CPT revision Flashcards
What is the pathophysiology of rheumatoid arthritis?
Hypertrophy of joint synovial to form pannus.
Infiltration of inflammatory cells, release of pro-inflammatory cytokines.
Pannus erodes cartilage and bone
What criteria aids RA diagnosis?
Morning stiffness > 1 hour > 3 joints affected Hand joints affected Symmetrical Rheumatoid nodules Serum rheumatoid factor
What are the side effects of corticosteroids?
Hypertension Osteoporosis Weight gain Bruising Hyperglycaemia Infections Skin thinning
What is the MOA of corticosteroids?
Inhibit T cell activation
Prevent IL-1 and IL-6 synthesis by macrophages.
What SE are common to all immunosuppressants?
Hepatitis
Infection risk
Malignancy
BM suppression
Name 4 highly protein bound drugs.
NSAIDS
Methotrexate
Warfarin
Sulphonylureas
What tests are necessary to monitor if giving calcinuerin inhibitors?
eGFR - renal toxicity
BP - accelerates hypertension
What tests must be done before methotrexate treatment?
CXR - pnueumonitis
FBC
LFT
What are the side effects of methotrexate, how can they be reduced?
Mucositis BM suppression Liver cirrhosis, hepatitis Lungs - pneumonitis Teratogenic
Folic acid reduces mucositis + BM suppression.
Which DMARD has poor intestinal absorption and can therefore be used to treat IBD?
Sulphasalazine
What is the MOA of sulphasalazine?
Inhibit T cell proliferation and IL-2 synthesis
Decrease neutrophil chemotaxis and degranulation.
Which DMARD causes haemorrhagic cystitis, how can this be minimised?
Cyclophosphamide - acrolein metabolite is toxic to bladder epithelium.
Mesna and hydration - mesna binds bladder ep and prevents interaction
What is the MOA of anti-TNF alpha?
Inhibit cytokine cascade and leukocyte recruitment
Decrease angiogenesis
Give 4 conditions methotrexate is used to treat.
Cancer
RA
Psoriasis
Crohn’s
How can oseltamivir resistance arise?
Neuroaminidase enzyme mutation
Which viral enzyme activates aciclovir?
thymidine kinase
What is the MOA of nucleoside RT inhibitors and non-nucleoside RT inhibitors?
NRTI - analogues of nucleosides, bind and halt reverse transcriptase.
NNRTI - non-competitive inhibition of HIV reverse transcriptase. Bind to allosteric sight and cause conformational change, inhibiting RT.
What is the MOA of protease inhibitors?
Inhibits protease enzyme responsible for cleavage of the viral polyprotein into a number of essential enzymes and proteins.
What is the MOA of integrase inhibitors?
Inhibits insertion of viral DNA into host genome
What is the advantage of virus resistance testing?
Increases outcome
Reduces costs
No ADRs of ineffective therapy
Decreases resistant virus pool
How is virus resistance testing done?
Phenotypic characterisation
What advice should you give to patients when prescribing warfarin?
Risk of bruising and bleeding
Teratogenic
Avoid NSAIDs and aspirin - bleeding risk
Food - too many leafy greens reduce effectiveness
What should you check before administering heparin?
Renal function - renal clearance
What are ADRs of heparin?
Bleeding
Osteoporosis
Thrombocytopenia
What is used to reverse heparin if actively bleeding?
Protamine sulphate - dissociates heparin from antithrombin III. Irreversibly binds.
Name 3 anti-platelet drugs and their MOA.
Aspirin - COX - 1 inhibitor, inhibits thromboxane A2 synthesis
Clopidogrel - ADP antagonist
Dipyridamole - phosphodiesterase inhibitor
What are the benefits of anti platelet drugs?
Decreased risk of intracranial haemorrhage
No monitoring
What are the disadvantages of anti-platelet drugs?
Increased risk GI bleed
May not have reversal agent
Which study designs are best for establishing a temporal sequence?
RCT
Prospective cohort
Poor -case-control, cross-sectional
What is a side effect of H2 antagonists in males?
Gynaecomastia
What are side effects of proton pump inhibitors?
Diarrhoea
Infection risk
C.difficile risk
Osteoporosis - increase pH, decrease Ca absorption
What are some causes of GORD?
Obesity - raised intrabdo pressure
LOS weakness
Delayed gastric emptying
Hiatus hernia
What is the treatment for peptic ulcer?
Stop NSAIDs if can
H2RA or PPI for 6 weeks
H-pylori eradication if relevant
What are SE of B2 agonists?
Tremor
Tachycardia, palpitations
What is the MOA of montelukast?
Leukotriene receptor antagonist
Mast cells release leukotriene - mucus secretion, mucosal oedema, bronchoconstiction
SE of LTRA?
Fever
Angioedema, Arthralgia, Anaphylaxis
Dry mouth
What is the MOA of methylxanthines?
Inhibit phosphodiesterase, increase cAMP
Inhibit adenosine receptors
What are the characteristics of methylxanthines?
Narrow therapeutic window - monitoring required
Poor efficacy
CYP450 metabolism - interactions
What are the SE of aminophylline?
Seizures, convulsions
Arrhythmia
Name 2 long acting anticholinergics?
Tiotropium bromide
Ipratropium bromide
What is the MOA of voltage gated Na blockers when treating epilepsy?
Bind to depolarised Na channels and prolong inactivation state to inhibit spread of hyperactivity.
Detach once membrane potential normal again = use dependent.
Name 4 VGSC blockers for epilepsy?
Carbamezepine
Phenytoin
Lamotrigine
Valproate
Which anti-epileptic drug half life reduces with repeated doses.
Carbamezepine - induces CYP450 enzymes which metabolise it.
Which AEDs are highly protein bound?
Carbamezepine
Phenytoin
Valproate
BZDs
What is a rare but serious ADR of carbamazepine?
Bone marrow suppression - neutropenia
What ADRs are associated with AEDS?
CNS - dizziness, drowsiness, ataxia
Rashes
Nausea and vomiting
Outline the pharmacokinetics of phenytoin, what is the significance of this?
Non-linear at therapeutic conc - t/12 unpredictable, monitoring required.
Highly protein bound
CYP450 - enzyme inducing - COCP, warfarin (not itself)
How are phenytoin and valproate levels monitored?
Salivary levels - indication of free plasma level
What is the MOA of lamotrigine?
Na channel blocker
Ca channel blocker
What are the advantages of lamotrigine?
Fewer CNS SE
No CYP induction - fewer DDI
Safest in pregnancy
What is the interaction between the OCP and lamotrigine?
OCP reduces plasma levels of lamotrigine - dose adjustment needed.
What are the risks of AEDs during pregnancy?
Neural tube defects - valproate in particular
Learning difficulties
What dietary supplements should be taken if to reduce risk of AEDs during pregnancy?
Folic acid - neural tube
Vit K in T3
What is the MOA of valproate?
Weak stimulation of GABA synthesis
Weak inhibition of GABA inactivating enzymes
VGSC blocker and weak CCB
Which AED is associated with hepatotoxicity and raised transaminase levels?
Valproate
What DDIs are associated with valproate?
Anti-depressants inhibit valproate action.
Anti-psychotics antagonist valproate - lower seizure threshold.
Aspirin increases plasma conc by competitive binding.
Which AEDs are indicated for absence seizures?
Lamotrigine
Valproate
Which AED is first line for generalised seizures?
Valproate
What is the protocol used in emergency seizure management or status epilepticus?
Benzodiazepines
2nd dose if continuing after 5 mins
Phenytoin IV
Name 2 BZDs used to treat epilepsy and their route of administration.
IV lorazepam
Rectal diazepam
What are the side effects of L-dopa?
Nausea
Hypotension (dopamine vasodilator!!)
Tachycardia
Psychosis - hallucinations
Name 2 DDI of L-dopa.
Vit B6 increases peripheral breakdown of L-dopa
Combined with MAOIs - risk of hypertensive crisis.
Describe the pharmacokinetics of L-dopa.
Short half life
Competes with AA for gut absorption - decreased after protein meal.
Name a non-ergot derived dopamine agonist.
Ropinirole
What are the disadvantages of dopamine agonists to treat Parkinson’s?
- Less efficacious than L-dopa
- Psychotic SE are dose limiting
- Impulse control disorders
What must you ask about before prescribing a dopamine agonist?
Impulse control disorders:
- pathological gambling
- hyper sexuality
- compulsive shopping
- punding
What are the SE of dopamine agonists?
Nausea
Hypotension - dopamine vasodilates!!
CNS - sedation, confusion, hallucinations
Name two MAOI’s.
Rasagiline, Selegiline
What is the MOA of COMT inhibitors?
Inhibits peripheral breakdown of L-dopa to 3-methyldopa which competitively inhibits L-dopa active transport into CNS.
What are anticholinergics used to treat in Parkinsons?
Tremor only - ACh may antagonise dopamine
Deep brain stimulation of what structure can be used to treat PD.
Subthalamic nucleus.
What are the clinical features of Parkinsons plus syndromes?
Early onset dementia Early onset postural instability Early onset hallucinations or psychosis Early onset postural hypotension + incontinence Ocular signs Symmetrical
What is the commonest presentation of myasthenia graves?
Diplopia, ptosis
When might you prescribe MAOIs?
Either with L-dopa to reduce wearing off effects
Alone to treat PD
What are the 3 theories of depression?
Monoamine hypothesis
Neurotransmitter receptor theory
Monoamine hypothesis of gene expression
What are common and rare SE of SSRIs?
Common - anorexia, nausea, diarrhoea
Rare - mania precipitation, suicidal ideation, tremor
Citalopram - prolongs QT
Give one advantage of prescribing SSRs rather than TCAs.
Relatively safe in OD.
TCAs - dangerous in OD due to cardiac effects
Name 2 TCAs.
Amitryptylline, imipramine
What is the MAO of TCAs?
Non-specific inhibitor of monoamine uptake - NA and 5-HT.
What receptors do TCAs have affinity for, what SE do these cause?
alpha 1 adrenoceptors - postural hypotension
Muscarinic receptors - dry mouth, blurred vision, constipation
Histamine receptors
What other SE do TCAs cause?
CNS - sedation, lower seizure threshold
CVS - tachycardia, impaired contractility
ANS - decrease gland secretions
Give an example of an SNRI.
Venlafaxine.
Explain the dose-dependent effects of SNRIs.
Low dose - serotonin action = anti-depressant
High dose - NA action = anxiolytic
Inhibition of which dopamine pathway leads to sexual dysfunction and infertility?
Tuberoinfundibular
Name 2 typical antipsychotics.
Haloperidol
Chlorpomazine
Name 2 atypical antipsychotics.
Olanzapine, clozapine.
What are 3 features of all antipsychotics?
Sedation
Delayed onset - days to weeks
Extrapyramidal SE
Compare and contrast the SE of typical and atypical antipsychotics.
Typical - more extrapyramidal SE - parkinsonism
Atypical - more metabolic SE - weight gain, hyperprolactinaemia
Which atypical antipsychotic is associated with weight gain?
Olanzapine
Which atypical antipsychotic is associated with sexual dysfunction and hyperprolactinaemia?
Risperidone
Why is clozapine only 3rd line therapy despite being most effective antipsychotic?
Side effects - require weekly FBC
Neutropenia, agranulocytosis
Constipation, weight gain, hypersalivation.
What are the side effects of benzodiazepines?
Tolerance
Dependence
Drowsiness, dizziness, ataxia
What antidote is used for a benzodiazepine OD?
Flumazenil
Outline the pharmacokinetics of Lithium to treat bipolar disorder.
Narrow therapeutic window + long half life - monitoring essential.
Renal excretion
What tests must be done before starting lithium treatment and every 6 months?
Renal function - renal toxicity
Thyroid function - hypothyroidism
What are SE of lithium?
Memory problems Thirst + polyuria (ADH antagonist) Tremor Drowsiness Weight gain Renal toxicity Hypothyroidism
Other than lithium, name 3 drugs which can act as mood stabilisers.
Carbamezepine
Sodium valproate
Lamotrigine
Which two drug classes can be used to treat dementia?
Mild-moderate: ACh esterase inhibitors - galantine
Mod -severe: NMDA antagonist - Memantine
Name 3 endogenous opioids?
Enkaphalins
Dynorphin
Endorphins
What effect do opioids have on pre-synaptic receptors?
Inhibit adenyl cyclase, less cAMP.
Less Ca influx.
Decreased NT release.
What effect do opioids have on post-synaptic receptors?
Increased K+ efflux, decreased excitability.
What ADRs are associated with opioids?
Nausea + vomiting Constipation Confusion Drowsiness, decreased consciousness Respiratory depression Constricted pupils Dependence + tolerance.
Why must steroid therapy never suddenly be stopped?
Exogenous steroids mimicking cortisol negatively inhibit the hypothalamus and reduce endogenous cortisol release.
If suddenly stopped, low cortisol levels cause hypo-adrenal crisis.
Does prednisolone have more or less mineralocorticoid activity than cortisol?
Less - more glucocorticoid selective
What effect do corticosteroids have on bone?
Inhibit osteoblast formation
Increase osteoclast proliferation
Decrease calcium absorption in gut
When are cortisol levels the highest?
Morning
What are the symptoms of addison’s disease?
Hypoglycaemia Hypotension Weight loss Nausea Hyponatraemia Hyerkalaemia
What are the symptoms of Cushing’s disease?
Same as corticosteroid SE:
- hyperglycaemia
- weight gain
- hypertension
What is Cushing’s disease?
Excess ACTH resulting from a pituitary adenoma.
What drug class is tolbutamide?
Sulphonylurea
What 4 pieces of lifestyle advice might you give someone before prescribing oral hypoglycaemic agents?
Diet - low calorie, low sugar
Exercise
Low alcohol
Stop smoking
What are the 3 main consequences of inhibiting ACE?
- Reduced vasoconstriction
- Reduced sympathetic activity
- Reduced aldosterone leads to reduced salt and water retention.
What advice would you give a patient taking SSRIs?
- Can take 2-6 weeks to be effective
- Continue taking for at least 1 year even if feeling better to reduce risk of relapse
What is the risk of giving NSAIDs + SSRIs together?
GI bleeding + ulcer formation
- Platelets need 5-HT to clot
How would you determine a patients fluid status?
Skin turgor
HR, BP
Mucous membranes
Urine output + colour
How is a viral load used clinically?
- Effectiveness of treatment - dose adjustment
- Transmissibility
- When ‘cured’ - undetectable Hep C viral load
What is a ‘low genetic barrier to resistance’?
Only 1-2 mutations needed before resistance is likely to develop - more likely
What is an ‘unfit’ virus?
a virus that has mutated to the point where it can no longer replication quickly/at all.
What is Zollinger Ellison Syndrome, how does it manifest clinically?
Gastrinoma - G cell cancer
Gastrin -secreting tumor - recurrent peptic ulcers.
Thiazides + carbamezepine result in what?
Hyponatraemia
Steroids + thiazide/loop result in what?
Hypokalaemia
What does a high blood gas partition mean in terms of solubility and potency?
High blood gas partition = more soluble = more potent
How does oil gas partition effect onset and offset?
High = slower onset as lipid partitioning Low = faster onset
How does pKa of a local anaesthetic alter onset?
Low pKa = faster onset