Drugs Flashcards
What kind of drug is clarithromycin? What is the mechanism of action?
Macrolides works via the 50s subunit
N/V common SE and can prolong QT interval, can also cause cholestatic jaundice
Inhibit P450 enzymes in the liver
Measure LFTs if LT treatment needed and measure QT on EG if patient CV unstable
• Avoid with hepatic insufficiency
• Reduce if renal insufficiency
• Avoid in pregnancy but not known harmful
Avoid in cardiac conduction abnormalities or in drugs that can prolong QT
What do benzothiazepines affect vascularly? And what is an example of a drug
Diltiazem
These are calcium channel blockers that affect both the peripheral and the heart vasculature
Often used with Verapamil (Phenylalkylamines) for supraventricular arrythmias
Should not be giving non dihydropyridine calcium blockers (verapamil and diltiazem) with BB w/o close supervision both are negatively inotropic, chronotropic- may give HF, bradykinesia, asystole
Caution with verapamil and diltiazem in patients with poor left ventricular function can worsen heart failure
Avoided in AV nodal conduction delay with non dihydropyridine
What do Phenylalkylamines affect vascularly? And what is an example of a drug? What side effects can it cause?
Verapamil
These are calcium channel blockers which affect mainly the heart
Often used with diltiazem (benzothiazpeines) supraventricular arrythmias
verapamil- can cause constipation, bradykinesia, heart block or cardiac failure (note diltiazem may too due to peripheral effects)
Should not be giving non dihydropyridine calcium blockers (verapamil and diltiazem) with BB w/o close supervision both are negatively inotropic, chronotropic- may give HF, bradykinesia, asystole
Caution with verapamil and diltiazem in patients with poor left ventricular function can worsen heart failure
Avoided in AV nodal conduction delay with non dihydropyridine
What do Dihydropyridines affect vascularly? What are some examples, uses, and SE?
(amlodipine, felodipine, isradipine, lacidipine, lercanidipine, nicardipine, nifedipine, nimodipine, nisoldipine)-
These are principally affect peripheral vascular
Amlodipine and to a less extend nifedipine used for 1st line (black or +55) or 2nd like for hypertension, stroke, MI, death from CVD
Amlodipine and nifedipine: Flushing, headaches, palpitations, peripheral oedema due to vasodilation and compensatory tachycardia
Dihydropyridines avoid in unstable angina as contraction/tachycardia increase O2 demand reflex from vasodilation or in severe aortic stenosis as they may cause collapse
What kind of drug is indapamide?
Thiazide like diuretic
What drug can cause fibrosis of the lung?
amiodarone (others include bleomycin, methotrexate)
When should you take bisphosphonates, SE and CI
Take at least 30 minutes before breakfast with plenty of water + sit-upright for 30 minutes following (this is to avoid oesophageal irritation)
Work by decreasing the osteoclasts
SE
Oesophagitis (when taken orally)-oesophageal ulcers
Hypophosphatemia
Osteonecrosis of jaw- high dose IV therapy- therefore good dental care reducing risk
Atypical femoral fracture especially on long term
CI:
Renally excreted therefore avoid in severe renal impairment
CI in hypocalcaemia
Oral administration is CI in upper GI disorders
Smokers and major dental diseases should exhibit care
As they bind calcium, absorption is therefore reduced with calcium salts (including milk) as well as antacids and iron salts
What type of infections do aminoglycosides treat? e.g gentamicin, tobramycin, amikacin, neomycin.
What is their MAO AND THEIR MAIN SE
Used to treat severe infections especially gram-ve aerobes (e.g pseudomonas aeruginosa)
1. Severe sepsis including when the source is not known
2. Pyelonephritis and complicated UTI
3. Biliary and other intraabdominal sepsis
4. Endocarditis
Topical (e.g neomycin) for:
Bacterial skin, eye or external ear infections
WORK VIA THE 30S subunit- enter via aerobic (therefore do not work against streptococci and anaerobes)
Main SE: nephrotoxicity (potentially reversible - rising creatinine and urea) and ototoxicty (often the later is not noted until resolution of acute infection)
Gentamicin is only given IV monitor plasma [] and adjust to prevent damage
CI: in neonates, elderly and those with renal impairment
Not been given with MGravis due to NM transmission effect
MONITOR RENAL FUNCTION
What drugs increase the likihood of otoxocity with amino-glycosides?
Loop diuretics and vancomycin
What drugs increase the likihood of nephrotoxocity with amino-glycosides?
ciclosporin, platinum chemotherapy, cephalosporins or vancomycin
What antibiotic is associated with the red main syndrome- erythema, less commonly hypotension and bronchospasm?
Vancomycin (gram +Ve- staph aureus)- peptidyloglycan cell walls in gram-ve
Also causes thrombophlebitis
Also causes nephrotoxicity and otoxicity
Increased with amino-glycosides
Is benzylpenicillin pencillase (B lactamase) sensitive or resistance? and how is it given?
Sensitive
Administered by injection (IV or IM) only, as hydrolysis by gastric acid prevents GI absorption. It is prescribed for the treatment of severe infections
What is co-amoxiclav combined with
Amoxicillin plus clavulanic acid (augmentin)
How does metronidazole work? What major SE does it cause?
Enters bacterial cells by passive diffusion. In anaerobic bacteria- reduction of metronidazole generates a nitroso free radical. This binds to DNA- reduce the synthesis and causes widespread damage. DNA degradation and cell death (bactericidal)
AB associated colitis, oral infections or aspiration pneumonia, surgical and gynae infections (Gram-ve anaerobic from colon), protozoal infections e.g trichomonas vaginal, giardias, amoebic dysentery)
NEUROLOGICAL AE: peripheral and optic neuropathy, seizures, encephalopathy
Hypersensitivity and GI upset
Metabolised by P450 inhibitor acetaldehyde dehydrogenase- causes disulriam like reaction- headache, flushing, N/ do not drink for more than 48 hrs during or after treatment
What kinds of drugs are Tetracycline, oxytetracycline, doxycycline, minocycline, demeclocycline, chlortetracycline, lymecycline
Tetracycline drugs- which bind to 30S ribosome- are bacteriostatic
1. Acne vulgaris- esp in inflamed papules, pustules and/or cysts (Propionibacterium acnes)
2. Lower respiratory tract infections e.g infective exacerbation of COPD (e.g haemophilus influenzas), pneumonia and atypical pneumonia (mycoplasma, chlamydia psittaci, Coxiella burnettii or Q fever)
3. Cylamida infection including PID
4. Other infections e.g typhoid, anthrax, malaria, and lyme disease (borrelia burgdorferi)
• Intracellular organisms:
• Chlamydiae (non specific urethritis, psittacosis, trachoma)
• Rickettsiae (e.g Q fever)
• Brucellae (with streptomycin or rifampicin)
• Spirochaetes
Uses
• Tetracyclines used for acne
• Demeclocycline used to treat SIADH
Doxycycline is used vs. prophylaxis against malaria
What kind of drugs are Ciprofloxacin Moxifloxacin Levofloxacin What is their MOA
What drugs increase their risk of AE
Quinolones
Broad spectrum of activity, esp against gram-ve. Bactericidal
Ciprofloxacin- unusual as has significant activity against pseudomonas aeruginosa
Newer quinolones Moxifloxacin and Levofloxacin-enhanced activity against gram +
They inhibit DNA synthesis but reserved for 2nd or 3rd line due to resistance and C.difficle
- UTI (mostly gram-ve)
- Severe gastroenteritis (e.g due to shigella, campylobacter)
- LRT (gram positive and gram negative- therefore moxifloxacin or levofloxacin preferred
SE: GI upset, hypersensitivity, lower seizure threshold, hallucination, inflammation and rupture of muscle tendons, prolong QT and increase arrthymia. Broad spectrum therefore associated with c.diff with cephalosporins
AVOID: increase risk of seizures, children and young adults at risk of arthropathy, RF for QT prolongation, drugs with divalent cations (e.g calcium and antiacids) reduce absorption and efficacy, inhibits certain P450 enzymes, NSAIDS increase seizures, prednisolone increase risk of tendon rupture
What effect does demeclocycline have in patients with SIADH
a tetracycline notable for ability to increase sodium [] in patients with SIADH by blocking binding of ADH to receptor
What SE and CI does tetracylcines have?
• N/V and diarrhoea but they have a lower risk of C.diff than other broad spectrum AB
• Hypersensitivity occurs in 1%
• No cross reactivity with penicillins or other B lactam antibiotics
• Can cause oesophageal irritation they should be taken with water - includes ulceration, irritation, dysphagia
• Photosensitivity (increased sunburn reaction with light)
• Discoloured and/or hypoplasia of tooth enamel
Serious: hepatotoxicity and intra cranial hypertension (headaches and visual disruption)
Avoid in pregnancy, breastfeeding children <12 caution in renal impairment, bind to divalent cations, enhance anticoagulant effect by killing normal bacteria
How should patients be advised to take tetracylcines
swallowed whole with plenty of water when sitting or standing to stop them getting stuck - avoid indigestion and medications with iron or zinc 2hrs before and after taking antibiotic (bind to divalent cations and they cause oesophageal irritation, ulcer, dysphagia)
Should protect skin from sunlight (can cause photosensitivity)
What drug used in angina can cause tolerance- how do you prevent this
TOLERANCE (tachyphylaxis) can occur with prolonged use of nitrates- this can reduce efficacy
• Prevent this, time doses to ensure there is a nitrate free period every day during a time of inactivity, usually overnight
• For example, patients should take x2 a day isosorbide mononitrate morning and mid-afternoon to ensure >12 hrs between pm and am dose
Transdermal patches applied in morning and removed at bed time
How do nitrates work? What are their common SE?
• Nitrates are converted to nitric oxide (NO) increases guanosine monophosphate (cGMP) synthesis and reduces intracellular Ca2+ vascular smooth muscle cells, causing them to relax- results in venous and to lesser extend arterial vasodilation
• Relaxation of the venous capacitance vessels- reduces cardiac preload and left ventricular filling- reduces cardiac work and myocardial oxygen demand, relieving angina and cardiac failure
• Nitrates can relieve coronary vasospasm and dilate collateral vessels, improve coronary perfusion
• Relax systemic arteries, reducing peripheral resistance and afterload
However most of the anti anginal affects are mediated by a reduction of the preload
cause hypotension, lightheadness, flushing, headaches and tolerance
Avoid in hypovolaemia- haemodynamic instability, hypotension
Severe aortic stenosis and CVD such as hypertrophic cardiomyopathy
Avoid with drugs that also lower BP e.g sildenafil or similar
What is the mechanism of aspirin?
Thrombotic events: when platelet rich thrombus forms in atheromatous arteries and occludes circulation
Aspirin: irreversibly inhibits COX- to reduce pro aggregatory factor thromboxane from arachidonic acid- reduces platelet aggregation and risk of arterial occlusion
Occurs at low doses and lasts the lifetime of platelets
What SE do aspirin cause?
GI irritation- peptic ulcer and haemorrhage
Hypersensitivity - bronchospasm
High doses- tinnitus
Life-threatening in overdose: hyperventilation, hearing changes, metabolic acidosis, confusion, followed by convulsions, CV collapse, respiratory arrest
When is aspirin CI or caution needed?
Children <16- Reye syndrome- affects the brain and liver
Third trimester in pregnancy- premature closure of ductus arteriosus
Those with hypersensitivity to aspirin and NSAIDS
Caution: peptic ulcer disease (give gastroprotection, and gout (may trigger an acute attack)
Caution with other anticoagulants and anti platelet drugs
What CI and SE are ADP receptor anti platelet drugs
Bleeding esp after GI, intracranial or surgical procedure
GI upset- dyspepsia, pain, diarrhoea
Can affect platelet #= thrombocytopenia
CI:
Not with active bleeding
Stopped 7 days before elective surgery and other procedures unless risk of stopping > risk of continuing
Caution with renal and hepatic impairment, especially where patients otherwise have increased risk of bleeding
Product- need CYP enzymes to active form to have anti platelet effect
Therefore reduced effect with CYP inhibitors- omeprazole, ciprofloxacin, erythromycin, some antifungals and SSRIS
When need PPI- better to use others lansoprazole or pantoprazole than omeprazole
Prasugrel is also pro drug but less susceptible to interactions
Ticagrelor is not pro drug and interacts with CYP inhibitors- increases risk of toxicity, and induces (which may reduce efficacy)
Co prescription with other anti platelet drugs, anti coagulations e.g heparin, or NSAID increase bleeding risk
What is Ivabradine, used for, SE, and CI
Used as option for third line in angina
In mild to severe chronic heart failure
Reduces HR with minimal impact on BP by acting on the sinus node -heart-rate-lowering agent that acts by selectively and specifically inhibiting the cardiac pacemaker current (If), a mixed sodium-potassium inward current that controls the spontaneous diastolic depolarization in the sinoatrial (SA) node and hence regulates the heart rate
SE
Arrythmia, atrioventricular block, dizziness, headaches, hypertension, vision disorders
CI:
Must be in sinus rhythm - CI if heart rate <70 in angina or 75 in hear failure, heart block or acute MI, or unstable angina, shock, unstable or acute heart failure
What is ranolazine, used for, SE, and CI
Third line in angina
Affect sodium dependent calcium channels- increases coronary flow
Asthenia, constipation, headache, vomiting
Weight <60kg, elderly, moderate- sever congestive heart failure, QT interval prolongation , renal/liver failure
What is Nicorandil, used for, SE, and CI (remember the anaemic guy in AMU was on this! will help with SE)
Third line in angina
K+ channel activator- laterals the vessels also acts like nitrates
Asthenia, dizziness, haemorrhage, nausea, vasodilation, vomiting
But Headache common usually transitory
LVF, hypotension, acute pulmonary odema, hypovolaemia, shock
What are some examples of low potency steroids
hydrocortisone, desonide
What are some examples of mid potency steroids
fluticasone, triamcinolone, fluocinolone.
What are some examples of high potency steroids
mometasone, betamethasone, desoximetasone
What are some examples of v. high potency steroids
clobetasol, ulobetasol, diflorasone
What are some SE of steroids
Atrophy of the skin, hyperpigmentation, straie, telangiectasia, and low response after increased use (tachyphylaxis)
How does azathioprine work and what do you need to check before? What do you need to check after? what are the SI and CI
- Maintenance of crohns and UC in remission
- Disease modifying in rheumatoid arthritis and autoimmune conditions which are not responding to corticosteroids or other standard treatment
- To prevent organ rejection in transplant patient
Prodrug therefore not on it own pharmacologically active but on metabolism converts to substances that are
Main metabolite: 6 mercaptopurine which is further metabolised to active substances
Inhibit synthesis of purines (nucleosides adenine and guanine) therefore inhibit DNA and RBA
Most cells can salvage or recycle purines but lymphocytes are dependent on purine syntheses therefore particularly affected
Metabolism and elimination involves xanthine oxidase and thiopurine methyltransferase (TPMT)- this is reduced in some
MOST SERIOUS: bone marrow suppression - significantly in leukopenia and increased risk of infection (reduced dose or break may needed)
Nausea
Hypersensitivity reaction: diarrhoea, vomiting, rash, fever, myalgia, hypotension and pancreatitis may occur
Others: veno-occlusive disease, hepatotoxicity, lymphomas
TMPT phenotyping should be done before and not prescribed for patients with absent TPMT
Those with reduced levels- should be treated by specialist
Hypersensitivity reactions stop drug
Reduce in hepatic and renal
Not iniatited in pregnancy but may continue if benefits>risks
Risk of infection increased with other immunosuppressants e.g steroids - but may be unavoidable
Not prescribed with xathine oxidase inhibitors such as allopurinol as they reduce its metabolism
Increased risk of leukopenia with myelosuppressive or drugs affecting purine synthesis like trimethoprim
Also may reduce the effect of warfarin
Only really given with specialised
May be high dose for remission, lower for maintenance
Warn to seek urgent advice if: sore throat, fever (infection) bruising, bleeding (low platelet count)or rash, diarrhoea, vomiting, or abdominal pain (hypersensitivity)
TMPT phenotyping should be done before and not prescribed for patients with absent TPMT
Those with reduced levels- should be treated by specialist
Hypersensitivity reactions stop drug
Reduce in hepatic and renal
Not iniatited in pregnancy but may continue if benefits>risks
Risk of infection increased with other immunosuppressants e.g steroids - but may be unavoidable
Not prescribed with xathine oxidase inhibitors such as allopurinol as they reduce its metabolism
Increased risk of leukopenia with myelosuppressive or drugs affecting purine synthesis like trimethoprim
Also may reduce the effect of warfarin
Only really given with specialised
May be high dose for remission, lower for maintenance
Warn to seek urgent advice if: sore throat, fever (infection) bruising, bleeding (low platelet count)or rash, diarrhoea, vomiting, or abdominal pain (hypersensitivity)
Full blood count in the first 4 weeks weekly or after changing dose, and 3 monthly thereafter
What is Teriparatide
Recombinant human parathyroid hormone peptide 1-34 (teriparatide)
Anabolic agent that stimulates bone formation
• Teriparatide reduces vertebral and non-vertebral fractures in post menopausal women with established osteoporosis, although data on hip fracture not available
Recombinant human parathyroid hormone peptide 1-34 (teriparatide)
What Strontium ranelate
- Dual action bone agent- increases deposition of new bone by osteoblasts and reduces osteoclast
- Two stable strontium atoms linked to organic acid ranelic acid
- MOA is uncertain but weak anti resorptive activity while maintaining bone formation
- Reduces risk of vertebral, hip and other non-vertebral fractures in post menopausal woman
However • Nausea, diarrhea and headaches • Small increase in VTE • CVD concerns • Recent safety issues therefore not recommended unless any other treatments Stevens Johnson
What is Denosumab
• Monoclonal antibody to RANKL
• Anti resorptive agent increases bone mineral density and reduces fractures at spine, hip and other non-vertebral sites
• Fracture risk reduction similar to bisphosphonates
However-Due to RANKL having a role in the immune system, denosumab also increases exacerbations of eczema and small increase in severe cellulitis
What is Raloxifene
• Selective oestrogen receptor modulator
• No stimulatory effect in the endometrium but activates oestrogen receptors in the bone
• Prevents BMD loss at spine and hip in post menopausal woman, thought fractures rates only reduced in spine
Also reduces incidence of oestrogen receptor positive breast carcinoma in woman treated for up to 4 years
However, • Prevent bone loss and reduces the risk of veretbral fractures but not yet shown to reduce the risk of non vertebral
• Leg cramps and flushing may occur
• Risk of VTE complications are increased to a degree similar to seen with HRT
• Use associated with a small increase in stroke
Increase menopausal symptoms
What kind of drug is Metoclopramide, domperidone, what are they mainly used for? What SE does metoclopramide have that domperidone doesn’t
Antiemetics Dopamine D2 receptor antagonists
Prophylaxis and treatment of N/V in a wide range of conditions but particularly in the context of reduced gut motility
They act in 2 areas:
- D2 main receptor in the chemotrigger zone
-Act in the gut and promotes relaxation of stomach, lower oesophageal spincter and inhibtis the gastroduodenal []
Metoclopramide acts in the BBB- therefore extrapyramidal SE- ocluogyric crisis- acute dystonic reaction while domperidone does not cross the BBB
This effect is more common in children and young adults
What kind of drug is Cyclizine, cinnarizine, promethazine ? What are they mainly used for? SE/CI?
Anti emetics
Histamine H1 receptor antagonist
Prophylaxis and treatment of N/V in a wide range of conditions but particularly in motion sickness or vertigo
Block the histamine H1 and acetylcholine receptors- most useful for N/V of many conditions but especially vertigo or motion
Drowsiness is the most common SE but cyclizine is least sedating
May give anticholinergic effects: dry throat and mouth, excitation or depression
AVOID: in BPH and other sedating drugs and also hepatic encephalopathy
What are some DMARBS
DMARCS:
Methotrexate, Sulphasalazine, Leflunomide, (Hydroxychloroquine),(Cyclosporine)
Older DMARDsGold,Penicillamine,Azathioprine (Cyclophosphamide)
What is the MOA of methotrexate, SE, and CI
Methotrexate:
Folic acid antagonist
Weekly folic acid supplements are co-prescribed
MONITOR FBC/LFTS Side effects - mucosal damage- ulcers - bone marrow suppression - liver cirrhosis (LFT) - pneumonitis -CXR before -Tetratogenic -Can increase RA nodule numbers
Contraindications
- pregnancy- should wait at least 6 months after treatment stop, men should use contraception for at least 6 months after
- renal impairment
- abnormal liver function (as hepatotoxic)
Drug interactions
-NSAIDs,penicillin, folate agonists,
• avoid prescribingtrimethoprimorco-trimoxazoleconcurrently - increases risk of marrow aplasia
• high-doseaspirinincreases the risk of methotrexate toxicity secondary to reduced excretion
what is the MOA of hydroxychloroquine and SE
Hydroxychloroquine
Inhibition of phospholipase A2
Increasing the lysosomal pH in APC
Blocks toll like receptors
LEAST TOXIC DMARD
Side effects
Retinopathy, corneal deposits, myopathy
What is the MOA of sulsalazine and SE
Unknown MOA
Side effects
Oligospermia, rash, bone marrow suppression (leucopenia, thrombocytopenia), nausea and vomiting
What is the MOA of leflunomide and SE?
Pyrimidine synthesis inhibitor- inhibits cell division
Rash, diarrhoea, bone marrow suppression, hepatotoxic and teratogenic
What kind of drugs are these. what SE and CI do they have?
Etanercept, infliximab, adalimumab, certolizumab pegol, golimumab
TNF-a inhibitors
Side effects:
Infections severe to minor, reactivation of TB, Hep B/C , worsening cardiac failure, hepatotoxicity, possible maligancies (skin), haematologic events, neurological events, lupus like symptoms
CI:current/previous neoplasm & infections and congestive heart failure
What is Abatacept?
It is a selective co-stimulator modulator which inhibits T cell activation blockings its interaction with CD80/CD86
What is sarilumab?
works vs. IL-6 R
What are Tofacitinib and Baricitinib:
interferes with the JAK-STAT signaling pathway, which transmits extracellular information into the cell nucleus, influencing DNA transcription.
What are Rituximab and what SE?
B cell depletion (CD20 inhibitor)
Side effects
Severe mucocutaenous reactions, infections, Hep B reactivation
What drugs do you give in pregnancy for RA
Paracetamol is the analgesic of choice
- Oral NSAID and selective COX2-after implantation up until last trimester if symptoms justify their use
- Cortosteroidscan be used but main maternal risk- hypertension, glucose intolerance, osteoporosis
- DMARDS:DO NOT USE METHOTREXATE, LEFLUNOMIDE, CYCOPHOSPHAMIDE, GOLD AND PANCILLAMINE
- Cytokinemodulators not clear
What is phytomenadion
It is vitamin K given to reverse Warfarin- also can give prothrombin complex
What is the deal with digoxin?
- In AF and atrial flutter- used to reduce the ventricular rate. However BB or non-dihydropyridine CCB is usually more effective - however as it relies on PNS tone it tends to be loss in stress or exercise therefore only really used in sedentary patients
- Severe heart failure- option when already taking ACI, BB, and either aldosterone antagonist or angiotensin blocker. Used earlier in patients with co-existing AF
Negatively chronotropic (reduces HR) Positively inotropic (increases force of contraction)
In AF/atrial flutter: indirect pathway involving increased PNS tone, reduces conduction at the AVN preventing impulses being transmitted to ventricles- reducing ventricular rate
In heart failure: direct effect on myocytes --] Na+/K+ ATPase pumps, causing Na+ to accumulate, this causes Ca2+ to accumulate, increasing contractile force AE: Bradycardia Gi disturbance Rash Dizziness Visual disturbance Range of arrythmias can occur in digoxin toxicity- narrow therapeutic index CI: Worsen conduction problems therefore • Second degree heart block • Intermittent complete heart block • Ventricular arrythmias or those at risk Reduced in renal failure
Certain electrolyte problems increase risk: hypokalaemia, hypomagnesaemia, hypercalcaemia
Hypokalaemia is the most important as digoxin competes with potassium to bind to the Na+/K+ ATPase pump, when levels are low then effects are reduced
Loop and thiazide cause hypokalaemia increase risk
Amiodarone, CCB, spironolactone, quinin all increase plasma [] therefore increase risk of toxicity
Other:
Oral - 2hrs for effect and IV in 30 mins By either a loading dose is needed.
Check symptoms and HR
Check ECG, electrolytes, renal function
Therapeutic doses can cause ST segment depression- reverse tick sign
What are some SE of aldosterone antagonists and some CI?
- Ascites/oedema due to liver cirrhosis-spironolactone 1st line diuretic, increase aldosterone in these conditions
- CHF of at least moderate severity or arising 1 month after MI usually with BB or ACE/ARB
- Primary hyper aldosterone (conn syndrome ) for patients waiting for surgery or who surgery not appropriate
Aldosterone is produced from the adrenal cortex (zona glomerulosa) mineralocorticoid acts on mineralocorticoid R in distal tubule, increases ENAC activity, increases Na+/water reabsorption, K+ excretion. But antagonist competitively inhibit increased Na+ excretion, increases K+ retention
Hyperkalaemia Gynaecomastica Impotence Liver impairments Steven Johnson syndrome
Hyperkalaemia, addison’s (deficient in aldosterone), renal impairment severe, and avoid in pregnancy and breastfeeding
- Monitor with K+ elevating drugs e.g ACEi and ARBs
And also supplements
NOTE THAT ONLY EPLERENONE is used for heart failure
Monitor with renal function and serum potassium []
Note that they are week diuretics therefore combinations are used
What are some SE, CI, and notes about statins (what drugs increase SE)
- Generally safe and well tolerated
- Headaches , Gi disturbances (nausea, cramps)
- MUSCLE DAMAGE- myopathy or rarely rhabdomyolysis
- Rise in liver enzymes
- Drug induced hepatitis is rare but serious affect
CI:
• Use in caution in hepatic impairment/renal
• Not used in pregnancy- cholesterol is needed for development or breastfeeding
• Decrease metabolism by CYP450 inhibitors e.g amiodarone, diltiazem etc, increases amount in body, therefore SE increases, avoid grapefruit juice
• Myopathy is increased when these drugs are given with fibrates, or ciclosporin avoid unless + >-
Taken orally enters systemic circulation through intestinal cells both passive/active
Major metabolism/elimination through liver vs. kidney
Can cause an increase in liver enzymes (alanine transaminase) therefore check liver tests
Check bloods in 3 months and 12
Alcohol at minimum (rise in ALT up to x3 the upper limit may be acceptable but above this should be stopped)
Check thyroid function- as hypothyroidism may cause hyperlipidaemia and is treatable also increases risk of myositis
Note on for life as stopping increases cholesterol
Taken in evening
Check cholesterol levels for target- for efficacy
Ask patient to report muscle symptoms - weakness or pain
What is Amiloride
K+sparing diuretic work on ENAC in distal convulting part of the kidney (same as aldosterone inhibitors) used to treat hypokalaemia of other diuretics- weak diuretic in own right
What is Bupropion (Zyban)?
Smoking cessation medication
Free on prescription
· Anti depressant- reduces withdrawal cravings
· One of two non- nicotine licensed products
· This is started 1-2 weeks before quite
· Similarly effect to NRT (e.g 9% extra quit)
· Only tested with behavioural support
· CI: epliepsy or increase risk of seizures, eating disorder or bipolar
What is Varenicline (champix)?
· Varenicline tartrate: nicotine receptor partial agonist
· Maintains dopamine levels to counteract the withdrawal
· Start taking 1-2 weeks before you quit
· Reduces the smoking satisfaction
· Similar effect on abstinence as NRT and bupropion i.e 9% extra quit
Caution with psychiatric illness
Salbutamol. Salmeterol, formoterol, terbutaline- uses, MOA, SE, CI
B2 agonists
- Asthma- short acting for breathlessness. Long acting as step 3 with inhaled corticosteroids
- COPD-short acting and long acting
- Hyperkalaemia: nebuliser salbutamol used with insulin, glucose, calcium gluconate for increase K+ into the cells
B adrenergic receptors within the lung SM, dilates and open up airway via Gas- adenyl cyclase to CAMP with ATP, reduce Ca2+ and activate protein kinase A- inactive myosin light chain, also activates the Na+/K+ ATPase- therefore hyperpolarization the cells as K+ moves in- leads to smooth muscle relaxation
However their effects are less reliable than other therapies so not used in isolation
Fight or flight: tachycardia, palpitations, anxiety, tremor
Increase glycogenolysis, increase serum glucose
At high levels lactate may cause muscle cramps- long acting
Care with CVD as tachycardia- angina
Note in asthma- long acting B2 agonists should only be used with ICS
BB may reduce the effectiveness
Concomitate use of high dose nebulised B2 agonists with theophylline and corticosteroids may lead to hypokalaemia
Inhaled however suits patient e.g aerosol or drug powder,
Spacer- may increase airway deposition and treatment efficacy
Short acting- as needed
Long acting- maintenance, x2 regularly may be with steroid in the inhaler
When in hospitalized- nebulized is more often used- note whether to use with air or oxygen (air usually for asthma, and air for COPD due to CO2 retention
- spacer may be used provided not life-threatening
May have combination with steroid
What are some short acting B2 agonists
salbutamol, terbutaline
