The Thirty Drugs We Must Know Seminar Two

Question 1

Prednisilone

Answer 1

Group: Endocrine (glucocorticoid similar to cortisol)
Receptor: glucocorticoid receptors

Mechanism of action: decrease vasodilation and permeability of capillaries. Decrease migration of leucocytes to site of inflammation. Inhibit neutrophil apoptosis / demmargination, inhibit PLA2 –> decreases formation of arachidonic acid –> inhibits NF-Kappa-B –> promotes IL-10 (anti-inflammatory). Higher doses are immunosuppressive. Also bind to mineralocorticoid receptors –> increased sodium / decreased potassium.

Clinical indication: treats endocrine, rheumatic and haematological disorders. Treats collagen, dermatologic, ophthalmic, respiratory and GI diseases. Can treat tuberculous meningitis. Treats allergic and oedematous states. Reducing the pain, swelling and allergic type reactions associated with these conditions.

Side affects: aggression, blurred vision, decreased volume of urine, irregular cardiac rhythm, SOB, weight gain.

Extra information: leads to HPA suppression and therefore, is immunosuppressive and can increase incidence of infection.

Question 2

L-Thyroxine (Levothyroxine)

Answer 2

System: Endocrine (Thyroxine T4 analogue),
Binding site(s): DNA (TREs / Promoter region) & integrin aVb3.

Mechanism of action: Synthetic T4 (isomer) –> increases metabolic rate / decreases TSH from APG. T4 –> T3 (4x more potent) in periphery. Maintains brain function / food metabolism / temperature. Binding to DNA TREs –> conformational change –> gene regulation. Also regulates heart rate / cardiac output / systemic vascular resistance. aVb3 activation –> mitogen - activated protein kinase –> angio / tumour genesis.

Clinical indication: replacement therapy in 1º, 2º, 3º hypothyroidism. Also used as a supplement after thyroidectomy or radio-iodine therapy.

Side affects: Minor effects are those one would imagine would occur due to increased T4/3, major side effects are heart attack / failure, tachycardia (irregular rhythms in general).

Extra information: Risk of side effects increase when given with ADs, SNS drugs, blood thinners and ketamine.

Question 3

Actrapid (Insulin)

Answer 3

System: Endocrine
Receptor: Extracellular alpha subunits of insulin receptor (tyrosine kinase)

Mechanism of action: Binds to alpha subunits –> tyrosine kinase activity in beta subunits – downstream signalling –> Akt –> GLUT4 and PKC regulation –> increases glucose uptake and storage as glycogen and conversion into fat / inhibits glucose production in the liver / increases protein synthesis, lipo and proteolysis. Stimulates growth and DNA replication.

Clinical indication: treatment of hyperglycaemia in TI / II DM (complete destruction of beta cells in DMTI) and when there is cellular resistance.

Side affects: Hypokalaemia (problems with breathing and heart rhythm) and heart failure.

Extra information: interactions with other drugs that increase or lower blood glucose such as MAOIs, thiazolidinediones (diabetes drugs), BP, antidiuretics, corticosteroids, oestrogen, thyroxin.

Question 4

Glibenclamide

Answer 4

System: Endocrine

Mechanism of action: 2nd gen sulfonylurea. Closes ATP-sensitive K+ channels on beta cells (SUR1) –> raising intracellular K+ and Ca2+ –> secretion of insulin.

Clinical indication: Treats DM in metformin resistant DMTII patient.

Side affects: Nausea, heartburn, weight gain, bloating, hypoglycaemia, cholestatic jaundice.

Extra information: May cause hemolysis in patients with G6PD deficiency.

Question 5

Oxytocin

Answer 5

System: Endocrine
Receptor: Oxytocin receptor (uterine myometrium) (GqPCR);

Mechanism of action: Produced: hypothalamus –> stored: PPG –> (released in response to high plasma osmolality / parturition) –> binds to GPCR on myometrium –> increase of intracellular calcium –> MLCK activation –> MLC phosphorylation –> actomyosin formation –> smooth muscle contraction. In mammary glands –> contraction of myoepithelial cells around alveoli.

Clinical indication: obstetrics –> stimulates uterine contraction to induce labour. Also stimulates milk ejection.

Side affects: Hypotension, uterine rupture, water retention, foetal death.

Extra information: If the patient is currently in labour or if there is obstruction during delivery oxytocin SHOULD NOT be given as it may cause foetal death. Hypertension can occur when given in conjunction with anaesthetic block.

Question 6

Ascorbic Acid (Vitamin C)

Answer 6

Group: Vitamins

Mechanism of action: Water soluble. Cofactor in production of 4 - hydroxyproline –> proline –> collagen –> connective tissue & vessel walls. Also involved in tyrosine metabolism, conversion of folic acid, carbohydrate metabolism, synthesis of lipids and proteins, iron metabolism, resistance to infection and cellular respiration.

Clinical indication: Treats vitamin C deficiency (scurvy), delayed wound and bone healing, urine acidification.

Side affects: Diarrhoea, dizziness, flushing, headache, increased micturition, nausea, vomiting, stomach cramps (at high doses).

Question 7

Pyridoxine Hydrochloride (B complex)

Answer 7

Group: Vitamins

Mechanism of action: hydrochloride salt pyridoxine –> pyridoxal 5’ - phosphate (PLP) –> cofactor in synthesis of AAs, NTs, sphingolipids. Also maintains blood glucose levels; and is essential to RBCs, the nervous and immune systems.

Clinical indication: Treats and prevents nerve disorders (peripheral neuropahty - a side effects of drugs such as isoniazid [which treats tuberculosis]).

Side affects: In doses > 2mg / day can causes sensory neuropathy and neuropathic syndrome (raised AST and reduced folate), can cause allergic reaction and can cause seizures in neonates if given in pregnancy.

Extra information: antihypertensive drugs act as antagonists of pyridoxine.

Question 8

Cyanocobalamin (B12)

Answer 8

Group: Vitamins

Mechanism of action: cofactor of methionine synthase and L-methylmalonyl-CoA mutase. Methionine is used in the production of pyrimidines and purines. L-methylmalonyl-CoA mutase converts L-methylmalonyl-CoA to succinyl CoA when propionate is being degraded - it is necessary for protein / fat metabolism. Build up of L-methylmalonyl-CoA –> neurological symptoms in B12 deficiency. Succinyl CoA used in Hb synthesis. B12 is also used in the synthesis of methionine from HCy and regenerates folate –> a deficiency can cause megaloblastic anaemia.

Clinical indication: Pernicious anaemia and megaloblastic anaemia as well as B12 deficiency.

Side affects: (high doses) diarrhoea, peripheral vascular thrombosis, itching, transitory exanthema, pulmonary oedema and congestive heart failure.

Extra information: Colchicine, metformin, antibiotics (e.g gentamycin), anti-epileptics and drugs for heart burn all reduce the absorption of B12.

Question 9

Tocopherol Acetate (Vitamin E)

Answer 9

Group: Vitamins

Mechanism of action: antioxidant –> modified PKC –> inhibits cell death –> anti-inflammatory as no arachidonic acid for COX. A radical scavenger of alkyls and peroxys. Antioxidant for lipid bilayer. Achieves these effects by being able to donate a proton.

Clinical indication: Vitamin E deficiency (i.e premies, abetalipoproteinaemia patients [fat soluble vitamin]).

Side affects: (High doses) haemorrhage.

Extra information: > 300mg / day –> interactions with aspirin, warfarin, tamoxifen and cyclosporine A.

Question 10

Retinol Acetate (Vitamin A)

Answer 10

Group: Vitamins

Mechanism of action: oxidised to retinoic acid – translocates to nucleus –> binds to intra - nuclear receptor (forms activated receptor complex) –> binds to chromatin activating gene transcription.

Clinical indication: treatment for acne, psoriasis, photoaging etc. Stimulates cellular and humoral immunity. Has a role in the metabolic function of the retina, growth and differentiation of epithelial tissue and bone growth.

Side affects: (High doses) irritation, dryness, skin peeling, photosensitivity, dry eyes and mucus membranes.

Extra information: Contraindications with isotretinoin, neomycin, warfarin, orlistat and mineral oil.

Question 11

Heparin

Answer 11

Group: Anti-coagulants
Binding site: anti - thrombin III (alpha globulin)

Mechanism of action: binds –> inhibits serine proteases of thrombin IIa and Xa. Limits expansion of thrombi and prevents fibrin formation.

Clinical indication: Can treat DVT and PE. Prophylaxis of DVT postoperatively. Treats AMI.

Side affects: Increased risk of bleeding. To reverse discontinue drug or administer protamine. Derived from porcine so can be antigenic –> anaphylactic shock. Thromboembolism –> venous / arterial Thrombocytopenia. Osteoporosis long term.

Extra information: does not cross the placenta because of its size so can be given in pregnancy. contraindicated in those who have had surgery involving the CNS and alcoholics.

Question 12

Warfarin

Answer 12

Group: Anti-coagulants

Mechanism of action: inhibits vit K and Vit K dependent synthesis of factor II, VII, IX, X, protein C, S and Zv. Vit K recycling is also inhibited as Vit K epoxide is inactivated by warfarin.

Clinical indication: used in the prevention of blood clot formation and migration.

Side affects: necrosis, osteoporosis, valve / artery calcification.

Extra information: crosses placental barrier and can cause foetal bleeding, spontaneous abortion, preterm brith, still birth neonatal death.

Question 13

Methyluracil (Thymine)

Answer 13

Group: Leukopoiesis stimulant

Mechanism of action: Leukocytes formed from multipotent myeloid and lymphoid stem cells in haemopoetic organs. Methyluracil stimulates this production; and therefore, can accelerate regeneration and healing of wounds, stimulates cellular and humoral factors of immunity and has an anti-inflammatory effect.

Clinical indication: treats agranulocyte angina, chronic benzene intoxication, leukopenia that occurs due to chemotherapy. Treats slow healing wounds.

Side affects: Urticaria, headache, dizziness.

Extra information: cannot be used in patients with acute or chronic leukaemia, lymphogranulomatosis and malignant bone marrow diseases.

Question 14

Menandione Sodium Bisulphate (Viaksol) (Vitamin K3)

Answer 14

Group: Vitamins

Mechanism of action: K3 (synthetic) –> K2 (active). Cofactor for post-translational gamma-carboxylation of glutamic acid residues of factor II, VII, IX, X, protein C, S and Zv. Osteocalcin and MGP (Vit K) dependent proteins in bone. Vit K hydroxyquinone works as a gamma decarboxylase.

Clinical indication: assists in clotting of blood and plays a role in bone calcification. Treats newborn who are prone to haemorrhaging.

Side affects: Excess K3 –> kernicterus in infants (bilirubin can be found in the brain of those affected), also causes hemolytic anaemia in those with G6PD deficiency.

Question 15

Diphenhydramine (Dimedrol) (Benadryl)

Answer 15

Group: Antihistamine
Receptor: H1 receptor antagonist (1st gen)

Mechanism of action: Anti - emitic –> inhibits medullary chemoreceptor trigger zone in the mid-brain. Anti - vertigo –> antimuscarinic (as they are similar to histamine receptors) affect on vestibular apparatus and vomiting centre. Mainly works via H1 antagonism so reduces capillary permeability, does not cause contraction of respiratory, GIT and cardiac smooth muscle.

Clinical indication: seasonal allergies, insect bites and rashes. Also used as a sleep aid. Has anti-tussive, anti-emitic, hypnotic and antiparkinson effects in combination with anticholinergic agents. Injection form - lessons allergic reaction to blood and plasma, can be used with epinephrine in anaphylactic shock. Treats motion sickness

Side affects: Can cause sedation.

Question 16

Loratadine (Clarityn)

Answer 16

Group: Antihistamine (2nd gen)
Receptor: H1 (GPCR) inverse agonist.

Mechanism of action: reduces histamine interaction with H1 receptors. Binds to H1 (GPCR) on endothelial cells, eosinophils, neutrophils, airway and vascular smooth muscle cells and keep the receptor in the inactive form.

Clinical indication: Treats allergic rhinitis, wheal formation, urticaria, allergic dermatitis in general.

Side affects: Can still cause sedation to some extent in some patients, headache, urinary retention, dry mouth, blurred vision, GIT problems. *anti-muscarinic effects.

Extra information: low penetrance in the CNS. Does not bind to CNS H1 so is unlikely to cause sedation.

Question 17

Calcium Chloride

Answer 17

Mechanism of action: Dissociates into Ca2+ and Cl-. Ca2+ restores normal gradient between threshold potential and resting membrane potential and therefore, can treat hyperkalemia.

Clinical indication: Treats hypoglycaemia when a rapid increase in calcium is required. Treats magnesium intoxication, combats deleterious effects of hyperkalaemia. Can also be used to treat hypotension.

Side affects: GI irritation and hypercalcemia.

Question 18

Interferon Alpha

Answer 18

System: Immune

Mechanism of action: (Cytokines) Natural IFN-alpha contains many sub-types and recombinant IFN-alpha contains only one. Natural subtype has a broader spectrum of specific anti-viral and immuno-regulatory activity. Stimulates production of proteins that inhibit growth and replication (e.g HLA-II). IFN-alphas also stimulate proliferation / activation of B cells, NK cells, dendritic cells as well as initiating the Th1 inflammatory response.

Clinical indication: Treats hepatitis C, lymphoid and myeloid leukaemia and melanoma.

Side affects: Flu-like syndrome, fatigue and low blood counts –> anaemia / increased risk of infection.

Question 19

Methotrexate

Answer 19

System: Immune

Mechanism of action: Methotrexate –> methotrexate polyglutamate by folypolyglutamate. Inhibits enzymes that synthesise nucleotides (e.g AICART) preventing cell division. In rheumatoid arthritis AICART is inhibited by methotrexate polyglutamate. AICART ribonucleotides build up –> inhibiting adenosine deaminase –> ATP accumulation –> adenosine receptors are stimulated –> anti - inflammatory action. Dihydrofolate reductase inhibitor / folic acid antagonist - inhibits cytokine production and purine biosynthesis which gives it immunosuppressive and anti-inflammatory effects.

Clinical indication: Paediatric acute lymphoblastic leukaemia / poly-articular juvenile idiopathic arthritis (PJIA), injections for severe rheumatoid arthritis and severe PJIA. Also used in the treatment of many cancers (e.g gestational choriocarcinoma, breast cancer, non - Hodgkin’s lymphoma, acute lymphocytic leukaemia. Can be given with leucovorin (synthetic folic acid) to prolong relapse free survival after removal of non - metastatic osteosarcoma.

Side affects: Hepatotoxicitiy, ulcerative stomatitis, leukopenia (increased risk of infection), kidney failure.

Extra information: Teratogenic (should not be taken by mother or father before pregnancy). Can cross blood brain barrier so has neurotoxicity.

Question 20

Glaucine (Glauvent)

Answer 20

System: Respiratory.

Pharmacodynamics: bronchodilator and anti-inflammatory PDE4 inhibitor and calcium channel blocker;

Indication for use: antitussive (coughs);

Side-effects: sedation, fatigue and hallucinogenic.

Question 21

Acetylcysteine

Answer 21

System: Respiratory

Pharmacodynamics: mucolytic agent;
Indication for use: COPD (obstructive lung disease);

Side-effects: uticaria (rash, itchiness), anaphylaxis, hypotension, wheezing.

Question 22

Ambroxol (Lasolvan)

Answer 22

System: Respiratory

Pharmacodynamics: mucolytic agent - breakdown of acid mucopolysaccharide fibres makes the sputum thinner and less viscous and therefore more easily removed by coughing;

Indications for use: tracheobronchitis, emphysema with bronchitis pneumoconiosis, chronic inflammatory pulmonary conditions, bronchiectasis, bronchitis with bronchospasm asthma;

Side-effects: gastrointestinal side-effects;
Contraindications: caution in patients with gastric ulceration.

Question 23

Omeprazole

Answer 23

System: Gastro-Intestinal

Pharmacodynamics: Proton pump inhibitors (PPIs) covalently bind directly H+/K+ ATPase in parietal cells (lasts for 18 hours); prodrug resistant to premature degradation by acid.

Indications for use: Used in treatment of GERD, prophylaxis in conjunction with NSAIDS to prevent ulcerations of the stomach, erosive esophagitis, active ulcers and diseases such as Zollinger - Ellison (gastrin producing tumor) and used in treatment of H.pylori ulcers.

Contraindications: may inhibit action of clopidegrel.

Question 24

Pancreatin

Answer 24

System: Gastro - Intestinal

Mechanism of action: mixture of lipase, protease and amylase that break down fats, proteins and starches respectively in the small intestine.

Clinical indication: Pancreatic enzyme replacement therapy due to insufficiency caused by cystic fibrosis, chronic pancreatitis or other diseases where there is destruction of parenchyma (which cause malnutrition, weight loss and steatorrhea).

Side effects: risk of fibrosing colonopathy, risk of viral infection; and as drug is porcine in origin (therefore, can also be anitgenic and cause anaphylactic shock).

Question 25

Bisacodyl

Answer 25

System: Gastro-Intestinal

Pharmacodynamics: irritants and stimulants - anthraquinone glycosides causing electrolyte and water secretion into bowels, bisacodyl acts on nerve fibres in the mucosa of the colon and castor oil’s product (ricinoleic acid) irritates the stomach producing peristalsis;

Indications for use: Used as laxatives;

Contraindications: can cause uterine contractions so should not be used in pregnancy.

Question 26

Magnesium Sulfate

Answer 26

Mechanism of action: Mg2+ 2nd most abundant cation and important for the function of enzyme systems, neuro-chemical transmission and muscle excitability. Magnesium sulfate reduces ACh release reducing striated muscle contraction and blocking NM transmission. Mg2+ inhibits Ca2+ influx –> relaxes vascular smooth muscle.

Clinical indication: treats convulsion related to pre-eclampsia and eclampsia and in the treatment of nephritis in children. Can also be used as an anti-arrhythmic. Replacement therapy in magnesium deficiency.

Side effects: heart disturbances, breathing difficulty, confusion, weakness, lowered blood pressure.

Question 27

Famotidine

Answer 27

System: Gasto-Intestinal

Pharmacodynamics: H2 - histamine receptor blockers (reversible competitive antagonist);

Indications for use: used to treat peptic ulcers (if-NSAID induced then PPIs should be used), acute stress ulcers (temporary), gastroesophageal reflux disease;

Clinical information: also inhibits basal, food stimulated and nocturnal stimulation; the use of these has been diminished due to PPIs.

Question 28

Sodium Picosulfate

Answer 28

System: Gastro-Intestinal

Pharmacodynamics: Saline and osmotic laxative - hold water via osmosis (increased salt or sugar concentration within the lumen) causing peristalsis;

Indications for use: Laxative (PEG specifically used for colonic lavage and causes less cramping and gas), lactulose used to treat hepatic encephalopathy as it reduces ammonia levels.

Question 29

Loperamide

Answer 29

System: Gastro - Intestinal

Receptor: Mu opioid agonist in myenteric plexus of large intestines.

Mechanism of action: Decreases activity of myenteric plexus of large intestine decreasing circular and longitudinal smooth muscle contraction. Also affects water and electrolyte movement through the bowel. Non-selective calcium channel blocker. At high concentrations may also bind to calmodulin.

Indication for use: Controls and provides symptomatic relief of acute non-specific diarrhoea associated with IBD or gastroenteritis. Also reduces discharge during ileostomies.

Side effects: Constipation, nausea, abdominal cramps, drowsiness, vomiting, abdominal pain.

Extra - information: If blood is observed in the stool loperamide is contraindicated. Loperamide also increases the risk of toxin retention so should not be given to those with clostridium infections. Due to reduced first pass metabolism loperamide should be avoided in those with liver failure. Can cause paralytic ileus in children under the age of two. Possibly teratogenic so should be avoided in pregnancy and when breast feeding.

Question 30

Aprotinin (Contrykal) (Bovine pancreatic trypsin inhibitor)

Answer 30

System: Blood

Mechanism of action: inhibits serine - proteases (e.g trypsin, chromotrypsin, plasmin) and kallikrein inhibiting the formation of factor XIIa inhibiting the intrinsic pathway. The inhibition of plasmin also slows fibrinolysis.

Indication for use: Prophylactic use to reduce peri-operative blood loss and the need for transfusion in those undergoing cardiopulmonary by-pass.

Side effects: Anaphylaxis, thrombosis, acute renal failure, MI, heart failure, stroke.

Question 31

Protamine (Sulfate)

Answer 31

System: Blood

Mechanism of action: basic protein that binds with the acidic heparin to produce a stable salt. Protamine degrades Xa.

Indication for use: counteracts and reverses the anticoagulant effect of heparin. Required before surgery, renal hemodialysis, post open heart surgery, whenever there is excessive bleeding due to heparin.

Side effects: sudden fall in blood pressure, pulmonary hypertension, SOB, flushing.

Question 32

Chloroquine (Chingamin)

Answer 32

System: Immunity

Mechanism of action: inhibits heme polymerase –> prevents conversion of heme to hamzoin –> build up of toxic heme in plasmodium species –> kills parasite. Chloropquine also diffuses into endosomes, lysosomes and Golgi –> protonated –> raise pH –> prevent utilisation by virus for entry by fusion.

Indication for use: treatment of P. Vivax, P. Malariae, P. Ovale, P. Falciparum and extra-intestinal amebiasis.

Side effects: Retinopathy, muscle weakness and toxicity in children in high doses.

Question 33

Filgrastim

Answer 33

Class: Chemotherapeutic Drugs

Mechanism of action: G-CSF (granulocyte colony stimulating factor) analog - controls proliferation of committed progenitor cells –> neutrophil maturation. Stimulates release of neutrophils from bone marrow. Increases phagocytic activity of neutrophils. Reduces neutropenic phase after chemotherapy.

Indication for use: leucocyte growth factor that decreases the incidence of infection that may occur as a result of febrile neutropenia and those with non-myeloid malignancies under going myelosupressive therapy. In patients with acute myeloid leukema. Those under going myeloblative chemotherapy after bone marrow transplantation.

Side effects: Mild bone pain, local skin reaction due to injection.

Question 34

Vincristine

Answer 34

Class: Chemotherapeutic Drugs

Mechanism of action: Inhibits mitosis at metaphase by crystallising microtubules leading to arrest of mitosis and cell death. Also interferes with amino acids, cyclic AMP, glutathione metabolism, calmodulin - dependent Ca2+ transport ATPase activity, cellular respiration, nucleic acid and lipid biosynthesis.

Indication for use: treatment of acute lymphocytic leukaemia, (non-)Hodgkin lymphoma, Wilms’ tumour, neuroblastoma, rhabdomyosarcoma.

Side effects: chemotherapy induce peripheral neuropathy, hyponatremia, constipation and hair loss.

Question 35

Pirenzepine

Answer 35

System: Gastro-Intestinal

Mechanism of action: muscarinic receptor antagonist (binds to MACh 1 receptors) inhibiting adenylate cyclase, reducing gastric acid secretion and muscle spasms.

Indication for use: treatment of peptic / gastric / duodenal ulcers.

Side effects: Dry mouth, blurred vision and constipation.

Question 36

Alteplase

Answer 36

Class: Thrombolytic

Mechanism of action: binds to fibrin via fibronectin and kringle 2. The protease domain then cleaves plasminogen to plasmin which degrades the fibrin matrix of the thrombus.

Indication for use: For management of acute MI, acute ischaemic stroke and lysis of PE.

Side effects: (intracranial / GI) bleeding, allergic reaction.