Drugs List

Question 1

Antacids

Answer 1

• Aluminium Hydroxide and Magnesium Hydroxide - Maalox
• Calcium Carbonate and Magnesium Carbonate - Rennie

Gastric Acid Neutralisation

Uses: Reflux oesophagitis - OTC & prescribed

SE: Mg –> Diarrhoea

Al –> Constipation

Question 2

Antacids + Alginates

Answer 2

• Sodium Alginate with Sodium Bicarbonate and Calcium Carbonate (Gaviscon)

Anionic polysaccharides - form a viscous gel raft upon binding with water increasing stomach content viscosity this floats to the top of the stomach reducing symptoms. Also contains antacid to neutralise excess acid

Uses: Reflux oesophagitis - OTC + prescribed

Question 3

H₂ Receptor Antagonists

Answer 3

• Cimetidine
• Ranitidine

Competitively inhibits gastric H2 receptors to decrease acid secretion.

OTC

Cimetidine inhibits many cytochrome P450 enzymes

Question 4

Proton Pump Inhibitors

Answer 4

• Omeprazole
• Lansoprazole

Blockade of parietal cell proton transporters:

Irreversibly inhibits H⁺/K⁺-ATPase pump, terminal step in acid secretion pathway. Decreases basal and stimulated acid production.

Very specific - inative at neutral pH thus accumulate in secretory canaliculi or parietal cells and are activated in acidic environment.

Prescribed drug of choice for reflux oesophagitiss.

More effective than H₂ antagonists.

PK:

• Increased doses give disproprtionatley higher increase in [plasma]
• 1/2 life approx 1hr
• Single daily dose affects acid secreions 2-3 days

Question 5

Bulk Laxatives

Answer 5

• Methylcellulose
• Isphagula Husk

Polysaccharide polymers not broken down by normal digestion so retain water in the GI lumen, softening and increasing bulk load and promoting increased motility.

Act over 1-3 days.

First line for constipation & IBS

Question 6

Stimulant Purgatives (2)

Answer 6

• Bisacodyl

Stimulates rectal mucosa resulting in massmovements - defaecation in 15-30 mins

Use: Short courses. W/ Opoids

• Senna

​Derivatives anthracene with sugars forming glycosides passes unchanges into colon where bacterial action = release free anthracene derivatives which are absorbed & causes direct effect on myenteric plexus to increase intestinal motility

• Increases activity on distal colon on serosal strain guage
• Chronic use (>3/week for >year) can cause cathartic colon (laxative dependency + req. higher doses) can lead to serious consequences*

Question 7

Faecal Softeners

Answer 7

• Docusate
• Arachis oil

Anionic surfactants. Lower surface tension allowing water or fats to enter the stool, softening faeces. Stimulates water & electrolyte secretion into the intestinal lumen

Act 3-5 days

Used for constipation and fissures/piles

Question 8

Osmotic Laxatives (3)

Answer 8

• Saline purgatives - Magnesium sulphate, Magnesium Hydroxide -

Uses: Bowel prep before procedure. Potent, rapid action (1-2hrs)

• Macrogol Uses: Faecal impaction in children, LT management of chronic constipation

Poorly absorbed solutes that maintain increased fluid volume in GI tract by osmosis, accelerating small intestine transit - large fluid volume in colon leads to distension and purgation.

• Lactulose

Semi-synthetic Galactose & Fructose (disaccharide) converted to poorly absorbed monocaccharides by colonic bacteria - Fermentation yields lactic & acetic acid which acts as an osmotic laxative

Acts 1-3 days

Uses: Chronic constipation, Hepatic Encephalopathy, Negate effect of opiods

SEs: Abdo cramp, gas, flatulence

Question 9

Oral Rehydration Therapy

Answer 9

• Isotonic/hypotonic solution of glucose and NaCl

​Exploits ability of glucose to enhance absorption of Na⁺ and so water.

Question 10

Opioid Anti-Motility Agents

Answer 10

• Codeine
• Loperamide

Agonist on mu-opioid receptors in the myenteric plexus. Increases tone and rhythmic contractions of the colon, but diminishes propulsive activity. Pyloric, illocaecal and anal sphincters are contracted

SEs: Chronic use = constipation. Abdo cramps, dizziness

Uses: Acute uncomplicated diarrhoea in adults

Question 11

Carbonic Anhydrase Inhibitor

Answer 11

• Acetazolomide

Inhibits carbonic anhydrase in PCT to stop the reapsorption of HCO_3^- and therefore Na⁺ so increasing the volume of urine (osmotic balance). Weak diuretic action as only a small amount of sodium is reabsorbed this way

SE: Also prevents H⁺ secretion –> metabolic acidosis

Uses: Reduce intraocular pressure in glaucoma (aqueous humour prod. req. HCO3- secretion)

Question 12

Osmotic diuretic

Answer 12

• Mannitol

Increases the osmolarity of glomerular filtrate thus prevents water reabsorption. Acts mostly where water reabsorption occurs - PCT + descending limb of LOH)

Uses: reducing intracranial pressure + reducing intraocular pressure (glaucoma)

Question 13

Loop Diuretics

Answer 13

• Furosemide

​Powerful diuretics. Act on thick ascending limb og LOH. Inhibits the Na⁺K⁺2CL^- co-transporter (competes with Cl^- binding). Decreased NaCl reabsorption in thick ascending loop causes decreased osmotic concentration in the medulla thus decreased ADH mediated water absorption.

Reduced Mg & Ca reabsorption

Increase in NaCl to DCT. Increase Na uptake by principle cells –> K+ loss –> Metabolic Alkalosis

Binds to plasma proteins so not filtered but secreted directly into the PCT thus effective in renal impairment/ Nephrotic syndrome.

SEs: Hypovolaemia + hypotension, hypokalaemia + hyponatremia, Ototoxicity

Uses: peripheral oedema (chronic heart failure), acute pumonary oedema, Resistant HTN

Question 14

Thiazide Diuretics

Answer 14

• Bendroflumethiazide
• Indapamide
• Hydrochlorothiazide
• Chlortalidone

(BICH)

Weak/moderate diuresis. Acts on the Early DCT. Inhibits Na⁺/Cl^- co-transporter (competes with Cl^- binding). Slower acting but longer lasting than loop diuretics.

Notes:

• Filtered & not secreted- not good in renal impairment
• Increased NaCl to Distal nephron & decreased blood volume –> Increase K secretion
• Intercalated cells may also secrete H+ –> Alkalosis

SEs: Hyponatraemia/Hypokalaemia, increased plasma uric acid (gout), ED, Hyperglycaemia

Uses: Peripheral oedema (chronic heart failure), hypertension

Question 15

Potassium Sparing Diuretics

Subclass: Aldosterone Antagonists

Answer 15

• Spironolactone
• Eplerenone

Weak diuretic alone. Aldosterone antagoniss, binds to and blocks mineralocorticoid (MR) receptor. Prevents synthesis of ENaC and Na⁺/K⁺ATPase activity which stops Na⁺ reabsorption (and water by osmosis) and reduces K⁺ secretion into the lumen to K_{^{+ i}}s retained.

Notes: Act on Late DCT/ Collecting duct on principle cells (Na/K ATPase)

SEs: Hyperkalaemia, gynaecomastia

Uses:

• Chronic HF
• Periph oedema +ascites caused by cirrhosis
• Resistant HTN
• Primary Hyperaldosteronism

Can be used in comination to prevent K⁺ loss from use of loop/thiazide diuretics.

Question 16

Potassium Sparing Diuretics

Subclass: ENaC Antagonists

Answer 16

• Amiloride

Weak diuretic alone. ENaC antagonist - blocks ENaC, competes for Na⁺ binding site thus decreasing luminal permeability to Na⁺. This causes reduced Potassium secretion into the lumen to potassium is retained

SEs: Hyperkalaemia, Gynaecomastia

Uses:

• Chronic heart failure
• Peripheral oedema and ascites caused by cirrhosis
• Resistant HTN
• Primary Hyperaldosteronism

Can be used in combination to prevent K+ loss from use of loop/thiazide diuretics

Question 17

Renin Inhibitor

Answer 17

• Aliskiren

​Inhibits the action of Renin thus stopping formation of Angiotensin I so the RAAS system cannot be used to increas BP

Renin release from granular cells of AA

Question 18

Angiotensin-converting Enzyme (ACE) Inhibitor

Answer 18

• Ramipril

Binds to ACE stopping the converstion of Ang I to Ang II so the RAAS system cannot increase BP

SEs: Dry cough (bradykinin build up as not inactivated by ACE), hypotension.

Caution in renal failure - ACE normally constricts efferent arterioles thus ACEI can lead to decreased GFR

Question 19

Angiotensin-II receptor antagonists

Answer 19

• Losartan
• Valsartan

Binds to the angiotensin-II receptor, preventing it from working. RAAS cannot increase BP

Question 20

Aldosterone Antagonist

Answer 20

• Spironolactone

​Antagonist of aldosterone by blocking the mineralocorticoid receptor. Means RAAS cannot increase BP

Question 21

Thyroid Hormones

Answer 21

• Levothyroxine (Synthetic T₄)
• Liothyonine (Synthetic T₃)

Use: Hypothyroidism

Activation of Thyroid Hormone Receptor

Mimics thyroid hormone by binding to incracellular alpha & beta thryoid receptors

Question 22

Alpha-adrenergic blocker

(to treat altered voiding)

Answer 22

• Doxazosin

Selective alpha 1 adrenergic receptor blocker on bladder neck, urethra. Relaxation smooth muscle —> Urinary flow facilitated

Uses: Urinary retention, BPH/ Overflow Incontinence

SE: Hypotension, Drowsiness, Nausea, Fatigue, Constipation

• Doxazosin - ZO sounds like GO - makes you GO for a wee*
• (*Blocks alpha- 1 adrenoreceptors of the sympathetic autonomic nervous system, this relaxes smooth muscles around the bladder (internal and external urinary sphincters) allowing micturition)

Question 23

Urinary anti-spasmodic; anticholinergic

(Tx of Urinary Incontinence)

Answer 23

• Oxybutinin

MOA: Competitively antagonizes the muscarinic 2/3 acetylcholine receptor leading to reduction of bladder detrusor activity

Use: Urinary Incontinence/ OAB (Urge incontinence)

SE: Blurred vision, Constipation, Dry Mouth, Urinary Retention

Question 24

B₂-Adrenergic Agonists

(tx of airway disease)

Answer 24

• Salbutamol (short acting)
• Terbutaline (short acting)
• Salmeterol (long acting)
• Formoterol (long acting)

Cellular Target: Bronchiolar Smooth Muscle

Molecular Target: Stimulation B₂ adrenergic receptors

B₂ agonists bind to B₂-adrenergic receptors that activate adenylate cyclase. AC increases cAMP levels/ action, activting protein kinase A (PKA). PKA :

• Drives Ca²⁺ –> Storage vesicles
• Inactivates MLCK by reducing phosphyrlation –>

This ^ plus less Ca²⁺ in Cytoplasm –> reducation in smooth muscle contraction resulting in relaxation of smooth muscle in the airway.

SEs: Tremor, tachycardia, cardiac arrythmia

Question 25

**Anti-cholinergics** **(Airways)**

Answer 25

* **Ipratropium (short acting)** * **Tiotropium (long acting)** Cellular Targets: bronchiolar smooth muscle cells. Blocks **M3 muscarinic ACh receptors**. Actives G protein --\> Decreases action of **PLC**: * Reducing Ca²⁺ release into the cytoplasm, reducing smooth muscle contraction causing bronchodilation. SEs: Dry mouth, constipation, urinary retention

Question 26

**Methylxanthines**

Answer 26

* **Theophylline** * **Aminophylline** Cellular targets: bronchiolar smooth muscle cells. Mollecular targets: Blockage PDE Binds to **B₂ adrenergic receptor**. Activation associated G protein. Increases action Adenylate cyclase- covnverts ATP --\> cAMP in Cytoplasms. This is normally inactivated by phosphodiesterase (PDE). **Durgs block PDE sustains cAMP** levels activating PKA * Drives Ca²⁺ into storgae vesicles * Inactives MLCK by reducing phosphorylation Less Ca²⁺ in cytoplasm and reduced phosphorylation MLCK--\> Smooth muscle relaxtion--\> bronchodilation. *Toxic side effects to must monitor serum - **cardic arrythmias** + **seizures***

Question 27

**Leukotriene Antagonists**

Answer 27

* **Montelukast** * **Zafirlukast** Cellular targer: **Eosinophils & Bronchiolar Smooth Muscle** Blocks **CysLT₁ leukotriene receptors**. This r**educes the inflammatory response in early and late phases of asthma** * Additive effect when used with other drugs (eg: inhale glucocorticoids) * No evidence of effect on remodelling SEs: **Abdo pain, headache**

Question 28

**Glucocorticoids** **(Airways)**

Answer 28

* **Beclomethasone** * **Fluticasone** * **Prednisolone** * **Hydrocortisone** Targets immune cells of the lungs especially macrophages, T-lymps and eosinophils. Activates the glucocorticoid receptor (GR) which interacts with selected nuclear DNA sequences and influences the expression of g=key genes: - **Repression of pro-inflammatory mediators (TH2 cytokines)** **Expression of anti-inflammatory products (B2 adrenoceptors)** SEs: MANY - Moon face, weight gain, osteoporosis, hyperglycaemia

Question 29

**Beta-adrenergic receptor antagonists** **(Beta blockers)**

Answer 29

* **Bisoprolol (Cardioselectiv B1 antag.)** * **Atenolol (cardioselective B1 antag.)** * **Propanolol (B1 & 2 antag.)** **Competitive** inhibitors of **adrenaline** and **noradrenaline** at **B-adrenoceptor** sites. **Inhibit sympathetic stimulation** of heart muscle. *Heart Specific:* **B₁ antagonists** are selective for the cardiomyocytes: **Negative inotropes & chronotropes.** Reduce workload on the heart relieving oxygen demand. * Molecular Mechanism in the heart:* * Blocked Beta-adrenergic receptors* * Blcoked Beta-adrenergic receptors * Less ATP --\> cAMP by Adenylyl Cyclase * Less Protein Kinase (PK) A activity * Less release of Ca from SR- Less free Ca inside cell * Less contraction SEs: **Dizziness, constipation**

Question 30

**Calcium Channel Antagonists** **(for heart failure and hypertenison)**

Answer 30

* **Nifedipine** * **Amlodipine** (Dihydropyradine subclass) Prevent opening of VGCCs (L type) Less Ca influx Less binding of Ca to Cm As less Ca-Cm complex less phosphrylation MLCK therefore less contraction *Notes:* Does not generally act on veins Drives coronary artery dilation- Improves blood flow Vasodilatory effect therefore reduced afterload (Vascular smooth muscle) SEs: **Ankle swelling, palpitations**, interact with B-blockers & grapefruit juice (Bind to K-type calcium channels on cardiac and smooth muscle - act on BOTH the heart and vessels. Cause coronary artery dilation. Negative chronotropic effects, negative inotropic effects.)

Question 31

**Nitrate Vasodilators**

Answer 31

* **Glycerol trinitrate (GTN)** * **isosorbide mononitrate (ISMN)** Metabolised to release **Nitric Oxide NO** which stimulates soluble **guanylate cyclase**. Increases **cGMP** in vasc. smooth muscle cells. Drives **dephosphorylation of MLC** via activation of **MLC Phosphatase** causing **vascular smooth muscle relaxation**. *Heart Effects:* Can act to dilate arteries AND veins. **Venodilation** decreases **preload**. **Coronary artery dilation** increases blood and oxygen supply to the myocardium. Promote moderate **arteriolar dilation**- reduces cardiac **afterload** SE: Headache

Question 32

**Anti-cholinergic** **(for emergency bradycardia treatment)**

Answer 32

* **Atropine** IV. Binds to and blocks **muscarinic M2 Ach receptors** in the heart. Inhibits effects of cholinergic vagus nerve transmission (normally -ve chronotropic effects). Accelerates repolarisation rate in cardiac muscle cell, so raises heart rate Uses: Sinus Bradycardia SE: Dry mouth, Blurred vision, Urinary retention, Constipation

Question 33

**Sympathomimetics**

Answer 33

* **Noradrenaline (alpha)** * **Dobutamine (beta)** * **Adrenaline (alpha and beta)** Positive inotrope * Binds & Stimulates Cardiomyocytes B₁ adrenergic receptors * Drives heart muscle contraction * Resotres function Uses: Cardiac Arrest

Question 34

**ACE inhibitors**

Answer 34

* **Ramipril** Inhibits conversion of Ang I to Ang II. Reduces vasoconstriction in **peripheral blood vessles --\> Reduced afterload --\> Lower BP** *Singal Transduction in Smooth Muscle cells:* * Less activation at AG II receptors * Less increase IP₃ * Less Ca release from SR * Less Ca-Cm * Less MLCK phosporylation * Less contraction SE: Persistant cough *Notes:* Aldosterone secretions also reduced: * Less water retention * Less plasma volume * Decreased cardiac preload

Question 35

**HMG-CoA Reductase Inhibitors** **(statins)**

Answer 35

* **Atorvastatin** * **Simvastatin** HMGCR enzyme is essential & rate-limiting in cholesterol synthetic pathway HMGCR Inhibitors reduce circulating cholesterol levels, Promote uptake of excess cholesterol from bloodstream into liver Use: CVD prevention WITHOUT affect BP

Question 36

**Neprilysin inhibitors** **(used with an ARB drug)**

Answer 36

* **Sacubitril (used with valsartan)** Neprilysin = Enzyme Inhibition of natriuretic peptide breakdown --\> Promote Water & Sodium excretion

Question 37

**Antiplatelet Drugs (2)**

Answer 37

**Aspirin** * Blocks enzyme actions of platelet COX enzyme * COX required for synthesis Thromboxane A2 production * Reduced TXA2 synthesis inhibits platelet activation & thrombus formation * SEs: GI bleeding, gastric ulcers due to decreased prostaglandins E2 and I1* * **Clopidogrel** Binds to and **blocks the platelet Adenosive Diphosphate (ADP)** receptor, causes decreased platelet activation & therefore thrombus formation USE: ACS prevention Can treat CVD without affecting BP *_The cloppy dog has 5 limbs (2+3) GPIIb and GPIIIa_*

Question 38

**Anticoagulants (4)**

Answer 38

* **Warfarin** ​Targets extrinsic pathway which inhibits vitamin K dependent synth of dependent clotting factors 10, 9, 7 and 2 (PT). By inhbiting vitamin K carboxylation of the factors it decreases thrombin production. **WKD TimE = _W**_arfarin inhibits vitamin _**K_, _d_**ecreasing **_T_**hrombin which is **_E_**xtrinsic pathway. _Vit K is clotting factors 1972 - 10,9,7,2._ * **Heparin, Unfractioned heparins, low molecular weight heparins** **Reversibly bind antithrombin III** which inactivates **thrombin** and **FXa**. * Unfractionated = Inactivated FXa & Thrombin * LMWH = Inactivated FXa **HAITTI - _H**_eparins activate _**A_**nti-thrombin 3, **_I_**nactivating **_T_**hrombin and **_T_**enA -**_I_**ntrisic pathway * **Dabigatran** Competitive, reversible inhibitor of thrombin Direct inhibition of thrombin - thrombi cannot convert fibrinogen into fibrin and formation of secondary plug is inhibited Use: Prophylaxis & Tx of Venous Thromboembolism (2) Warfarin- " & ischeamic stroke prevention in AF

Question 39

**Thrombolytics**

Answer 39

* **Altepase** * **Streptokinase** * **Urokinase** Activates plasminogen to plasmin which **digests fibrin** and fibrinogen to **re****store blood flow**. SEs:Arrhythmias, bleeding. Can only use streptokinase one as an immune response is generated againset the bacteria (streptococci) and memory B cells produce anti-streptokinase ABs. USe: IHD/ ACS

Question 40

**Dopaminergics** **(pharma basal ganglia disorders)**

Answer 40

* **Levodopa (DA precursor)** ​Levodopa converts to dopamine as dopamine does not cross BBB - restores activity in the nigrostriatal pathway. * **Pramipexole (synthetic agonist)** * **Ropinirole (synthetic agonist)** * **Rotigotine (synthetic agonist)** DA Receptor agonist ​Synthetic dopamine agonists stimulate D2 receptors on striatal neurons improving dopaminergic transmission. SEs: Anorexia, drowsiness, hypomania, hypotension, **sudden onset sleep, 'on-off effects',** Arrythmia, Tachycardia Synthetic more likely to have psych SE Uses: Parkinsonism. Synthetics used in younger patients

Question 41

**Dopa-decarboxylase inhibitor**

Answer 41

* **Carbidopa** * **Benserazide** **​**Inhibits dopa-decarboxylase, preventing GI and **peripheral metabolism** of levodopa meaning more is available to the CNS Uses: Used with levodopa for Parkinsonism

Question 42

**COMT inhibitor** **(catechol-O-methyl transferase inhibitor)**

Answer 42

* **Entacapone** * **Tolcapone** Inhibits COMT in the periphery (outside CNS), reducing dopamine breakdown and allowing for more in the CNS

Question 43

**MAOI_B Inhibitor** **(Monoamine oxidase inhibitors, B form inhibitor)**

Answer 43

* **Rasagiline** * **Selegiline** Inhibits MAOI_B so reducing central metabolism breakdown of dopamine in the CNS Use: Adjunct with levodopa/carbidopa for Parkonsonism

Question 44

**Anticholinergics** **(BG disorders)**

Answer 44

* **Orphenadrine** * **Procyclidine** * **Trihexphenidyl** **Muscarinic cholinergic receptor antagonist** - in Parkinsons a decrease in dopamine lease to an increase in Ach concentration. Anticholinergics (antimuscarinics) readdress this balance). SEs: may reduce absorption of levodopa **_Uses:_** Iatrogenic PD (Orphenadrine) Dystonia (Trihexphendyl & Procyclidine)

Question 45

**Dopamine-depleting Drugs**

Answer 45

* **Tetrabenazine** I**nhibits VMAT₂** within basal ganglia, **preventing uptake of DA into vesicles.** Depletes serotonin, noradrenaline and dopamine. Dopamine is req for fine motor movement, so inhibition is helpful for kyperkinesis. SEs: Causes **depression by decreasing 5HT and NA levels** *Uses: Chorea e.g. Huntington's, Athetosis, Ballismus*

Question 46

**Weak analgesic/Antipyretic**

Answer 46

* **Paracetamol** Non-selective COX inhibitor, decreasing prostaglandin production. Also improves peripheral vasodilation (anti-pyretic effects). * No PG * No prostanoid receptor activation * Reduced activation VDNC SE: Constipation Interactions: Warfarin *In OD - conjugation (phase II metab.) pathway is saturated, phase I metab yields toxic metabolite NAPBQI which in high levels is toxic to hepatocytes --\> liver failure.*

Question 47

**NSAIDs**

Answer 47

* **Aspirin** * **Ibuprofen** * **Diclofenac** * **Naproxen** COX inhibitors. Decreased prostaglandins so less inflammation * Non selective COX inhibitor * No PG * No prostanoid receptor activation * Reduced activation VDNC Uses: **Anti-inflammatory**, antipyretic, anticoagulant, analgesic SEs: **GI side effects**- gastric ulcers and medication overuse headaches * **Hypertension, Aspirin not for under 16's** * Aspirin --\> Reye's Syndrome: Following viral infection asprin can cause RS (Fatty deposits in liver and brain) * NSAID intoxication: Salicylism (high dose of acute or chronic NSAID ingestion. Classic symptom = Tinnitus) Interactions: Diuretics, ACEi

Question 48

**COX-2 selective NSAIDs**

Answer 48

* **Celecoxib** * **Etoricoxib** MOA: Selective COX 2 Inhibitor --\> localised PG bloackage --\> No prostanoid receptor activation --\> Reduced activation Voltage Gated Na+Channel * Directly inhibit COX-2 enzymes - specific for inflammation USE: Pain, inflammation SE: **Indigestion,** Thombosis Interactions: ACEi, SSRI

Question 49

**Weak opioid analgesics**

Answer 49

* **Codeine** * **Dihydrocodeine** MOA: Opioid Receptor Agonist --\> Decrease opening VDCC--\> Decrease Ca release from intracellular stores --\> Decrease exocytosis of transmitter vesicle and Increasing K outflow (post-synaptic) Uses: **analgesia** (chronic and acute) and anaesthesia. Nociceptive pain SEs: Resp depression, decreased GI motility, **constipation**, tolerance and dependance, **nausea** Interactions: Sedatives (Mimic endogenous opioids acting on opioid receptors to modulate pain at all CNS levels. Hyperpolarises the neuron so it is less likely to fire when a stimulus comes through)

Question 50

**Strong Opioid Analgesics**

Answer 50

* **Morphine** * **Diamorphine** MOA: Opioid Receptor Agonist --\> Decrease opening VDCC--\> Decrease Ca release from intracellular stores --\> Decrease exocytosis of transmitter vesicle and Increasing K outflow (post-synaptic) Uses: Nociceptive pain SEs: Resp depression, decr GI motility, **constipation**, tolerance and dependance, **N**& V, Mood alterations Interactions: Sedatives

Question 51

**Partial/Mixed Agonist opioid analgesics**

Answer 51

* **Buprenorphrine** * **Pentazocine** Opiod receptor partial agonist @ Mu & Kappa Opioid Receptor and Antagonist at delta Use: Maintenance therapy, pain relief (moderate to severe) SE: Constipation, nausea Interactions: Sedatives

Question 52

**Opioid receptor antagonists**

Answer 52

* **Naloxone (short lasting)** * **Naltrexone (longer lasting)** Compete for the same binding site as opioids, particularly the u receptor so reducing the effect of opioids (**Opioid receptor antagonist**) Uses: 1 &2/ Opiod OD, Respiratory depression 2/ Prevent relapse of opiod/ alcohol abuse SE: Nausea & Tachycardia

Question 53

**Drugs used to manage opioid addiction**

Answer 53

* **Methadone** * **Buprenorphine** Opioid receptor agonists: Methadone = Mu receptor, longer lasting. Buprenorphine = partial Mu and Kappa R agonist and antagonist at delta Use: Opiate addiction SE: Constipation INteractions: Sedatives

Question 54

**Drugs to treat neuropathic pain** **+ 4 types of neuropathic pain?**

Answer 54

* **TCAs** (Amitriptyline- NRI, 5HTRI, H1 anatgonist, A1 antagonist, M1 antagonist) * **Gabapentin (AED) - inhibits VDCC, increases GABA transmission** * **Pregabalin (AED)-Inhibits VDCC, increase GABA transport** * **Carbamazepine (AED)-Sodium channel blocker in inactivated state** * **​**Teratogenic SE: Dizziness, fatigue Interactions: Antidepressants 4 types: Phantom limb, trigeminal neuralgia, post-stroke pain, post-herpetic pain (persistent pain after shingles). **T**all **Ga**ls **Pre**fer **Carb**s

Question 55

**Tricyclic Antidepressants**

Answer 55

* **Amitriptyline** * **Nortriptyline** * **Dosulepin** 1. NA reuptake blocker - MAIN action 2. Serotonin reuptake inhibitor 3. a₁ adrenoreceptor antagonist 4. H1 receptor antagonist 5. M1 receptor antagonist SEs: **Anticholinergic syndrome,** Sedation (H1 blocker), Dry mouth, constipation (M1 muscarinic blocker), cardiac dysfunction (a1 adrenoreceptor blocker)

Question 56

**Selective Serotonin Reuptake Inhibitors (SSRIs)**

Answer 56

* **Sertraline** * **Citalopram** * **Fluoxetine** **Inhibits 5HT reuptake pump in synaptic cleft** so increases 5HT levels. SEs: Sickness**, sleep disorders (insomnia)**, sexual dysfunction, serotonin syndrome, slow onset. (5S's), **Nausea** *Interactions:* Lithium, NSAIDs Seratonin syndrome = Overactiation ANS * Hyperthermia * CV Problems * Aggresion * Tremor * Rigidity

Question 57

**MAOIs**

Answer 57

* **Moclobemide** **Stops breakdown of monoamines in CNS. Increases Na and 5HT levels by inhibiting enzymatic breakdown.** **Reversible inhibitor of monoamine oxidase A** (RIMA) * SEs*: **Tachycardia**, * Postural hypotension, restlessness, convulsions, sleep disorders, Cheese Reaction- increase tyramine which increases NA --\> Hypertensive crisis- vasoconstriction. "**S**ee **P**eople's **C**heese **R**eaction" * Many cross-drug reactions- dont use with SSRIs or TCAs*

Question 58

**Atypical Antidepressants**

Answer 58

* **Reboxetine** - NRI, inhibits reuptake of NA, elevating mood * **Bupropion**- Inhibits NA and dopamine reuptake, elevating mood * **Buspirone -** Partial 5HT agonist, reduce activity to increase transmitter levels in the synaptic cleft * **Agomelatine -** Melatonon agonist, increases slow wave sleep patterns. * **Venlafaxine -** SNRI - Inhibits reuptake of 5HT & NA * **Mirtazapine -** a2-adrenergic antagonist * SE: Postural hypotension, Sleep disorder, Bronchoconstriction, Decreased HR Ruboxetine- Depression Venlafaxine- GAD/ PSTD/ Depression Busprione- GAD/ OCD/ Depression Mirtazapine- Depression Bupropion: Depression following smothin cessation

Question 59

**Mood Stabiliser**

Answer 59

* **Lithium** MOA Unclear **but possible neuronal calicum channel blockade** Uses: Mainly **bipolar disorder specturm** and Depression- resitant, recurrent unipolar as an adjunct to anti-depressants *Interactions:* NSAIDs, ACEi

Question 60

**1st generation (classical) Anti-psychotic**

Answer 60

* **Chlorpromazine** * **Haloperidol** Selective dopamine receptor antagonists - D2. Also affect H1, M1 and a1 *Use:* Schizophrenia SEs: * **Blurred vision, Tremor, EPS, Hypotension** * Tardive Dyskinesia (disabling involuntary movements) * Tongue Twisiting, Choreiform movements * Extrapyramidal symptoms * **Slowed movement** * **Tremor** * **Akasthisia,** * **Sedation** * Neuroleptic malignant syndrome: * Altered consciousness, Hyperthermia, Tachycardia, Incontinence M1 receptor: Dry mouth, Constipation, Blurred vision H1 receptor: Weight gain, Sedation D2 Receptor: Slow movement, Rigidity, Prolactin elevation Alpha1 Receptor: Hypotension, Drowsiness

Question 61

**2nd generation (Atypical) Antipsychotics**

Answer 61

* **Amisulpride** **​**5HT7 and Dopamine (D2) antagonist * **Risperidone** ​5HT2A and Dopamine (D2) antagonist * **Clozapine** ​5HT2A and domapine (D2) antagonist * **Olanzapine** ​​​Selective D2 and 5HT antagonist * **Quetiapine** ​​​Selective D2 and 5HT antagonist *SE:* **EPS, Hypotension** EPS- less likely: Akathisia, Tremor, Slowed movement, Sedation Neuroleptic Malignant Syndrome: Hyperthermia, Tachycardia, Altered Conciousness, Incotinence D2 Anatagonist: Rigidity, Slow speech, Stiffness, Tremor 5HT antagonist: Consiptation, Somnolence, Weight gain, Dizziness

Question 62

**General Anaethetic**

Answer 62

* **Isoflurane -** Unclear * **Nitrous Oxide -** Unclear * **Sevoflurane -** Unclear SE: Respiratory depression, Irritation of respiratory tract, Bronchospasm, Laryngospasm * **Propofol -** Unclear * **Ketamine -** NMDA (glutamate receptor antagonist) * Blocks Ca & Na channels * SE: Hallucinations, Raised HR and BP * Midazolam- GABA PAM y subunit * Can be used with no LOC IV Notes: * Decrease cardiac contracility * Respiratory depression * Decreased CNS function * Reduced sympathetic activity Ketamine/ Midazolam --\> Less CV/ Resp effects

Question 63

**Local Anaesthetic**

Answer 63

* **Lidocaine** * **Bupivacaine** * **Levobupivacaine** Blocks voltage-gated Na⁺ channels --\> Enter through cell membrane unionioned. Ionised IC space & block inside of Na channel Not useful in inflamed tissue due to the acidic pH of 'inflammatory soup' reducinng effectiveness of LA Uses: Levobupivicane- Epidural Anaesthesia

Question 64

**Neuromuscular blockers**

Answer 64

* **Suxamethonium (depolarising)** * **Atracurium (non-depolarising)** * **Vecuronium (non-depolarising)** * **Neostigmine -** peripheral inhibitor of acetylcholinesterase (depolarising). Also used in MG *Depolarising* : MOA: (non-competitive, agonist) Bind AchR --\> Prologned depolarisation (receptor closes & repolarises w/ agonist still bound) --\> prevents further depolarisation * Fast onset, short duration AChEi: Increase Ach in junctional cleft, paralysis by overload- all AchR @ max * SE: (PNS increase) * Bradycardia, Increased secretions & Peristalsis *Non-depolarising* - (competitive, agonist): Binf AChR prevent depolarisation post synaptically. Pre synaptically reduced Ca entry --\> Less NT from pre-synaptic vesicle Notes: Do not cross BBB * Slow onset, long duration

Question 65

**Drugs used to reverse NMB block**

Answer 65

* **Sugammadex** Oligosaccharide that forms a complex with NMB, encapsulating and inativating it then removing them from NMJ. ONLY for VECURONIUM * **Neostigmine** **​**Peripheral inhibtor of acetylcholinesterase - can **reverse non-depolarising blockers** by increasing Ach levels so neurone can fire again * Use in Myasthenia Gravis * SE: Bradycardia

Question 66

**Muscle Relaxants/Sedatives/Anxiolytic-hypnotic** (Think more sedatives and one that works in a similar way)

Answer 66

* **Zolpidem (Z drug) -** GABA PAM (mechanistically identical to BDZ) * USE: Anxiety- short term crisis * **Temazepam, Diazepam, Lorazepam, Midazolam (BDZ) -** GABA PAM Y subunit. Open Cl^- channels --\> Hyperpolarisation GABA PAMs increase the effect of GABA by making the channel open more frequently or for longer periods. However, they have no effect if GABA or another agonist is not present.

Question 67

**Muscle Relaxants/Sedatives/Anxiolytic-hypnotic** (Think more sedatives but less in anaesthesia in theatre)

Answer 67

**Dexmedetomidine** - a2-adrenergic receptor agonist. Inhibits NA release & terminates pain USE: Sedation ICU when verbal communication needs to maintained SE: Bind to a receptor so decrease sympathetic acitivty- Hypotension, Bradycardia

Question 68

Muscle Relaxants/Sedatives/Anxiolytic-hypnotic (Think more triad of anaesthesia)

Answer 68

**Afentanil, Fentanil, Remifentanil** - Opioid receptor agonists (Mu receptor). MOA: Decrease opening VDCC, Decrease Ca intracellular store, Decrease exocytosis of transmitter vesicles, Increase of K outflow post synaptically --\> Decrease AP & repolarisation time USE: Sedation but usually Analgesia SE: Respiratory depression, Miosis, Coma, Tolerance & Addiction

Question 69

**Benzodiazepine** **(Antagonist)**

Answer 69

* **Flumazenil** BDZ antagonist - revers bezodiazepine sedatives

Question 70

**Anti-Epilepsy drugs (AEDs)**

Answer 70

* **Sodium Valporate** * **Lamotrigine** * **Carbemazepine** **​**Block sodium channels in the inactivated state Use: All types of seizures except absence seizures SEs: Cognitive impairment, visual impairment, peripheral neuropathy, skin problems * **Ethosuximide - Ca2+ blocker** **​**Targets low threshold voltage dependent T-type calcium channels Use: Absence seizures - first line

Question 71

**Benzodiazepines for Epilepsy**

Answer 71

* **Midazolam -** GABA PAM (Y subunit) * **Lorazepam -** GABA PAM (Y subunit) * **Diazepam -** GABA PAM (Y subunit) GABAA PAMs increase the effect of GABA by making the channel open more frequently or for longer periods. However, they have no effect if GABA or another agonist is not present.

Question 72

**Barbituates (Barb)**

Answer 72

* **Phenobarbitone-** GABA PAM (B subunit) * **Pentobarbitone-** GABA PAM (B subunit) * **Primidone-** GABA PAM (B subunit) GABA PAMs increase the effect of GABA by making the channel open more frequently or for longer periods. However, they have no effect if GABA or another agonist is not present. **Use: Status Epileptics** and Primidone **Essential Tremor**

Question 73

**Anticholinesterases** **(for dementia)**

Answer 73

* **Donepezil** * **Galantamine** * **Rivastigmine** Reversible inhibitor of acetylcholinesterase Use: mild- moderate AD SE: Nausea & vomiting

Question 74

**Glutamate NDMA receptor antagonists**

Answer 74

* **Memantine** VD blocker of NMDA receptors (NMDA NAM) Interferes with glutamate mediated cell death as prevents Calcium getting into cell Use: Moderate to severe AD SE: Constipation, hypertension

Question 75

**Antimicrobial/Antiviral drugs for CNS infection**

Answer 75

* **Ceftriaxone** **​**Inhibits synthesis of cell walls in bacteria- Bacteriocidal Use: Bacterial meningitis SE: CDAD * **Acyclovir** **​**Inhibits viral DNA synthesis Use: viral encephalitis * **Amoxicillin -** **​**Induces cell lysis by blocking last stages of cell wall synthesis- Bacteriocidal. Increased uptake by bacteria USE: Listeriosa Meningitis *USES: CNS and meningococcal infections e.g. menigitis and encephalitis*

Question 76

**Corticosteroid** **(CNS infections)**

Answer 76

* **Dexamethasone** Glucocorticoid receptor agonist

Question 77

**Drugs used to treat hypercalcaemia**

Answer 77

* **Fluids (normal saline)** ​Volume expansion stimulates excretion of Ca2+ * **Furosemide (loop diuretic)** ​​Inhibits Na⁺K⁺2Cl^- transporter keeping Na+ and K+ in the lumen hence it is excreted * **Calcitonin****​** Decreases Ca2⁺ and PO₄ reabsorption in the kidneys, inhibits bone reabsorption by preventing osteoclast action (↓ serum Ca2⁺ and PO₄) * **Alendronic Acid (bisphosphonates)** Prevents osteoclast bone reabsorption which could further increase serum Ca2+

Question 78

**Drugs used in the management of hypocalcaemia**

Answer 78

* **IV calcium gluconate** **​**Replaces lost calcium in the body * **Vitamin D** vit D in activ form Calcitriol prevents Ca2+ and PO4 excretion from the kidney and increases reabsorption in the intestines

Question 79

**Drugs used in the management of vitamin D deficiency**

Answer 79

* **Vitamin D (colecalciferol** * **Calcitriol (only in advanced CKD)** Replaces vit D - active form Calcitriol prevents Ca2+ and PO4 excretion from the kidney and increases reabsorption in the intestines.

Question 80

**Drugs used to manage osteoporosis**

Answer 80

* **Alendronic acid (bisphosphonates)** **​**Prevents osteoclast bone reabsorption. Ruffled boarder impaired. Decrease osteoclast pregenitor development & recruitment. Promote osteoclast apoptosis. SE: Asymptomatic hypoclacaemia, Osteophageal reaction, GI disturbance, Osteonecrosis, Atypical # * **Raloxifene (selective oestrogen receptor modulator, SERM)** ​Inhiibits the cytokines which recruit osteoclasts thus less bone reabsorption * **Parathyroid hormone** **​**Stimulates calcitriol production which prevents Ca2+ and PO4 ecretion from kidney and increases absorption in the intestines Promote: Osteoblastic differentiation and activity. Inhibit osteoblast apoptosis SE: Hypercalcaemia, Muscle Cramps, Nausea & Vomiting * **Denosumab** **​**MoAb which targest RANKL or RANK receptir so inhibits maturation of osteoclasts so less bone reabsorption. Inhibits OC function, formation & survival SE: Hypocalcaemia, Diarrhoea, Dysponsea, Constipation * **Vitamin D**

Question 81

**Anti-proliferative agents** **(DMARDs)**

Answer 81

* **Methotrexate** ​Folic acid antagonist (req for DNA synth) so inhibits the S phase of the cell cycle * **Azathioprine** **​**Reduces purine synthesis and reduces DNA synthesis **Both reduce lymphocyte proliferation** SE: Increased infection risk Teratogenic GI: Mouth ulcers, Nausea, Diarrhoea Hair loss

Question 82

**Aminosalicylates** **(DMARDs)**

Answer 82

* **Sulphasalazine****​** * **Mesalazine** **Mechanism unclear - possible COX inhibition**

Question 83

**Biologics (monoclonal antibodies)**

Answer 83

* **Infliximab** Anti-TNF cytokine - bind and block proinflammatory function of TNF-alpha * **Rituximab** Depletion of B-lymphocytes CD20

Question 84

**Beta lactams - Penicillins**

Answer 84

* ***Flucoxacillin*** * **​SSTI** (use for **Staph** initially) * **Bone & Joint infections**- Empirical for ^ * **Penicillinase- Resistant** * ***Benzylpenicillin*** * **​SSTI** (use for **strep**) * **Bone & Joint infections**- Empirical for ^ * ***Amoxicillin*** * **​LRTI** * **Enhanced uptake by bacteria** * ***Co-amoxiclav*** * **​Mixed infections** (eg: chronic chest) * **Beca Lactamase Inhibitor** * ***Penicillin*** * Tonsillitis Bactericidal - cell lysis by blocking cell wall synthesis

Question 85

**Beta lactams - Carbapenem**

Answer 85

* **Meropenem** Use: Infections in ITU & Complex, multi drug resistant infections Bacteriocidal - cell lysis by blocking cell wall synthesis

Question 86

**Cephalosporins**

Answer 86

* **Ceftriaxone** Bacteriocidal - cell lysis by blocking cell wall synthesis Uses: Bacterial Meningitis, Abdominal sepsis, Ortho infection SE: CDAD NOtes: Later generations (like this one) Kill more natural flora & less effective against gram +ve infections. 10% of those with penicillin allergy are allergic to this

Question 87

**Nitroimidazole**

Answer 87

* **Metronidazole** USE: Anaerobic infecitons- abscess MOA: Bacteria DNA strucutre & function

Question 88

**Macrolides**

Answer 88

* **Erythromycin** **​**Bacteriostatic - inhibition of bacterial protein/ RNA synthesis Uses: URTI, LRTI, SSTI, Atypical LRTI * SSTI in place of penicillin * Atypical LRTI ie: Legionella

Question 89

**Lincosamides**

Answer 89

* **Clindamycin** Use: SSTI * In place of penicilin or where IV access is limited * Excellent bioavailability & tissue penetration when taken orally MOA: Bacteriostatic - inhibition of bacterial & RNA protein synthesis

Question 90

**Tetracyclines**

Answer 90

* **Tetracycline** * **Doxycycline** Bacteriostatic - inhibition of RNA & bacterial protein synthesis Use: Atypical bacteria lacking cell wall. Eg: Chlamydia, Mycoplasma Rickettsia infections, Typhus SE: GI Upset- Reflux Oesophagitis, Diarrhoea & Photosensitivity

Question 91

**Fluoroquinolones**

Answer 91

* **Ciprofloxacin** Use: Gram -ve infections Bacterial DNA strucutre & function SE: CDAD

Question 92

**Oral combination pill contraceptives**

Answer 92

* **Oestrogen/Progestrogen** Uses: Contraception, Dysmenorrhea, Menorrhagia MOA Molecular: Act on Oestrogen & Progesterone Receptors = INTRACEULLAR TRANSCRIPTION FACTORs- ER⍺and ERβ (Oestrogen) and PR-A, PR-B(Progesterone) Steroid hormones = Hydrophobic molecules therefore diffuse across cell membrane to IC receptors Hormone binding drives Receptor Activation viadissociation from HSP90 Active Receptor Dimersform --\> Cell Nucleus & Influence Gene expression MOA: Suppresses Ovulation and Reduces LH & FSH Secretion. Low Oestrogen has negative effect on Anterior Pituitary- Inhibits LH Progesterone has negative effect on Anterior Pituitary- Inhibits LH & FSH SE: Breakthrough bleeding, Nausea, Depression, Increased CV Risk (Oestrogen): IHD, Riased BP, THromboembolism, Stroke, Slight Breast Cancer risk w/ long term use

Question 93

**Oral mini-pill contraceptives**

Answer 93

* **Progesterone only** Suppresses ovulation (negative feedback AP for LH and FSH), alters endometrium (inhibits endometrial glands & makes mucus thicker) preventing sperm/egg interaction MOA: **Intracellular Transcription Fractors: PR-A, PR-B** Steroid hormones = Hydrophobic molecules therefore **diffuse across cell membrane to IC receptors** Hormone binding drives **Receptor Activation** via **dissociation** from **HSP90** **Active Receptor Dimers form** --\> **Cell Nucleus** & **Influence Gene expression** * Uses:* Contracpetion, Dysmenorrhagia, Menorrhagia, Emergency contraception * Benefits:* can be used instead of COCP when oestrogen is contraindicated * SEs:* slight increased risk of thrombotic events (stroke, DVT) and breast cancer. Breakthrough bleeding, Nausea, Vomiting

Question 94

**Implants/injectible contraceptives**

Answer 94

* **Long acting progesterone** Moderate/high dose progesterone causing HPO onhibition suppresses ovulation. Also has mucus/endometrial effects. SEs: nausea, breakthrough bleeding, depression

Question 95

**Hormone Replacement Therapy (HRT)**

Answer 95

* **Oestrogen alone** * **combined oestrogen and progestin** * **selective oestrogen receptor modulatoes (SERMs( - tamoxifen** Uses: Treats symptoms of menopause- hot flushes, vaginal dryness, sweats, loss of libido and reduces risk of osteoporosis. MOA: **Oestrogen & Progesterone restore the hormone levels.** Molecules **cross membrane** and bind to Intraceullar receeptors (**INTRACEULLAR TRANSCRIPTION FACTORS**)- ERalpha & ERbeta or PR-A & PR B. Binding drives **Receptor Acitvation** via **dissociation from HSP90**. **Active Receptor Dimer** forms --\> Cell nucleus & inflences gene expression. Combination w/ Progestin avoid cystic endometrial hyperplasia MOA SERM tamoxifen: Partial Agonist at bone & antagonist & brest & uterine receptors SEs: Thromboembolism, Stroke. Breakthrough Bleeding, BReast tenderness, Increased breast cancer risk, Increased dementia risk \>65yrs

Question 96

**Drugs used to induce labour** **(vaginal administration)**

Answer 96

* **Prostaglandin E2 (PGE2; dinoprostone)** Stimulates uterine contraction and cervical ripening

Question 97

**Drugs used to augment labour** **(IV administration)**

Answer 97

* **Oxytocin** Oxytocin increases uterine contractions and delivery of the placenta in 3rd stage of labour Given as an infusion

Question 98

Non-benzodiazepine Hypnotics

Answer 98

Zopiclone MOA: Enhances GABA binding to GABA-A receptors Use: Insomnia

Question 99

Inhaled analgesics

Answer 99

Nitrous Oxide + Oxygen ## Footnote MOA: unclear Use: analgesia during childbirth SE: Decrease synthesis vitamin B12