue - glycopyrrolate, hyoscine
* Bronchodilator - ipratropium
* Anti-emetic - hyoscine
* Anti-spasmodic - hyoscine
* Anti-Parkinonian - benztropine, procyclidine
* Mydriatic - tropicanamide
Anti-Parkinsonian Drugs
- replace dopamine (+COMT inhibitor/dopamine de-carboxylase inhibitors to preserve levodopa) e.g. co-beneldopa/co-careldopa
- mimic dopamine
— dopamine agonists - apomorphine
— non ergot dopamine receptor agonists - ropinirole, rotigotine - MAO-B inhibitors - preserve existing dopamine e.g. seligiline
- COMT inhibitors - prevent breakdown of dopamine by COMT e.g. entacapone
- Glutamate antagonist - inhibit activity of glutamate receptors + slow down rate of nerve cell loss in the brain e.g. amantadine
- Anti-cholinergic - decrease effect of ACh to balance the effect of decreased dopamine e.g. procyclidine
Antibiotics
- Inhibit cell wall synthesis (bactericidal)
– beta lactams incl. penicillins, cephalosporins - prevent cross linking of peptidoglycans by binding to penicillin binding proteins in the bacterial wall and replacing the natural substrate with their beta lactam ring
– glycopeptides e.g. vancomycin - Inhibit protein synthesis (bacteriostatic apart from aminoglycosides)
– tetracyclines (30s)
– aminoglycosides (30s) - bactericidal, irreversibly bind to the ribosomal subunit, preventing mRNA transcription e.g. gentamicin
– macrolides (50s)
– lincosamides (50s) - may be bacteriostatic or bacteriocidal depending on the concentration and the particular organism
– oxazolidones (50s) - Inhibit nucleic acid synthesis
– metronidazole - preferential reduction, capturing electrons that would usually be transferred to other molecules –> built dup of cytotoxic intermediate metabolic compounds and free radicals –> DNA breakage and subsequent cell death
– rifampicin
– fluoroquinolones - bactericidal
– trimethoprim
Antidepressants
- Tricyclic antidepressants (TCA) e.g. amitriptyline
– competitively inhibit reuptake of NA and 5HT, muscarinic antagonism, H1 and H2 antagonism, alpha-1 antagonism, NMDA antagonism - Selective Serotonin Reuptake Inhibitors (SSRI) e.g. fluoxetine, citalopram, sertraline
– inhibit neural reuptake of 5HT - Serotonin and Noradrenaline Reuptake Inhibitors (SNRI) e.g. duloxetine, venlafaxine
– inhibit reuptake of 5HT and NA in the synaptic cleft - Monoamine Oxidase Inhibitors (MAO-I)
– inhibit monoamine oxidase on external mitochondrial membrane, preventing breakdown of amine neurotransmitters (NA, 5HT) –> increasing level in CNS and PNS
– reversibly bind to MAO-A enzyme e.g. moclobemide
– irreversibly bind to MAOs e.g. phenelzine - Norepinephrine Reuptake Inhibitors e.g. bupropion, atomoxetine, tapentadol
– block the action of the norepinephrine transporter (NET) –> increased extracellular concentrations or NAd and Ad - Noradrenergic and specific serotonergic antidepressants (NaSSAs) e.g. mirtazepine
– antagonise a2 adrenergic receptor and certain serotonin receptors, enhancing NA and 5HT neurotransmission - Serotonin Antagonist and reuptake Inhibitors (SARI) e.g. trazodone
– antagonise serotonin receptors, inhibiti the reuptake of 5HT, NA and/or dopamine, most also antagonise a1-adrenergic receptors
Antifungals
- Azoles - inhibit ergosterol synthesis by inhibiting CYP450 enzyme
– triazoles e.g. fluconazole, itraconazole, voriconazole
– imidazoles e.g. ketoconazole - Echinocandins - prevent cell wall synthesis by blocking production of beta-glucan e.g. caspofungin, anidulafungin
- Polyenes - disrupt osmotic integrity of cell membrane by binding sterols e.g. amphotericin B, nystatin
- Alkylamines - disrupt squalene epoxidase —> inhibits ergosterol synthesis e.g. terbinafine
- Nucleoside analog - impair pyramidine metabolism e.g. flucytosine
- Griseofulvin - acts by interfering with fungal mitosis
Antihistamines
1st Generation - cross the BBB
* ethylenediamines e.g. phenbenzamine
* ethanolamines e.g. diphenhydramine
* alkylamines e.g. chlorphenamine
* piperazines e.g. cyclizine
* tricyclics + tetracyclics e.g. promethazine
2nd Generation - do not readily enter the CNS
* more specific for H1 receptors, little to no affinity at muscarinic receptors e.g. loratidine, cetirizine
3rd Generation - an active metabolite or enantiomer of a 2nd generation drug e.g. fexofenadine, desloratidine
Antivirals
- Nucleoside reverse transcriptase inhibitor - ziclovudine, abacavir
- Nucleotide reverse transcriptase inhibitor - tenofovir
- Non nucleoside reverse transcriptase inhibitor - nevirapine, efavirenz, delavirdine
- Protease inhibitors - ritonavir, indinavir
- Viral entry inhibitor - enfuvirtide
- Anti-herpes - nucleic acid analogue —> decreases viral DNA production
— aciclovir - Anti-influenza -
— prevent virus de-coating —> amantadine
— prevent release of viral particles —> tamiflu - Anti-Hep C - ribonucleic analog —> stops viral RNA synthesis —> ribavarin
Benzodiazepines
Short acting - midazolam
Medium acting - lorazepam
Long acting - diazepam
Beta-Blockers
— selective B1 antagonism - bisoprolol, esmolol, atenolol, metoprolol
– non selective B1 and B2 antagonism - propranolol, sotalol, timolol
– non selective B and A antagonism - carvedilol, labetalol
Calcium Channel Blockers
Bind to a specific site on the alpha subunit of the L-type calcium channels on vascular smooth muscle, cardiac myocytes, and cardiac nodal tissue – > inhibiting slow calcium influx into cells leading to vascular smooth muscle relaxation, decreased myocardial force generation, decreased heart rate, decreased conduction velocity (particularly at the AV node.
Indications
* treatment of angina - as primary or adjunct agent
* treatment of hypertension - acute or chronic
* antiarrhythmic e.g. 5-10mg IV verapamil over 3 minutes for SVT/AF
* vasospasm following SAH (4-14 days post SAH with high morbidity and mortality, nimodipine IV/PO/NG for 21 days)
* preterm labour
* Raynaud’s
General Pharmacokinetics
* well absorbed orally
* bioavailability reduced due to hepatic 1st pass metabolism
* significant protein binding
* rapid therapeutic effects
* differ depending on their predeliction for various sites of action
Class I e.g. verapamil
* Phenylalkylamines
* Relatively selective for the myocardium, less effective as a systemic vasodilator drug
* Important role in treating angina (by reducing myocardial oxygen demand and reversing coronary vasospasm) and arrhythmias
Class II e.g. nifedipine, amlodipine, nimodipine
* Dihydropyridines
* Most smooth muscle selective - high vascular selectivity
* Primarily used to reduce SVR and arterial pressure
* Can lead to baroflex cardiac stimulation with tachycardia and increased inotropy
Class III e.g. diltiazem
* Benzothiazepines
* Intermediate between verapamil and dihydropyridines in its selectivity for vascular calcium channels
* Cardiac depressant and vasodilatory actions
Anaesthetic Implications
* verapamil combined with beta blockers carries a high risk of AV block
* combined with volatiles —> risk of exaggerated hypotension, MAC depressant properties
* reduced LOS tone
* sudden withdrawal may be associated with exacerbation of angina
* may prolong/increase neuromuscular block with non depolarising NMBA
Immunotherapy
- Cancer vaccines - exposure to tumour antigens activates a tumour-specific humoral response e.g. sipuleucel-T for Ca prostate
- Non specific immunotherapies - use of cytokines to boost immune system or slow angiogenesis e.g. IL-2 therapy, BCG
- Chimeric antigen receptor T cell (CAR-T) therapy - T cells are removed from the patient and genetically modified to express specific chimeric antigen receptors, cells are then clones and returned to the patient to trigger an immune response
- Immune checkpoint inhibitors - monoclonal antibodies that target specific receptor-ligand pathways on T cells, ensuring the immune system continues trying to attack cancer cells
– cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) e.g. ipilimumab
– programmed cell death protein 1 (PD-1) e.g. nivolumab, pemborlizumab
– programmed cell death ligand 1 (PD-L1) e.g. atezolimumab, avelumab, durvalumab
Chemotherapeutic Agents
- Antimetabolites - imitate the role of purine or pyrimadine, stopping cell division
– 5-fluorouracil - pyrimidine antagonist that inhibitis thymidylate synthase, preventing synthesis of thymidine
– 6 merceptopurine - purine antagonist that prevents synthesis of adenosine and guanine
– methotrexate - folate antagonist that inhibitis dihydrofolate reductase and thymidine synthase, preventing synthesis of thymine
– hydroxyurea - ribonucleotide reductase inhibitor that prevents formation of deoxyribonucleotides - Alkylating agents - act by adding alkyl groups, chemically altering the cellular DNA and leading to programmed cell death
– platinum agents e.g. cisplatin - platinum ion, surrounded by organic ligands that acts on DNA strands to permanently modify the DNA structure
– cyclophosphamide
– nitrogen mustards e.g. chlorambucil - Topoisomerase inhibitors - interfere with enzymes that are essential for normal functions of DNA (e.g. transcription, replication, repair)
– irinotecan - inhibitis topoisomerase I resulting in breakdown of single stranded DNA, leading to cell cycle arrest
– etoposide - inhibitis topoisomerase II resulting in breakdown of double stranded DNA, leading to cell cycle arrest - Anti-tumour antibiotics - either break up DNA strands or slow down or stop DNA synthesis
– anthracyclines e.g. doxorubicin - form free radicals causing oxidative DNA damage, stabilise the topoisomerase II DNA complex, prevent DNA synthesis
– bleomycin - binds to metallic ions forming complexes that generate reactive oxygen species
– mitomycin C - alkylates DNA strands causing DNA damage and preventing further DNA replication - Mitotic inhibitors - block cell division by inhibiting microtubule function required for cell replication
– taxanes e.g paclitaxel - bind to polymerised microtubules and cause hyperstabilisation, preventing demolymerization and chromosomal separation
– vinca alkaloids e.g. vincristine - bind to b-tubulin units and prevent microtubule polymerization and spindle formation - Hormonal agents
– corticosteroids - bind to glucocorticoid receptor, inhibiting pro-inflammatory signals and promoting anti-inflammatory signals
– sex hormones e.g. tamoxifen - selective estrogen receptor modulator that inhibits growth and promotes apoptosis in oestrogen receptor positive tumours (? by inhibiting protein kinase C, preventing DNA synthesis) - Nitrosoureas - act similarly to alkylating agents - slow down or stop enzymes that help repair DNA
– carmustine - causes cross-links in DNA and RNA, inhibiting DNA synthesis, RNA production and RNA translation. also binds to and carbamolylates glutatione reductase leading to cell death
– streptozocin - thought to crosslink strands of DNA, inhibiting DNA synthesis - Monoclonal antibodies - attach themselves to tumour-specific antigens, increasing the immune response to the tumour cell
– rituximab - anti-CD20 antibody that targets CD20 expressed on the surface of B lymphocytes and promotes cell lysis of these cells
– trastuzumab (Herceptin) - anti-human epidermal growth factor receptor 2 protein antiboty (HER-2), inhibitis HER-2 mediated intracellular signalling cascades - Protein kinases - target enzyme involved in the cell signalling pathway triggering cell division
– imatinib - BCR-ABL tyrosine kinase inhibitor
– erlotinib - epidermal growth factor receptor tyrosine kinase inhibitor
– idrutinib - brunton kinase inhibitors
– sunitinib - multiple receptor kinase inhibitors
Cholinesterase Inhibitors
- Short acting - competitive antagonist of ACh at active site of AChE
— edrophonium - Medium acting - carbamylates active site
— neostigmine
— pyridostigmine
— physostigmine - Long acting - phosphorylates active site of enzyme
— echothiophate
CNS Stimulants
- Analeptic stimulants
— convulsants - strychnine
— respiratory stimulants - doxapram - Psychomotor stimulants
— sympathomimetic amides - cocaine, amphetamines, ephedrine, MDMA
— methylxanthines - caffeine, theophylline (increase cAMP) - Other
— phencyclidine derivatives - ketamine
— opiate antagonists
— benzodiazepine antagonist
Intravenous Fluids
- Colloids
Natural - albumin
Artificial - gelatins
- dextrans
- hydroxyethylstarches
- Crytalloids
- N. Saline
- Hartmann’s
- Dextrose based
- Combination dex/saline
- Sodium bicarbonate
Diuretics
By site of action
Act directly on the cells of the nephron:
* Proximal convoluted tubule
— carbonic anhydrase inhibitors e.g. acetazolamide - accumulation of carbonic acid in tubular cells leads to excretion of HCO3/Na/Cl along with excess water)
* Loop of Henle
— loop diuretic (Na+Cl-K+) e.g. frusemide - inhibits action of Na+/K+/2Cl- symporter resulting in increased concentration of solutes in lumen and movement of water into tubular fluid
* Distal convoluted tubule
— thiazides (Na+Cl- symporter) e.g. bendroflumethiazide - increases tubular concentration of these ions, leading to movement of water into the tubule
— potassium sparing (ENaC) e.g. amiloride - inhibits uptake of Na from tubular fluid
* Distal convoluted tubule and collecting duct
— aldosterone antagonists - increase sodium excretion and K+ reabsorption with water following sodium. act by directly modifying content of filtrate throughout the renal tract
* Osmotic diuretics e.g. mannitol
DMARDS
Conventional synthetic DMARDs
* Chloroquine - suppression of IL-1, induce apoptosis of inflammatory cells and decrease chemotaxis
* Hydroxychloroquine - TNF-alpha, induces apoptosis of inflammatory cells and decreases chemotaxis
* Ciclosporin - calcineurin inhibitor
* Sulfasalazine - suppression of IL1 and TNF alpha, induces apoptosis of inflammatory cells and increases chemotactic factors
* Methotrexate - purine metabolism inhibitor
* Leflunomide - pyramidine synthesis inhibitor
* Azathioprine - purine synthesis inhibitor
* D-Penicillamine - reduces numbers of T lymphocytes
* Gold
Biological DMARDS
* TNF inhibitors
— adalimbumab
— etanercept
— inflixamab
* T cell costimulatory inhibitor
— abatacept
* IL6 receptor inhibitors
— tocilizumab
— sarilumab
* anti-CD20 antibodies
— rituximab - chimeric monoclonal antibody against CD20 on B cell surface
— anakinra - IL1 receptor antagonist
Targeted synthetic DMARDS
* Janus kinase inhibitors
— baricitinib - JAK1 and JAK2 inhibitor
— tofacitinib
* phosphodiesterase 4 inhibitor
—apremilast
Drugs Acting on the Eye
- Promote mydriasis
— sympathomimetics - phenylephrine 2.5%
— anti-muscarinic - cyclopentolate 0.5-1% (up to 24hrs)
– mydricaine - contains procaine, atropine and adrenaline, risk of CVS side effects - Promote meiosis (contraindicated in acue iritis and anterior uveitis)
— muscarinic antagonist - pilocarpine 1-4% - Decrease production of aqueous humour
— beta blockers - timolol
— carbonic anhydrase inhibitors - acetazolamide
— mannitol - Increase drainage of aqueous humour
— muscarinic agonist -pilocarpine
— prostaglandins - latanoprost - Decreases intraocular pressure
— opioids
— hypnotics
— volatiles - Increases intraocular pressure
— suxamethonium (transient)
— ketamine - Nitrous oxide - avoid during vitreo-retinal surgery or if “gas bubble” present in the eye
Drugs Acting on the Uterus
Tocolytics - relaxation
* GTN
* MgSO4
* Beta agonists - salbutamol
* NSAIDs
* Oxytocin receptor antagonist - atosiban
* Ritodrine
* Calcium channel blocker - nifedipine
* Alcohol
* Progesterone
Uterotonics - contraction
* Oxytocin analogues - syntocinon
* Ergot alkaloids - ergometrine
* Prostaglandins
— PGF 2-alpha - carboprost
— PGE1 - misoprostil
(B lynch suture, Bakri balloon, interventional IR, subtotal hysterectomy)
Drugs Affecting Gastric Motility
Increase motility
* metoclopramide (D2, 5HT3, 5HT4, GIT)
* domperidone
* erythromycin - agonist at motilin receptors
* neostigmine - increase ACh at myenteric plexus
* cisapride (5HT4) - withdrawn
Decrease motility
* antimuscarinics (antagonise M3)
* opioids (agonists at MOP receptors in myenteric plexus)
Drugs used in dementia
Alzheimer’s Disease
Drugs that change disease progression
* aducanumab - monoclonal antibody that removes amyloid plaques in the brain but has shown limited effectiveness
* lecanemab - monoclonal antibody prevents amyloid plaques from clumping in the brain
Drugs that treat symptoms
Cognitive symptoms
* cholinesterase inhibitors - donepezil, rivastigmine, galantamine
* glutamate regulators (NMDA receptor agonist) - memantine
Non cognitive symptoms
* SSRIs
* Aspirin/secondary prevention drugs
* Sleeping tablets
* Risperidone - binds to 5HT2A and D2 receptors
Haematological Drugs
Anticoagulants
* Vit K epoxide reductase inhibitor - prevents the return of vitamin K to its reduced form, therefore producton of vitamin K dependent clotting factors (2, 7, 9, 10), protein C and S - warfarin
* Antithrombin enhancers - potentiate action of antithrombin III, increasing its 2a and 10a inhibition - LMWH, heparin
* Direct thrombin inhibitor - prevents cleavage of fibrinogen to fibrin - dabigatran
* Factor Xa inhibitors
– direct - rivaroxaban
– indirect - fondaparinux
Antiplatelets
* COX inhibitors - prevent thromboxane A2 production - aspirin
* ADP receptor inhibitors -
– clopidogrel - irreversibly prevents binding of ADP to its receptor on the platelet, preventing activation of GP2b/3a receptors
– prasugrel - irreversibly binds to P2Y12, preventing platelet activation and aggregation
– ticagrelor - reversible, non competitive P2Y12 receptor antagonist
* Phosphodiesterase inhibitors - inhibitis platelet adhesion to walls, potentiates prostacyclin activity and increases platelet cAMP, reduces Ca and inhibits platelet aggregation and deformation - dipyridamole
* GP2b/3a inhibitors - reversible antagonism of 2b/3a receptor, prevents platelet aggregation via fibrin linkages between GP2b/3a receptors - abciximab, tirofiban
Antifibrinolytics
* Tranexamic acid - prevents breakdown of fibrin by competitively inhibiting plasminogen activator, reducing rate of fibrinolysis
Immunosuppressants
- Glucocorticoids - suppress cell-mediated immunity
- Cytostatics (chemotherapy, immunotherapy) - antiproliferative drugs that inhibit cell division
- Antibodies
– polyclonal antibodies e.g. antithymocyte antigens, IVIg
– monoclonal antibodies
– T-cell receptor directed antibodies
– IL-2 receptor directed antibodies - Drugs acting on immunophilins
– ciclosporin - calcinuerin inhibitor, inhibits synthesis of interleukins
– tacrolimus - calcineurin inhibitor, inhibiting T cell proliferation
– sirolimus - m-TOR inhibitor (mammalian target of rapamycin), inhibit calcium based events during G1 phase of cell cycle, inhibiting release of interleukin and VEGF from neutrophils - Interferons - suppresses production of Th1 cytokines and activation of monocytes
- TNF binding proteins - prevent induction of synthesis of IL-1 and IL-6 and adhesion of lymphocyte activating molecules
- Mycophenolate - non competitive, selective and reversible inhibitor of a key enzyme in guanosine nucleotide synthesis (B and T cells are very dependent on this process)
Induction Agents
Intravenous
* Barbiturates
* Non-barbiturates
— phenol
— imidazole
— phencyclidine derivative
Inhalational
Inotropes/Vasoactive Agents
Natural vs Synthetic
Direct vs Indirect Action
Inotropes - increase myocardial contractility
Vasopressors - cause vasoconstriction
Inodilators - cause vasodilatation
Others
Drugs that increase intracellular calcium
— contain calcium salts - Calcium chloride
— increase cAMP - B1 agonists, glucagon, phosphodiesterase inhibitors
— inhibit Na/K ATPase - digoxin
Drugs that improve actin-myosin binding to Ca - levosimendan
Drugs that influence metabolism - thyroid hormones
Inotropes + Vasopressor action
* Adrenergic
— endogenous catecholamines
— synthetic catecholamines
— direct acting non-catecholamines
— indirect acting non-catecholamines
* Non-Adrenergic
— phosphodiesterase inhibitors
— calcium sensitisers
— miscellaneous
Vasopressors
* Adrenergic
— endogenous catecholamines
— synthetic non-catecholamines
* Non-Adrenergic
— vasopressin
Insulins
- Ultra Short Acting - lyumjev
- Rapid Acting - novorapid
- Short Acting - actrapid
- Intermediate Acting - isophane/humulin I
- Long Acting - glargine (Tougeo/Lantus), detemir (Levemir)
- Ultra Long Acting - degludec (Tresiba)
Local Anaesthetics
Amides
- lidocaine
- bupivicaine
- prilocaine
Esters
- cocaine
- amethocaine
- procaine
Magnesium
- Treatment of torsades de pointes, digoxin induced and ventricular arrhythmias unresponsive to over treatment
- Suppression of catecholamine release during surgery for phaeochromocytoma
- Prevention and treatment of eclamptic seizures
- Tocolysis
- Reduce spasms and autonomic instability in tetanus
- Analgesic activity - reduction in conventional analgesic requirements
- Bronchodilation in acute severe asthma
- Suppression of pressor response to intubation
- Replacement in hypomagnesaemia
- Reduced incidence of cerebral palsy in babies delivered preterm (especially <30/40 gestation)
NB: Potentiates effects of NMBAs
Neuromuscular BlockingDrugs
Depolarising
- suxamethonium
Non-depolarising
- aminosteroids —>
- benzylisoquinoliniums —>
Opioids
- Natural
- morphine, codeine, thebaine
- Semi-synthetic
- diamorphine, oxymorphone, hydromorphone, oxycodone, buprenorphine
- Synthetic
- phenylpiperidines - fentanyl, pethidine
- propionate anilides - methadone
- morphinans - levorphanol
- benzomorphans - pentazocine
Mu beta-endorphin enkephalins
* agonist - morphine, fentanyl, remifentanil, diamorphine, codeine, methadone, pethidine, alfentanil
* partial agonist - buprenorphine
* antagonist - naloxone, naltrexone, pentazocine
K dysnorphin
* agonist - morphine, pentazocine, nalorphine, nalbuphine
* antagonist - naloxone, naltrexone
D enkephalins
* agonist - etorphine
* antagonist - naloxone
Oral Hypoglycaemic Agents
Sensitisers
* Biguanides e.g. metformin - inhibits amount of glucose produced by the liver, increases the insulin-receptor binding and stimulates tissue uptake of glucose
* Thiazolidinediones e.g. pioglitazone - bind to a receptor in adipocytes and promote maturation of fat cells and deposition of fat into peripheral tissues. By reducing circulating fat concentrations, sensitivity to insulin is improved.
Secretagogues
* Sulphonylureas e.g. gliclazide - stimulate insulin release from functioning beta cells of the pancreas by blocking ATP sensitive potassium channels.
* Meglitinides e.g. repaglinide - blocks potassium channels in pancreatic beta cells, leading to opening of calcium channels and influx of calcium, inducing insulin secretion.
Inhibitors - decrease need for glucose, decrease glucose absorption/supply
* alpha-glucosidase inhibitors - acarbose - competitive and reversible inhibition of intestinal enzyme responsible for breaking down carbohydrates into glucose
* di-peptidyl peptidase (DPP-4) inhibitors - sitagliptin - slow the inactivation and degradation of GLP-1 which is involved in glucose removal from the gut
* amylin analogues - pramlintide - assists insulin in postprandial glucose control - inhibits glucagon secretion, delays gastric emptying, signals satiety
* incretins - GLP-1 mimetics- exenatide, semaglutide - bind to GLP-1 receptors and stimulate glucose dependent insulin release
* SGLT-2 inhibitors e.g. dapagliflozin - inhibits reabsorption of glucose by the SGLT2 co-transporter in the kidney, increasing glucose elimination in urine
Pulmonary Anti-Hypertensives (+ other management of pulmonary hypertension)
- PGI2 - direct vasodilation and inhibits platelet activation
— prostacyclin, epoprostenol, iloprost - Endothelin receptor antagonists - reverse effect of endothelin (builds up on the walls of blood vessels)
— Bosentan - Soluble guanylate cyclase stimulator - increase production of intracellular cGMP —> vascular smooth muscle relaxation
— vericiguat - PDE5 inhibitors - prevents breakdown of cGMP
— sildenafil - Calcium channel blockers
- Digoxin
- Diuretics
- Oxygen
- Anti-coagulation
Sympathomimetics
Drugs that exert their effects via adrenoceptors or domamine receptors
Naturally Occurring Catecholamines
* Adrenaline - alpha 1 (Gq), alpha 2 (Gi), beta (Gs)
* Noradrenaline - alpha 1, beta
* Dopamine - alpha, beta, D1 (Gs), D2 (Gi)
Synthetic agents
* Alpha-1 agonists - phenylephrine
* Beta agonists - isoprenaline (b1, b2), dobutamine (B1>B2), dopexamine (B1, D1), salbutamol (B2), salmeterol (B2), ritodrine (B2, B1), terbutaline (B2>B1)
* Mixed alpha and beta - ephedrine, metaraminol
Other inotropic agents
* Non selective phosphodiesterase inhibitors - aminophylline
* Selective phosphodiesterase inhibitors - enoximone (PDE III), milrinone (PDE III)
* Levosimendan - calcium sensitiser
* Glucagon
* Calcium
* T3
Volatiles
Gases
- N2O
- Xenon
Liquids
- sevoflurane
- isoflurane
- desflurane
- enflurane
- halothane
