clinical pharmacology questions pps (15/30)
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Clinical Pharmacology Questions pps (15/30). Define:. Pharmacokinetics (1) What the body does to the drugs Pharmacodynamics (1) What the drug does to the body. Give three ways in which you would improve patient compliance (3). Keep regimen simple Provide patient education - PowerPoint PPT PresentationTRANSCRIPT
Clinical Pharmacology Questionspps (15/30)
Define:
Pharmacokinetics (1) What the body does to the drugs
Pharmacodynamics (1) What the drug does to the body
Give three ways in which you would improve patient compliance (3)
Keep regimen simple
Provide patient education
Avoid side effects
Define:
Bioavailability (3) The proportion of administered drug which
reaches systemic circulation and available for distribution to site of action
S/R (1) Slow release
E/C (1) Enteric coating
Name the 4 factors involved in the pharmacokinetic process (4)
Absorption Distribution Metabolism Excretion
“A D M E”
Name three factors that can affect the rate of absorption in the GI tract (3)
Gastrointestinal motility
Food
Malabsorptive state (cealiac disease)
What are the 2 biochemical pathways of metabolism in the liver (4)?
Phase 1 Reactions increase polarity of drug (unmask functional
groups) controlled my microsomal mixed function oxidase
system (NADPH, CYP450 + O2)
Phase 2 Reactions conjugation of drug to promote excretion (more
hydrophillic) glucuronyl, acetyl, methyl
What 4 factors affect metabolism by the liver (4)?
Age elderly + neonates have reduced function
Drug Interactions EtOH, rifampacin, carbamazepine increase CYP450 cimetidine, azoles, macrolides decrease CYP450
Genetic Polymorphisms CYP2D6 = codeine to morphine (underactive i.e.
poor effect)
Liver Disease decreases metabolism increased bioavailability as decreases 1stPM and
decreased protein binding (hypoalbuminaemia)
What is first pass metabolism (1) and where does it occur (3)?
“extent of metabolism occurring before the drug enters the systemic circulation – oral route only”
Occurs in the… gut lumen
gut wall
liver
How can first pass metabolism be avoided (5)?
give drug to avoid porto-hepatic system:
mucosal – sublinual, buccal rectal, vaginal
inhalation
transdermal
IV
IM
Describe the molecular action of insulin release (6)
glucose uptake by GLUT2 glucose ATP ATP causes ATP-senstive K+ channels to close depolarisation of the membrane voltage-gated Ca2+ channels open increase in i[Ca2+] PIP2 PLC IP3 + DAG Insulin vesicles fuse to membrane and release
State 5 broad actions of insulin (5)
Carbohydrate metabolism increased glycogenesis increased glucose uptake decreased gluconeogenesis
decreases lipolysis increases fatty acid and TG synthesis increases protein synthesis
decreases protein degredation Increased cellular uptake of K+
What are the types of diabetes (6)?
Type 1 Insulin Dependent B-cell destruction
Type 2 Non-Insulin Dependent insulin resistance
Gestational Diabetes insulin resistance
Genetic: MODY genetic defect in insulin production
Drug-Induced cortisol, steroids
Disease-Induced Cushing’s pheochromocytoma
State some long term complications associated with diabetes (6)
Blindness (diabetic retinopathy) Kidney failure (diabetic nephropathy) Nerve damage (diabetic neuropathy)
diabetic foot Atherosclerosis
CHD/Stroke Hypoglycaemia and DKA
Coma and death Infection
What treatments are available for type I diabetes sufferers? (4)
Lifestyle Insulin Diet, exercise Islet transplantationWhat are the types of insulin available (4)?
• short acting – human insulin or analgue (novorapid)• intermediate acting – isophane insulin• long acting - glargine• premixed – fast + inter/long acting
Name three types of diabetic emergency and their general treatments (6)
Ketoacidosis Hypoglycaemia Lactic acidosis
IV fluids (saline) Insulin (DKA) + K+ replacement Treat the cause (glucose for hypo)
What is the main treatment given in type II diabetes?
Metformin
Generally what strategy should be used in a diabetes consultation / examination? (8)
Alphabet strategy:
Advice
Blood pressure
Cholesterol
Diabetes control
Eye examination
Feet examination
Guardian drugs
Heart risk score
What effect does metformin have on the body? (2)
Increased peripheral insulin action Increased glucose uptake
What other drug is metformin usually taken in combination with? (1)
Insulin
What three side effects can metformin have?
GI symptoms
B12 malabsorption
Lactic acidosis
What is the mechanism of action for sulphonylureas?
Increased insulin release via KATP channel blocking
What do sulphonylureas need in the body to work properly?
Working B-cells i.e. won’t work in type 1 DM
State three adverse effects of sulphonylureas (3)
Hypoglycaemia Weight gain Reactions
Why is insulin said to have a biphasic response (2) Early spike Late plateau
What is the mechanism of action of thiazolidinediones (1)?
Reduced insulin resistance
Name three side effects Weight gain Oedema Hypoglycaemia
List some adverse effects of insulin (4)
Weight gain Hypoglycaemia Retinopathy Reactions Lipoatrophy Insulin resistance Infection at site of injection
Give an example of... Gram positive cocci
Staphlococcus aureus Streptoccus pneumoniae
Gram negative cocci Neisseria meningitides Neisseria gonorrhoeae
Gram positive baccili Bacillus cereus Clostridium difficile
Gram negative bacili Haemophilus influenzae Campylobacter jejuni
In what 3 main ways do antibiotics work ?
Inhibit DNA synthesis
Inhibit protein synthesis
Inhibit cell wall synthesis
Give 3 classes of antibiotics that inhibit DNA synthesis with examples (6)?
Sulphonamides Trimethoprim
Quinolones Ciprofloxacin
Nitroimidazoles Metronidazole
Give 3 classes of antibiotics that inhibit protein synthesis with examples (6)?
Tetracyclins doxycyclin
Macrolides erythromycin
Aminoglycosides Gentamycin
Give 4 classes of antibiotics that inhibit bacterial cell wall synthesis
with examples (8)?
Penicillins amoxycillin
Carbapenems meropenam
Cephlosporins Ceftriaxone
Glycopeptides Vancomycin
What two drugs make up co-amoxiclav (2)?
Amoxicillin Clavulanic acid
What is the mechanism behind penicillin resistance (2)? increase in Beta-Lactamase breaks down beta-lactam ring
State some long term complications of asthma (4)
Hypertrophy of airways muscle Hyperplasia of mucous secreting cells Angiogenesis Subepithelial fibrosis
Define Asthma (3) Reversible, inflammatory, obstructive disease of lungs
COPD
Give two examples Emphysema Chronic bronchitis
What can cause it? Chronic irritation (smoking)
What is the cell that is mostly involved with COPD? Neutrophils
Give three symptoms of COPD
Dyspnoea Chronic cough Production of sputum
Why is there an increased risk of infection in COPD (2)? destruction of mucociliary escalator cannot remove pathogens
How is COPD treated (5)?
Early – Lifestyle (prevent irritant) Physiotherapy B2-adrenoreceptor agonists Corticosteroids Late – combined therapy with oxygen
What principle cell is involved in inflammation of allergic asthma (1)?
Eosinophils
What are the 4 main treatments of asthma + give an example of each (8)?
B2-adrenoreceptor agonist Salbutamol, terbutaline
Glucocorticoids Prednisolone (oral), budesonide (inhaled)
Anti-cholinergics Ipratropium bromide
Methylxanthine / PDE inhibitors Theophylline, aminophylline / roflumilast
What are the other possible drug treatments for asthma (4)?
O2
Leukotrine receptor antagonists monteleukast
IgE mAb omalizumab
Mast cell stabiliser sodium cromoglycate
Mucolytics carbocysteine
What are the mechanisms of action of B2 agonists (5)?
Gs -> adenylate cyclase -> cAMP -> PKA -> inactivates MLCK (needed for myosin phosphy) activates K+ channels = membrane depolarises decreases intracellular Ca2+ levels
increase mucocillary clearance decrease neutrophil function decreases cholinergic transmission
State the mechanism of action for...
Glucocorticoids expression of anti-inflammatory genes: IL-10, IL-1 antagonist decreases pro-inflammatory genes: NF-Kb, AP-1, IL-1, IL-2
Methylxanthines Stops cAMP being degraded = muscle relaxation
Anti-cholinergic blocks M3 receptors = stops parasympathetic constriction
USUALLY: M3 (Gq) -> PLC -> PIP2 + DAG -> PKC + Ca2+
Why would a patient with acute asthma be given IV hydrocortisone (2)?
To prevent late-stage asthma attack (4-72 hours later)
IV as unlikely to be able to swallow tablet or inhale
What are the side effects of B2 agonists (6)?
Muscle tremor Cramps palpitations/tachycardia hyperkalaemia insomnia headache dry mouth anxiety flushing myocardial ischaemia (steel syndrome)
Give 6 side effects of corticosteroids on different body systems (6)
• MSK: atrophy, osteoporosis, myopathy• Metabolic: weight gain, adrenal
supression, hypokalaemia• CV: hypertension, oedema• Immune: candidiasis (poor immune
function)• GIT: peptic ulcers, pancreatitis,
oesophagitis• Neuro: psychosis
How do methylxanthines work synergistically with B2-agonists?
B2 agonists increase cAMP = bronchodilation. cAMP is broken down by phosphodiesterases. Methylxanthines block the action of the
phosphodiesterase therefore, enhancing the levels of cAMP
State some side effects of anticholinergics (9)
Nausea Constipation Dry mouth and cough Pharyngitis URTI’s Bitter taste Supraventricular tachycardia Atrial fibrillation Urinary retention
State three side effects of over-use of theophyllines
Seizures Cardiac arrhythmia's Nausea
What are the ANS actions of the GIT + what neurotransmitters
are released (4)?
Parasympathetic (Ach and 5-HT) increase GI motility increase secretions
Sympathetic (NA) decrease GI motility decrease GI secretions
Give 2 types of anti-emetic and explain how they work (4)?
5-HT antagonist ondansetron
D2 antagonist metoclopramide
both drugs inhibit 5-HT or D2 receptors in emesis centre of medulla decrease vagal tone
What 5 types of drugs can be given for constipation with
examples (10)? Purgatives/Motility Stimulants
metoclopramide, domperidone stimulate myenteric plexus = increase GI motility
Bulk laxative methylcellulose Increase volume of non-absorbable residue = stimulating peristalsis
Osmotic laxative Lactulose Increases water content
Faecal softener arachis oil + docusate Alter faecal consistency
Stimulant laxative senna (anthracene) Increases secretions and motility
Describe the MOA of lactulose (5)?
broken down into fructose + galactose fermentation produces lactic and acetic acid both poorly absorbed, causing an osmosis increasing water content of the bowel increased volume (water and gas from fermentation)
stretches bowel, triggering peristalsis increased water content softens stools, making them
easier to pass
What 2 drugs would be first choice and why (3)?
bulk laxative and faecal softners very few side effects
What lifestyle modifications would you advise (2)? increased fibre e.g. fruit and veg increase bulk e.g. bran drink more water
What are the side effects to laxative use (5)?
explosive diarrhoea
cramps + gas
electrolyte loss
dehydration
cathartic colon chronic malapsorption, steatorrhoea + decreased Na/K levels
State the four reasons a patient may develop diarrhoea (4)?
Secretory – cholera toxin Osmotic pull – Mg2+, lactose in chyme Inflammatory – salmonella, IBD Increased motility – drug-induced
What are the 4 main treatments used for diarrhoea?
Oral Rehydration glucose + NaCl (increases water reabsorption)
Anti-Motility Opoids e.g. loperamide doesn’t cross BBB, decreases Ach levels
Anti-Spasmodics atropine + buscan Muscarinic antagonists = decreased Ach levels
Abx where needed
Give 3 factors that increase HCL production gastrin
histamine
Ach (parasympathetic)
Give 3 factors that decrease HCL production somatostatin
PGE2
enteric hormones (VIP, CCK + secretin)
Give 3 disorders that require treatment for acid secretion
Zollinger-Ellison syndrome gastrinoma of duodenum/pancreas
Peptic Ulcers increased irritation due to mucosal damage
GORD inflammation leading to metaplasia
Give 4 drug therapies aimed at treating excess gastric acid
production (8) Antacids
aluminium hydroxide, MgOH base: raises pH
H2 Antagonists cimitidine, ranitidine
Proton-Pump Inhibitors omeprazole, esomeprazole irreversibly inhibits K+/H+ATPase
Mucosal Protectants bismuth chelate coats mucosa + increases PG + HCO3
- synthesis
State the triple therapy used to treat h. Pylori infections?
omeprazole Clarithromycin or metronidazole Amoxycillin
Give 3 IBD conditions and macro/microscopic changes associated (6)?
Crohn’s deep ulceration skip lesions and transmural inflammation
Ulcerative colitis superficial ulceration depleted goblet cells and inflammatory cell infiltrate
Coeliac disease smooth mucosa loss of villi
Give 4 types of treatment for IBD with examples (8)?
Steroids prednisone, budesonide
Aminosalicylates sulfasalazine + mesalazine inhibits synthesis of PGs, PCs + IL-2
Immunomodulators Methotrexate dihydrofolate reductase inhibitor
Biologicals Infliximab anti-TNF alpha mAb
Describe the three basic types of anaemia and give examples (6)
Normocytic, normochromic Acute blood loss, AoCD, aplastic anaemia
Microcytic, hypochromic Iron deficiency, AoCD, sideroblastic anaemia
Macrocytic, normochromic Folate insufficiency (alcoholism) Pernicious anaemia (IF->B12 deficient)
If a patient had anaemia, what things would you look for in the blood (6)?
MHC, MCHC, MCV + reticulocytes FBC Thyroid hormones Iron levels B12 / folate levels Bilirubin
What is the at immediate treatment for acute anaemia? (1)
Blood transfusion (PRCs w/ or w/o FFP)
What other treatments are available for anaemia (2)?
erythropoitein (renal disease, cisplatin) oral or IV B12/folate (if deficient)
What is the treatment for iron deficiency (2)? Ferrous sulphate tablets iron dextran (IM; as oral can produce GIT irritation)
What is the treatment for iron toxicity (1)? iron chelator (deferoxamine)
Give some side effects of ferrous sulphate treatment (3)?
N and V Constipation Black faeces
In terms of blood volume, what can be used for the treatment of kidney failure?
EPO
Why does a lack of folate/B12 cause anaemia (2)? Folate/B12 are essential co-factors in thymidine synthesis required for DNA synthesis and DNA methylation
What is the immediate and longer-term treatment for a neutropenic patient (3)?
granulocyte infusion G-CSF or GM-CSF IV antibiotics
What is the treatment for a thrombocytopenic patient (2)? Platelet infusion and FFP thrombopoeitin
Which pathway does prothrombin time (PT) measure? Extrinsic
Why is PT measured in International normalised ratio (INR)? Prothrombin time is too variable
Which pathway does the activated partial thromboplastin time (aPTT) measure?
Intrinsic
When would this value be raised? presence of heparin
When would this value be lowered? DIC, traumatic venepuncture
Which test is used for...
Heparin aPTT
Warfarin PT (INR)
Why wouldn’t you discharge a patient on heparin? Acute and direct action
Can you discharge a patient on warfarin? Yes, action is indirect and long term
When is warfarin indicated (3)? atrial fibrillation thrombosis/emboli (MI, PE, cardiomyopathy) Prosthetic heart valves
What is the MOA of warfarin (3)? inhibits vitamin K epoxide reductase reduces + activates vitamin K Vit K activates prothrombin, F7, F9 + F10
What is warfarin not used for (2)? immediate treatment as takes 2-4 days to work removal of already activated vitamin K
How would you treat a patient that has had too much warfarin? (2) Vitamin K Clotting factors (FFP)
What are the side effects (4)? skin necrosis haemorrhage osteoporosis drug interactions
Abx increase warfarin action (decrease metabolism) phenytoin, carbmazapine decrease warfarin action
Heparin…For patients (3)
surgery prophylaxis, that have thrombus (prophylactic) or DIC
Mechanism of action (2) Activates anti-thrombin III this irreversibly inactivating thrombin + F10a
Side effects (4) Excessive bleeding thrombocytopaenia hyperkalaemia loss of hair
How is overdose treated (2)? Protamine sulphate removal of heparin
State 4 anti-platelet drugs and their mechanism of action (8)?
Aspirin COX inhibitor -> decreases TXA2 levels
Clopidogrel ADP-receptor antagonist, cAMP = decreased i[Ca2+]
Dipyridamole PDE inhibitor, cAMP = decreases i[Ca2+]
Abciximab mAb to GPIIb/IIIa receptor
Describe the cardiac action potential (4)
1. Na+ influx - depolarisation2. K+ efflux – initial repolarisation3. Ca2+ influx – plataeu phase4. K+ efflux - repolarisation
Name four mechanisms which decrease intracellular calcium (4)
Uptake into SR Removal from cell by sodium – calcium
exchanger Uptake by sarcolemmal calcium ATPase Uptake into mitochondria
What are the 2 arms of treatment for hypertension?
Reduce CO β-blockers: atenolol
Reduce SVR Thiazide: bendroflumothiazide K+ sparing: amiloride Ca2+ channel blocker: verapamil ACE inhibitor: ramipril AT-II antagonist: losartan Renin inhibitor: aliskiren α-receptor antagonist: prazosin
Define angina pectoris (1)?
ischaemia due to inadequate flow to the myocardium
Give causes (4)? coronary atheroma aortic stenosis severe anaemia arteritis (teriary syphilis)
Some Non-Rx treatments for angina (4)? weight loss reduce BP and cholesterol smoking cessation exercise
Broadly, how can angina pectoris be prevented or treated (2)?
Increase coronary blood flow B-blockers + anti-thrombotics
Reduce metabolic demand of LV reduce HR: B-blockers + ivabradine reduce arterial BP: Ca2+ channel blockers reduce ventricle size: GTN
Which adrenoreceptor is found in the heart (1)? β1-receptors (β2 found in lungs + periphery)
How do β-blockers work in angina (4)? block action of Adrenaline at β1 reduces HR/contractility decreases metabolic demand increases time in diastole (increased CA filling)
Give examples of cardioselective β-blockers (2)? atenolol + metoprolol + bisoprolol
What are the side effects (4)? heart failure and conductive block cold periphery (α1 receptors in periphery) fatigue + lethargy (slow HR) worsening of asthma increased TG levels
What are the types of Calcium channel blocker available and where do they act
(4)?
Verapamil + Diltiazem AVN and smooth muscle heart and periphery
Nifedipine + Amlodipine smooth muscle periphery
What is the major side effect with peripherally-selective Ca channel blockers (1)?reflex tachycardia – drugs lower BP -> sensed in carotid body causing an increase in HR
How do Calcium channel blockers work in angina (6)?
‘reduces arterial BP -> afterload + thus -> LV work’
inhibit L-type voltage-sensitive Ca2+ channels reduce i[Ca2+] levels in SM reduced contraction and vaso-dilation
decrease i[Ca2+] levels at the AVN decreased i[Ca2+] influx during plateau phase slowing the AP and thus, HR
What are the side effects to Calcium channel blockers (6)?
reflex tachycardia bradycardia heart failure oedema headache flushing
What is the molecular action of nitrates (6)?
prodrug metabolised to NO NO activates guanylate cyclase increases cGMP increases PKG decreases i[Ca2+] levels decreases in MLCK activation
What is the use of GTN in angina (4)?
relaxes veins this increases venous capacitance reducing preload + EDV decreases LV size decreases LV metabolic demand
Starling’s Law ‘what goes in must come out’
Why are GTNs given sublingually (2)? bypass 1st pass metabolism quicker onset of action
What 2 types of nitrates can be given (2)? short acting: GTN long acting: isosorbide mononitrate
What are the side effects of GTNs (5)? headaches (intercranial vasodilation) reflex tachycardia hypotension tolerance (give intermitantly to avoid) steal syndrome (good arteries steal blood)
How does Ivabradin work (2)? If current inhibitor in pacemaker cells of SA node slows HR + increases time in diastole thus,
increasing coronary artery filing
How does nicorandil work (3)? K+ channel opener causes K+ efflux, leading to hyperpolarization this inactivates L-type Ca2+ channels, reducing free
i[Ca2+] and reducing force of contraction
What are the differences between unstable angina, NSTEMI and STEMI (3)?
Unstable Angina partial blockage of artery, limited infarct
size
NSTEMI partial artery block, sufficient to cause infarct with
enzyme release
STEMI complete arterial occlusion with transmural infarct
What are the risks following an acute myocardial infarction? (6)
Arrhythmia Heart failure Thrombo-embolism Cardiac rupture Mitral regurgitation Ventricular aneurysm
Which gender has a higher probability of having a heart attack? (1)
Neither
State four ways in which the outcome of the MI can be improved Rapid admission to a CCU Early clot busting treatment Aspirin Beta-blockers
Define heart failure (1) and describe the pathophysiology (4)?
“insufficient CO to adequately perfuse the body, despite normal heart filling”
Insult or myocardium damage ->¯ CO -> ¯ BP ->
- SNS and RAAS activation ->- vasoconstriction, BP + HR ->- preload, ¯ LV function + ischaemia ->- myocardial damage ->-¯CO
What are the aims of treatment for HF + give examples (10)?
Reduce blood volume loop diuretics thiazides ACE inhibitors spironolactone
Reduce heart work β-blockers
Inhibit RAAS pathway ACE inhibitors AT-II antagonists
Coronary Vasodilation GTN
Increase work of the heart (acute only) dolbutamine (B1 agonist)
What four drugs would you use to treat acute left heart failure? State their mode
of action
Loop diuretic Decreased extracellular volume and preload on heart
Opiate (+anit-emetic) Decreased cardiac preload and anxiety
Nitrovasodilator Decreased prelaod
ACE-inhibitor Decreased after load and decreased salt and water
retention
What five drugs would you use in chronic heart failure? State their modes of action
Diuretics Reduce preload – reduced ECF and venous tone
ACE inhibitor Reduce cardiac output by decreasing ECF
Angiotensin II Type 1 receptor blocker (ARBs) Reduce CO by decreasing ECF
Cardiac glycoside Increased force of contraction
Beta-blockers Reduce SNS drive though may worsen heart failure
What effects are induced by ACE-inhibitors (6)
Decreased angiotensin II Vasoconstriction Salt and water retention Intrarenal effects on blood flow Modulation of SNS
Increased vasodilator bradykinin
What tests are available to measure success of treatment? (4)
• Biochemical measurements• Ca homeostasis (Ca2+/PO4, vit D, PTH, urinary Ca2+)• Bone turnover (alkaline phosphatase, osteocalcin, collagen breakdown/formation)
• Imaging• plain X-ray• radionucleotide scans (technetium, Tc)• MRI/CT/ultrasound
• Bone biopsy - histology
• Bone density (BMC vs BMD)• DEXA (Dual Energy X-Ray Absorptiometry)
State some effects of oestrogen (5)
Growth / maintenance of Endometrium Myometrium Bone Breast skin
prothrombotic increases HDL:LDL ratio Suppression of HPO axis development of secondary sexual characteristics
State some effects of progesterone (5)
Maintenance of Endometrium Myometrium Breast
Slowing down peristalsis Pregnant women can become constipated
Suppression of HPO axis inhibits lactation pro-diabetic (gestational diabetes) smooth muscle relaxant
What would be the effect of the combined birth control pill on a patient that has irregular menses?
Make menstruation regular
Define dysmenorrhoea and dysparunia Painful menstruation and painful sex
Define endometriosis
Foci of endometrial tissue outside the uterine cavity that continues to respond to monthly cycles
What are the symptoms of endometriosis Pelvic pain
Irregular menses
Vaginal discharge
Constipation
Difficulty getting pregnant
What would you expect the levels of TSH and T4 to be in...
Hyperthyroidism TSH low, T4 high
Hypothyroidism High TSH, low T4
What can cause a decreased iodine uptake (4)? Thyroid carcinoma Thyroiditis Factitious Struma ovarii
What can cause excess uptake of iodine (4)? Graves TMG Adenocarcinoma Pituitary tumour
What are the treatments for hyperthyroidism (4)?
Thionadmides inhibit TPO Carbimazole and propylthiouracil
Iodine131 (radioactive iodine) irradiates thyroid + destroys thyroid tissue local uptake into thyroid only
Symptom modulators β-blockers (broad acting e.g. propanolol)
Surgery total or lobe thyroidectomy
What is thyroid storm (1) and how is it treated (4)?
“rapid deterioration of hyperthyroidism characterised by severe tachycardia, arrhythmia, pyrexia, vomiting + coma/death”
propanalol carbimazol or propyluracil potassium iodide corticosteroids IV fluids, O2 as needed + general supportive measures
What are the 6 types of diuretics, and give an example of each (6)?
Loop frusemide
Thiazides bendroflumethiazide
Potassium-sparing spironolactone + amiloride
Carbonic anhydrase inhibitors acetazolamide
Osmotic mannitol
ADH antagonists conivaptan
How do carbonic anhydrase inhibitors work (3)?
inhibit CA in tubule lumen this blocks HCO3
- reabsorption (H2O + CO2) decreasing i[H+] and therefore, increases Na+ in tubule lumen (as Na+:H+
anti-porter).
Give 2 uses for CAIs• used mostly in
glaucoma• correct alkalosis
How + where do loop diuretics work (4) what are their side effects (3)?
inhibit Na+Cl-K+ cotransporter in ascending loop of Henle increases tubule [Na+] = less Na+ in medulla therefore, less H2O is reabsorbed in CCD
polyuria hypokalaemia deafness hyponatraemia hypovolaemia
How + where do thiazides work (3) and what are their side effects (3)?
inhibit Na+Cl- symporter in distal tubule increase tubule [Na+] osmotic diuresis
hypokalaemia
alkalosis
gout (hyperuricaemia)
hypercalcaemia
hyperglycaemia
hyperlipidaemia
Why do loop and thiazide diuretics cause hypokalaemia (3)?
increased tubule [Na+] forces increased Na+ reabsorption in CD via ENaC
Na+ has to then be pumped out at basal membrane via Na+K+ATPase
K+ is excreted to maintain electrical gradient
How can hypokalaemia lead to metabolic alkalosis (2)?
H+ are exchanged for K+ via the H+K+ATPase H+ exchange in PT causes increase in HCO3
- reabsorption
How do spironolactone and amiloride work (4) and what are the side effects (4)?
Spironolactone aldosterone receptor antagonist
Amiloride ENaC blocker
Both work in principle cells in CD Increase tubule [Na+] by decreasing Na+ reabsorption osmotic diuresis
gynocomastia
hyperkalaemia
libibo loss
testicular atrophy
erectile dysfunction
menstrual irregularities
breast enlargement and tenderness
In what ways can you make prescribing safer? (4)
Review of prescriptions Electronic records Clear treatment plans Double check
Two types of pain (2) and broadly what drug classes are used to treat them (4)?
Nociceptive pain NSAIDs opioids
Neuropathic pain Anti-depressants anti-epileptics
What is the underlying pathology in epilepsy (4)?
altered neuronal excitability neurons fire repetitively + uncoordinated
decrease in GABA increase in NA + Ach
What are the 3 approaches in epilepsy treatment (3) + give an
example drug for each approach (3)?
inhibit Na channels carbemazepine phenytoin
inhibit Ca channels gabapentin ethosuximide
enhance GABA activity tiagabine BDZ phenobarbital
What are the first line treatments of partial/focal or grand mal seizures (3)
+ why (1)?
Carbamazepine Lamotrigine Sodium Valproate
reduced cognitive side effects
What is the 1st line treatment in a petit-mal seizure (1)?
ethosuximide soidum valproate
What is the treatment for status epilepticus (3)? IV lorazepam
IV phenytoin
IV midazolam
What is the major concern of anticonvulsants (2)?
Antiepileptic hypersensitivity syndrome
occurs 1-8 weeks later with rash, lymphadenopathy + fever blood, liver, kidney + respiratory dysfunction vasculitis and organ failure
How do phenytoin + carbemazapine + lamotrigone work (2)?
inhibit inactivate Na+ channels stabilizing this inactivated form, not allowing
them to open again i.e. no further AP
What are their major side effects (5)?
cognitive impairment peripheral neuropathy gum hyperplasia tetragenic - not to be used in preggers nystagmus anaemia agranulocytosis
What is a major consideration when prescribing anti-convulsants (2)?
liver CYP450 enzyme inducers increase metabolism and therefore, decrease
activity of other drugs warfarin in particular
How do ethosuximide + gabapentin work (2)?
inhibits voltage-gated T type calcium channels
found in thalamus inhibition reduces oscillatory firing of these
What are the major side effects (3)?
nausea + vomiting drowsiness confusion ataxia insomnia
How do Tiagabine + Vigabatrin work (4)?
TIAGABINE inhibits GABA reuptake transporter
VIGABTRIN inhibits GABA transaminase
What are the side effects (3)?
sedation confusion dizziness fatigue weight gain visual disturbances dysarthria
How do benzodiazepines and phenobarbital work (4)?
BZD binds to γ-subunit of GABAA receptor enhancing activity
PHENOBARBITAL binds to β-subunit of GABAA receptor enhancing activity
What are the side effects (5)?
short term use only (<12weeks) tolerance dependence + withdrawal symptoms sedation decreased cognitive ability decreased muscle coordination retrograde amnesia