All Drugs Flashcards
1
Q
Lisinopril/ramipril
A
Indication: hypertension and heart failure
Class: ACEi
Actions:
- inhibit angiotensin I to angiotensin II
- build up of bradykinin - vasodilation via NO
Adverse effects:
- dry cough (bradykinin)
- hyperkalaemia (low aldosterone)
- cause/worsen renal failure (dont give renal artery stenosis)
- angiodema (afro-carribean patients)
Warnings:
- preganncy - may cause newborn hypotension via breastfeeding
- dont give in low renin patients - loss of RAAS and become hypotensive
- renal artery stenosis
- afro-carribean
Interactions:
- potassium increasing drugs (amiloride, ARBs)
- NSAIDs
- other antihypertensives
Other:
- less effective than ARBs as angiotensin II produced from angiotensin I independently of ACE via chymases
- used in hypertension with type II diabetes - decreases peripheral vascular resistance and dilates efferent arteriole so reduces glomerular pressure
2
Q
Losartan
A
Inidication: hypertension and heart failure
Class: Angiotensin receptor II antagonist - AT1 receptor
Adverse effects:
- hypotension
- hyperkalaemia (low aldosterone)
- cause/worsen renal failure (dont give w/ renal artery stenosis)
Interactions:
- potassium increasing drugs (amiloride, ACEi)
- NSAIDs
Warnings:
- pregnancy
- low renin patients - loss of RAAS so become hypotensive
Other:
- more effective at inhibiting angiotensin II mediated vasoconstriction - block further down stream
- no effect on bradykinin and angiodema less likely than with ACEi
3
Q
Amlodipine/nimodipine
A
Indication: hypertension
Class: dihydropyridine calcium channel blocker
Action:
- amlodipine selective for peripheral calcium initiated vascular smooth muscle contraction
- nimodipine selective for cerebral vasculature - useful for ischaemic effects of subarachnoid haemorrhage
Adverse effects:
- ankle swelling
- flushing + headaches (vasodilation)
- palpitations (compensatory tachycardia)
Contraindications:
- unstable angina
- severe aortic stenosis
Interactions:
- simvastatin (increases statin effect)
Other:
- give instead of ACEi for low renin patients
- amlodipine has long half life
4
Q
Verapamil
A
Indication: arrythmia, angina
Class: phenylalkylamines - non dihyropyridine CCB
Actions: negative chronotropic and inotropic effects
Adverse effects:
- constipation
- bradycardia (dont give w/ AV nodal delay)
- heart block and cardiac failure (dont give with poor LV function)
Interactions:
- beta blockers
- other antihypertensives and atiarrythmics
5
Q
Indapamide
A
Indication: hypertension
Class: thiazide diuretic
Action:
- inhibit Na+/Cl- transporter in distal convoluted tubule - decrease Na+ and h20 reabsorption
- Long term - sensitivty of vascular smooth muscle to vasoconstrictors (calcium and noradrenaline)
Adverse effects:
- hypokalaemia, hyponatreamia, hyperuricemia (gout)
- increase glucose
- increase cholesterol and triglyceride
Interactions:
- NSAIDs
- K+ decreasing drugs e.g loop diuretics
Other:
- useful over calcium channel blockers in oedema
- single dose in morning - causes you to urinate so could disrupt sleep if taken later in the day
6
Q
Doxazosin/tamulosin
A
Indication: resistant hypertension
Class: alpha adrenoreceptor blocker
Action:
- reduce peripheral vascular resistance
- tamsulosin used in BPH - dilation of bladder neck and prostate
Adverse effects:
- postural hypotension, dizziness, syncope, headache
Interactions:
- dihydropyridine CCB - increase oedema
7
Q
Labetalol/bisoprolol
A
Indication: resistant hypertension and heart failure
Class: beta blocker
Action:
- decrease sympathetic tone by blocking NAd
- reduce myocardial contraction, decreasing CO
- decrease renin secretion - beta 1
Adverse effects:
- bronchospasm (dont give w/ asthma)
- heart block (dont give w/ Haemodynamic instability)
- raynauds
- mask tachycardia (insulin induced hypoglycaemia)
Interactions: non-dihydropyridine CCBs - overload
Other:
- used in resistant hypertension
- used in gestational diabetes and pregnancy hypertension
8
Q
Spirinolactone
A
Indication: resistant hypertension and heart failure
Class: aldosterone receptor antagonist - block transcription (dont give w/ addisons)
Adverse effects:
- hyperkalaemia
- gynaecomastia (anti-androgen)
Interactions:
- K+ increasing drugs
- pregnancy
9
Q
Furosemide
A
Indication: heart failure
Class: loop diuretic
Action: inhibit N+/K+/2Cl- in ascending LoH, decrease H20 absorption
Adverse effects:
- dehydration and hypotension
- hypokalamia, hyponaetreamia, hyperuricemia (gout)
- tinnitus (ototoxicity)
Interactions:
- aminoglycosides - ototoxicity
- digoxin - hypokalaemia
- lithium
10
Q
Amiloride
A
Indication: heart failure
Class: potassium sparing diuretic
Action: directly block ENaC - decrease sodium reabsoprtion and decrease potassium excretion (dont give w/ addisons)
Adverse effects: hyperkalaemia
Interactions: other K+ sparing drugs (ACEi, ARBs)
Other:
- often used w/ loop or thiazide diuretics to decrease potassium loss
11
Q
Atorvastatin/simvastatin
A
Indication: hyperlipidaemia
Class: statin
Action:
- competitive inhibition of HMG- CoA reductase
- upregulation of hepatic LDL receptors
- increased clearance of circulating LDL
Adverse effects:
- GI disruption, nausea, headache
- myalgia
- rhabdomylosis
Warnings:
- renal/hepatic impairement
- pregnancy and breastfeeding
Interactions:
- amlodipine - increases plasma statin
- amiodarone, macrolides - increase statin (CYP3A4 inhibtion)
- grapefruit juice inhibits CYP3A4
Other:
- simvastatin - prodrug activated by FPM - short half life
- atorvastatin - FPM produces further active metabolites - long half life
12
Q
Fenofibrate
A
Indication: hyperlipideamia
Class: fibric acid derivatives
Action: activation of nuclear transcription factor PPARa - increase production of lipoprotein lipase
- increase triglyceride removal from lipoprotein in plasma
- increase fatty acid uptake by liver
- increase levels of HDL
- increase LDL affinity for receptor
Adverse effects:
- gall stones (avoid w/ gall bladder disease)
- GI upset
- myositis
- photosensitivity
Interactions: warfarin - increase anticoagulation
13
Q
Ezetimibe
A
Indication: hyperlipideamia
Class: cholesterol absoprtion inhibitors
Action:
- inhibit NPC1L1 transporter at brush border in SI
- redcues absorption of cholesterol by gut
- increase expression of hepatic LDL receptor
- prodrug, hepatic metabolism, enterohepatic circulation, limits systemic exposure, secreted by bile
Adverse effects:
- abdo pain, GI upset
- angioedema
Warning: hepatic failure - pro drug so part of hepatic metabolism and enterohepatic circulation
Interactions:
- mindful with statin - increased risk of rhabdomyloysis
- ciclosporin - increases ezetimibe
Other: adjunct to statin
14
Q
Alirocumab
A
Indication: hyperlipideamia
Class: monoclonal antibody
Action: PCSK9 inhibitor - prevent protein binding to internalised LDL-R, prevent degradation, decrease blood levels of LDL cholesterol
Adverse effects:
- long term effects unknown
- requires lifetime injections
15
Q
Inclisiran
A
Indication: hyperlipideamia
Class: siRNA
Actions: inhibits hepatic translation of PCSK9 so less produced, less binding to internalised LDL-R, less degradation, less blood LDL-C level
Adverse effects:
- long term effects unknown
- requires lifetime injections
16
Q
Oestrogen
- actions
- side effects
A
Actions:
- mild anabolic
- sodium and water retention
- raises HDL, lowers LDL
- decrease bone resorption
- impaired glucose tolerance
- increase blood coaguability
Side effects:
- water retention
- nausea, vomiting
- thromboembolism
- imapaired glucose tolerance
- increase blood coaguability
- breast tenderness
- endometrial + breast hyperplasia and cancer
- ovarian metaplasia and cancer
17
Q
Progesterone
- actions
- side effects
A
Actions:
- anabolic
- fluid retention
- increase bone mineral density
- secreteroy endometrium
- mood changes
- maintains pregnancy
Side effects:
- anabolic
- fluid retention
- nausea/vomiting
- acne
- weight gain
- irritability, depression, PMS
- lack of concentration
18
Q
Testosterone
- actions/side effects
A
- anabolic
- male secondary sexual characterstics
- acne
- voice changes
- agression
- decrease HDL-C/LDL-C (increase atherosclerotic risk)
19
Q
Alendronic acid
A
Indication: osteoporosis, pagets disease, malignancy
Class: bisphosphonates
Actions: control osteoclast activity - reduce bone turnover
Adverse effects:
- oesophagitis (remain upright for 30 mins after)
- hypocalcaemia (check ca and vit D levels before)
Other:
- long half life
- poor gut absoprtion
- absoprtion affected by food - empty stomach
20
Q
Mifepristone
A
Indication: termination of pregnancy
Class: progesterone (and glucocorticoid) receptor antagonist
Actions: sensitises the myometrium to prostaglandin-induced contracions
21
Q
Finasteride
A
Indication: BPH
Class: 5-alpha reductase inhibitor
Actions: prevent conversion of testosterone to dihydrotestosterone
22
Q
Clomiphene
A
Indication: anovulation
Class: SERM
Action:
- competes with oestrogen for ER binding
- increased production of anterior pituitary hormones
- leads to ovulation induction
23
Q
Raloxifene
A
Indication: osteoporosis
Class: SERM
Action: bone specific
24
Q
Tamoxifen
A
Indication: breast cancer
Class: SERM
Action:
- active metabolites compete with oestrogen for binding to the ER
- causes cells to arrest in the cell cycle
Adverse effects: in endometrium acts as an ER agonist - increased risk of endometrial hyperplasia/cancer
Other:
- pro drug therefore metabolised in the liver to active derivatives
- genetic differences in enzymes in the liver means tamoxifen is not metbaolised and therefore not active in some people
25
Ulipristal acetate
Indication: emergency contraception, uterine fibroids
Class: SPRM
Action: delay/inhibit ovulation
26
Insulin
Indication: type 1 diabetic/ late stage type 2
Adverse effects:
- hypoglycaemia
- lipodystophy (rotate site of administration)
Warning: renal impairement - hypoglycaemia risk
Interactions:
- systemic steroids - need to increase insulin dose
- other hypoglycaemic agents
Other:
- protein so must be given paraenterally to avoid digestion
- short half life so slow absoprtiom via soluble insulin or insulin analogues
27
Metformin
Indication: hyperglycaemia
Class: biguanides
Hypoglycaemia: no
Weight: supress apetite
Route: oral
Action: reduces hepatic glucose by inhibiting gluconeogenesis
Adverse effects: GI upset - nausea, vomiting, diarrhoea
Warnings:
- stop if eGFR <30 - excreted unchanged by the kidneys so can quickly accumulate
- alcohol intoxication
Interactions:
- ACEi, NSAIDs, diuretics - may impair renal function
- loop and thiazide can increase glucose so reduce metformin action
28
Gliclazide
Indication: hyperglyceamia
Class: sulfonylureas
Hypoglycaemia: yes
Weight: increased - anabolic effecrs of insulin
Route: oral
Action: stimulate pancreatic insulin secretion by blocking ATP-dependant K+ channels
Adverse effects: GI upset
Warnings: hepatic and renal disease
Interactions:
- other hypoglycaemic agents
- loop and thiazide can increase glucose so reduce SU action
29
Pioglitazone/rosiglitazone
Indication: hypergylycaemia
Class: glitazone
Hypoglycaemia: yes
Weight: increased - fat cell differentiation
Route: oral
Action: enhanced insulin sensitivty and utilisation
Adverse effects:
- GI upset
- fluid retention
- fracture risk
- bladder cancer
Warnings: heart failure because of fluid retention
Interactions: other hypoglycaemic agents
30
Dapagliflozin/canagliflozin
Indication: hyperglycaemia
Class: SGLT-2 inhibitors
Hypoglycaemia: no
Weight: decrease
Route: oral
Actions: reduce glucose reabsorption
Adverse effects:
- UTI
- genital infection
- thirst and polyuria
Warnings: hypovolaemia - possible hypotension due to osmotic diuresis
Interactions: antihypertensives and other hypoglycaemic agents
31
Sitagliptin/saxagliptin
Indication: hyperglycaemia
Class: DPP-4 inhibitor
Hypoglycaemia: no
Weight: reduce apetite
Route: oral
Action: prevent incretin degradation - promote insulin secretion and supress glucagon release
Adverse effects:
- GI upset
- pancreatitis
Warnings:
- pregnancy
- pancreatitis
Interactions:
- other hypoglycaemic agents
- drugs which increase glucose oppose gliptin action e.g thiazides
32
Exenatide/liraglutide
Indication: hyperglycaemia
Class: GLP-1 receptor agonist
Hypoglycaemia: no
Weight: increased satiety
Route: SUBCUTANEOUS
Actions: increase glucose dependent synthesis of insulin
Adverse effects:
- GI upset
- decreased apetite with weight loss
Warnings: renal impairment
Interactions: other hypoglycaemic agents
33
Aspirin
Indication: antiplatelet
- AF patients post stroke
- secondary prevention of stroke, TIA, ACS
- post PCI to reduce ischaemic complications
Class: cyclo-oxygenase inhibitor
Action: low doses inhibits COX-1 mediated production of thromboxane A2 whcih reduces platelet aggregation - irreversible
Adverse effects:
- GI irritation + bleeding (Peptic ulcer)
- haemorrhage (stroke)
- hypersensitivity
Warnings:
- <16yrs - reye’s syndrome
- 3rd trimester - premature closure of the ductus arteriosus
- hypersensitivty
Interactions: other antiplatelets and anticoagulants
Other:
- does not completely inhibit platelet aggregation due to other endodgenous pathways
- absorbed by passive diffusion - hepatic hydrolysis to salicylic acid
- COX1 polymorphisms result in lack of efficacy in some
- lasts lifespan of the platlet (7-10 days) - non nucleated therefore unable to produce more of COX1
- gastric protection (PPI) required for long term use in at risk patients
34
Clopidogrel/prasugrel/ticagrelor
Indication: dual antiplatlet therapy
- ischaemic stroke and TIA
- long term monotherapy where aspirin in contraindicated
Class: ADP receptor antagonists
Actions: inhibit binding of ADP to P2Y12 receptor therefore inhibits activation of GPIIb/IIIa receptors (independent of COX pathway)
Adverse effects:
- bleeding
- GI upset (dyspepsia and diarrhoea)
- trombocytopenia
Warning: high bleed risk patients with renal and hepatic impairment
Interactions:
- CYP inhibitors - omeprazole, ciprofloxacin, erythromycin, SSRIs (clopidogrel requires CYPs for activation)
- tricagrelor can interact with CYP inhibitors and inducers
- other antiplatelts, anticoagulants + NSAIDs - increase risk of bleeding
Other:
- clopidogrel/prasugrel are irreversible inhibitors of P2Y12
- ticagrelor acts reversibly at different site
- clopidogrel/prasugrel are prodrugs - active hepatic metabolites
- ticagrelor has active metabolites
- most cases stopped 7 days prior to surgery
35
Dipyridamole
Indication: antiplatelet
- secondary prevention of ischaemic stroke and TIA
- adjunct for prophylaxis of thromboembolism following valve replacement
Class: phosphodiesterase inhibitor
Action:
1. inhibits cellular reuptake of adenosine - increased adenosine inhibits platelet aggregation via A2 receptors
2. PDE inhibitor - prevents cAMP degradation therefore inhibits expression of GPIIb/IIIa
Adverse effects: V+D, dizziness
Interactions: antiplatelets, anticoagulants, adenosine
36
Abciximab
Indication: antiplatelet
- specialist use in high risk percutaneous transluminal coronary angioplasty
Class: GP IIb/IIIa inhibitor
Action: blocks binding of fibrinogen and vWF - targets final common pathway therefore more complete reduction in aggregation (>80%) - i.v
Adverse effect: bleeding - dose adjusted for body weight
Interactions: other antiplatlets and anticoagulants
37
Streptokinase/alteplase
Indication: fibrinolytic
Action: inhibit plasminogen to plasmin therefore inhibits degradation of fibrin clot
Adverse effects: bleeding
Interactions: antiplatelets and anticoagulants
Other:
- alteplase (tPA) in acute ischaemic stroke
- streptokinase following STEMI
- streptokinase can only be used once - antibodies develop as it is derived from bacteria
38
Lidocaine/mexiletine
Indication: arrythmias
- ventricular tachycardia
Class: Ib
Action:
- fast binding offset kinetics
- blocks the open/inactive Na+ channels (fast beating/ischaemic tissue)
- decrease phase 0 depolarisation - decrease conduction velocity in ischaemic tissue
ECG: prolong QRS
Side effects:
- CNS: dizziness, drowsiness
- abdominal upset
Route:
- lidocaine iv only
- mexiletine oral only
39
Flecainide
Indication: arrythmias
- supraventricular arrythmias
- premature ventricular contrcations
- wolff-parkinson-white syndrome
Class: 1c
Action:
- very slow binding offset kinetics
- block open/inactivated Na+ channels - slow phase 0 in normal tissue
- increase threshold, decrease automaticity
- increase APD and refractory period in rapdily depolarizing atrial tissue
ECG: increase PR, QRS, QT
Side effects:
- pro-arrythmia and sudden death especially with chronic use
- felcainide flutter - increase ventriuclar response to supraventricular arythmias
- CNS and GI effects (local anesthetics)
Route: oral or iv
40
Propanolol/bisoprolol/metoprolol/esmolol
Indiction: arrythmias
- tachycardia
- re-entry arryhthmias
- atrial fibrilation - slow AVN conduction, protect ventricles
- CAN give in stable heart failure, NOT in partial AV block or acute heart failure
Class: II
Actions:
- act at beta 1 receptors in the heart (block sympathetic effect)
- pacemaker cells = decrease phase 4 depolarization, decrease AVN conduction velocity
- non pacemaker cells = increase APD and refractory period
ECG: increase PR, decrease HR
Side effects:
- bronchospasm - non selective beta2 receptors in the lungs
- hypotension
Route:
- propanolol/metoprolol = oral or iv
- bioprolol = oral
- esmolol = iv only (very short acting/half life)
41
Amiodarone
Indication: arrythmias
Class: III
Action:
Non pacemaker cells=
- K+ block - increase APD and refractory period
- Na+ block - decrease phase 0, decrease conduction
Pacemaker cells =
- beta and Ca+ block - decrease phase 4 depolarisation, decrease AVN conduction
ECG: increase PR, QRS, QT, decrease HR
Side effects:
- pulmonary fibrosis
- hepatic injury
- increase LDL cholesterol
- thryoid disease
- photosensitivty
- optic neuritis
- reduce dose of digoxin and monitor warfarin more closely
Route: oral or iv
42
Sotalol
Indication: arrythmias
- supraventricular and ventircular tachycardia
Class: III
Action:
- K+ block - increase APD and refractory period
- beta blocker - decrease phase 4 depolarisation, decrease AVN conduction
ECG: increase QT, decrease HR
Side effects:
- proarrythmia
- fatigue and insomnia
Route: oral
43
Verapamil/diltiazem
Indication: arrythmias
- supraventricular tachycardia - control ventricles and convert to normal sinus rhythm (re-entry around AVN)
Class: IV
Action:
- Ca+ channel blocker
- decrease phase 0, decrease conduction through AVN
- increase refractory period in AVN
- negative chronotropic and inotropic effects
ECG:
- increase PR
- increase/decrease HR - depends on BP response and baroreflex
Side effects:
- hypotension, decreased CO, sick sinus
- asystole - if partial AV block and beta blocker present
- GI problems - constipation
Route:
- verpamil = oral or iv
- diltiazem = oral
44
Adenosine
Indication: arrythmias
- convert re-entrant supraventricular arrythmias
- diagnosis of coronary artery disease (compare perfusion of the heart when beating slowly vs fast)
Class: V
Action:
- binds to a1 receptors and blocks adenyl cyclase - reduce cAMP
- decrease Ca+, increase refractory period, slow AV conduction
- activation of K+ currents in SAN/AVN - hyperpolarisation - decrease HR
Route: rapid iv bolus (very short half life)
45
Ivabradine
Indication: arrythmias
- sinus tachycardia
- reduce HR in heart failure and angina
Action:
- blocks funny current in SAN
- slows SAN
- DOESN’T effect blood pressure
Side effects:
- flashing lights
- avoid in pregnancy
Route: oral
46
Digoxin
Indication: arrythmias
- heart failure with arryhtmia present
Class: cardiac glycoside
Action:
- enhances vagal activity - slows AV conduction and HR
- block Na+/K+ ATPase, increase intracellular Na+, decrease activity of NCX, increase intracellular Ca+, increase force of contraction
Side effects: v dependent on renal function - decrease function can increase blood levels and cause extreme bradycardia
47
Atropine
Indication: arrythmias
- treat vagal bradycardia e.g fainting
Action:
- selective muscarinic anatgonist
- block vagal activity - increase AV conduction and HR
48
Corticosteroids
Indication: immunosuppressant
Action:
- Prevent IL-1 and IL-6 production by macrophages
- inhibit all stages of T cell activation
49
Azathioprine
Indication: immunosuppresant
- MAINTENANCE therapy for SLE and vasculitis
- IBS
- atopic dermatitis, bullous skin disease
- steroid sparing drug
Action:
- cleaved to 6-MP
- metabolised by TPMT to TIMP
- anti-metabolite decreases DNA and RNA synthesis (purine)
Adverse effects:
- bone marrow supression - monitor FBC
- increased risk of malignancy - especially transplanted patients
- increased risk of infection
- hepatitis - monitor LFT
Other: TPMT gene highly polymoprhic so test activity before prescribing (low/absent levels = risk of myelosupression)
50
Ciclosporin/tacrolimus
Indication: immunosupressant
- transplantation
- atopic dermatitis and psoriasis
- not often rheumatology - renal toxicity - check BP and eGFR
Class: calcineurin inhibitor
Action:
- ciclosprin binds to cyclophilin protein
- tacrolimus binds to tacrolimus-binding protein
- drug/protein complexes bind to calcineurin
- inhibit calcineurin, prevent production of IL-2 from T helper cells
Adverse effects:
- bone marrow supression - monitor FBC
- increased risk of malignancy - especially transplanted patients
- increased risk of infection
- hepatitis - monitor LFT
Other: inhibit CYP 450 - multiple drug intercations possible
51
Mycophenolate mofetil
Indication: immunosupressant
- transplants
- INDUCTION and MAINTENANCE in lupus nephritis
- MAINTENANCE in vascultitis
Action:
- prodrug derived from fungus penicllium stoloniferum
- inhibits inosine monophosphate dehydrogenase (guanosine synthesis)
- impairs B and T cell proliferation
- spares other rapidly diving cells - guanosine salvage pathways
Adverse effects:
- nausea, vomiting, diarrhea
- myelosupression
52
Cyclophosphamide
Indication: immunosupression
- lymphoma, leuakemia, solid cancers
- lupus nephritis
- wegener’s granulomatosis
Actions:
- prodrug - active metabolites are 4-hydroxycylcophosphamide and its tautomer aldophosphamide
- alkylating agents - cross link DNA so that it cannot replicate and supress B and T cell activity
- aldophosphamide converted to carboxyphosphamide (inactive), phosphoramide mustard (good metabolite), acrolein (toxic metabolite to the bladder leading to hemorrhagic cystitis - prevented by aggressive hydration and mesna)
Adverse effects: toxicity
- increased risk of badder cancer, lymphoma and leukaemia
- infertility (risk relates to cumulative dose and pateint age)
- monitor FBC and adjust dose in renal impairment
Other:
- mycophenolate mofetil safer and as effective in lupus nephritis
53
Methotrexate
Indication: immunosuppressant
- gold standard for RA
- malignancy
- psoriasis
- crohn’s
- abortions
Action:
1. Malignant disease:
- competitively and reversibly inhibits dihydrofolate reductase
- inhibits conversion of dihydrofolate to active tetrahydrofolate (key in purine and thymidine synthesis)
- inhibits synthesis of DNA, RNA and proteins - cytotoxic effect during S phase therefore more effective on rapdily dividing cells
2. Non malignant disease:
- unclear
- NOT via anti-folate action
- possibly inhibition of accumulationof adenosine
Route: oral, IM or SC (if only partial response or nausea)
Dosing: WEEKLY - long half life
Adverse effects:
- mucositis (responds to folic acid supplementation)
- marrow supression (responds to folic acid supplementation)
- hepatitis/cirrhosis
- pneumontis
- infection
- highly tetratoegnic and abortifacient
Other:
- 50% protein bound - NSAIDS displace
- renal excretion
54
Sulfasalazine
Indication: immunosupressant
- IBD (poorly absorbed - main activity in the intestine)
- RA
Action:
- 5-ASA anti-inflamatory, sulfapyridine antibiotic
- T cell inhibtion of proliferation and IL-2 production, apoptosis
- neutrophil - reduce chemotaxis and degranulation
Adverse effects:
- myelosuppression
- hepatitis
- rash
- nausea, vomiting, abdo pain
Other:
- safe in pregnancy
- few drug interactions
- effective and favourable toxicity
55
Adalimumab, infliximab
Indication: immunosupressant
- RA
- IBD
- psoriasis
- psoriatic arthritis
- ankylosing spondilitis
Class: monoclonal antibody
Action: blocks/binds TNFa
- decrease inflamation - cytokine cascade, leukocutes to joint
- decrease angiogenesis - VEGF levels
- decrease joint destruction - MMps, bone reorption/erosion, cartilage breakdown
Adverse effects: TB reactivation - TNFa released by macrophages in response to TB infection and is essential for development and maintenenace of granulomata (screen for latent TB before anti-TNF treatement)
56
Rituximab
Indication: immunosupressant
- RA
- vasculitis
- systemic lupus erythramotosus
- lymphoma
Class: monoclonal antibody
Action:
- binds to CD20 found on a specific subset of B cells (not stem or plasma cells)
- causes B cell apoptosis (loss of antigen presentation to T cells, cytokines, antibodies)
57
Aspirin, ibuprofen, naproxen
Indication: anti-inflamatory, analgesia, antipyretic
- inflammatory conditions
- oestoarthritis
- post operative pain
- menorrhagia
- low dose asprin for platelt aggregation (COX1)
Class: NSAIDs
Action:
- inhibit COX1 - decrease prostaglandins, prostacylcin, thromboxane synthesis
Adverse effects:
- GI - dyspepsia, nausea, ulceration, bleeding (PGE2 regulates acid secretion in parietal cells, PGI2 maintains blood flow and mucosal repair)
- renal - reversible decreased GFR and renal blood flow (PGE2/PGI2 vasodilation of afferent arteriole), increased blood pressure (PGE2 inhibits sodium absoprtion in the collecting duct)
Warnings:
- GI - IBD, elderly, prolonged use, smoking, alcohol, H.pylori, ulcers
- renal - CKD, heart failure (greater reliance on PGE2 for vasodilation)
- pregnancy - delayed labour and early closure of ductus arterosus
Interactions:
- GI - aspirin, glucocorticoid steroids, anticoagulants (PPI considered)
- renal - ACEi, ARbs, diuretics
Other:
- displace other highly protein bound drugs (sulfonylurea + hypoglycaemia, methotrexate + haeptoxicity, warfarin + increaed bleed risk)
58
celecoxib, etoricoxib
Indication: antiinflammatroy, analgesic, antipyretic
- long term osteo/rheumatoid arthritis
Class: NSAID
Action: selective COX2 inhibitors
Adverse effects:
- less gi
- renal - CKD, heart failure (greater reliance on PGE2 for vasodilation)
- increase MI risk - inhibit PGI2 - unopposed aggregatory effects
59
Paracetemol
Indication: analgesic and antipyretic
Action: COX2 selective inhibtion in CNS - decrease pain signals to higher centres (little anti-inflmatory action as peroxides in peripheral inflamation)
Adverse effects:
- few ADRs
- no effect on platelets
- limited effect on GI
- well abrobed from GI - inactivated by conjugation in liver
Overdose:
- at normal doses conjugation with glutathione renders NAPQI harmless
- hepatic glutathione is limited
- NAPQI highly nucleophilic - oxidises key enzymes causing necrosis and apoptosis
- asymtomatic initially, nausea + vomiting in 24hr, liver damage 3-4days
- iv acetylcysteine - glutathione thiol replacement (glutathione itself cannot get into hepatocytes)
60
Morphine
Indication: opioid
- analgesic
Class: opioid agonist (strong)
Action:
- binds to MOP receptor
- decrease cAMP
- efflux of potassium - hyperpolarisation
- decrease substance P and GABA release
- increase dopamine release
Absorption:
- PO, IV, IM, SC, PR
- erratic gut absorption
- FPM - 40% oral bioavilability
Distribution:
- very lipophilic - enters all tissues (including foetal)
- not protien binding so struggles to cross BBB
Adverse effects:
- respiratory depression -decreases sensitivity of MRC to CO2
- GI tract - constipation, vomiting
- CVS
- miosis
- histamine release - caution in asthmatics
Other:
- metabolism = morphine + glucoronic acid = M6G + M3G
- elimination = renal
61
Fentanyl
Indication: opioid
- analgesic
- anasethetic
Class: opioid agonist (stronger)
Action:
- binds to MOP receptor
- decrease cAMP
- efflux of potassium - hyperpolarisation
- decrease substance P and GABA release
- increase dopamine release
Absorption:
- IV, epidural, inrathecal, nasal
- 80- 100% oral bioavilability
- 100x more potent and higher affinity than morphine
Distribution:
- very lipophilic - enters all tissues (including foetal)
- high protien binding so crosses BBB
Adverse effects:
- respiratory depression -decreases sensitivity of MRC to CO2
- GI tract - constipation, vomiting
- histamine release - caution in asthmatics
- LESS than morphine
Other:
- metabolism = hepatic via CYP3A4
- elimination = renal
62
Codeine
Indication: opioid
- analgesic
- cough depressant
Class: opioid agonist (moderate)
Metabolism:
- codeine to morphine via CYP2D6 (inhibited by fluoxetine)
- variable expression of CYP = variable response
- 1/10th potency of morphine
Action:
- binds to MOP receptor
- decrease cAMP
- efflux of potassium - hyperpolarisation
- decrease substance P and GABA release
- increase dopamine release
Absorption:
- PO, SC
Adverse effects:
- respiratory depression - worse in children
- GI tract - constipation
Other:
- elimination = glucoronidation and renal excrection
63
Buprenorphine
Indication: opioid
- analgesic
- addiction
Class: opioid partial agonist
Action:
- binds to MOP receptor - low kd (high affinity), low Emax (effiacy)
- decrease cAMP
- efflux of potassium - hyperpolarisation
- decrease substance P and GABA release
- increase dopamine release
- antagonist at KOP receptor
Absorption:
- transdermal, buccal, sublingual
Distribution:
- very lipophilic - enters all tissues (including foetal)
Adverse effects:
- respiratory depression -decreases sensitivity of MRC to CO2
- low bp, dizziness
- nausea
Other:
- metabolism = hepatic via CYP3A4
- elimination = biliary excretion
64
Naloxone
Indication: opioid
Class: competitive opioid antagonist
Action:
- greater affinity for MOP than morphine, less than buprenorphine
- inhibits normal cascade
- 0 Emax
Absorption:
- IV, IM, intranasal, PO
- FPM - v low oral availability
- rapid onset of action
Distribution:
- very lipophilic - enters all tissues (including foetal)
Adverse effects:
- short half life
- slow infusion
Other:
- metabolism = hepatic - naloxone -3 - glucuronide
- elimination = renal
