Clinical Pharmacology and Therapeutics Flashcards
What are the side-effects of thiazolidinediones?
Weight Gain, liver impairment (monitor LFTs), Fluid retention (contraindicated in heart failure), increased risk of fractures, bladder cancer (pioglitazone)
What are thiazolidinediones?
PPAR-gamma receptor agonists that reduce peripheral insulin resistance therefore used in the treatment of type 2 DM. e.g. pioglitazone
What are the side-effects of verapamil?
Constipation, hypotension, bradycardia (caution in heart failure), flushing
What are the side-effects of diltiazem?
hypotension, bradycardia (caution in heart failure), ankle swelling
What are the side-effects of dihydropyridines (e.g. nifedipine, amlodipine)?
flushing, headache, ankle swelling
Which drugs must be avoided during breastfeeding?
Carbimazole Lithium Aspirin Sulphonylureas Tetracycline
Sulphonamides Ciprofloxacin Amiodarone Benzodiazepines Cytotoxics
What are the side-effects of loop diuretics?
hypotension, hypokalaemia, hyponatraemia, otoxicity, hypocalcaemia, renal impairment, hyperglycaemia, gout
What are the side-effects of LMWH and UFH?
Increased Bleeding, heparin-induced thrombocytopenia, osteporosis with long-term use. HIT and osteporosis less common with LMWH than UFH. Also hyperkalaemia
What is tamsulosin?
Tamsulosin is an alpha1-blocker used in the treatment of BPH. It acts to relax smooth muscle in BPH leading to an increase in urinary flow-rate and an improvement in obstructive symptoms.
Contra-indicated in patients with a history of postural hypotension.
What is citalopram and what are its side effects?
A type of Selective Serotonin Re-uptake Inhibitors used in depression and panic disorder. Can prolong QT interval. Can also cause hepatitis and general GI upset.
What are the side effects of alpha1 selective blockers.
Drowsiness, hypotension, syncope, headache, dry mouth, depression
What are some side effects of chloroquine?
Headache, psychosis, retinopathy (chronic use)
What are some side-effects of primaquine?
Epigastric pain, haemolysis if G6PD deficient, methaemoglobinaemia
What are the main types of anti-fungals?
Triazole antifungals e.g. fluconazole, itraconazole, posaconazole, and voriconazole. Voriconazole is broad-spectrum anti-fungal used for life-threatening infection.
Polyene antifungals e.g. Amphotericin B used for CNS fungal infections and cryptococcal meningitis.
What are the main types of anti-biotics?
- Beta-lactams
- Penicillins (-cillin)
- Cephalosporins (cef-)
- Carbapenems (-penem)
- Quinolones (-acin)
- Macrolides (-thromycin)
- Aminoglycosides (-micin)
What are the main penicillins?
Benzylpenicillin is a useful narrow spectrum antibiotic mainly against gram+ve organisms. It is poorly absorbed orally and is usually given IV.
Flucloxacillin is indicated in infection cause by penicillinase-producing penicillin resistant staphyloccoi. Which includes most hospital acquired staphylococcal infections, SEs include Cholestasis
Ampicillin and Amoxicllin are broad-spectrum penicillins active against non-beta lactamase producing gram+ve bacteria and because they diffuse into gram-ve bactera more readily than benzylpenicilin they are also active against many strains of E.coli, haemophilus, and salmonella. For oral amoxicllin (SEs rash with infectious mononucleosis) is the drug of choice for IV ampicillin. Co-amoxiclav can be used for resistant strains, SEs include Cholestasis.
What are the main Cephalosporins?
Used for the treatment of meningitis, pneumonia, and septicaemia. Ceftriaxone is a third generation which is active against staphs, most streps, enterococci, pneumoccoci and gram-ve such as shigella haemophilus, klebsiella, some proteus and e.coli.
What are the main Carbapenems?
Meropenem is a carbapenem but is high resistant to most beta-lactamases, it has a wide spectrum and it bactericidal against most gram-ve and gram+ve, only occasional pseudomonas and MRSA are resistant. It is given IV.
What are the main Macrolides?
Erythromycin and Clarithromycin can be given either orally or IV. They have a narrow spectrum mainly active against gram+ve can be used as an alternate in pen-allergic patients. but they are ineffective in meningitis. They are very safe drugs. Erythromycin may cause gastrointestinal upset and prolonged QT interval.
What are the main Aminoglycosides?
Gentamicin is the most important its main use is in life-threatening gram-ve infections. AmiKacin is used in gentamicin resistant gram-ve infection. Streptomycin is used in mycobacterium multiple resistant TB. Be wary of Ototoxicity and Kidney damage.
What are the main Quinolones?
Ciprofloxacin is well absorbed orally and can be given intravenously it is excreted mainly by the kidneys unchanged and so can be used in UTIs. They are useful for intracellular organisms. SEs include decreased seizure thershold and tendonitis
What are the side effects of rifampicin?
- decreased liver function ( stop if bilirubin increases small AST rise is OK)
- thrombocytopenia
- orange discolouration of urine, tears
- inactivation of Pill
- flu-like symptoms
What are the side effects of isoniazid?
- decreased liver function
- decreased white cell count
- neuropathy (stop and give pyridoxine (vitaminB6))
What are the side effects of ethambutol?
Optic neuritis with deterioration of colour vision first
What are the side effects of pyrazinamide?
- hepatitis
* arthralgia (hyperuricaemia so CI in acute gout it porphyria)
Describe the four main dopamine pathways in the brain
- Brainstem to Limbic system - too much dopamine is thought to be cause for Positive symptoms of Schizophrenia
- Brainstem to Mesocortical system - too little dopamine is thought to be the cause of negative symptoms in schizophrenia
- Brainstem to Basal Ganglia - blocking dopamine here causes movement disorders (drug induced parkinsonism)
- Brainstem to Hypothalamus - blocking dopamine leads to hyperprolactinaemia
What are Extrapyramidal Side-Effects (EPSEs)?
- Dystonia: sustained involuntary muscle contractions, twisting of neck, limbs, trunk or face. acute form more likely in younger, more ill patients. particular problem in antipsychotic naive patients with predominant negative symptoms. switch to an atypical with less risk of EPSEs. Procyclidine IM or IV in acute situations
- Parkinsonism: akinesia, rigidity, course tremor at rest but no pill rolling, may occur within weeks, remit on withdrawal of drug. Switch to atypical. if not an option consider procyclidine oral
- Akathisia: uncontrolled restlessness with feelings of inability to keep still, constantly shifting posture, may resemble agitation or psychosis, switch to atypical if possible if no consider propranolol.
- Tardive Dyskinesia: Involuntary hyperkinesia, increased with anxiety and relieved by sleep, may be irreversible. symptoms include tics, choreas and dystonias, repetitive involuntary purposeless movements of jaw, neck and tongue. switch to atypical if neccessary consider tetrabenzine.
Describe Polypharmacy
The use of 4 or more medications by a patient typically adults aged over 65 years.
Concerns include:
- increased adverse drug reactions
- drug interactions
- prescribing cascade
- higher costs
Can ultimately lead to decreased quality of life, decreased mobility and cognition. Patients with polypharmacy require regular medication review to ensure that the medications they are on are not causing harm and are still appropriate.
Describe NSAIDs, give some examples and list some Side-effects.
Non-steroidal Anti-Inflammatory Drugs, have analgesic effect, particularly useful in inflammatory arthritides, also used in back pain, and soft-tissue disorders. They work by inhibiting cyclo-oxygenase to reduce the production of prostaglandins. Selective inhibition of COX-2 is associated with less GI SEs
Examples: Ibuprofen is an example it had the lowest risk of GI SEs of non-selective NSAIDs but its anti-inflammatory properties are weaker. Naproxen is one of the first choices due to its good efficacy and low incidence of SEs (though more than ibuprofen). Celecoxib and etoricoxib are selective NSAIDs.
Side-Effects: GI discomfort, ulceration, hypersensitivity reactions (bronchospasm), headache, dizziness, depression, sleep change, increased risk of thrombotic events
Describe Diuretics, give some examples, and list some SEs
Thiazides are used to relieve oedema due to chronic heart failure and in lower doses to reduce blood pressure. Examples are Bendroflumethiazide (HF) indapamide (Hypertension)
Loop diuretics are used in pulmonary oedema due to left ventricular failure and in patients with chronic heart failure. Examples are furosemide.
Potassium-Sparing used in conjunction with other diuretics to conserve potassium e.g. amiloride, spironolactone (aldosterone antagonist)
Side-effects: hypokalaemia (in non K-sparing), postural hypotension, hyponatraemia, Hyperuricaemia, hyperglycaemia
Describe Warfarin and some of its SEs
Used as prophylaxis of embolisation in rheumatic heart disease and atrial fibrillation, after insertion of prosthetic heart valve. Also used in treatment and prophylaxis of venous thrombosis and pulmonary embolism, TIAs.
Side-effects: Haemorrhage, N+V, diarrohoea, jaundice, pancreatitis, alopecia, purpura, rash.
Describe ACE-inhibitors, gives some examples and list some SEs
Used in heart failure usually in combination with a beta-blocker. Also used in hypertension particularly in younger caucasian patients as first line. Check renal function 2wks after starting, as can cause decline if underlying Renal Artery Stenosis.
Examples include lisinopril, ramipril, enalapril.
Side-effects: hypotension, dizziness, headaches, renal impairment, dry cough, angioedema, hyperkalaemia, pancreatitis, GI upset.
Describe anti-muscarinic SEs
Dry mouth, blurred vision, constipation, urinary retention.
what are some side-effects of tricyclic anti-depressants
Arrhythmias, anxiety, dizziness, agitation, confusion, drowsiness, hallucinations, mania, antimuscarinic SEs, sexual dysfunction, galactorrhea
Describe beta-blockers, give some examples, and list some side-effects
Block beta-adrenoceptor in heart, peripheral vasculature, bronchi, pancreas and liver. Used in hypertension, heart failure, Post MI, anxiety, angina.
Examples: cardioselective B-blockers e.g. atenolol, bisoprolol may have a lesser effect on airway resistance and be preferred in diabetics. Water-soluble blockers e.g. atenolol, sotalol are less likely to enter the brain and may therefore cause less sleep disturbance and nightmares.
Side-effects: bronchospasm, fatigue, sleep disturbances, nightmares, cold extermities, bradycardia, hypotension
Describe opioid analgesics, give some examples, and list some SEs
Used to relieve moderate to severe pain particularly of visceral origin. Split into normal (morphine, tramadol, fentanyl) and weak opioids (codeine)
Side-effects: N+V, constipation, dry mouth, muscle rigidity in large doses, respiratory depression, hallucinations, mood changes, confusion, urinary retention.
What are the side-effects of digoxin
N+V, arrhythmias, conduction disturbances, blurred/yellow vision, eosinpphilia.
Describe memantine, its indications, dose, and SEs
It is a glutamate receptor antagonist used in moderate to severe dementia in Alzheimer’s disease.
Dose: 5mg OD increased in steps of 5mg every week to 20mg OD
SEs: Constpation, dizziness, drowsiness, dyspnoea, headache, hypertension. May also cause confusion, hallucinations, heart failure and rarely seizures (caution use if history of convulsions)
What is Alendronic Acid and what are the side-effects.
It is a bisphosphonate used in the treatment of osteoporosis and other bone disease (paget’s). It inhibits osteoclast bone resorption.
Side-Effects: GI ulceration, rarely Steven-Johnson syndrome, osteonecrosis of the jaw.
What are some side-effects of metronidazole?
Reaction following alcohol ingestion
What are some side-effects and CIs of doxycycline?
SEs: Photosensitivity
CIs: Pregnancy
What are Triptans, their main side effects and contraindications?
5HT1 Agonists constricting cranial arteries can be used in migraines.
Side-effects: nausea, dizziness and dry mouth. Strange sensations such as tingling, flushing, feelings of tightness or heaviness. Rarely can cause angina +/- MI or arrhythmias.
Contra-indications: IHD, coronary spasm, uncontrolled hypertension, recent lithium, SSRIs or ergot use.
Describe tocolytics and their contraindications.
Medications used to suppress premature labour. Nifedipine is effective and associated with less newborn respiratory distress and admission to intensive care. Nifedipine 20mg PO then 10-20mg/6-8h according to uterine activity. SEs include hypotension, headaches flushing, tachycardia so requires BP monitoring
Contraindications: Chorioamnionitis, foetal growth restriction or distress, pre-eclampsia, placenta praevia, abruption, cervix dilated more than 4cm.
What are the discontinuation symptoms when abruptly stopping SSRIs?
Increased mood change Restlessness Difficulty sleeping Unsteadiness Sweating GI upset Paraesthesia
What are some side-effects of ciclosporin?
(Everything increases) Nephotoxicity Hepatotoxicity Fluid retention Hypertension Hyperkalaemia Hypertrichosis Gingival hyperplasia Tremor Impaired glucose tolerance Hyperlipidaemia Increased susceptibility to severe infection
What are the main P450 enzyme inducers?
PC BRAS:
- Phenytoin
- Carbamazepine
- Barbiturates
- Rifampicin
- Alcohol (Chronic)
- Sulphonylureas
What are the main P450 enzyme inhibitors?
O-DEVICES:
- Omeprazole
- Disulfiram
- Erthromycin
- Valproate
- Isoniazid
- Cimetidine/Ciprofloxacin
- Ethanol intoxication
- Sulphonamides
Describe VTE prophylaxis, it’s risk factors, Risk factors for bleeding, and management.
VTE assessment on all inpatients.
Risk factors: reduced mobility e.g. Bed bound, active cancer or cancer treatment, age over 60, critical care admission, dehydration, known thrombophilia, obesity I.e. BMI over 30, one or more significant comorbidities e.g. IHD, Metabolic or endorphin or respiratory pathology, inflammatory conditions, personal or first degree history of VTE, HRT, Oestrogen-containing contraceptive, varicose veins with phlebitis, pregnancy
Risk Factors for bleeding: Active bleeding, liver disease, anticoagulants, lumbar puncture, epidural, spinal expected within 12 hours or had in previous 4 hours, acute stroke, thrombocytopenia, uncontrolled systolic hypertension (230/120mmHg), untreated inherited bleeding disorder e.g.
Management:
-ensure adequate hydration
-encourage to mobilise
-Mechanical VTE prophylaxis e.g. Anti-embolism stockings (CI if peripheral arterial disease, peripheral neuropathy, local skin conditions e.g. Dermatitis, cardiac failure, severe leg oedema or pulmonary oedema, stroke)
- Pharmacological VTE prophylaxis e.g. Fondaparinux 2.5mg SC OD or Dalteparin 2500 units SC OD
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What are the main side effects of PPIs?
Most common:
- Headache
- GI distubance e.g. Diarrhoea, N+V, abdominal pain.
- increased risk of fracture if used at high doses for more than 1year in elderly.
Less common:
-dry mouth, parietal cell hyperplasia, peripheral oedema, dizziness, sleep disturbances, arthralgia, myalgia.
Describe some types of anti-emetics their uses and side-effects.
Haloperidol good for opiate, general anaesthetic, post operative, chemo/radio, first choice in liver failure. Beware of increased prolactin, Extrapyramidal features, reduced seizure threshold, hypotension and prolonged QT.
Levomepromazine is a broad spectrum useful in resistant cases beware sedation, hypotension, reduced seizure threshold and prolonged QT
Metoclopramide good for GI causes, migraine and drugs e.g opiates. Beware hyperprolactinaemia, Extrapyramidal features (should not be taken for longer than 5 days due to risk of neurological adverse effects) and CI in GI obstruction as increases GI motility.
Domperidone Good for Parkinson’s disease, morning-after pill, chemotherapy beware hyperprolactinaemia, and should not be used for more than 7 days due to risk of cardiac side-effects QT prolongation
Cyclizine is good for GI obstruction, post-op N+V, vestibular disorders. Beware antimuscarinic features and try avoid in IHD.
Ondansetron a serotonin antagonist, good for resistant cases, side effects include headache QT prolongation and constipation and dizziness
On
Describe Metformin, it’s use, side-effects, and contraindications
Oral antidiabetic increases insulin sensitivity without hypoglycaemic affect. Used 1st line in T2DM if diet unsuccessful also used in PCOS. Usually used 500mg OD upto 2g OD.
SEs: GI upset, taste disturbance, rarely Vit B12 deficiency, lactic acidosis
Contraindications: DKA, Shock, Recent MI, General anaesthetic, renal failure, liver failure, sepsis.
Describe Statins, the indications, side-effects, and monitoring.
HMG-CoA reductase inhibitors that lower cholesterol by decreasing synthesis, reduce LDL by increase in uptake and mildly reduce TGs. Atorvastatin recommended first line
Indications: Primary (Q-RISK over 10%, CKD, T1DM) and Secondary Prevention of IHD, CVA, PVD.
SEs: Hepatitis, myositis, headache, GI upset,
Monitoring: Monitor LFTs at baseline, 3 months, 12 Months and CK if myositis-like symptoms develop.
King’s criteria for paracetamol OD acute transplant
Blood pH <7.3, 24 hour after ingestion or all of the following INR >6.5 (PT >100) Creatinine >300 Grade 3 or 4 hepatic encephalopathy
