Pharmacology - Examples Flashcards
How is Type 2 diabetes typically managed in adults?
Lifestyle modification
If HbA1c > 48 mmol/mol, standard dose metformin
If HbA1c > 58 mmol/mol, metformin with one of DD-4 inhibitor, pioglitazone, sulphonylurea or SGLT-2 inhibitor
If HbA1c > 58 mmol/mol (second intensification), consider insulin or triple therapy
How does metformin work?
Metformin is used to treat diabetes by activating 5’-AMP-activated protein kinase (AMPK) in hepatocyte mitochondria. This inhibits ATP production, blocks gluconeogenesis and HGO. It also blocks adenylate cyclase (promotes fat oxidation).
What are the side effects of metformin? How are they mitigated?
Abdominal pain, decreased appetite, diarrhoea, vomiting
Gradual introduction helps with tolerability
What is an example of a DPP-4 inhibitor?
Sitagliptin
How do DPP-4 inhibitors work?
Diabetes management:
They inhibit the action of DPP-4. This enzyme is present in vascular endothelium and can metabolise incretins in the plasma. Incretins help stimulate the production of insulin, reduce production of glucagon, slow down digestion and decrease appetite.
What are the side effects of DPP-4 inhibitors?
Upper respiratory tract infections (5% of patients)
Flu-like symptoms e.g. headache, runny nose, sore throat
Serious allergic reactions/ avoid in patients with pancreatitis
How do sulphonylurea work?
Diabetes management:
Inhibit the ATP-sensitive potassium (KATP) channel on the pancreatic beta cell. This channel controls beta cell membrane potential. Inhibition causes depolarisation which stimulates Ca2+ influx and subsequent insulin vesicle exocytosis.
What are the side effects of sulphonylurea?
Weight gain
Hypoglycaemia (should be discussed with patient)
What is an example of a SGLT2 inhibitor?
Dapagliflozin
How do SGLT2 inhibitors work?
Diabetes manegement:
Reversibly inhibits sodium-glucose co-transporter 2 (SGLT2) in the renal proximal convoluted tubule to reduce glucose reabsorption and increase urinary glucose excretion.
What are the side effects of SGLT2 inhibitors?
Uro-genital infections due to increased glucose load (5% of patients)
Slight decrease in bone formation
Can worsen diabetic ketoacidosis (stop immediately)
Weight loss
Reduction in BP
What are the different types of seizures?
Absence Focal Generalised tonic-clonic Myoclonic Tonic/atonic
What is the diagnostic approach to determining the type of seizure?
EEG
What is the most commonly prescribed drug for individuals without child-bearing potential suffering from seizures?
Sodium valproate
How does lamotrigine work?
Seizure management:
Blocks voltage gated Na+ channels preventing Na+ influx. Prevents depolarisation of glutamatergic neurones and reduces glutamate excitotoxicity.
What are the side effects of lamotrigine?
Rash (can be avoided by gradual administration)
Drowsiness
Steven-Johnson’s syndrome (less common)
Suicidal thoughts (less common)
How does sodium valproate work?
Seizure management:
Inhibition of GABA transaminase prevents the breakdown of GABA. This increases GABA concentrations directly in the synapse presynaptically and also indirectly prolongs GABA in the synapse due to the fact that extra neuronal metabolism of GABA is slowed.
What are the side effects of sodium valproate?
Stomach pain and diarrhoea Drowsiness Weight gain Hair loss Hepatotoxicity Teratogenicity Pancreatitis
Why is sodium valproate contraindicated for those with child-bearing potential?
Neural tube defects, decreased IQ and autism after in utero exposure
How do diazepams work?
Seizure management:
Increases chloride ion influx in response to GABA binding at the GABAA receptor. Increased chloride ion influx associated with hyperpolarization of excitatory neurons.
What are the side effects of diazepams?
Drowsiness
Respiratory depression (if I.V. or at high dose)
Haemolytic anaemia (uncommon)
Jaundice (uncommon)
Why are diazepams not used for long-term suppression?
Increased tolerance and high possibility of dependence
How does levetiracetam work?
Seizure management:
Inhibition of the synaptic vesicle protein SV2A. It inhibits this protein and prevents vesicle exocytosis. A reduction in glutamate secretion reduces glutamate excitotoxicity.
What are the side effects of levetiracetam?
Dizziness
Somnolence
Fatigue
Headache
How can depression be diagnosed?
The Patient Health Questionnaire-9 (PHQ-9) can be used to screen for depression. It describes the severity of MDD (minor, moderate or severe).
What are some examples of SSRIs?
Sertraline, citalopram and fluoxetine.
How do SSRIs work?
Inhibition of serotonin reuptake predominantly in the hippocampus results in an accumulation of serotonin. Serotonin in the central nervous system plays a role in the regulation of mood, personality, and wakefulness.
What are the side effects of SSRIs?
Inhibition of serotonin reuptake results in an accumulation of serotonin. Serotonin in the central nervous system plays a role in the regulation of mood, personality, and wakefulness.
What types of drugs is citalopram contraindicated with?
Drugs that prolong QT interval as likely to cause Torsades de pointes.
Why must SSRIs and SNRIs be gradually discontinued?
To prevent withdrawal symtoms
What is an example of a SNRI?
Venlafaxine
How do SNRIs work?
Venlafaxine is a more potent inhibitor of serotonin reuptake than norepinephrine reuptake. Noradrenaline in the central nervous system is implicated in the regulation of emotions and cognition.
What are the side effects of SNRIs?
GI effects (nausea, diarrhoea) Sexual dysfunction Anxiety Insomnia Hypertension (at higher doses due to adrenergic effects)
How does mirtazapine work?
Depression management:
Antagonises central presynaptic alpha-2-adrenergic receptors, which causes an increased release of serotonin and norepinephrine.
Antagonises central 5HT2 receptors, which leaves 5HT1 receptors unopposed causing anti-depressant effects.
What are the side effects of mirtazapine?
Weight gain
Sedation (due to action on H1 receptors)
Sexual dysfunction (rare)
Exacerbates REM sleep behaviour disorder
What’s an important metric that is used for hypertension management?
Q-risk score
What is the management of hypertension focused around?
Lifestyle and diet (DASH)
Drugs
Smoking
Weight loss
What are examples of ACE inhibitors?
Ramipril, lisinopril and perindopril
How do ACE inhibitors work?
Hypertension management:
Inhibit the angiotensin converting enzyme. Prevent the conversion of angiotensin I to angiotensin II by ACE.
What are the side effects of ACE inhibitors?
Cough
Hypotension
Hyperkalaemia (care with K+ supplements or K+ sparing diuretics)
Foetal injury (must avoid in pregnant women)
Renal failure (in patients with renal artery stenosis) - eGFR muust be monitored
Urticaria/angioedema
What are examples of calcium-channel blockers?
Amlodipine, felodipine and nifedipine
How do calcium-channel blockers work?
Hypertension management:
Block L-type calcium channels – predominantly on vascular smooth muscle. This results in a decrease in calcium influx, with downstream inhibition of myosin light chain kinase and prevention of cross-bridge formation. The resultant vasodilation reduces peripheral resistance.
What are the side effects of calcium-channel blockers?
Ankle oedema Constipation Palpitations Reflex tachycardia Flushing/headache
What are examples of thiazide/thiazide-like diuretics?
Bendroflumethiazide (thiazide) and indapamide (thiazide-like)
How do thiazide diuretics work?
Hypertension management:
They block the Na+/Cl- cotransporter in the early DCT. Therefore Na+ and Cl- reabsorption is inhibited. As a result the osmolarity of the tubular fluid increases, decreasing the osmotic gradient for water reabsorption in the collecting duct. This decreases blood volume, venous return and consequently cardiac output.
What are the side effects of thiazide/thiazide-like diuretics?
Hypokalemia
Hyponatremia
Metabolic alkalosis (increased hydrogen ion excretion)
Hypercalcemia
Hyperglycemia (hyperpolarized pancreatic beta cells)
Hyperuricemia
What are examples of angiotensin receptor blockers?
Losartan, Irbesartan and Candesartan
How do angiotensin receptor blockers work?
Hypertension management:
These agents act as insurmountable (i.e. non-competitive) antagonists at AT1 receptors (found on kidneys and on the vasculature).
What are the side effects of angiotensin receptor blockers?
Hypotension
Hyperkalaemia (care with K+ supplements or K+ sparing diuretics)
Foetal injury (must avoid in pregnant women)
Renal failure (in patients with renal artery stenosis)
Why is the inhaled route preferred over the oral route for asthma drug administration?
Many drug solutions and combinations can be made
Minimal patient cooperation is required
Concentration and dose can be modified
There is a normal breathing pattern
Less drug loss through exhalation, lung/oral cavity absorption, mucociliary clearance and GI tract
How does salbutamol work?
Agonist at the β2 receptor on airway smooth muscle cells. Activation reduces Ca2+ entry and this prevents smooth muscle contraction.
What are the side effects of salbutamol?
Palpitations/agitation
Tachycardia/Arrhythmias (due to beta 1 receptor action)
Hypokalaemia (at higher doses)
How does fluticasone work?
Fluticasone directly decreases inflammatory cells such as eosinophils, monocytes, mast cells, macrophages, and dendritic cells by targeting the glucocorticoid receptor. It reduces the number of these cells and also the number of cytokines they produce.
What are the side effects of fluticasone?
Sore throat Hoarse voice Opportunistic oral infections Growth retardation in children Hyperglycaemia Decreased bone mineral density Immunosuppression Effects on mood
How does mometasone work?
Fluticasone directly decreases inflammatory cells such as eosinophils, monocytes, mast cells, macrophages, and dendritic cells by targeting the glucocorticoid receptor. It reduces the number of these cells and also the number of cytokines they produce.
What are the side effects of mometasone?
Sore throat Hoarse voice Opportunistic oral infections Growth retardation in children Hyperglycaemia Decreased bone mineral density Immunosuppression Effects on mood
How does budesonide work?
Fluticasone directly decreases inflammatory cells such as eosinophils, monocytes, mast cells, macrophages, and dendritic cells by targeting the glucocorticoid receptor. It reduces the number of these cells and also the number of cytokines they produce.
What are the side effects of budesonide?
Sore throat Hoarse voice Opportunistic oral infections Growth retardation in children Hyperglycaemia Decreased bone mineral density Immunosuppression Effects on mood
How does montelukast work?
Asthma management:
Antagonism of CysLT1 leukotriene receptor on eosinophils, mast cells and airway smooth muscle cells which decreases eosinophil migration, broncho-constriction and inflammation induced oedema.
What are the side effects of montelukast?
Diarrhoea Fever Headaches Nausea or vomiting Mood changes Anaphylaxis
What type of asthma is montelukast more useful for?
NSAID-induced asthma due to preferential breakdown of arachidonic acid into leukotrienes.
