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