Pharmacology Flashcards
Bosentan
Used in pulmonary HTN
Mechanism:
- Competitive agonist at ETA (endothelin-A) and ETB (endothelin-B) receptors
- Dose-dependent
- Decreases both pulmonary and systemic vascular resistance
Side-effects:
- Hypotension
- Flushing
- Dyspepsia
- Fatigue
- Hepatotoxicity
- Haemodilution
- Teratogenic
Contra-indications
- Moderate or severe liver disease
- Pregnancy (is teratogenic)
Monitoring:
- Monitor LFTs in the first 3-4 months
Nicorandil
Activator of ATP-dependent K+ channels used in the treatment of angina
Mechanism:
- Relaxes venous smooth muscle -> increased venous capacitance -> reduced afterload
- Also causes dilatation of coronary arterioles
Side-effects:
- Headache (35%)
- Dose-dependent
- Oral ulceration
- Flushing
- Gastrointestinal disturbance
Contra-indications
- Prescription of a phosphodiesterase inhibitor
- May cause massive vasodilation and
hypotension
Carbamazepine
Indications:
- Epilepsy
- Bipolar disorder
- Diabetic neuropathy
- Trigeminal neuralgia
Monitoring:
- Check plasma levels + U&Es every 6 months
- Check LFTs and FBC after first 6 months of treatment
Side-effects:
- Hyponatraemia - via water intoxication
- Drowsiness - usually issue on initiation
- Steven-Johnson’s
- Blood dyscrasias
- Jaundice
Contra-indications
- Acute porphyria
- Underlying cardiac conduction abnormalities
- Known blood dyscrasia
ADR classification
Type A
- An anticipated effect arising from the pharmacological properties of a drug
- e.g. bradycardia with beta-blockers
Type B
- Unpredictable, idiosyncratic effects unrelated to pharmacological properties of a drug
Type C
- An effect occurring after prolonged drug use
- e.g. NSAID-associated nephropathy
Type D
- An effect occurring late after treatment
- e.g. thalidomide-associated teratogenicity
Type E
- An effect occurring during drug withdrawal
- e.g. agitation and SSRIs
Amiodarone
Mechanism:
- Blockade of voltage-gated K+ and Ca2+ channels
- Prolongs phase III
- Therefore slows conduction + prolongs
refractory period
Side-effects:
- Pulmonary fibrosis
- Hepatotoxicity
- Hyper- or hypothyroidism
- Skin discolouration
- QT prolongation
- Pancreatitis
- Vortex keratopathy (cornal microdeposits)
CYP inducers
PC BRAS
P - phenytoin
C - carbamazepine
B - barbiturates
R - rifampicin
A - alcohol (chronic)
S - sulfonyulreas (e.g. glyclazide)
Also St John’s Wort, smoking.
CYP inhibitors
AO DEVICES
A - allopurinol, amiodarone
O - omeprazole
D - disulfirams
E - erythromycin + other macrolides
V - valproate
I - isoniazid
C - ciprofloxacin + other fluoroquinolones
E - ETOH (acute)
S - sulfonamides, SSRIs
Also - azoles, grapefruit
Metolazone
A thiazide-like diuretic
- Inhibits sodium reuptake in DCT, increases
excretion of Na+, Cl-, water
- Adjuvant to loop diuretics in severe CCF
- Prescribe by brand name
- Start as 2-3x/week, can then increase to
alternate days
Monitoring:
- U&Es
Side-effects
- Hyponatraemia
- Hypokalaemia
- Hypomagnesaemia
- Hyperuricaemia
Thiazide diuretics
e.g. bendroflumethazide, indapamide
Mechanism:
- Block Na/Cl co-transporter in the TAL and early DCT to promote natriuresis
- Can also have long-term on the vasculature
Uses:
- HTN
Monitoring:
- U&Es
Side-effects
- Hypokalaemia
- Hypercalcaemia
- Hypomagnesaemia
- Hyponatraemia
- Metabolic acidosis
- Prolonged QT
Contra-indications:
- Concurrent digoxin use - potentiates digoxin
Ciclosporin
Calcineurin inhibitor used to suppress immune response in cancer, transplant, autoimmune disease etc.
Notes:
- Prescribe by brand name
- Monitor levels, routine bloods (incl. lipid profile)
Side-effects:
- Nephrotoxicity
- Tremor
- Gingival hyperplasia
- HTN
- Hypertrichosis
- Peripheral neuropathy
- Headache
- Nausea and diarrhoea
- Hyperlipidaemia
- CYP inhibition
Sulfasalazine
An immunosuppressant and anti-inflammatory used in UC, RA, etc.
Cautions:
- G6PD deficiency
- Slow acetylator status
- Renal or hepatic disease
Side-effects:
- Pancytopenia
- Hypersensitivity reactions
- Periorbital oedema
- Stomatitis
- Parotitis
Sodium bicarbonate
Indications:
- Hyperkalaemia
- Sodium-channel blocker (e.g. TCAs) with ECG changes
- Urinary alkalisation (e.g. salicylates)
- Normal anion gap metabolic acidosis e.g. RTA
Dose:
body weight x 3 x (desired [HCO3] - measured [HCO3])
Anti-thyroid medications
Radioiodine
- Contraindicated in pregnancy
- Patients cannot get pregnant within 6 months, interact with pregnant women/young children for 3 weeks, and should avoid everyone for several days
Carbimazole
- Risk of agranulocytosis - stop therapy if febrile, mouth ulcers, sore throat
- Small risk of skin reactions
Propylthiouracil
- 2nd line therapy unless pregnant
- Higher risk of skin reactions
- Lower risk of agranulocytosis
- Rarely can cause acute hepatitis
Antidiabetic medications
Metformin:
- Mechanism:
- Activates AMPK
- Increases insulin sensitivity
- Limited efficacy in late T2DM
- Cautions:
- U&Es after 1 yr - if eGFR < 45 then reduce
dose, if < 30 then stop
- Side-effects:
- Gastrointestinal discomfort
- Risk of lactic acidosis due to inhibition of
hepatic lactate uptake
Gliclazide:
- Mechanism:
- Binds SUR1 (ATP-dependent K+ channel),
causing depolarisation of beta-cells and
insulin release
- Limited efficacy in late T2DM
- Does not reduce cardiovascular risk
- Side-effects:
- Hypoglycaemia
- Weight gain
- Cautions:
- Avoid glibenclamide in renal failure
- Can cross placenta and into breast milk so
contraindicated in pregnancy
SGLT-2 inhibitors e.g. dapagliflozin
- Can be used as initial monotherapy or in combination with metformin as early treatment in patients with a high QRISK
- Mechanism:
- Inhibit SGLT-2, decreasing renal re-
absorption of glucose and therefore
increasing excretion
- Side-effects
- UTIs
- Thrush
DPP4 inhibitors e.g. sitagliptin
- Mechanism:
- Inhibits DPP-4, increasing levels of incretins
- Never used as monotherapy
- Causes weight loss
- Safe in renal impairment
- No risk of hypoglycaemia
- Mildly increases cardiovascular risk
Exenatide:
- Mechanism:
- GLP-1 mimetic, potentiating the effects of
insulin
- Causes weight loss
- No risk of hypoglycaemia
- Contraindications:
- Poor kidney function
Pioglitazone:
- Mechanism:
- PPAR-gamma activation, increasing insulin
sensitvitiy
- Side-effects:
- Weight gain
- Fluid retention
- Contraindications:
- Bladder CA
- Heart failure (causes fluid retention)
Medications for alcohol abuse
Disulfiram
- Inhibits aldehyde dehydrogenase -> accumulate acetaldehyde
- When alcohol is consumed causes flushing + palpitations + N/V + hypotension
- Contraindications:
- Liver disease, heart disease, psychosis
Acamprosate
- NMDA receptor antagonist used to reduce alcohol cravings
- Contraindications:
- Liver disease
Naltrexone
- An opiate antagonist used to reduce cravings and relapses by preventing release of endorphins associated with drinking
