drug mechanisms + side effects + reactions Flashcards
What is a common side-effect of using triptans?
Tightness of throat and chest
What is a side effect of ethambutol?
Optic neuritis
Which drugs may exacerbate myasthenia gravis?
penicillamine
quinidine
procainamide
beta-blockers
lithium
phenytoin
antibiotics: gentamicin, macrolides, quinolones, tetracyclines
Which drugs can cause bilateral vestibular failure?
aminoglycosides (especially gentamicin)
side effects of statins
myopathy - myalgia, myositis, rhabdomyolysis, and asymptomatic raised CK. Risk factors for these adverse effects - female, older age, low BMI, presence of multisystem disease e.g. diabetes.
liver impairment - LFTs to be done at baseline, 3 months, and 12 months. stop if transaminases rise to and persist at 3x upper reference range
statins contraindications
- pregnancy
- macrolides
when to stop beta blockers in heart failure?
HR < 50, second or third degree AV block, shock (‘tick tock, shock, block’)
side effects of ACE inhibitors?
- dry cough (increased bradykinin levels)
- hyperkalaemia
- angioedema
- first dose hypotension
cautions and contraindications for ace inhibitors?
- pregnancy
- breastfeeding
- renovascular stenosis
- aortic stenosis => hypotension
- potassium ≥ 5
when to stop ACE inhibitors in CKD?
potassium ≥ 6
what to do if CHADS-VASc score suggests no need for anticoagulation?
transthoracic echocardiogram for valvular disease - an absolute indication for anticoagulation
adverse effects of furosemide
hypotension
hyponatraemia
hypokalaemia, hypomagnesaemia
hypochloraemic alkalosis
ototoxicity
hypocalcaemia
renal impairment (from dehydration + direct toxic effect)
hyperglycaemia (less common than with thiazides)
gout
[INSERT DRUG] should not be used for tachyarrhythmias where the QRS complex is wide (i.e. broad complex) unless a supraventricular origin has been established beyond reasonable doubt.’
verapamil
how can drug-induced liver disease be categorised?
hepatocellular picture, cholelithiasis picture, cirrhotic picture
hepatocellular picture of drug-induced liver disease
PATH MANS
* Paracetamol, phenytoin * Amiodarone * Tuberculosis drugs - rifampicin, pyrazinamide, isoniazid * Halothane * Methyldopa, MAOIs * Alcohol * Nitrofurantoin * Statins, sodium valproate
Cholelithiasis picture of drug-induced liver disease
- Fibrates
- Anabolic steroids
- Testosterone
- COCP
- Antibiotics (flucloxacillin, co-amoxiclav, erythromycin)
- Phenothiazines (chlorpromazine, prochlorperazine)
- Sulphonylureas
Cirrhosis picture of drug-induced liver disease
methotrexate, methyldopa, amiodarone
draw out toxicity bear
drug causes of hyponatraemia
- diuretics
- but most commonly thiazide and thiazide-like
- loop can cause but more in combination with meds such as ACEi or spironolactone
- SSRIs - especially citalopram
- antipsychotics - haloperidol and phenothiazines
*carbamazepine
- drugs that increase production/potentiate action of ADH
- opiods
- ACEi
- PPIs
- anticonvulsants
- amiodarone
- theophylline
- dopamine antagonists (metoclopramide and domperidone)
- antidiabetics (insulin, chlorpropamide, tolbutamine)
- NSAIDs
- MDMA
-
drug causes of hypokalaemia
- loop or thiazide diuretics
- laxatives
- insulin or glucose administration
- corticosteroids
- beta-agonists
- xanthines
drug causes of hyperkalaemia
- tacrolimus
medicines affecting RAS system
- ACEi
- beta blockers
- NSAIDs
- ARB
- digoxin
- potassium sparing diuretics
side effects of sodium valproate
Teratogenic (harmful in pregnancy)
Liver damage and hepatitis
Hair loss
Tremor
Reduce fertility
Achilles rupture after a course of antibiotic treatment
fluoroquinolone antibiotics e.g. ciprofloxacin
NSAIDs mechanism of action
Inhibit prostaglandins and cause afferent arteriole vasoconstriction
Aminoglycosides: renal damage
Intrinsic - need to monitor drug levels to prevent toxicity associated with medications
Lithium: renal damage
Intrinsic
- preferably absorbed over sodium in PCT => accumulation and nephrotoxicity, may see hyponatraemia
nephrogenic diabetes insipidus as lithium inhibits expression of aquaporin-2 ie kidneys resistant to effect of ADH
ACEi mechanism of action
efferent vasodilation, reducing eGFR
Drug causes of pre-renal damage
- ACEi
- NSAIDs
due to altered renal haemodynamics
Drug causes of intra-renal damage
Acute interstitial nephritis
- penicillins
- anti TB therapy
- sulphadiazine
- cephalosporins
Glomerular damage
- Rifampicin
- Dapson
- penicillins
- isoniazid
Acute tubular necrosis
- amphotericin
- aminoglycosides
Medications that should be reviewed when patient presents with AKI
CANDA
contrast
ACEi
NSAIDs
Diuretics
Aminoglycosides
Key tacrolimus drug interactions
accumulation caused by cytochrome p450 inhibitors
- clarithromycin
- erythromycin
- azole antifungals: fluconazole, itraconazole, voriconazole
- antiretrovirals: ritonavir, nelfinavir, saquinavir
reduced levels caused by cytochrome p450 inducers:
- rifampicin
- rifabutin
- phenytoin
Site of action of diuretics
(COLTs Pee)
Carbonic anhydrase inhibitors - proximal tubule
Osmotic diuretics - thin descending loop of Henle
Loop diuretics - thick ascending limb
Thiazides - distal tubule
Potassium-sparing diuretics - collecting duct
metformin - mechanism? drug type? side effects?
- GI symptoms
○ Pain
○ Nausea
○ Diarrhoea- Lactic acidosis
Secondary to AKI
- Lactic acidosis
SGLT-2 inhibitors - mechanism? side effects?
- Sodium-glucose cotransporter 2 found in proximal tube of kidneys
- Reabsorbs glucose back from urine to blood
- SGLT2 inhibitors => glucose excretion in urine
○ Reduces BP
○ Weight loss
○ Improves heart failure
§ Empagliflozin and dapagliflozin licensed
○ Dapagliflozin licensed for CKD
○ CAN cause hypoglycaemia with insulin or sulfonylureas
Side effects:
· Glycosuria
· Increased urine output and frequency
· Genital and urinary tract infections
· Weight loss
· DKA - only moderately raised glucose
· Lower limb amputations common in patients on canagliflozin
· Fournier’s gangrene
Severe infection of genitals or perineum
Pioglitazone - mechanism? side effects?
· Thiazolidinedione
· Increases insulin sensitivity and decreases liver production of glucose
· Does NOT cause hypoglycaemia
Side effects:
· Weight gain
· Heart failure
· Increased risk of bone fractures
Small increase in risk of bladder cancer
DPP-4 inhibitors - mechanism? example? side effects?
Incretins are hormones produced by the GI tract - secreted in response to large meals and act to reduce blood sugar by:
· Increasing insulin secretion
· Inhibiting glucagon production
· Slowing absorption by GI tract
Main incretin is GLP-1. Incretins are inhibited by enzyme DPP-4.
DPP4 inhibitors block action of DPP-4, increasing incretin activity.
· Do not cause hypoglycaemia!
Side effects:
· Headaches
· Low risk of acute pancreatitis
GLP-1 mimetics - mechanism? example? side effects?
· Imitate action of GLP-1
· Examples: exenatide and liraglutide
· Give subcutaneous. Liraglutide can also be used for weight loss in non-diabetic obese patients
Side effects:
· Reduced appetite
· Weight loss
· GI side effects
○ Discomfort
○ Nausea
Diarrhoea
Starting ACEi in CKD in patients with diabetes vs without
- ACE inhibitors are started in type 2 diabetics with chronic kidney disease when the albumin-to-creatinine ratio (ACR) is above 3 mg/mmol (as opposed to 30 mg/mmol in patients without diabetes).
which diabetic meds cause weight loss and weight gain?
loss:
- metformin
- SGLT-2 inhibitors
- GLP-1 mimetics
weight neutral:
- DPP4 inhibitors
gain:
- pioglitazone
- sulfonylureas
when not to use metformin first line for diabetes? what do you use instead?
if contraindicated ie poor renal function
and no risk of CVD, established CVD or chronic heart failure
- DPP-4 inhibitor or Pioglitazone or Sulfonylurea or even SGLT-2
What is prescribed with isoniazid? Why?
isoniazid causes peripheral neuropathy, and pyridoxine (vitamin B6) is co-prescribed to help prevent this
rifampicin side effect
- red/orange secretions
- cytochrome p450 inducer: can reduce effects of drugs like COCP
Isoniazid
- peripheral neuropathy
- pyridoxine (vitamin b6) co-prescribed
Pyrazinamide
Hyperuricaemia (high uric acid levels) => gout and kidney stones
Ethambutol
- colour blindness
- reduced visual acuity
Which TB drugs associated with hepatotoxicity?
RIP
- rifampicin
- isoniazid
- pyrazinamide
doxycycline side effects
diarrhoea, thrush, photosensitivity, sunburn, skin reactions
antiarrhythmic drugs - mechanism of action
Class I antiarrhythmics work by blocking the voltage-gated sodium channel (e.g. flecainide, propafenone and lidocaine).
Class II antiarrhythmics are beta-blockers (e.g. bisoprolol, metoprolol).
Class III antiarrhythmics are potassium channel blockers (e.g. amiodarone, sotalol). It is worth noting that amiodarone also has some effect on sodium channels, beta-adrenergic receptors and calcium channels.
Class IV antiarrhythmics are calcium channel blockers (e.g. verapamil, diltiazem).
Salt Blocks Koko Cheese
- salt: sodium voltage gated
- blocks: beta blocker
- koko: potassium channel blocker (koko the gorilla, eats bananas)
- cheese: calcium channel blocker
common causes of SIADH
- diuretics
- SSRIs
- antipsychotics
- carbamazepine
MoA and side effects of thiazide & thiazide-like diuretics
inhibiting sodium reabsorption at the beginning of the distal convoluted tubule (DCT) by blocking the thiazide-sensitive Na+-Clˆ’ symporter
- potassium lost as a result of more sodium reaching collecting ducts
- dehydration
- postural hypotension
- hypokalaemia
- hyponatraemia
- hypercalcaemia (and hypocalciuria)
- gout
- impaired glucose tolerance
- erectile dysfunction
EVERYTHING GO DOWN except GC (gout and calcium)
sodium valproate side effects
teratogenic
neural tube defects
maternal use of sodium valproate is associated with a significant risk of neurodevelopmental delay in children
guidance is now clear that sodium valproate should not be used during pregnancy and in women of childbearing age unless clearly necessary. Women of childbearing age should not start treatment without specialist neurological or psychiatric advice.
P450 inhibitor
gastrointestinal: nausea
increased appetite and weight gain
alopecia: regrowth may be curly
ataxia
tremor
hepatotoxicity
pancreatitis
thrombocytopaenia
hyponatraemia
hyperammonemic encephalopathy: L-carnitine may be used as treatment if this develops
medication that should be stopped 1 week before surgery
aspirin
avoid nitrofurantoin if…
eGFR < 45
use within caution for short course with eGFR 30-44
creatinine rise after starting ACEi
<20% rise acceptable
aim with statin therapy?
reduction in non-HDL cholesterol > 40%
chronic open angle glaucoma medicines - mechanism of action + side effects
drug mechanisms of action
metoclopramide, domperidone
phenothiazines
haloperidol
very rare: SSRIs, opioids
nephrotic syndrome commonly associated with HIV
focal segmental glomerulosclerosis
