Pharmacology Flashcards
what is the management of motion sickness?
Motion sickness - hyoscine > cyclizine > promethazine
Management
• The BNF recommends hyoscine (e.g. Transdermal patch) as being the most effective treatment. Use is limited due to side-effects
• Non-sedating antihistamines such as cyclizine or cinnarizine are recommended in preference to sedating preparation such as promethazine
what is motion sickness?
Motion sickness describes the nausea and vomiting which occurs when an apparent discrepancy exists between visually perceived movement and the vestibular systems sense of movement
how are monoclonal antibodies manufactured?
Monoclonal Antibodies: have an increasing role in medicine. They are manufactured by a technique called somatic cell hybridization. This involves the fusion of myeloma cells with spleen cells from a mouse (recent advances: rabbit B-cells) that has been immunized with the desired antigen. The resulting fused cells are termed a hybridoma and act as a ‘factory’ for producing monoclonal antibodies. The main limitation to this is that mouse antibodies are immunogenic leading to the formation of human anti-mouse antibodies (HAMAs). This problem is overcome by combining the variable region from the mouse antibody with the constant region from a human antibody
what type of antibody and use:
Rituximab
Anti-CD20
non-Hodgkin’s lymphoma
what type of antibody and use:
Infliximab
anti-TNF
rheumatoid arthritis and Crohn’s
what type of antibody and use:
Cetuximab
anti epidermal growth factor receptor
metastatic colorectal cancer and head and neck cancer
what type of antibody and use:
Trastuzumab
anti-HER2, anti EGF receptor
metastatic breast cancer
what type of antibody and use:
Alemtuzumab
anti-CD52
chronic lymphocytic leukemia
what type of antibody and use:
abciximab
anti-glycoprotein IIb/IIIa receptor
undergoing PCI, prevention of ischemic events in patients
what type of antibody and use:
OKT3
anti-CD3
prevent organ rejection
what are phase 1 reactions in pharmacology? what enzyme is this mainly performed by?
• Phase I reactions: oxidation, reduction, and hydrolysis. Mainly performed by the P450 enzymes but some drugs are metabolised by specific enzymes, for example alcohol dehydrogenase and
xanthine oxidase. Products of phase I reactions are typically more active and potentially toxic
what are phase 2 reactions in pharmacology?
• Phase II reactions: conjugation. Products are typically inactive and excreted in urine or bile.
Glucuronyl, acetyl, methyl, sulphate and other groups are typically involved.
where do you majority of phase 1 and phase 2 take place?
• The majority of phase I and phase II reactions take place in the liver.
what is first pass metabolism?
First-Pass Metabolism is a phenomenon where the concentration of a drug is greatly ↓ before it reaches the systemic circulation due to hepatic metabolism. As a consequence much larger doses are need orally than if given by other routes. This effect is seen in many drugs, including: • Aspirin • Isosorbide dinitrate • Glyceryl trinitrate • Lignocaine • Propranolol • Verapamil
what is zero-order kinetics?
Zero-Order Kinetics describes metabolism which is independent of the concentration of the reactant. This is due to metabolic pathways becoming saturated resulting in a constant amount of drug being eliminated per unit time. This explains why people may fail a breathalyser test in the morning if they have been drinking the night before
what drugs exhibit zero-order kinetics?
Drugs exhibiting zero-order kinetics • Phenytoin • Salicylates • Heparin • Ethanol
what is acetylator status?
Acetylator Status
50% of the UK population is deficient in hepatic N-acetyltransferase
what drugs are affected by acetylator status?
Drugs affected by acetylator status: • Isoniazid • Procainamide • Hydralazine • Dapsone • Sulfasalazine
what are the p-450 dependant drugs?
P-450 Dependent Drugs TEWPD: • Theophylline • Estrogen • Warfarin • Phenytoin • Digoxin
do p450 inhibitors cause toxicity or under dosing of p-450 dependant drugs?
toxicity
name a few p-450 inhibitors?
P450 inhibtors: (causing low metabolism of TEWPD → Toxicity) • Acute alcohol intake • Allopurinol • Amiodarone • Cimetidine, omeprazole • Dapsone • Imidazoles: ketoconazole, fluconazole • INH • Macrolides (Azithro-Clarithro-Erythro mycins) • Quinolones (ciprofloxacin) • Quinupristin • Sodium valproate • Spironolactones • SSRIs: fluoxetine, sertraline • Grapefruit juice (potent inhibitor of the cytochrome P450 enzyme CYP3A4) • Protease inhibitors (ndinavir, nelfinavir, ritonavir, saquinavir)
what is auto-inducer?
Carbamazepine is an inducer of the P450 system. This in turn increases the metabolism of carbamazepine itself - auto- induction
name a few p-450 inducers?
- Antiepileptics: phenytoin, carbamazepine (note that valporate is an inhibitor)
- Barbiturates
- Chronic alcohol intake
- Griseofulvin
- Quinidine
- Rifampicin
- Smoking (affects CYP1A2, reason why smokers require more aminophylline)
- St John’s Wort
- Sulfa drugs
- Tetracycline
- Nevirapine (NNRTI)
what drugs can be cleared with haemodialysis?
• Barbiturate
• Lithium
• Alcohol (inc methanol, ethylene glycol)
• Salicylates
• Theophyllines (charcoal hemoperfusion is
preferable)
below are all... • Tricyclics • Benzodiazepines (diazepam,midazolam,alprazolam) • Dextropropoxyphene (co-proxamol) • Digoxin, β-blockers
Drugs which cannot be cleared with HD include
• Tricyclics
• Benzodiazepines (diazepam,midazolam,alprazolam)
• Dextropropoxyphene (co-proxamol)
• Digoxin, β-blockers
what drugs to avoid in renal failure?
- Antibiotics: tetracycline, nitrofurantoin
- NSAIDS
- Lithium
what drugs are likely to accumalate in renal failure?
Drugs likely to accumulate in renal failure - need dose adjustment
• Most antibiotics including penicillins, cephalosporins, vancomycin, gentamicin, streptomycin
• Digoxin, atenolol
• Methotrexate
• Sulphonylureas
• Furosemide
• Opioids
what drugs are relatively safe in renal failure?
Drugs relatively safe - use in normal dose
• Antibiotics: erythromycin, rifampicin
• Diazepam
• Warfarin
• Thiazides, furosemide (less common) • Steroids • Tacrolimus, cyclosporin • Interferon-α • Nicotinic acid (vitamin B3) what do all the above do? what other drug may cause this slightly?
Drug Induced Impaired Glucose Tolerance
β-blockers cause a slight impairment of glucose tolerance. They should also be used with caution in
diabetics as they can interfere with the metabolic and autonomic responses to hypoglycemia
how do you categorise drug induced liver disease?
Drug induced Liver Disease is generally divided into hepatocellular, cholestatic or mixed.
what type of liver disease do the below cause • Alcohol • Amiodarone • Anti-tuberculosis: isoniazid, rifampicin, pyrazinamide • Halothane • MAOIs • Methyldopa • Paracetamol • Sodium valproate, phenytoin • Statins
Hepatocellular picture
what type of liver disease do the below cause: • Anabolic steroids, testosterones • Antibiotics: flucloxacillin, co-amoxiclav, erythromycin*, nitrofurantoin • Fibrates • Oral contraceptive pill • Phenothiazines: prochlorperazine/clorpromazine • Rarely: nifedipine • Sulphonylureas
cholestasis +/- hepatitis
*risk may be ↓ with erythromycin stearate
what type of liver disease do the below cause:
• Amiodarone • Methotrexate • Methyldopa
liver cirrhosis
what drugs cause cataracts?
• Steroids
what drugs cause corneal opacities?
• Amiodarone • Indomethacin
what drugs cause optic neuritis?
- Ethambutol
- Amiodarone
- Metronidazole
what drugs cause retinopathy?
• Chloroquine, quinine
what drug causes a blue tinge in vision and non-arteritic anterior ischemic neuropathy?
• Sildinafil
what drugs causes a yellow-green tinge in vision?
• Digoxin
what drugs cause gingival hyperplasia?what else causes this?
- Phenytoin
- Cyclosporin
- Calcium channel blockers (especially nifedipine)
Other causes of gingival hyperplasia include
• Acute myeloid leukemia (myelomonocytic and monocytic types)
what drugs cause urticaria?
- Aspirin
- Penicillins
- NSAIDs
- Opiates
what drugs can precipitate acute intermittent porphyria?
- Alcohol
- Barbiturates
- Benzodiazepines
- Halothane
- Oral contraceptive pill
- Sulphonamides
what are the below drugs safe in: • Paracetamol • Aspirin • Codeine • Morphine • Chlorpromazine • β-blockers • Penicillin • Metformin
acute intermittent porphyria
what the do the below drugs cause: • Heparin • Abciximab • NSAIDs; ASA • Diuretics: furosemide • Quinine • Antibiotics: penicillins, sulphonamides, rifampicin • Anticonvulsants: carbamazepine, valproate
Drug Induced Thrombocytopenia (probable immune mediated)
what do the below drugs cause:
• Cytotoxics
• Antibiotics: trimethoprim, chloramphenicol
• Anti-rheumatoid: gold (sodium aurothiomalate), penicillamine
• Carbimazole
• Anti-epileptics: carbamazepine
• Sulphonylureas: tolbutamide
Drug Induced Pancytopenia
carbimazole also causes both agranulocytosis and pancytopenia
what do the below drugs cause and what does this present like
• Thiazides
• Tetracyclines, sulphonamides, ciprofloxacin
• Amiodarone
• NSAIDs e.g. Piroxicam
• Psoralens
• Sulphonylureas
Drug Induced Photosensitivity:
Rash on the forearms and face is typical of a photosensitivity rash
what can be offered for smoking cessation therapy?
patients should be offered nicotine replacement therapy (NRT), varenicline or bupropion - NICE state that clinicians should not favour one medication over another
when should smoking cessation be offered? how long should this be prescribed for? when should further prescriptions not be offered? if unsuccessful - when should a repeat prescription be offered?
NRT, varenicline or bupropion should normally be prescribed as part of a commitment to stop smoking on or before a particular date (target stop date)
prescription of NRT, varenicline or bupropion should be sufficient to last only until 2 weeks after the target stop date. Normally, this will be after 2 weeks of NRT therapy, and 3-4 weeks for varenicline and bupropion, to allow for the different methods of administration and mode of action.
Further prescriptions should be given only to people who have demonstrated that their quit attempt is continuing
if unsuccessful using NRT, varenicline or bupropion, do not offer a repeat prescription within 6 months unless special circumstances have intervened do not offer NRT, varenicline or bupropion in any combination
what are adverse effects of nicotine replacement therapy? what should be offered as part of nicotine replacement therapy?
- Adverse effects nausea & include vomiting, flu-like headaches and symptoms
- Nice recommend offering a combination of nicotine patches and another form of NRT (such as gum, inhalator, lozenge or nasal spray) to people who show a high level of dependence on nicotine or who have found single forms of NRT inadequate in the past
what is the mode of action of varenicline?
Nicotinic receptor partial agonist
when should varenicline be started? what is the recommended course? is it more or less effective of bupropion? what are the adverse effects? who should this be used in caution with? what is this contraindicated in?
- Should be started 1 week before the patien target date to stop
- The recommended course of is 12 weeks (but patients should be monitored regularly and treatment only continued if not smoking)
- Has been shown in studies to be more effective than bupropion
- Nausea is the most common adverse effect. Other include headache, insomnia, abnormal dreams
- V arenicline should be used with caution in patients with a history of depression or self-harm.
- Contraindicated in pregnancy and breast feeding
what is the mode of action of Bupropion?
Norepinephrine and dopamine reuptake inhibitor, and nicotinic antagonist
when should bupropion be started? what is there a small risk of? who should this not be prescribe for?
- Should be started 1 to 2 weeks before target date.
- Small risk of seizures (1: 1,000)
- Bupropion should not be prescribed to individuals with epilepsy or other conditions that lower the seizure threshold, such as alcohol or benzodiazepine withdrawal, anorexia nervosa, bulimia, or active brain tumors. It should be avoided in individuals who are also taking MAOIs. When switching from MAOIs to bupropion, it is important to include a washout period of 2 weeks. Also pregnancy and breastfeeding are contraindications.
what does salicylate overdose cause on ABG?
Salicylate Overdose: a key concept for the exam is to understand that salicylate overdose leads to a mixed respiratory alkalosis and metabolic acidosis. Early stimulation of the respiratory centre leads to a respiratory alkalosis whilst later the direct acid effects of salicylates (combined with acute renal failure) may lead to an acidosis. In children metabolic acidosis tends to predominate
The mixed respiratory alkalosis and metabolic acidosis in a sweaty, confused patient point
towards what? The development of pulmonary edema suggests severe poisoning and
is an indication for what?
The mixed respiratory alkalosis and metabolic acidosis in a sweaty, confused patient point
towards salicylate overdose. The development of pulmonary edema suggests severe poisoning and
is an indication for hemodialysis
what are features of salicylate overdose?
Features • Hyperventilation (centrally stimulates respiration) • Tinnitus • Lethargy • Sweating, pyrexia • Nausea/vomiting • Hyperglycemia and hypoglycemia • Seizures • Coma
what is the management of salicylate overdose?
Treatment
• General (ABC, charcoal)
• Urinary alkalinization is now rarely used - it is contraindicated in cerebral and pulmonary
edema with most units now proceeding straight to hemodialysis in cases of severe poisoning
• Hemodialysis
what are the indications for haemodialysis in salicylate overdose?
- Serum concentration > 700mg/L
- Metabolic acidosis resistant to treatment
- Acute renal failure
- Pulmonary edema
- Seizures
- Coma
how do salicylates cause pyrexia?
salicylates cause the uncoupling of oxidative phosphorylation leading to ↓ adenosine triphosphate production, ↑ oxygen consumption and ↑ carbon dioxide and heat production
what is the management of paracetamol overdose?
Management:
• Start N-acetyl cysteine immediately
• Naloxone if there is hypoxia or respiratory depression
what is the criteria for liver transplantation in paracetamol overdose?
King’s College Hospital criteria for liver transplantation (paracetamol liver failure) Arterial pH < 7.3, 24 hours after ingestion OR all of the following:
• Prothrombin time > 100 seconds
• Creatinine > 300 μmol/l
• Grade III or IV encephalopathy
how does intravenous acetylcysteine work?
Intravenous acetylcysteine is indicated for the treatment of paracetamol (acetaminophen) overdose. When paracetamol is taken in large quantities, a minor metabolite called N-acetyl-p-benzoquinone imine (NAPQI) builds up. It is normally conjugated by glutathione, but when taken in excess, the body’s glutathione reserves are not sufficient to inactivate the toxic NAPQI. This metabolite is then free to react with key hepatic enzymes P450, therefore damaging hepatocytes.
For this indication, acetylcysteine acts to augment the glutathione reserves in the body and, together with glutathione, directly bind to toxic metabolites. These actions serve to protect hepatocytes in the liver from NAPQI.
which patients are at an increased risk of developing hepatotoxicity?
The following patients are at ↑ risk of developing hepatotoxicity following a paracetamol overdose:
• Chronic alcohol excess
• Patients on p450 enzyme inducers (rifampicin, phenytoin, carbamazepine)
• anorexia nervosa: ↓ glutathione stores
• HIV
what is the half-life of digoxin?
The half-life of digoxin is around 36-48 hours. This results in a delay before steady plasma levels
are seen, it may take a week to start its action
what are the actions of digoxin?
Actions
• ↓ conduction through the atrioventricular node which slows the ventricular rate in atrial fibrillation and flutter
• ↑ the force of cardiac muscle contraction due to inhibition of the Na+/K+ ATPase pump
what are the features of digoxin toxicity?
Features
• Generally unwell, lethargy, nausea & vomiting, confusion,
• Arrhythmias (e.g. AV block, bradycardia)
what can precipitate digoxin toxicity?
• Classically: Hypokalemia (also hyperkalaemia can worsen toxicity)
• Myocardial ischemia
• Hypomagnesemia, acidosis (Hypo pH), Hypercalcemia, Hypernatremia
• Hypoalbuminemia
• Hypothermia
• Hypothyroidism
• Drugs: amiodarone, quinidine, verapamil, spironolactone (compete for
secretion in distal convoluted tubule therefore ↓ excretion)
what is the management if digoxin toxicity?
Management
• Digibind
• Correct arrhythmias
• Monitor K+
what are indications for administration of digoxin specific Fab Fragment?
Indications for administration of Digoxin specific Fab Fragment are:
• Hemodynamic instability
• Life-threatening arrhythmias
• Serum potassium >5 mmol/l in acute toxicity
• Plasma digoxin level >13nmol/l
• Ingestion of more than 10 mg digoxin in adults and 4 mg in children
what is cyanide found in? what does toxicity result from?
Cyanide may be used in insecticides, photograph development and the production of certain metals. Toxicity results from reversible inhibition of cellular oxidising enzymes
what is the presentation of cyanide toxicity?
Presentation
• ‘Classical’ features: BRICK-RED SKIN, smell of bitter almonds
• Acute: hypoxia, hypotension, headache, confusion
• Chronic: ataxia, peripheral neuropathy, dermatitis
what is the management of cyanide toxicity?
Management
• Supportive measures: 100% oxygen
• Definitive: hydroxocobalamin (intravenously), also combination of amyl nitrite (inhaled), sodium nitrite (intravenously), and sodium thiosulfate (intravenously)
what is ethylene glycol?
Ethylene glycol is a type of alcohol used as a COOLANT OR ANTIFREEZE
what are the features of toxicity of ethylene glycol?
Features of toxicity are divided into 3 stages:
• Stage 1: symptoms similar to alcohol intoxication: confusion, slurred speech, dizziness
• Stage 2: metabolic acidosis with high anion gap and high osmolar gap. Also tachycardia,
hypertension
• Stage 3: acute renal failure
what is the management of ethylene glycol toxicity?
Ethylene glycol toxicity management - fomepizole. Also ethanol / hemodialysis
Management has changed recently:
• Ethanol has been used for many years
• Works by competing with ethylene glycol for the enzyme alcohol dehydrogenase, this limits the
formation of toxic metabolites (e.g. Glycoaldehyde and glycolic acid) which are responsible for
the hemodynamic/metabolic features of poisoning
• fomepizole, an inhibitor of alcohol dehydrogenase, is now used first-line in preference to
ethanol
• Hemodialysis also has a role in refractory cases
what are the cardiovascular effects of cocaine use?
Cardiovascular effects • Myocardial infarction • Both tachycardia and bradycardia may occur • Hypertension • QRS widening and QT prolongation • Aortic dissection
what are the neurological effects of cocaine use?
Neurological effects
• Seizures
• Hypertonia
• Hyperreflexia
what are the psychiatric effects of cocaine use?
Psychiatric effects
• Agitation
• Psychosis
• Hallucinations
- Hyperthermia
- Metabolic acidosis
- Rhabdomyolysis leading to renal failure.
all the above are caused by what?
cocaine
What are the clinical features of ecstasy?
Clinical features
• Neurological: agitation, anxiety, confusion, ataxia
• Cardiovascular: tachycardia, hypertension
• Water intoxication
• Hyperthermia
• Rhabdomyolysis
• Hyponatremia
what is the management of ecstasy use?
Management
• Supportive
• Dantrolene may be used for hyperthermia if simple measures fail
what are the features of mercury poisoning?
Features • Paraesthesia • Visual field defects • Hearing loss • Irritability • Renal tubular acidosis
what should be considered with the combination of abdominal pain and neurological signs?
Lead Poisoning: Along with acute intermittent porphyria, lead poisoning should be considered in questions giving a combination of abdominal pain and neurological signs
what are the features of lead poisoning?
Features • Abdominal pain • Peripheral neuropathy (mainly motor) • Fatigue • Constipation • Blue lines on gum margin (only 20% of adult patients, very rare in children)
what are the investigations found in lead poisoning?
- Microcytic anemia
- Blood film shows red cell abnormalities including basophilic stippling and clover- leaf morphology
- Raised serum and urine levels of delta aminolaevulinic acid may be seen making it sometimes difficult to differentiate from acute intermittent porphyria
- Urinary coproporphyrin is also ↑ (urinary porphobilinogen and uroporphyrin levels are normal to slightly ↑)
what is the management of lead poisoning?
Management - various chelating agents are currently used:
• Dimercaptosuccinic acid (DMSA)
• D-penicillamine
• EDT A (EthyleneDiamineTetraAcetic acid)
• Dimercaprol
what are the features of carbon monoxide poisoning?
Confusion, pyrexia and pink mucosae are typical features of carbon monoxide poisoning
Features of carbon monoxide toxicity • Headache: 90% of cases • Nausea and vomiting: 50% • V ertigo: 50% • Confusion: 30% • Subjective weakness: 20% • Severe toxicity: 'pink' skin and mucosae, hyperpyrexia, arrhythmias, extrapyramidal features, coma, death
what are typical carboxyhemoglobin levels?
• < 3% non-smokers
• < 10% smokers
• 10 - 30% symptomatic: headache, vomiting, dizziness
• > 30% severe toxicity:
-50-60%: Syncope, tachycardia, fits
-> 60%: ↑ risk of cardiorespiratory failure and death
what is the management of carbon monoxide poisoning?
Management
• 100% oxygen
• Hyperbaric oxygen
what are indications for hyperbaric oxygen in carbon monoxide poisoning?
Indications for hyperbaric oxygen
• Loss of consciousness at any point
• Neurological signs other than headache
• Myocardial ischemia or arrhythmia • Pregnancy
what is a oculogyric crisis?
Oculogyric Crisis is a dystonic reaction to certain drugs or medical conditions
Features (extra pyramidal)
• Restlessness, agitation
• Involuntary upward deviation of the eyes
what are causes of oculogyric crisis?
Causes • Phenothiazines • Haloperidol • Metoclopramide • Postencephalitic Parkinson’ s disease.
what is the treatement of oculogyric crisis?
Treatment
• Procyclidine • Benztropine
what drugs are contraindicated in pregnancy?
- ACE inhibitors, ARBs
- Statins
- W arfarin
- Sulfonylureas
- Retinoids (including topical)
- Cytotoxic agents
what antibiotics are contraindicated in pregnancy?
• Tetracyclines • Aminoglycosides • Sulphonamides • Trimethoprim • Quinolones: the BNF advises to avoid due to arthropathy in some animal studies
are antiepileptics contraindicated in pregnancy?
Majority of antiepileptics including valproate, carbamazepine and phenytoin are known to be potentially harmful. Decision to stop such treatments however is difficult as uncontrolled epilepsy is also a risk
what non-drug contraindications of pregnancy exist?
• Galactosemia
• Viral infections - this is controversial with respect to HIV in the developing world. This is
because there is such an ↑ infant mortality and morbidity associated with bottle feeding that some doctors think the benefits outweigh the risk of HIV transmission
is breast feeding safe in anti-epileptic drugs?
Breast feeding is acceptable with nearly all anti-epileptic drugs
• Antibiotics: penicillins, cephalosporins, trimethoprim
• Endocrine: glucocorticoids (avoid high doses), levothyroxine
• Epilepsy: sodium valproate, carbamazepine
• Asthma: salbutamol, theophyllines
• Psychiatric drugs: tricyclic antidepressants,
antipsychotics (except from clozapine)
• Hypertension: β-blockers, hydralazine,
methyldopa
• Anticoagulants: warfarin, heparin
• Digoxin
are safe/not safe in pregnancy?
SAFE
- Antibiotics: ciprofloxacin, tetracycline, chloramphenicol, sulphonamides
- Psychiatric drugs: lithium, benzodiazepines, clozapine
- Aspirin
- Carbimazole
- Sulphonylureas
- Cytotoxic drugs
- Amiodarone
are safe/not safe in pregnancy?
not safe
what is the administration of standard vs LMWH heparin?
standard: Intravenous
LMWH: Subcutaneous
what is the duration of action of standard vs LMWH?
standard: short
LMWH: long
what is the mechanism of action of standard vs LMWH?
Standard: Activates antithrombin III. Forms a complex that inhibits thrombin, factors Xa, IXa, Xia and XIIa
LMWH: Activates antithrombin III. Forms a complex that inhibits factor Xa
what are the side effects of standard vs LMWH?
Standard:
Bleeding
Heparin-induced thrombocytopaenia (HIT)
Osteoporosis
LMWH:
Bleeding
Lower risk of HIT and osteoporosis with LMWH
when is standard heparin used?
Useful in situations where there is a ↑ risk of bleeding as anticoagulation can be terminated rapidly
when is LMWH used?
Now standard in the management of venous thromboembolism treatment and prophylaxis and acute coronary syndromes
what electrolyte imbalance can be caused by both unfractionated and LMWH?
Both unfractionated and low-molecular weight heparin can cause hyperkalaemia. This is thought to be caused by inhibition of aldosterone secretion.
HIT:
- what is this caused by?
- when does this develop?
- does this increase or decrease clotting?
- what are the clinical features?
- what are the treatment options?
Heparin-induced thrombocytopaenia (HIT)
• Immune mediated - antibodies form which cause the activation of platelets
• Usually does not develop until after 5-10 days of treatment
• Despite being associated with low platelets HIT is actually a prothrombotic condition
• Features include a greater than 50% reduction in platelets, thrombosis and skin allergy
• Treatment options include alternative anticoagulants such as lepirudin and danaparoid
what can reverse heparin?
Heparin overdose may be reversed by protamine sulphate, although this only partially reverses the effect of LMWH.
what is adrenaline?
Adrenaline is a sympathomimetic amine with both α and β adrenergic stimulating properties
what can be used for accidental injection of adrenaline?
Adrenaline induced ischemia - phentolamine
Phentolamine, a short acting α blocker, may be used as local infiltration in situations like accidental injection of adrenaline. It is normally used mainly to control blood pressure during surgical resection of Pheochromocytoma.
when is adrenaline indicated?
Indications
• Anaphylaxis - 0.5ml 1:1,000 IM
• Cardiac arrest - 10ml 1:10,000 IV or 1ml of 1:1000 IV
what 4 drugs require therapeutic drug monitoring?
Phenytoin
• Trough levels immediately before dose
Cyclosporin
• Trough levels immediately before dose
Digoxin
• At least 6 hrs post-dose
Lithium
• Range = 0.4 - 1.0 mmol/l
• Take 12 hrs post-dose
when is botulinum toxin indicated?
- Blepharospasm
- Hemifacial spasm
- Focal spasticity including cerebral palsy patients, hand and wrist disability associated with stroke
- Spasmodic torticollis
- Severe hyperhidrosis of the axillae
- Achalasia
list some adverse effects of isoretinoin?
Adverse effects
• Teratogenicity: ♀s MUST be using two forms of contraception (e.g. COCP and condoms)
• Dry skin, eyes and lips: the most common side-effect of isotretinoin
• Low mood, depression
• Raised triglycerides
• Hair thinning
• Nose bleeds (caused by dryness of the nasal mucosa)
• Benign intracranial hypertension: isotretinoin treatment should not be combined with
tetracyclines for this reason
what can be used for metastatic bone pain?
• metastatic bone pain may respond to NSAIDs, bisphosphonates or radiotherapy
how do you initiate morphine treatment in palliative care? what else should be prescribed?
- when starting treatment, offer patients with advanced and progressive disease regular oral modified-release (MR) or oral immediate-release morphine (depending on patient preference), with oral immediate-release morphine for breakthrough pain
- if no comorbidities use 20-30mg of MR a day with 5mg morphine for breakthrough pain. For example, 15mg modified-release morphine tablets twice a day with 5mg of oral morphine solution as required
- oral modified-release morphine should be used in preference to transdermal patches
- laxatives should be prescribed for all patients initiating strong opioids
- patients should be advised that nausea is often transient. If it persists then an antiemetic should be offered
- drowsiness is usually transient - if it does not settle then adjustment of the dose should be considered
in CKD what opiates should be used?
oxycodone is preferred to morphine in palliative patients with mild-moderate renal impairment
if renal impairment is more severe, alfentanil, buprenorphine and fentanyl are preferred
how do you convert oral codeine and oral tramadol to oral morphine?
Oral codeine Oral morphine Divide by 10
Oral tramadol Oral morphine Divide by 10
how do you convert oral morphine to oral oxycodone?
Oral morphine Oral oxycodone Divide by 1.5-2
what is the equivalent of a transermal fentanyl 12microgram patch in oral morphine?
a transdermal fentanyl 12 microgram patch equates to approximately 30 mg oral morphine daily
what is the equivalent of a transdermal buprenorphine 10microgram patch in oral morphine?
a transdermal buprenorphine 10 microgram patch equates to approximately 24 mg oral morphine daily.
how to convert oral morphine to subcutaneous diamorphine?
Oral morphine to Subcutaneous diamorphine - Divide by 3
how to convert oral oxycodone to subcut diamorphine?
Oral oxycodone to Subcutaneous diamorphine - Divide by 1.5
how much is 1mg dexamethasone equal to in pred and in hydrocortisone?
- 1mg prednisolone = 4mg hydrocortisone
* 1mg dexamethasone = 7mg prednisolone
what are risk factors of developing symptoms of chemo?
Nausea and vomiting are common side-effects of chemotherapy
Risk factors for the development of symptoms include: • Anxiety • Age less than 50 years old • Concurrent use of opioids • The type of chemotherapy used
what is used for symptoms of chemo for patients at low risk or high risk?
For patients at low-risk of symptoms then drugs such as metoclopramide may be used first-line. For high-risk patients then 5HT3 receptor antagonists such as ondansetron are often effective, especially if combined with dexamethasone
what are features of medication overuse headache?
Features
• Present for 15 days or more per month
• Developed or worsened whilst taking regular symptomatic medication
• Patients using opioids and triptans are at most risk
• May be psychiatric co-morbidity
what is the management of medication overuse headache?
Management
• Simple analgesics and triptans should be withdrawn abruptly (may initially worsen headaches)
• Opioid analgesics should be gradually withdrawn
what is doxazosin?
Doxazosin is an α-1 adrenoceptor antagonist used in the treatment of hypertension and benign
prostatic hypertrophy
name 4 α antagonists?
- α-1: doxazosin
- α-1a: tamsulosin - acts mainly on urogenital tract
- α-2: yohimbine
- Non-selective: phenoxybenzamine (previously used in peripheral arterial disease)
name 2 beta blockers
β antagonists
• β-1: atenolol
• Non-selective: propranolol
what are Carvedilol and labetalol?
Carvedilol and labetalol are mixed α and β antagonists
what is lithium?
Lithium is mood stabilising drug used most commonly prophylatically in bipolar disorder but also as an adjunct in refractory depression. It has a very narrow therapeutic range (0.4-1.0 mmol/L) and a long plasma half-life being excreted primarily by the kidneys
what tremor is seen in lithium toxicity?
Lithium: fine tremor in chronic treatment, coarse tremor in acute toxicity
what is the mechanism of action of lithium?
Mechanism of action - not fully understood, two theories:
• Interferes with inositol triphosphate formation
• Interferes with cAMP formation
what are adverse effects of lithium?
Adverse effects • Nausea/vomiting, diarrhea • Fine tremor • Polyuria • Thyroid enlargement, may lead to hypothyroidism • ECG: T wave flattening/inversion • W eight gain
what is involved in the monitoring of patients on lithium therapy?
Monitoring of patients on lithium therapy
• Inadequate monitoring of patients taking lithium is common - NICE and the National Patient
Safety Agency (NPSA) have issued guidance to try and address this. As a result it is often an
exam hot topic
• Lithium blood level should ‘normally’ be checked every 3 months. Levels should be taken 12
hours post-dose
• Thyroid and renal function should be checked every 6 months
• Patients should be issued with an information booklet, alert card and record book
Lithium toxicity generally occurs following concentrations > 1.5 mmol/L.
