PA30325 3. Pharmacology Flashcards
Whata re the 5 key functions of the kidney?
- Hydroxylation Vitamin D
- Excretion waste products
- Control blood pressure
- Excretion of salt and water
- RBC production
What is ‘Think Kidneys’ ?
- national programme set up with the aim of preventing the avoidable harm caused by acute kidney disease
- review and, if appropriate, revise prescribing and local policies that relate to assessing the risk of acute kidney injury to ensure these are in line with the NICE guideline on the AKI
- review and, if appropriate, revise prescribing and local policies that relate to preventing, identifying and managing AKI, to ensure these are in line with the NICE guideline
How does NSAIDs / COX II inhibitors effect renal/fluid/electrolyte physiology?
- Altered haemodynamics within the kidney leading to underperfusion and reduced glomerular filtration
What are the change in side-effects of the following drugs when renal function is reduced?
- Opioid analgesics
- Tramadol
- Benzodiazepiens
- Aciclovir
Opioid analgesics
- accumulation of active metabolites
- increased incidence of CNS side effects & respiratory depression
Tramadol
- may accumulate leading to increased sedation, mental confusion and respiratory depression
Benzodiapezines
- accumulation of drug & active metabolites leading to increased sedation & mental confusion
Aciclovir
- accumulation leading to mental confusion, seizures
What is AKI?
- Acute Kidney Injury (AKI) is a sudden reduction in kidney function over hours to days
- It is not a physical injury to the kidney and usually occurs without symptoms, making it difficult to identify
- Not a disease itself: result of underlying pathology
- diagnosed by blood test only
- Late diagnosis can miss opportunities for early treatment, leading to prolonged and complex treatment and reducing the chances of recovery
What is Chronic Kidney Disease?
- abnormality of kidney function and structure that is present for more than 3 months
- in CKD, the kidney gradually loss function over a longer period of time compared to AKI
- Can get AKI on background of CKD
- AKI can lead to CKD
Describe 3 different stages of AKI
RISE in Creatinine, REDUCTION in Urine Output
Stage 1
- Serum Creatinine 1.5-1.9 times baseline or >26.5 micromol/L increase
- Urine Output <0.5ml/kg/h for 6-12hrs
Stage 2
- Serum Creatinine 2.0-2.9 times baseline
- Urine Output <0.5ml/kg/h for >12hrs
Stage 3
- Serum Creatinine 3.0 times baseline OR increase serum cretainine to >353.6 micromol/L OR initiation of RRT OR in patients <18yrs, decrease in eGFR to <35ml/min/1.73m2
- Urine Output <0.3ml/kg/h for >24hrs or Anuria for >12hrs
What are the causes of AKI?
Pre-renal
- volume depletion (dehydration, bleeding)
- sepsis
- cardiogenic (shock)
Intrinsic
- prolonged pre-renal insult causing tubular necrosis
- inflammation/glomerulonephritis
- drugs
Post-renal - Outflow obstruction \: Bladder \: Prostate \: Ureter
Describe AKI management
- Treat precipitating insult
- Stop nephrotoxic medication
: ACEi/ARB
: NSAID
: Aminoglycosides - Maintain euvolaemia (normal body fluid volume)
- Treat electrolyte abnormalities
- RRT if needed
How do NSAIDs, ACEi and ARB cause AKI?
- NSAIDs inhibit prostaglandin synthesis
- ACEi and ARB cause vasodilation of the efferent blood vessels
What are the roles of Pharmacist in AKI?
- preventing AKI
: education/risk assessment - recognising AKI
- identify possible drug causes
- stop nephrotoxic drugs
- review drugs that may worsen biochemistry e.g hyperkalaemia
- review doses of other medication that may accumulate
- review doses/restart medicines when renal function improves
What is CKD?
- Chronic Kidney Disease is a progressive and irreversible condition
: defined as an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73m2 and/or kidney damage present for at least 3 months - The physiological changes that occur in CKD result in subsequent alteration of PK and PD of many drugs
- Hence, for medications and/or active metabolites that depend on the renal system for their excretion, dosage adjustment is necessary to prevent their accumulation that may eventually lead to toxicity
- Likewise, medications may also be contraindicated in patients with CKD due to the increased risk of adverse effects
Describe Glomerular filtration rate
- Volume of fluid filtered from glomerular capillaries to Bowman’s capsule per unit time
- GFR = urine concentration x flow / plasma concentration
- GFR = clearance rate of a solute
: free filtered
: not secreted or reabsorbed
How is renal filtration measured?
- waste product from muscle
- generated at a relatively constant rate in an individual
- largely removed by filtration alone
- standarised lab measurement
but. .
- significantly affected by age, race, weight
- non-linear relationship with true GFR
Describe Estimated creatine clearance (eCrCl)
- multiple formulae
- most common is Cockroft-Gault
eCrCl = (140-age) x Weight (kg) x Constant / Serum Cretainine (micromol/L)
- constant male = 1.23 / female = 1.04
Describe different stages of CKD
GFR = ml/min/1.73m2
Stage 1
- GFR >90
- normal or increased glomerular filtration rate with other evidence of kidney damage
Stage 2
- GFR 60-89
- slight decrease in GFR, with other evidence of kidney damage
Stage 3A
- GFR 45-59
- moderate decrease in GFR with or without other evidence of kidney damage
Stage 3B
- GFR 30-44
- moderate decrease in GFR with or without other evidence of kidney damage
Stage 4
- GFR 15-29
- Severe decrease in GFR, with or without other evidence of kidney damdage
Stage 5
- GFR <15
- established renal failure
What are the causes of CKD?
- Diabetes
- Hypertension
- Glomerulonephritis
- Reflux nephropathy
- Polycystic disease
- Previous acute kidney injury
- many others, including nephrotoxicity
What are the signs and symptoms of CKD?
- increased BP
- Shortness of Breath
- Kidney size and shape
- altered Urine output
- Blood / protein in urine
- itching & cramps
- cognitive function
- GI symptoms
- peripheral oedema
What are the complications of CKD?
- Electrolyte imbalance
- renal bone disease
- hyperetnsion
- anaemia
- oedema
- hyperphosphataemia
- itching
- nausea
- resless legs/cramps
How is CKD managed?
- management of complications
- proteinuria reduction
- salt free diet
- preparation for renal replacement therapy (RRT)
Describe renal anaemia
Reduction in red cell production
- low EPO (epoetin)
- functional iron deficiency
Increased red cell turnover
- Uraemia
Treatment
- EPO replacement
- iron replacement
Describe Erythropoiesis Stimulating Agents (ESA) and Hb targets in CKD to treat anaemia
- Initially aimed to normalise Hb
- Erythropoiesis stimulating agent (ESA) medicines are man-made versions of erythropoietin, which is a hormone (chemical messenger) produced naturally by the kidneys. The role of erythropoietin is to stimulate the bone marrow to produce more red blood cells
- try to avoid blood transfusion
- erythropoiesis stimulating agents and iron
- aim to maintain Hb between 10-12g/dL
Describe Renal bone disease
- Reduction in Vit D hydroxylation
- impaired gut absorption - Hypocalcaemia
- may cause tingling, cramps etc - Parathyroid stimulation
- increased sPTH - Calcium release from bones
- poor mineralisation, phosphate release
How is Mineral Bone disease treated?
- Alfacalidol: post-renal vitamin D
- Dietary phosphate restriction
- Phosphate binders
- Aim to balance serum Ca, PO4 and PTH
Describe the changes in Absorption in CKD patients
- reduced compliance due to uremic symptoms and polypharmacy
- gastric oedema
- phosphate binders
: bind drugs e.g quinolone antibiotics, levothyroxine - PPI and H2 receptor antagonists reduce gastric acidity
Describe the changes in Distribution in CKD patients
- low albumin reduces the amount of protein binding
- uraemia causes displacement from protein binding sites
- increased free drug
: phenytoin, diazepam, digoxin, sodium valproate, warfarin - therapeutic drug monitoring often required for drugs with a marrow therapeutic window
Describe the changes in Excretion in CKD patients
- Significant for drugs which are >25% excreted unchanged in the urine
- Remember metabolites
- drugs with a narrow therapeutic index
Ideal drugs in CKD?
- less than 25% excreted in the urine
- no active metabolites
- disposition unaffected by fluid balance changes
- disposition unaffected by protein binding
- disposition unaffected by tissue sensitivity
- wide therapeutic index
- not nephrotoxic
Backgrounds of CKD (JUST READ)
- Chronic kidney disease is common affecting 1 in 10 adults in UK
- CKD stage 5 is rare and often preventable
- Diabetic nephropathy is the most frequently documented primary diagnosis in patients starting RRT aged 35 years and over
- Other causes of CKD include glomerulonephritis, pyelonephritis, hypertension and renal vascular disease
-
What are the risk factors of CKD progression?
- Cardiovascular disease
- Proteinuria
- Acute Kidney Injury
- Hypertension
- Diabetes
- Smoking
- African, African-Caribbean or Asian family origin
- Chronic use of NSAIDs
- Untreated urinary outflow tract obstruction
What are the indications for starting Renal Replacement in CKD?
- symptoms of uraemia having impact on daily living
- biochemical measures e.g hyperkalaemia/acidosis
- uncontrollable fluid overload
- estimated glomerular filtration rate (eGFR) of around 5 to 7 ml/min/1.73m2 if there are no symptoms
Describe intermittent Haemodialysis
- requires access
: Arteriovenous fistula, Line, Graft - can be done at home or in hospital
- usually 4 hrs 3 x per week
Describe Haemodialysis
- Transfer of uraemic solutes from blood by across semi-permeable membrane
- Solute clearance
- Water removal
- Bicarbonate addition
Describe Peritoneal dialysis
- Performed at home
: continuous ambulatory, automated, assisted - Access to peritoneal cavity
: Tenckhoff catheter
What are the challenges of dialysis?
- fluid restriction
- restriction of salt intake
- restriction of potassium intake
- phosphate binders to reduce GI absorption of PO4
- Travel (for-in-centre haemodialysis)
- restriction in travel within UK
- continued symptoms
- access problems
- infectious problems
What are the important medicines management considerations in Dialysis?
Protein binding
- if patient is uremic, protein binding may be reduced resulting in more free drug available
- significant if drug has narrow therapeutic index and highly protein bound e.g phenytoin
- only free unbound drug can pass through pores for dialysis
- If more than 80% protein bound, consider as not dialysed
- Excretions
What is the role of pharmacists in Dialysis?
- advise on drug dosage and interactions
- ensure medication is given at correct time
: phosphate binders with meal
: consider removal by dialysis - Encourage patients to have annual infleunza vaccine and pneumonia vaccine every 10 years
What are the typical Post-operative considerations?
- Venous thromboembolism (VTE) prophylaxis
- Antibiotic prophylaxis
- Post-operative nausea and vomitting
- Post-operative pain
- Fluid balance and electrolytes, Nutrition
- Medicines management and chronic conditions post-op
What are the risk factors for VTE
- Active cancer/cancer treatment
- age over 60 years
- critical care admission
- dehydration
- known thrombophilias
- obesity
- one or more significant medical comorbidities
- personal history of first-degree relative with a history of VTE
Medical patients
- have had or are expected to have significantly reduced motility for > 3 days
- expected to have ongoing reduced mobility relative to their normal state and have > one listed risk factors
Surgical patient
- total anaesthetic + surgery time >90mins or 60 minutes if pelvis/lower limb surgery
- acute surgical admission with inflammatory or intra-abdominal condition
- expected significant reduction in mobility
> one of the listed risk factors
What are the methods of VTE prophylaxis?
- Actions
- Mechanical
- Pharmacological
Actions
- mobilise as soon as possible
- avoid dehydration
- stop meds which increase risk where possible
Mechanical
- anti-embolism stockings
- intermittent Pneumatic Compression devices (IPC)
- Foot impulse devices
Pharmacological
- Low molecular weight heparin (LMWH)
- Unfractionated heparin
- Rivaroxaban, Dabigatran, Apixaban
- Fondaparinux
What is the VTE prophylaxis regimens for low risk and high risk patients?
Low risk
- Early mobilisation
- Anti-embolism stockings if not contra-indicated
High risk
- LMWH / DOAC
- Intermittent pneumatic compression during surgery
Describe the duration of VTE Prophylaxis treatment
- continue until returns to usual mobility
- extended prophylaxis is needed for some procedures
: fractured neck of femur (hip) 4 - 5 weeks
: abdominal / pelvic cancer surgery 4 weeks
: lower limb plaster cast until out of cast - patient taught how to give and monitoring required if SC LMWH used
What is the consequence of poorly managed pain after surgery?
Increase in…
- length of stay
- VTE risk
- BP and pulse
- anxiety & disturbed sleep
Decrease in…
- recovery
- mobility
- wound healing
What is Epidural?
- injection in the back
- can provide better pain relief than other method
- usually local anaesthetic + opiate
- synergistic action with decreased dose of each = less side effects
- analgesia localised to chest, pelvis, lower limb depending on catheter site
Describe Patient Controlled Analgesia (PCA)
- strong opiate
: fentanyl or morphine - controlled by patient
: reduced waiting time for analgesia / less anxiety / increase in patient experience - Bolus does when button is pressed with 5 min lockout time
- Improves quality of recovery but not suitable for all
Describe post-op nausea and vomitting (PONV)
- affects ~30% patients
- caused by
: anaesthetic agents, opioid agents, bowel surgery, antibiotics, U&E disturbances, bowel obstruction
Risk factors
- females at higher risk, history of motion sickness, previous PONV, non smokers higher risk, opiate use
- Apfel scoring used to assess PONV
How is Post Op Nausea and Vomitting treated?
- Local hospital policy
- Aim to prevent vomitting i.e give before end of surgery
- usually using ondansetron, cyclizine, dexamethasone or prochlorperazine
- number of medications prescribed depends on risk factors identified
- Metoclopramide not very effective for PONV
Describe Surgical Antibiotic Prophylaxis
- the use of antibiotics before, during, or after a diagnostic therapeutic, or surgical procedure to prevent infectious complications
Surgical site infections
- infections of surgical wound or involving the body cavity, bones, joints, meninges or other tissues involved in the operation
- also includes infections associated with implants or prosthetic devices
In simple terms…
Whether to give prophylatic antibiotics
- depends on type of surgery
Duration depends on degree of contamination
- 1 dose for clean-contaminated
- 5-7 days for contaminated
- Longer for ‘treatment’
Which antibiotic depends on likely causative organism
- bowel surgery
- local resitance patterns
- cost-effectiveness
- PK (tissue concentration)
To be effective concentration of antibiotic, in the tissue being operated on must be high enough at the time of incision
- high tissue conc at time of incision, IV route preferred
Describe Nil By Mouth (NBM) Post-op
- following most surgical procedures, patients can eat and drink by lunch/evening
- post GI surgery may be NBM for several days or have impaired absorption
- Regular medicines for underlying disease
: consider alternative routes, essential to be continued?
Describe Electrive Surgical pathway
Planned Procedure
- patient sees GP
- referred to specialist
- diagnosis
- adjunct treatment (e.g chemotherapy)
- decision made for surgery
- patient usually seen at pre-op assessment clinic a few weeks pre-op
- patient sent surgery date
- patient arrives in Admission in the morning
Describe Pre-Operative Assessment
- usually nurse led
- Patient clerked: medical history / HPC
- procedure explained: consent forms signed
- opportunity for questions
- post-operative care and needs on discharge
- ensures patient ready for surgery
- Fit for anaesthesia?
- blood tests: eGFR, Hb, Crossmatch
- weight: important for medication dose
- MRSA screen and eradication
- BP: may need treatment
- Cardiac function: ECG / ECHO
- blood glucose: optimise diabetes management pre-op
- medicaiton history
- prescribing
Why is Meds Reconciliation pre-op needed?
- if not performed, no accurate source of medication to inform prescribing
- potential for critical missed dose
- Pre-op patient is alert, with family/carer, medication is available
- Post-op patient is drowsy, family not available, medication may have been sent home
Describe Nil By Mouth pre-op
- pre-operative fast
: 6 hrs for food, 2 hrs clear fluids - risk aspiration of stomach contents during general anaesthetics
- general rule
: most regular medication should be given on day of surgery with small sips of water
What change is needed to Warfarin pre-op?
- long half-life
: stop 5 days pre-op - INR <1.5 for surgery to proceed
- Emergency surgery
: give Vit K or beriplex - Pre/Post op management depends on indication for anticoagulant and post-op bleed risk
- Consider risk of thrombo-embolism on stopping
- Bridging therapy
Describe Warfarin bridging
- Take last dose of warfarin 6 days before surgery
- start LMWH at 8am 2 days after stopping warfarin
- Do not give LMWH on the morning of surgery and stop unfractionated heparin 6 hrs before surgery
Describe Post-op management of Warfarin
- Usually restart Warfarin ASAP post-op, depending on bleeding risk
- Role of pharmacist intervention to ensure discharge is not delayed due to delay restarting anticoagulants
If patient at LOW/MODERATE risk
- cover with prophylactic dose LMWH until INR therapeutic
If patient at HIGH risk
- cover with treatment dose LMWH (or IV heparin infusion) until INR therapeutic for 2 days
What is the disadvantages of DOAC in surgery?
Side effect
- Bleeding
- GI upset
Lack of optimal reversing agents
New dabigatran reversal agent available but expensive only for immediate surgery
Describe uses of Cardiac medication in Surgery
- surgery can increase heart rate and BP so continue most cardiac medication
- ACEi/ARB and diuretics may be omitted due to risk of hypotension but some Trusts advise to give
- always continue beta-blockers as risk fo rebound tachycardia, arrhythmia
Describe the uses of Long term Steroids in Surgery
- stress of surgery causes plasma adrenocorticotrophic (ACTH) hormone and cortisol levels to rise
- Patients on oral steroids may have pituitary-adrenal suppression and natural stress response impaired which leads to circulatory collapse
- Keep steroid use to a minimum. Can affect wound healing, increase infection risk and delay recovery
How is Diabetes managed Pre-op?
Type 1 / Type 2 no more than one missed meal
Morning surgery
- generally omits all oral hypoglycaemics on morning of surgery
- continue long acting insulin at reduced dose
- halve A.M dose of biphasic insulin or intermediate insulin
- Omit A.M and lunch doses of short /rapid acting insulin
- Close monitoring of blood glucose levels
- Reintroduce usual diabetic regime when oral intake resumed
How is Oral contraceptives managed Pre-op?
- Oestrogen containing contraceptives carry 3 fold increase in VTE risk
- Progesterone only pills no increase in risk
- SPC, BNF, NICE recommend stopping COCP(Combined Oral Contraceptive Pill) 4-6 weeks before major elective surgery, leg surgery or surgery causing prolonged immobility
-
Describe the uses of MAOIs in surgery
Potentially fatal drug interaction
- analgesics
: tramadol increases serotonergic activity leading to CNS toxicity or increased convulsion risk
- Sympathomimetics
: risk of hypertensive crisis
Consult with prescriber of MAOIs before deciding to stop
- reduce down to stop 2 weeks before surgery
- switch to reversible MAOIs
Describe the use of Lithium in surgery
- narrow therapeutic range
- renally excreted
- fluid imbalance can prescipitate toxicity
- preferably stop 1-2 days before major surgery but consult psychiatrist
If continue…
- monitor lithium levels
- monitor fluid balance
- avoid NSAIDs
Describe the uses of anti-convulsants & Parkinson’s medication
- continuation of treatment essential
: ensure taken on morning of surgery - consider alternative routes of administration if NBM or not absorbing post-operatively
What is required from an anaesthetic?
- abolition of sensation
- aboilition of pain
- Triad of General Anesthesia
: unconsciousness
: analgesia
: muscle relaxation - multiple drugs
Describe the 4 stages of anaesthesia
Stage 1: analgesia
- conscious, drowsy, antinociception, amnesia
Stage 2: excitement
- loss of consciousness but delirium, irregular cardiorespiration, apnea, spasticity, gagging, vomitting
Stage 3: anaesthesia
- regular respiration, loss of reflex and muscle tone
Stage 4: medullary paralysis
- depression of cardiorespiration, death