Drugs Flashcards
Aluminium hydroxide
INDICATION:For relief of heartburn and acid indigestion
MOA:basic inorganic salt that neutralises HCl in gastric secretions to form Aluminium chloride and water
inhibits the action of pepsin by increasing pH
example of TNFa inhibitor
adalimumab- stop pro inflam action so no fever, activation of endothelium
pryidoxine
prophylaxis for isoniazid TB peripheral neuropathy
ligand for phyridoxal kinase
valsartan
treatment of hypertension to reduce risk of CV disasters + HF
Angiotensin receptor blocker-
selectively binds to AT1 and prevents ang II exerting its hypertensive effects (aldosterone and ADH production, cardiac stimulation, increased renal absorption of sodium)
by blocking AT1 you prevent downstream negative feedback RAAS activation (chronic assocaitation in HF)
gliclazide
INDICATION: sulfonylurea to treat hyperglycaemia in patients w T2DM
MECHANISM:
- binds to B cell sulfonyl urea receptor
- thus subsequently blocking the ATP sensitive potassium channels
- decrease in K+ efflux
- depolarisation of cell
- opens voltage gated Ca2+ channels
- calmodulin activation
- exocytosis of insulin
alteplase
thrombolytic
1* target plasminogen
activator
2* target fibrinogen alpha chain
binds to fibrin rich clots via fibronectin kringle 2 domain
the protease domain cleaces the arg/ val bonds in plasmin
plsmin casues degradatoin of fibrin matric
efavirenz
Non-nucleoside reverse transcriptase inhibitor
Believed inhibition reverse transcriptase interferes with generation of DNA copies of viral RNA, which, in turn, are necessary for synthesis of new virions. Intracellular enzymes then eliminate HIV particle that previously had been uncoated and left unprotected, during entry into host cells.
Clarithromycin
INDICATION: treatment of many infections- otitis media, H pylori influenza
macrolide
MOA: metabolised
penetrates bacterial cell wall and reversibly binds to the 23S and 50S subunits of the bacterial ribosome, blocking translocation of tRNA and polypeptide synthesis
stops action of P-glycoprotein a drug efflux pump
norepinephrine
precursor of epinephrine that is secreted by adrenal medulla and acts as a central autonomic NT
used as a vasopressor in shock situations- e.g, septic
acts on B1- inotropic effect— increased contractility and hr
trimethoprim
antibacterial (mainly gram positive) , antifolate, antiprotozoal
1* target- dihydrofolate reductase (bacterial)
reversible inhibitor (antagonist)
2* target- human dihydrofolate reductase
folate metabolism:
can’t form tetrahydrofolic acid —- can’t produce bacterial nucleic acids
omalizumab
Monoclonal antibody against human IgE
MOA:
- binds to IgE w higher afinity than the Fc epsilonRI receptor on the surface of mast cells and basophils
- this decreases the availability of free IgE for binding and to trigger the allergic cascade
- reduction in surface bound IgE on FcERI cells limits the degree of release of inflam mediators e.g., Il4, Il5 and Il13
Metformin
INDICATION: adjunct to exercise and diet control in T2DM patients
MOA: taken up into hepatocytes
positively charged so accumulates in mitochondria
inhibits mitochondrial complex 1
prevents production of ATP
activates AMPK- important in glucose metabolism
inhibits gluconeogenesis and adenylate cyclase
ampk inhibits fat synthesis- reduces hepatic lipid stores, increase liver sensitivity to insulin
Amoxicillin
INDICATION:
Amoxicillin alone is indicated to treat susceptible bacterial infections of the ear, nose, throat, genitourinary tract, skin, skin structure, and lower respiratory tract.
Used in combo with clarithromycin to treat H. pylori infections.
MOA:
competitively inhibits penicillin-binding protein 1 and other high molecular weight PBPs
PBPs are responsible for glycosyltransferase and transpeptidase reactions that lead to cross-linking of D-alanine and D-aspartic acid in bacterial cell walls.
Without the action of penicillin binding proteins, bacteria upregulate autolytic enzymes and are unable to build and repair the cell wall, leading to bacteriocidal action
Hydroxychloroquine
INDICATION: acute RA, Chronic Ra, prophylaxis for malaria
Accumulates in cells and raises the pH
inhibits antigen processing by preventing the alpha and beta chains of the MHC II dimerisation
thereby inhibits APresentation of cell
self peptides bind to MHC with low affinity anyway so this decreases chances even more
Baclofen
INDICATION:
relexant for painful muscle spasms, antispastic agent especialluy against flexor compartment
parkinsons, cerbral palsy, stroke
MOA: depresses synaptic reflex transmission by stimulation of GABA- B receptors
inhibition of excitatory NT release (glutamate and aspartate)
Tenofivir
antiretroviral drug- nucleotide analogue reverse transcriptase inhibitor
tenofovir is absorbed and converted into its active form (nucelotide analgue)
tenofovir diphosphate inhibits HIV-1 reverse transcriptase by direct binding with the natural substrate
after integration into DNA it causes viral DNA chain termination
clopidogrel
antiplatelet antithrombotic
irreversibly inhibits ADP mediated platelet activation and interfering with GPIIb/IIIa aggregation
methotrexate
INDICATIONS: idiopathic joint pain, brain effusion, cancer
MOA: Methotrexate enters tissues and is converted to a methotrexate polyglutamate by folylpolyglutamate. inhibition of enzymes responsible for nucleotide synthesis including dihydrofolate reductase
In rheumatoid arthritis- accumulation of adenosine triphosphate and adenosine in the extracellular space, stimulating adenosine receptors, leading to anti-inflammatory action.
dabigatran
NOAC
inhibitor of thrombin stimulated platelet aggregation
Budosenide
corticosteroid—- asthma, ulcerative colitis
lipid soluble so they diffuse through the plasma membranes of cells and into the nucleus
where they bind to positive and negative glucocorticoid receptors
positive GREs increase anti inflam mediator expression (transactivation)
negative GREs reduce inflam expression (transrepression)
lactulose
treat acute onset hepatic encephalopathy assocaited with alcohol related liver disease
non curative but improves mental status
MOA:
nonabsorbale synthetic disaccharide that is broken down by sacchorolytic bacteria in the large intestines into organic fatty acids
high transient acid content in the gut draws nitrogenous bases from the blood
Gentamycin
braod spectrum aminogylcoside antibiotic used mainly on gram negatives
made of gentamycins C1, C2 and C1a
bind to ribosomal 30S subunit, casuding misreading of tRNA leaving the bacterium unable to synthesise new proteins needed for growth, survival and replication
trastuzumab
recombinant IgG1 kappa humanised monoclonal antibody
used to treat cancers positive for HER2 (human epidermal growth factor receptor)
binds to the extracellular ligand binding domain and blocks the cleavage of HER-2 to induce its receptor downmodulation. Inhibition of MAPK and P13K/Akt parhways lead to an increase in cell cycle arrest, suppression of cell growth and proliferation.
atorvastatin
INDICATION: antilipodaemic
MOA: reversibly competitively inhibits HMG-CoA reductase
HMG reductase is rate limiting step in cholesteropl synthesis
decreases hepatic cholesterol concs, stimulating the upregulation of LDL receptors–> increases LDL uptake
Emtricitabine
nucleoside reverse transcriptase inhibitor
gets phosphorylated
competes with normal HIV reverse transcriptase
gets integrated into DNA and terminates new chain formation .
phentolamine
Antihypertensive
1* target– A1 receptor (GPCR) effect- partial antagonist
causes vasodilation usually
2* target- B1 receptor (GPCR) effect- agonist
stimulates positive inotropic effect
Bisoprolol
B blocker
stops inotropic effects of B1 receptors
Esomeprazole
INDICATION: PPI used in acid refluc disorders, pewptic ulcer diease and H pylori infection, NSAID abuse
MOA: prevents final step in HCl production by covalently binding to sylfhydral group found on H+K+-ATPase enzyme at the secretory surface of gastric parietal cells. Limits secretion of HCL
antiretroviral medication examples brief
nucleoside reverse transcriptase inhibitors- inhinit dna synthesis via reverse transcriptase and act as DNA chain terminators
protease inhibitors- compeitive inhibnition of HIV aspartyl protease- used to produce functional viral proteins
integrase inhibitors
fusion inhinitors
doxycylin
borad spectrum antibiotic used to treat gram positive and negative bacteria e.g., mycoplasma pneumoniae
mainly bacteriostatic (keep in stationary phase)
- target 30S prokaryotic ribosomal unit during protein synthesis
- prevents binding of tRNA and mRNA at the ribosomal subunit
- therefore no amino acids can be added to the polypeptide chain
- no new proteins
glyceryl trinitrate
Vasodilator so heart doesnt work as hard
1* target= mitochondrial aldehyde dehydrogenase
activity- produces more NO
2*target- guanylate cyclase agonist– more cGMP- more PKG- more myosin phosphatase- relaxation of sm muscle
Amlodipine and atropine
antihypertensive
L- type calcium channel antagonist inhibiting influx into vascular smooth muscle and cardaic muscle
less Ca2+/ calmodulin
less MLCK activation
more MLC-P activation
less sm muscle contraction
less vasoconstriction- lower blood pressure
stronger effect on smooth muscle e.g., than cardiac
Ramipril
INDICATION: mild to severe hypertension (associated w T2DM)
MOA: ACE inhibitor
inactive prodrug converted to ramiprilat in the liver
anatgonises RAAS by competitive inhibition
EFFECTS:
decreased production of AT-II
therefore less vasoconstriction and less release of aldosterone and less break down of bradykinin (dilator)
Magnesium triscillate Mg2O8Si3
INDICATION: antacid for peptic ulcers and releaving heartburn H.PYLORI BARRET’S
MOA: gelatinous silicon dioxide formed in a neutralisation reaction with H+ of Hcl is protective and favours healing
often prescribed w alumimium as mag has a longer lasting effect
location and action of
a1 receptor
B1
B2
Dopaminergic
a1 peripheral, renal and coronary circulation—— vasoconstriction
B1- heart—- increase contractility and HR
B2- lungs, periphery and coronary circulation—– vasodilation and bronchodilation
dopaminergic- mesneetric, renal and coronary arteries—— vasodilation
warfarin
anticoag
inhibits reduction of vitamin k
prevents y-carboxylation of glutamate residues in factors II, VII, IX and X
groups of antihypertensives
diuretics
ACE inhibs
ANG II converting blockers
Direct renin inhibitors
Beta blockers
calcioum channel blockers
alpha blockers
central agonists
prednisolone
glucocorticoid similar to cortisol
INDICATION: ANTIINFLAMMATORY – asthma relief
MOA: inhinbits neutrophil apoptosis
inhibits phospholipase A2 which decreases the formation of arachidonic derivatives- prostaglandins and thromboxanes
inhibit production of pro-inflams as they bind to intracellular glucocorticoid receptor and then translocate to nucleus to act as TFs
carbimazole
antithyroid agent—– hyperthyroidism part of blocking regime with levothyroxine
MOIA: decreases the uptake and concentration of inorganic iodine by thyroid, it also reduces the formation of di-iodotyrosine and thyroxine.
Once converted to its active from of methimazole, it prevents the thyroid peroxidase enzyme from coupling and iodinating the tyrosine residues on thyroglobulin, hence reducing the production of the thyroid hormone T3 and T4
salbutamol
symptomatic relief and prevention of bronchospasm caused by asthma, bronchitis (obstrucitve)
targets= B2 adrenoreceptor
partial agonist
analgoue of adrenaline
B2R’s present in smooth muscle cells and mast cells
Gas pathway– increase adenylylcylase – increase 2nd messenger camp– increased PKA and decreased calcium in cells– deactivate MLC kinase and activate MLC-P– decreased sm muscle contraction in bronchioles
induces opening of K+ channels inducing hyperpolarisation
atropine
antimuscarinic (m3 inhib acetylcholine)- eye dilator and vasodilator
competitive antagonist long lasting
causes contraction of radial muscles in eyes—– mydriasis
M3= Gq– increase PLCB-- increase (IP3)– increase {Ca2+}i– contraction
m3 also found in vascular smooth muscle
Morphine
Indication: ANALGESIA, SEDATIVE
MOA: acts on u opiod receptrors in the brain and spinal cord to inhibit pain transmission and modify the central perception of pain.
opioid receptors are GPCRs which inhibit adenylate cyclase, open k+ channels and inhibit Ca2+ channel opening, thus desensitising nerve endings and requiring larger stimuli to trigger depolarisation
mepolizumab
monoclonal antibody against Il5
IL5 receptor activation stimulates differentiation of leukocyte progenitor cells:
- Eosinophils proloferate and migrate into tissues in response to Il5— they secrete things like MMPs, TGFB,NO and ROS
- primary cytokine associated w maturation, activation and prolonged survivial of inflammatory neutrophils
ferrous sulphate tablets
INDICATION: treat and prevent anaemia
MOA: transported by DMT1 into macrophage
incorporated into ferritin and stored
eventually oxidised
isoniazid
antibacterial agent (bactericidal) used priamrily in TB
prodrug that is activated by bacterial catalase
inhibits production of mycolic acids
rivaroxaban
- anticoagulant
- competitive inhibitor of FX
- therefore inhibits the activation of FII
- thrombin can therefore not convert fibrinogen to fibrin to secure the primary haemostatic plug of aggregated platelets
treating RA
initial treatment
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>?
?
initial- treat to target with cDMARD- corticosteroid and NSAID
step up with bDMARD (biologic)- try TNFa inhibitors
ritixumab- b cell modifier
Il-6 inhibitors
Bismuth subsalicylate
Anti-diarrhoeal
antisecretory action for water and ions in the intestines
binds toxins made by E.coli
a calcidol
INIDCATION: hypothyroidism and rickets +T2DM bone weakness associated w kidney problems
form of vit D used to regulate calcium and phsophate
MOA: liver catalyses activation
now activated, binds to intracellular receptors that act as TFs
increase GI absorption of Ca and phosphorus
increase osteoclastic resorption
increasing renal absorption of calcium
Naproxen
inhibition of COX 1 and 2 enzymes
2- involved in convversion of arachidonic acid to prostaglandins that:
sensitise nerve endings, potentiate vasodilators, mediate thermoregulatory response
cox-1: pyhysiological
gastro-protective effects
regulate renal blood flow
co-careldopa
dopaminergic medicine as symptomatic relief in PD
contains levodopa and carbidopa
levodopa is a dopamine precursor which crosses the BBB before being converted into dopamine
Carbidopa- is a peripheral DOPA-decarboxylase inhinbitor which prevents levodopa from being broken down in areas other than the brain
furosemide
INDICATION: potent loop diuretic used in ascites , CHF, hypertension
MOA: blocking tubular reabsorption of sodium and chlride in the P and DCT
Compeitive inhinition of NKCC2 (sodium- potassium- chloride transporters), prevents transport of Na+ from luminal to basolateral side for reabsorption. More less NaCl- detected by macula densa- activate RAAS
Sildenafil
decreases pulmonary hypertension via vasodilation
selective phosphodiesterase 5 inhibitor
NO activates guanylate cyclase
increased cGMP which activates PKG
which activates myosin phosphatase
which dephosphorylates light chain of myosin II
relaxation
PDE5 present in sm muscle of vessels
it usually degrades cGMP
diazepam
INDICATION: benzodiazepine used as an anticonvulsant, anxiolytic and muscle relaxant in trmor, alcohol withdrawal, upper motor neurone disorders such as cerebral palsy
MOA: act centrally binding to receptors in the brain. increases inhinbitory effect of GABA
picolax
soidum picosulphate–> picosulfurinc acid
treat constipation or induce colon cleansing to prepare large bowels for colonoscopy or surgery
MOA: inhibits the absorption of water and elctrolytes and increases their secretion into the intestinal lumen. It is hydrolysed by colonic bacteria enzyme sulfatase to form the active metabolite which acts direcvtly on colonic mucosa to simtulate peristalsis
atenolol
B blocker
non selective- block catecholamines from activating B1 (inotropic- contractility and HR)
decreases renin releae and decreases sympathetic action
rifamipcin
treating tuberculosis
1* target- DNA directed RNA polymerase subunit
inhibitor
leads to suprpession of RNA synthesis and cell death
low molecular weight heparin
binds reversibly to antithrombin III changing it to its active form and forming a complex together
increases the rate at which ATIII inhibits IIa and Xa
also inhibits IX, XI, XII and XIII
shorter than natural heparin so have a shorter IIa length
sulfalazine
INDICATION: crohns and RA
?????? anti inflam properties
high affinity for CT
Propanolol
INDICATION: thyrotoxicosis, hypertension
ACTIONS: antidysrhtmic, antihypertensive, antianginal
MOA: blocks actions of catecholamines (adrenaline) on B-adrenoceptors thereby blocking sympathetic drive, reducing pacemaker activity and increasing AV conduction time. Reduces slow inward tCa2+ gate opening during phase 4 (slow depolarisation)
Hydroxycobalmin (Vitamin B12)
INDICATION: vit B12 deficiency
MOA: ?????
Loperamide
laxative, colonic cleansing
inhibits peristaltic activity by being non-selective calcium channel blockers and binding to opoid U receptors. Inhinits epristalsis pf circular and longitudinal muscles
Sacubitril
INDICATION: used in combo with valsartan as antihypertensives, CHF
1* TARGET= nephrilysin enzyme ACTIVITY= competitive inhibitor
Neprilysin is a natural endopeptidase that cleaves and degrades natriuretic peptides (ANP, BNP and CNP)
NP’s are released in response to atrial and ventricular stretching, they activate downstream receptors leading to vasodilation along with sodium and water excretion.
breaks down vasodilators and vasocosntrictors like ANg II therefore used in combo w valsartan to block ANGII receptors– further no constriction
