Unit 3/4 Drugs Flashcards
NAPROXEN
NSAID - LUPUS
Non-selective inhibitor of cyclooxygenase, an enzyme invovled in prostaglandin synthesis via the arachidonic acid pathway
Decreases the synthesis of prostaglandins involved in mediating inflammation, sensitizing nociceptors involved in transmitting pain, fever and swelling
Decrease in TXA2 so lack of platelet activation, adherence, aggregation
Folic acid
Heamolytic anemia
Folic acid= biologically inactive
converted to tetrahydrofolic acid-> methytetrahydrofolate from DIHYDROFOLATE REDUCTASE.
Transpoted across cells via endocytosis + synthesixe nucleic acids and hep erythropoesis
What type of drug is ivacaftor when is it indicated
Quinolone used treat CF
Side effects ivocaftor
Abdo pain + diarrhoea
MofA ivacaftor
G551D CFTR mutation - CFTR protein reach epithelial cell surface, but doesn’t let it transport chloride through the ion channel.
Ivacaftor = potentiator of the CFTR protein.
Ivacaftor facilitates increased chloride transport by potentiating the channel-open probability (or gating) of the G551D-CFTR protein.
What are the modulator drugs in CF used in triple therapy
Ivacaftor - potentiator of CFTR ion channel
tezacaftor is a CFTR corrector that moves the mutated CFTR protein to the correct place on the epithelial cell surface membrane
Other triple therapy drugs CF
Mycophenolate - inhibts IMPDH altering DNA formation - inhibiting proliferation t/b lymphocytes + supress AB formation
Tacrolimus - binds FKBP-12 therfore inhibitng t lymphocyte activation
Predisalone mofa
Glucocorticoid R agonist. Binds GR R - translocate nucleus binding GRE in promoter region in target gene. DNA bound R interacts TF to cause up/down reg specific target gene.
Anti inflam - phosphorylates + release annexin 1 - INHIBIT LEUKOCYTE TRAFFICKING
Supression AA
Depress macro function
Th1- Th2 responce
Belimumab mofa
Binds BAFF (over expressed SLE) * BAFF cant bind B cells * no longer survival or proliferative signal. Decrease B cell survival/ B cell mediated immunity
Rituximab mofa
Human monoclonal Ab against CD20 antigen found surface normal mature + malignant b lymphocytes. AB igG1 kappa IG leads selective lysis b cells * decreased b cell survival + b mediated immunity.
Drugs used in lupus
Predisalone
Belimumab
Rituximab
Tocilizumab
anti il-6 disrupting Th17 cells
Infliximab
Anti TNF alpha
drugs used triple therapy after bilateral lung transplant
prednislone
mycophenolate mofetil
tacrolimus
Oral flucox
Staph aureus found nasal passages + skin 15-40% healthy adults. Gram positive responsible MRSA/ MSSA. Start CF diagnosis long term AB for prophylaxis against staph aureus.
Narrow spec penicillin, beta lactam. Binds + inactivates PBP on inner cell membrane of bacterial wall. Inactivated PBP interferes cross linkage of peptidoglycan chains necc bacterial cell wall strength + rigidity. Interrupts bacterial cell wall synthesis * weakening wall + lysis.
IV vancomycin
Selective resistant strains gram +ve bacteria (staph aureous). Second line treatment failed respond oral AB
Glycopeptide. Binds to NAG/ NAM of synthesizing peptidoglycan preventing transpeptidase acting on these newly formed blocks * preventing cross linking peptidoglycan layer * layer more permeable/ less rigid – osmolysis.
Nebulised colistimethate sodium
Chronic colonisation gram neg pseudomonas aeruginosa as prophylaxis CF - rare eradicate chronic p.a * give regular use nebulized AB chronic p.a reduce r deterioration.
Use inhaled drugs target conducting upper airway tobramycin, colistin + aztreonam.
Broad spec polymyxins used against gram neg (except proteus) Polymyxins = polycationic + hydrophobic/ lipophilic molecules. Interferes cell membrane synthesis via LPS synthesis pathway
Ca2+ and Mg2+ displacement from LPS. Negatively charged LPS is unstable resulting in membrane leakage= bactericidal effect.
+ polymyxins enter the cell and precipitate cytoplasmic components, primarily ribosomes.
Nebulized aztreonam
Gram neg aerobic – pseudomonas aeruginosa - targets conducting upper airway used prophylaxis
Monocyclic Beta lactam – high affinity PBP 3. Binds + inactivates PBP on inner cell membrane of bacterial wall. Inactivated PBP interferes cross linkage of peptidoglycan chains necc bacterial cell wall strength + rigidity. Interrupts bacterial cell wall synthesis * weakening wall + lysis.
Oral ciprofloxacin
Ciprofloxacin good permeation respiratory lower airway but bad upper – prophylaxis pa
Broad-spec (gram +/- AB fluoroquinolone Inhibiting DNA gyrase, and a type II topoisomerase, topoisomerase IV, necessary to separate bacterial DNA * inhibiting cell division.
Tacrolimus
Triple therapy for immunosuppression after bilateral lung transplant -tacrolimus, mycophenolate, prednisolone
Macrolide lactam
Inhibits T-lymphocyte activation by first binding to an intracellular protein, FKBP-12- prevents tranlocation NF * inhibiting t lymphocyte signlas + transcription Il-2,3,4,5.
Down regulates expression FceRI on langerhans
Mycophenate mofetil
Triple therapy bilateral lung transplant
Prednisolone
Triple therapy bilateral lung transplant
Tobramycin IV
Lower respiratory airway target pa
Broad spec Aminoglycoside against gram neg bacteria. Binds irreversibly 30s ribosome inhibiting formation 70s unit * bacterial protein synthesis.
Oral valganciclovir
Anti viral used combination therapy after lung transplant
Converted Ganciclovir after admin - phosphorylated to triphosphate form which is metabolized and taken in intracellurlarly.
Phosphorylation dependent on viral kinase + mainly occurs virus infected cells.
Ganciclovir triphosphate incorporated DNA strand replacing Adenosine * phosphodiester bridges can longer to be built, destabilizing the strand inhibiting viral DNA synthesis.
Also inhibits Viral DNA polymerase.
Oral co- trimoxazole
Combination therapy after bi-lateral lung transplant.
Antibacterial. Blocks folic acid enzymes in synthesis pathway. Sulfamethoxazole component inhibits formation dihydrofolic acid from PABA, trimethoprim component inhibits dihydrofolate reductase
Oral itraconazole
Antifungal against aspergillus funigatus colonisation
Interacts 14- alpha demethylase (cytochrome p-450 enzyme) converts lanosterol to ergosterol. Ergosterol is essential component fungal cell membrane * inhibiting synthesis = increase cellular permeability/ leakage cellular contents.
IV methylpredisolone
USE IF REJECTION OCCURS
Combination therapy after lung transplant
Combination therapy as infection prophylaxis nystatin, valgancyclovir, co-trimoxazole, colomycin and amphotericin for 4 months. one year after transplant, lower doses of tacrolimus, mycophenolate and prednisolone; infection prophylaxis reduced to co-trimoxazole daily
Budesonide side effects and indications
Asthma preventer - give reg when controlled reduce dosage
Adrenal supression
candidiasis + dysphonia
Budesonide mechanism
Inhibitory activities against
mast Cells, Eosinophils, Neutrophils, Macrophages, Lymphocytes, Histamine, Eicosanoids + Leukotrienes.
Binds to GR receptor, Corticoreceptor-Ligand complex translocate itself into the cell nucleus + binds to (GRE) in the promoter region of the target genes
The DNA bound receptor Interacts with TF -> increase/ decrease in expression of specific target gene
Suppression of IL2, Leukotrienes, Arachidonic Acid, Prostaglandins + IgE synthesis
Induce expression of IL-10, Lipocortin, Annexin 1
Salmeterol
LABA - prophalaxis 2x daily
Fine tremor + headache
Salmeterol mofa
Stimulates beta (2)-adrenergic receptors via mimicking adrenaline * relaxation of bronchial smooth muscles.
Beta2-Gs-Adenylate Cyclase. Increases cAMP production by activating Adenylate Cyclase. Increased intracellular cyclic AMP increases the activity of cAMP-dependent PKA
Inhibits the phosphorylation of myosin-light chain kinase and lowers intracellular calcium concentrations -> smooth muscle relaxation and bronchodilation
Salbutamol
Reliever short acting 30-60mins
Fine tremor
Headache
Reflex tachycardia
Salbutamol MofA
Stimulates beta(2)-adrenergic receptors via mimicking adrenaline * relaxation of bronchial smooth muscles.
Beta2-Gs-Adenylate Cyclase. Increases cAMP production by activating Adenylate Cyclase. Increased intracellular cyclic AMP increases the activity of cAMP-dependent PKA
Inhibits the phosphorylation of myosin-light chain kinase and lowers intracellular calcium concentrations -> smooth muscle relaxation and bronchodilation
Inhibits the release of bronchoconstricting agents from mast cells
+ Inhibits microvascular leakage
+ Enhances mucociliary clearance
Stimulus-independent
Beclometasone
Corticosteroid used COPD
Adrenal suppression + LRTI
Ipratropium
Anticholinegic agent- muscarinic receptor antagonist
Constipation + dry mouth
Beclometasone mechanism of action
Binds Glucocorticoid R. Inhibitory activities
mast Cells, eosinophils, neutrophils, macro, histamine, Eicosanoids, Leukotrienes + cytokines involved in allergic and non-allergic-mediated inflammation.
Inhibits phosphorylation of myosin-light chain kinase.
Bind to to IL-13 * inhibits function * inhibits class switching to IgE – needed coating mast cells.
Up-regulate b2-adreno-ceptor expression.
Ipratropium mechanism of action
Blocks Muscarinic cholinergic receptors (M3-Gq subtype) * decrease formation cyclic guanosine monophosphate (cGMP)
Decreased activation on Phospholipase C+ formation of IP3 and DAG. Decreased PKC and IP3 and cGMP
Decrease intracellular calcium-> decreased contractility of smooth muscle.
Relaxation of bronchial smooth muscle + Inhibition of bronchial mucus secretion
Specific to parasympathetic bronchoconstriction
Theophylline
Methylxanthine bronchodilator
Narrow theraputic window + vomiting
Theophylline mofa
Relaxation of bronchial smooth muscle
Inhibition of cyclic nucleotide phosphodiesterase (PDE)
Less breakdown of cAMP, more cAMP
increases the activity of cAMP-dependent PKA, lowers calcium levels
* Inhibits the phosphorylation of myosin light chain kinase and lowers intracellular calcium concentrations -> smooth muscle relaxation and bronchodilation
Reduces airway responsiveness to histamine
Drugs give prophylactic CF
Inhaled antibacterial drugs Aminoglycosides (tobramycin)
Polymyxins (colistin)
Monobactams (aztreonam)
Good permeation of upper conduction airway.
Poor permeation lower respiratory airway
Parenteral/ systemic administration of antibacterial drugs
IV 3rd gen cephalosporins (ceftazidime)
IV aminoglycosides (tobramycin)
Oral fluoroquinolones (ciprofloxacin)
Poor permeation of upper conducting airways
Good permeation lower respiratory airway
Colistin indications and side effects
Severe Gram-negative, drug-resistant infections
Specific
Pseudomonas Acinetobacter
NOT Burkholderia, Proteus, Serratia, Neisseria (or anything Gram +ve)
Prophylaxis of colonisation in CF/COPD
Nephrotoxicity (tubular necrosis)
Neurotoxicity (can lead to respiratory failure) IV
Oral/inhaled (prophylaxis)
Colistin mofA
Polymyxins interfere with cell membrane synthesis through the lipopolysaccharide synthesis pathway
Ca2+ and Mg2+ displacement from LPS. Negatively charged LPS is unstable resulting in membrane leakage
tPA/ ALTEPLASE
Alteplase binds fibrin in clots via fibronectin finger like domain. Protease domain cleaves arg/val bond in plasminogen to form PLASMIN.
Plasmin degrades fibrin matrix of thrombus
Warfarin
Inhibtis vit K reductase - reduction reduced form vit KH2.
Vit k is cofactor carboxylation glutamate residues on n terminal regions of vit k dependent proteins
- limits gamma carboxylation and activation vit k dependent clotting factors
II, VII IX X protein c/s
Heparin
Binds endothelium reversibly - recruits + activates ATIII
UNfractionated heparin inactivates thrombin + factor X
also does II, IX,X, XII
LMW heparin only inactivates factor X
Dalteparin
LMWH
Binds high affinity to plasma protein ATIII inhbiting formation factor Xa
Dabigatran
INHIBITS THROMBIN
Rapid acting competitive + reversible direct inhibitor of thrombin (including free circulating thrombin, fibrin bound thrombin + thrombin induced platelet aggragation)
inhibitng thrmbin you inhibit platelet formation
Rivaroxaban
Competively and irreversibly inhibits free + clot bound factor Xa which is needed to activate prothrombin to thrombin
Clopidogrel
Anticoagulant - antagonistically binds P2y12 ADP receptor - needed aggregation platelets + cross linking protein fibrin.
Impairs ADP mediated activation GPIIb/IIA complex which is receptor for fibrininogen * impaired activation PREVENTS FIBRIN BINDING TO PLATELETS + INHIBITS PLATELET AGGREGATION
What class is gentamycin
Aminoglyceride
What class is ciprofloxin
Quinolone
What is asprin used for
Irreversibly binds COX 1/2
Anti platelet reduce risk MI patient with angina
MofA asprin
Acetlysalicyclic acid irreversibly inhibits COX 1/2 decrease formation prostaglandin + thromboxane from AA. Thromboxane A2 needed platelets aggregate - platelets cant synthesis new proteins + effect persists life platelet 7 days.
Indications Atenolol
BETA BLOCKER - allows decrease O2 demand due reduction HR + contractility - relief ischemic chest pain
Early intervention MI (12hrs) esp if STEMI
MofA atenolol
Binds B1 adrenergic receptors in heart + vascular SM.
inhibits sympathetic Stimulation * reduction reduction resting heart rate, CO, SBP + reflex orthostatic hypotension.
Higher does also block B2 bronchial + vascular SM
What is clopidogrel
Anti platelet reduced death after MI
Clopidogrel + asprin indicated STEMI
Nausea + vomiting
MofA clopidogrel
Impairs ADP mediated activation glycoprotein GPII/IIIa complex (receptor for fibrinogen). Impaired activation prevents fibrinogen binding platelets + inhibits platlet aggregation.
What is simvastatin
Lower cholesterol via inhibitng HMG- CoA reductase
potentially reduce risk second stroke
Mechansim simvastatin
SELECTIVELY INHIBITS HMG-CoA reductase in liver * inhibits formation mevalonic acid (rate limiting step in synthesis cholesterol) * reduction cholesterol levels + increase expression hepatic LDL receptor
Indications ramipril
Lower blood pressure ACE inhibitor
Mechansim ramipril
ACE inhibitor
Blocks conversion angiotensin I to angiotensin II
Angiotensin II vasocontrictor + stim release aldosterone * if inhibit production vasodilation + inhibition salt + water retention
What is Warfarin used for
Prophylaxis against dev new blood clots
MofA Warfarin
Inhibits vit K reductase enzyme * inhibit synthesis vit k dependent coagulation factors (II, VII, IX X) decrease coagulation factors get lowering prothrombin levels - reduced thrombin + fibrin - > reduced clotting
Morphine
Activates μ opioid receptors (Gi protein coupled) in the brain (thalamus, limbic system + PAG) and spinal cord dorsal horn . Also acts on delta receptor in limbic system, cortex + dorsal horn. And kappa receptors in cortex and dorsal horn. When binding opioid receptor inhibition adenylate cyclase activity, decrease cAMP open K+ channels (potassium diffuse out into synaptic cleft making it less likely A.P to be fired – post synaptic hyperpolarization) Inhibit the opening of Ca2+ channels in nerve endings – reduce release neurotransmitter.
Act directly on dorsal horn inhibiting the transmission of pain signals and by decreasing excitation peripheral nociceptive afferent neurons.
Stimulate the descending inhibitory pathways (supra-spinal analgesia) via PAG and NRPG which release enkephalin -synapses with Raphe magnus. Neurons arising from RM terminate DH releasing serotonin causing local neurons secrete endorphins * inhibition pain. inhibits sensory nerve transmission to spinal ascending pathways (spinal analgesia)
Paracetamol
Paracetamol – inhibits Cox I in hypothalamus = antipyretic action + weak inhibition peripheral cox isoforms ( * not used peripheral inflammation). Activation serotoninergic pathways. Little suppression of inflammation but good control of inflam pain.
Paracetamol metabolite inhibits reuptake of anandamide and increases activity cannabinoid receptors and TRPV1.
Gardasil
®: VLP of HPV6,11,16,18
Cervarix
VLP 16 18
What is amlodipine
Calcium channel blocker -> decrease her blood pressure via vasodilation + decrease pacemaker potential.
What is oral phenoxy benzamine
Irreversibly blocks Alpha receptors * Inhibits Alpha 1-Gq mechanism - lower BP
What is atenolol
Beta blocker
Inhibits sympathetic stimulation to lower HR and BP
Short acting
MOFA Amlodipine
Long Acting
Inhibits Calcium ion influx via L-type calcium channels -> stabilisation of channels in inactive conformation
Decreased (d) calcium binding to Calmodulin (calcium binding protein) -> d activation of MLCK
-> d phosphorylation of MLC
-> d CICR -> d arterial smooth muscle contractility * vasoconstriction -> VASODILATION -> decrease TPR -> decrease in BP
Inhibition of carbonic anhydrase = increases pH , regulate calcium influx + inhibits this in the SAN/AVN heart-decreases pacemaker potential
* d HR + inhibits this in myocytes, decreased force contraction -> decreased SV.
MofA oral phenoxy benzamine
Irreversibly blocks Alpha receptors * Inhibits Alpha 1-Gq mechanism
-> d activation on Phospholipase C -> d formation of IP3 and DAG -> d PKC and IP3 and cGMP -> d intracellular calcium -> d Contraction -> muscle relaxation + widening of the blood vessels * lowering of blood pressure.
Competitive irreversible antagonist of adrenaline – binds adrenaline receptors * less available adrenaline to act upon.
Mof A atenolol
Competes with sympathomimetic neurotransmitters (catecholamines) via binding beta (1)-adrenergic receptors in heart/ vascular smooth muscle * Inhibits sympathetic stimulation -> reduction in resting heart rate, cardiac output, systolic and diastolic blood pressure, and reflex orthostatic hypotension.
Higher doses atenolol competitively block beta (2)-adrenergic responses in the bronchial and vascular smooth muscles.
PODOPHYLLOTOXIN
Soft non keratinised warts
Blocks cell division via inhibition micro-tubule assembly in mitotic apparatus
Inhibits topisomerase II during S phase - bind and stabilize temporary break and disrupt reparation break - stopping DNA unwinding and replicating
Topical imiquid
larger keratinised warts
Allows innate + acquired IR recognize abnormal cells - inflam cell infiltration + apoptosis of diseased tissue.
induces expression Il-6, Il-8 + TNF alpha
Stim apoptosis in BCC cells
TCA
Trichloroacetic acid - chemically burns wart
Effects of adrenaline
Alpha 1 vasocontriction skin, kidney + brain
Beta 1 increase CO increase contractility HR + conduction
Beta 2 vasodilates + bronchodilates
Increase BP via stim alpha 1 > beta 2
What is the reflex bradycardia in response to adrenaline
NA stim Beta I increasing myocardium contractility but reflex mechanism do decrease HR. NA causes ABP + stroke vol to increase - strim baroreceptors in aorta - vagus centre. Reflex vagus bradycardia negates influence B1 R * CO not significantly changed
Heceptin/ Trastuzumab
IgG1 monoclonal AB selectively binds high affinity HER2 proto-oncagene -> AB mediated killing HER2 +ve cells - induce arrest G1 phase cell cycle * reduced proliferation
Dexamethasone
Glucocortiocoid receptor agonist. Binding GR loses inhibitory proteins translocation cell nucleus binds GRE on promoter region target genes - interacts TF up regulate/ down regulate expression target gene.
Supression Il-2 leukotrienes AA + prostaglandins.
Phosphoylates annexin I
Inhibits leukocyte infiltration
Beta interferon
Endogenous IFN B contributes mediation anti inflam + regenerative effects. Binds type 1 IFN R - activate JAK 1 - phosphorylate receptors - bind stat 1/2. Dimerize + activate immunoregulatory + anti viral proteins.
increase production neuronal growth factor + inhibit leukocyte migration across BB
Amoxicillin
Beta lactam
PBP 1a - inactivation transpeptidase * inhibits peptidoglycan polymer cross linking.
First line gram +ve
Pseudomonas + enterobacteriacae resistant
Ceftazidime
Broad spec beta lactam Inhibits PBP3 (Beta lactam ring mimics d-ala- d ala dimer between NAM) - inactivation transpeptidase * inhibits peptidoglycan polymer cross linking. Cell lysis mediated autolytic enzymes.
Staphylococci resistant
Good pseudomonas + E coli
Gentamicin
Aminoglyceride broad spec gram neg
Irreversibly binds 16S ribsosomal RNA within 30s sub unit. Interference INITIATION COMPLEX. Misreading mRNA * incorrect aa inserted polypeptide - non functional peptides * bacteria cant synthesize proteins for growth.
Ciprofloxacin
Quinolone - broad spec
Inhibits Topoisomerase II/DNA gyrase and Topoisomerase IV - Inhibition uncoiling & unwinding of DNA from histones -> required for bacterial DNA replication, transcription, repair, strand supercoiling repair, and recombination
Inhibits DNA replication
Good for Pseudonomas aeruginosa
Codeine
Converted into morphine
Selective Mu R (GPCR I) weaker than morphine. Bound inhibits AC * reduction cAMP. Acts on reticular formation, limbic system + PAG. Stim release endorphins (enkaphaline/ 5-HT). STIMULATES DESCENDING INHIBITORY PATHWAYS.
Inhibit sensory nerve transmission via substance P (c fibers)
Moderates integration processes in limbic system
REDUCES NEURONAL EXCITABILITY AND NEUROTRANSMITTER RELEASE.
Vancomycin
Glycopeptide
binds d ala- d ala blocking action transpeptidases
Stages clot formation
propagation organisation Re- canilzation Embolism Resolution
Tpa
binds thrombus - conformational change allows conversion plasminogen to plasmin
