Pharmacology Flashcards
(32 cards)
Clarithromycin
-CYP3A4 inhibitor
- interfere with Theophylline, simvastatin, cyclosporine, warfarin and Digoxin
PPI
Proton pump inhibitors (PPI) cause irreversible blockade of H+/K+ ATPase of the gastric parietal cell.
Examples include omeprazole and lansoprazole.
Adverse effects
1- hyponatraemia, hypomagnasaemia
2- osteoporosis → increased risk of fractures
3- microscopic colitis
4- increased risk of C. difficile infections
ACE inhibitors
Side-effects:
- cough: occurs in around 15% of patients and may occur up to a year after starting treatment. Thought to be due to increased bradykinin levels
- Angioedema: may occur up to a year after starting treatment
- Hyperkalaemia
- First-dose hypotension: more common in patients taking diuretics
Cautions and contraindications
- pregnancy and breastfeeding - avoid
renovascular disease - significant renal impairment may occur in patients who have undiagnosed bilateral renal artery stenosis
- Aortic stenosis - may result in hypotension
- patients receiving high-dose diuretic therapy (more than 80 mg of furosemide a day) - significantly increases the risk of hypotension
hereditary or idiopathic angioedema
Monitoring
- Urea and electrolytes should be checked before treatment is initiated and after increasing the dose
a rise in the creatinine and potassium may be expected after starting ACE inhibitors. Acceptable changes are an increase in serum creatinine, up to 30%* from baseline and an increase in potassium up to 5.5 mmol/l*.
Linezolid
Linezolid is a type of oxazolidinone antibiotic which has been introduced in recent years. It inhibits bacterial protein synthesis by stopping the formation of the 50s initiation complex and is bacteriostatic in nature.
Spectrum, highly active against Gram positive organisms including:
»MRSA (Methicillin-resistant Staphylococcus aureus)
»VRE (Vancomycin-resistant enterococcus)
>.GISA (Glycopeptide Intermediate Staphylococcus aureus)
Adverse effects
- thrombocytopenia (reversible on stopping)
- monoamine oxidase inhibitor: avoid tyramine containing foods
Loop Diuretics
Furosemide and bumetanide are loop diuretics that act by inhibiting the Na-K-Cl cotransporter (NKCC) in the thick ascending limb of the loop of Henle, reducing the absorption of NaCl. There are two variants of NKCC; loop diuretics act on NKCC2, which is more prevalent in the kidneys.
As loop diuretics work on the apical membrane they must first be filtered into the tubules by the glomerulus before they can have an effect. Therefore patients with poor renal function may require escalating doses to ensure a sufficient concentration is achieved within the tubules.
Indications
»heart failure: both acute (usually intravenously) and chronic (usually orally)
»resistant hypertension, particularly in patients with renal impairment
Adverse effects
>hypotension
>hyponatraemia
>hypokalaemia, hypomagnesaemia
>hypochloraemic alkalosis
>ototoxicity
>hypocalcaemia
renal impairment (from dehydration + direct toxic effect)
>hyperglycaemia (less common than with thiazides)
>gout
Neuropathic Pain
Drugs for neuropathic pain are typically used as monotherapy, i.e. if not working then drugs should be switched, not added
Adrenoceptor Agonists
Alpha-1 agonists
phenylephrine
Alpha-2 agonists
clonidine
Beta-1 agonists
dobutamine
Beta-2 agonists
salbutamol
Beta-3 agonists
being developed, may have a role in preventing obesity (stimulation causes lipolysis)
SGL-2 inhibitors
SGLT-2 inhibitors reversibly inhibit sodium-glucose co-transporter 2 (SGLT-2) in the renal proximal convoluted tubule to reduce glucose reabsorption and increase urinary glucose excretion.
Examples include canagliflozin, dapagliflozin and empagliflozin.
Important adverse effects include
urinary and genital infection (secondary to glycosuria). Fournier’s gangrene has also been reported
normoglycaemic ketoacidosis
increased risk of lower-limb amputation: feet should be closely monitored
Patients taking SGLT-2 drugs often lose weight, which can be beneficial in type 2 diabetes mellitus
Ectasy Poisoning
Clinical features
neurological: agitation, anxiety, confusion, ataxia
cardiovascular: tachycardia, hypertension
hyponatraemia
this may result from either syndrome of inappropriate ADH secretion or excessive water consumption whilst taking MDMA
hyperthermia
rhabdomyolysis
Topiramate
Topiramate can precipitate acute angle closure glaucoma
The Jarisch-Herxheimer reaction
The Jarisch-Herxheimer reaction is a known phenomenon following syphilis treatment that does not require any specific treatment or investigations other antipyretics.
Drug induced Lupus
PH-IMP
Most common causes
procainamide
hydralazine
Less common causes
isoniazid
minocycline
phenytoin
Drug induced Lupus
In drug-induced lupus not all the typical features of systemic lupus erythematosus are seen, with renal and nervous system involvement being unusual. It usually resolves on stopping the drug.
Features
- arthralgia
- myalgia
- skin (e.g. malar rash) and - pulmonary involvement (e.g. pleurisy) are common
- ANA positive in 100%, dsDNA negative
- anti-histone antibodies are found in 80-90%
anti-Ro, anti-Smith positive in around 5%
ACE inhibitors
Mechanism of action:
- inhibits the conversion angiotensin I to angiotensin II
→ decrease in angiotensin II levels → to vasodilation and reduced blood pressure
→ decrease in angiotensin II levels → reduced stimulation for aldosterone release → decrease in sodium and water retention by the kidneys
- renoprotective mechanism
Angiotensin II constricts the efferent glomerular arterioles
ACE inhibitors therefore lead to dilation of the efferent arterioles → reduced glomerular capillary pressure → decreased mechanical stress on the delicate filtration barriers of the glomeruli
this is particularly important in diabetic nephropathy
- ACE inhibitors are activated by phase 1 metabolism in the liver
Organophosphate poisoning
Features can be predicted by the accumulation of acetylcholine (mnemonic = SLUD)
Salivation
Lacrimation
Urination
Defecation/diarrhoea
cardiovascular: hypotension, bradycardia
also: small pupils, muscle fasciculation
Management
atropine
Riboflavin ( Vitamin B2)
Riboflavin is a cofactor of flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) and is important in energy metabolism.
Consequences of riboflavin deficiency:
angular cheilitis
VITAMINS
riboflavin (B2), niacin (B3), pyridoxine (B6), folate (B9) and cyanocobalamin (B12)
Vitamin B12 Deficiency
If no neurological involvement 1 mg of IM hydroxocobalamin 3 times each week for 2 weeks, then once every 3 months
»>if a patient is also deficient in folic acid then it is important to treat the B12 deficiency first to avoid precipitating subacute combined degeneration of the cord
Vitamin B12
It is absorbed after binding to intrinsic factor (secreted from parietal cells in the stomach) and is actively absorbed in the terminal ileum.
Warfarin
Inhibits epoxide reductase, preventing the reduction of vitamin K to its active hydroquinone form
this, in turn, acts as a cofactor in the carboxylation of clotting factor II, VII, IX and X (mnemonic = 1972) and protein C.
Adenosine
The effects of adenosine are enhanced by dipyridamole (antiplatelet agent) and blocked by theophyllines.
Hypokalemia
Hypokalaemia with alkalosis
- vomiting
- thiazide and loop diuretics
- Cushing’s syndrome
- Conn’s syndrome (primary - hyperaldosteronism)
Hypokalaemia with acidosis
- diarrhoea
- renal tubular acidosis
- acetazolamide
- partially treated diabetic ketoacidosis
Hereditary Angioedema
Hereditary angioedema (HAE) is an autosomal dominant condition associated with low plasma levels of the C1 inhibitor (C1-INH, C1 esterase inhibitor) protein. C1-INH is a multifunctional serine protease inhibitor - the probable mechanism behind attacks is uncontrolled release of bradykinin resulting in oedema of tissues.
Investigation
C1-INH level is low during an attack
low C2 and C4 levels are seen, even between attacks. Serum C4 is the most reliable and widely used screening tool.
