Drugs Flashcards
1
Q
Analgesic NNTs (number needed to treat to reduce pain by 50%)
A
- 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
2
Q
Analgesics
A
- 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
3
Q
Antacids
A
- 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
4
Q
Anti-Arrhythmics
A
- 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
5
Q
Anti-cholinergic Drugs
A
- 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
6
Q
Anti-Emetics
A
- 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
7
Q
Anti-Epileptics
A
- 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
8
Q
Anti-hypertensive Drugs
A
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
9
Q
Anti-Muscarinic Drugs
A
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
10
Q
Anti-Parkinsonian Drugs
A
- 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
11
Q
Antibiotics
A
- 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
12
Q
Antidepressants
A
- 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
13
Q
Antifungals
A
- 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
14
Q
Antihistamines
A
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
15
Q
Antivirals
A
- 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
16
Q
Benzodiazepines
A
Short acting - midazolam
Medium acting - lorazepam
Long acting - diazepam
