Essential Drug list

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vickrum
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Essential Drug list
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2016-04-28 02:56:11
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Drugs; 28 to go
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  1. Doxazosin* (dox AY zo sin)
    • Drug Class: α-blocker
    • - selective competitive blockers of the α1-receptor.
    • Indications: Management of mild-moderate hypertension
    • - urinary obstruction symptoms caused by benign prostatic hyperplasia
    • Mechanism/Target: Binds to and blocks α-receptors on vascular smooth muscle; hence inhibiting vasoconstrictor effect (of catecholamines nor/epinephrine)
    • → arterial and venous dilation →
    • → reduces the sympathetic tone of the blood vessels, resulting in decreased peripheral vascular resistance and BP
    • - also decreases tone in the smooth muscle of the bladder neck and prostate and improves urine flow.
    • Adverse effects: first dose of these drugs produces an exaggerated hypotensive response that can result in syncope (fainting). Dizzyness, malaise, fatigue and headache
  2. Terazosin
    • Drug Class: Alpha-blocker
    • Major effects: selective competitive blockers of the α1-receptor for treating hypertension
    • - blockade of these receptors reduces the sympathetic tone of the blood vessels, resulting in decreased peripheral vascular resistance.
    • - also decreases tone in the smooth muscle of the bladder neck and prostate and improves urine flow.
  3. Propofol*
    • Drug Class: Anaesthetics;
    • Indications: sedative/hypnotic used in the induction or maintenance of anesthesia.
    • - also for management of refractory status epileptics
    • Drug administration: Intravenously
    • Pharmacokinetics: Onset is smooth and occurs within about 40 seconds of administration.
    • - Effects are short lived and supplemenation with narcotics for analgesia is required.
    • Mechanism/Target: binds GABAA receptors in brain causing global CNS depression
    • - also reduced glutamanergic activity with NMDA receptor blockade
    • - Propofol decreases blood pressure without depressing the myocardium.
    • - Poor analgesia but rapid onset and lowers inter-cranial pressure
    • Adverse effects: While propofol facilitates depression in the CNS, high plasma levels can cause excitation.
  4. Lignocaine (Local Anaesthetic)
    • Drug Class: Anaesthetics
    • Local Anaesthetics are applied locally and block nerve conduction of sensory impulses from the periphery to the CNS;
    • - hence abolish sensation (and in higher concentrations, motor activity) in a limited area of the body without producing unconsciousness.
    • Mechanism: They inhibit sodium channels of the nerve membrane.
    • - The small, unmyelinated nerve fibers, that conduct impulses for pain, temperature, and autonomic activity, are most sensitive to actions of local anesthetics.
  5. Diazepam*
    • E.g. Valium
    • Drug Class: Antianxiety/hypnotic
    • Indications: Treatment of severe anxiety disorders
    • - hypnotic in short-term management of insomnia and alcohol withdrawl syndrome
    • - other uses/ effects; Anterograde amnesia (e.g. before endoscopy), Anticonvulsant/epileptic, and Muscle relaxant (muscle spasms/spasticity/disorders), sleep disorders
    • Drug administration and Pharmacokinetics: benzodiazepines are lipophilic. They are rapidly and completely absorbed after oral administration and distribute throughout the body
    • Mechanism: Target of benzodiazepines are GABAA receptors. Binding of GABA to its receptor triggers an opening of a chloride channel, which leads to an increase in chloride conductance. Benzodiazepines increase the frequency of channel openings produced by GABA. The influx of chloride ions causes a small hyperpolarization that moves the postsynaptic potential away from its firing threshold and, thus, inhibits the formation of action potentials.
    • - note; Binding of a benzodiazepine to its receptor site will increase the affinity of GABA for the GABA-binding site (and vice versa) without actually changing the total number of sites.
    • Adverse effects:
    • - Dependence; They are addictive.
    • - Abrupt discontinuation of the benzodiazepines results in withdrawal symptoms, including confusion, anxiety, agitation, restlessness, insomnia, tension, and (rarely) seizures. Because of the long half-lives of some benzodiazepines, withdrawal symptoms may occur slowly and last a number of days after discontinuation of therapy.
    • Precautions: Benzodiazepines should be used cautiously in treating patients with liver disease.
    • - Alcohol and other CNS depressants enhance the sedative-hypnotic effects of the benzodiazepines.
  6. Zopiclone
    • Drug Class: Antianxiety/hypnotic
    • Zopiclone is used for the long-term (upto 6 months) treatment of insomnia and for sleep maintenance
    • - No tolerance was observed, nor were signs of serious withdrawal, such as seizures or rebound insomnia, seen upon discontinuation of the drug
  7. Lorazepam
    • Drug Class: Antianxiety/hypnotic
    • - Another benzodiazepam
    • Immediate acting (10-20 hours) (whereas diazepam is longer acting ~1-3 days)
    • - Do not require Phase I metabolism and, therefore, show fewer drug interactions and are safer in patients with hepatic impairment.
    • Adverse effects: in general, benzodiazepines may disturb intellectual functioning and motor dexterity.
    • - The benzodiazepines have the potential for dependence, and withdrawal seizures may occur.
  8. Citalopram*
    • Drug Class: Antidepressant (SSRI)
    • Mechanism/Target: selectively inhibits seritonin reuptake in the presynaptic neurons with minimal effects on norepinephrine and dopamine
    • - onset of action is 1-4 weeks, however individuals vary
    • Adverse effects: Decrease risk of suicidal ideation
    • - bleeding risk with other drugs like asprin, warfarin and other anticoagulants
    • - serotonin syndrome
  9. Fluoxetine (a.k.a. Prozac)
    • Drug Class: Antidepressant (of the SSRI variety)
    • Mechanism: It selectively inhibits the serotonin reuptake transporter (NT in the brain)
    • - selective serotonin reuptake inhibitor (SSRI)
  10. Nortriptyline
    • Drug Class: Antidepressant (tricyclic type)
    • - block norepinephrine and serotonin reuptake into the neuron
    • They elevate mood, improve mental alertness, increase physical activity, and reduce morbid preoccupation in 50 to 70 percent of individuals with major depression.
    • The onset of the mood elevation is slow, requiring 2 weeks or longer
  11. Moclobemide
    • Drug Class: Antidepressant
    • - reversible inhibitor of monoamine oxidase (MAO)
    • # Don't learn;
    • MAO functions as a “safety valve” to oxidatively deaminate and inactivate any excess neurotransmitter molecules (norepinephrine, dopamine, and serotonin) that may leak out of synaptic vesicles when the neuron is at rest. The MAO inhibitors (MAOIs) may irreversibly or reversibly inactivate the enzyme, permitting neurotransmitter molecules to escape degradation and, therefore, to both accumulate within the presynaptic neuron and leak into the synaptic space.
    • - This is believed to cause activation of norepinephrine and serotonin receptors, and it may be responsible for the indirect antidepressant action of these drugs
  12. Lithium
    • Drug Class: Antidepressant
    • - Lithium salts are used prophylactically for treating manic-depressive patients and in the treatment of manic episodes and, thus, are considered “mood stabilizers.”
    • - the mode of action is unknown.
  13. Insulin*
    • Drug Class: Antidiabetic
    • Drug administration: Taken intravenously/subcutaneous injections because unstable in GI tract (it is peptide hormone)
    • Pharmacokinetics:
    • - Modifications of the aa sequence of human insulin have produced insulins with different pharmacokinetic properties. E.g. 3 such insulins, lispro, aspart, and glulisine, have a faster onset and shorter duration of action than regular insulin, because they do not aggregate or form complexes.
    • - Insulin is inactivated by insulin-degrading enzyme (also called insulin protease), which is found mainly in the liver and kidney.
    • Mechanism/Target: Insulin receptor
    • Adverse effects: hypoglycemia is the most serious and common adverse reactions to an excessive dose of insulin.
    • - symptoms include; headache, anxiety, tachycardia, confusion, vertigo and diaphoresis
    • - Weight gain, and caution required for children < 13 and elderly
  14. Describe the 4 types of Insulins we can prescribe
    • Lispro: Short acting insulin, rapid onset of action
    • - Two uses; in continuous sub-cutaneous infusion,
    • - or in the premeal component of an insulin (bolus) regime (inconjunction with intermediate/long-acting insulin), to provide good postprandial glycemic control
    • Aspart: Short acting insulin with rapid onset
    • - pretty much the same properties as lispro with subtle pharmokokinetic properties
    • Detemir: mid-long acting insulin (compared to human insulin coz it binds albumin)
    • - twice a day as basal component of therapy
    • - Less weight gain
    • Glargine: long acting insulin (aggregates)
    • - lasts 24 hrs but begins to wane at 15
    • - can have significant weight gain
  15. Gliclazide*
    • Drug Class: Antidiabetic
    • - Sulfonylurea (insulin secretagogue which promote insulin release from the β cells of the pancreas)
    • Mechanism/Target: Bind to a receptor in the plasma membrane of the pancreatic β cells
    • - causing closing of the ATP-sensitive K+ channel, which results in depolarisation of the cell
    • - Subsequent opening of Ca++ channels → SNAREs and exocytosis of insulin
    • Adverse effects: Hypoglycemia and weight gain
  16. Metformin*
    • Drug Class: Antidiabetic
    • - biguanide (or an insulin sensitizer)
    • Drug administration: Oral
    • Pharmacokinetics:
    • - reduces hepatic glucose output via inhibiting gluconeogenesis
    • - slows intestinal absorption of sugars and improves peripheral glucose uptake and utilization (i.e. it suppresses glucagon effects)
    • - important property of this drug is its long term ability to modestly reduce hyperlipidemia (except HDLs)
    • Mechanism/Target: Activates AMP kinase in the liver
    • - AMPK is activated by phosphorylation when cellular energy stores are reduced (i.e. high AMP)
    • - this stimulates βoxidation, glucose uptake, and nonoxidative metabolism
    • - it reduces lipogenesis (by inhibiting acetyl-CoA carboxylase for de novo FA synthesis) and gluconeogenesis.
    • - it increases uptake of glucose into peripheral tissues via GLUT-4
    • The net result of these actions is increased glycogen storage in skeletal muscle, lower rates of hepatic glucose production, increased insulin sensitivity, and lower blood glucose levels.
    • Adverse effects: Abdominal/GI discomfort, diarrhoea, lactic acidosis (inhibition of gluconeogenesis)
    • - Metformin is contraindicated with renal and/or hepatic disease, diabetic ketoacidosis, and cardiac failure
    • - Chronic use of metformin can result in lactic acidosis due to a build up of the precursors for gluconeogenesis - pyruvate and lactate - which are both organic acids.
  17. Sitagliptin
    • Drug Class: Antidiabetic
    • - dipeptidyl peptidase-IV (DPP-IV) inhibitors used for the treatment of patients with type 2 diabetes
    • This enzyme is responsible for the inactivation of incretin hormones such as glucagon-like peptide-1 (GLP-1).
    • - Prolonging the activity of incretin hormones results in increased insulin release in response to meals and a reduction in inappropriate secretion of glucagon.
  18. Pioglitazone
    • Drug Class: Antidiabetic
    • - Thiazolidinediones (glitazones) = PPAR agonists
    • They act to improve peripheral glucose utilisation and insulin sensitivity through acting at the level of transcription
    • - Although insulin is required for their action, these drugs do not promote its release from the pancreatic β cells, so hyperinsulinemia is not a risk.
    • Target the peroxisome proliferator–activated receptor-γ (PPARγ), a nuclear hormone receptor. Ligands for PPARγ regulate adipocyte production and secretion of fatty acids as well as glucose metabolism, resulting in increased insulin sensitivity in adipose tissue, liver, and skeletal muscle.
  19. Naloxone*
    • Drug Class: Antidotes (given to reverse an overdose)
    • - an opioid antagonists bind with high affinity to opioid receptors but fail to activate the receptor-mediated response
    • Indications: Naloxone [nal-OX-own] is used to reverse the coma and respiratory depression of opioid overdose.
    • - It rapidly displaces all receptor-bound opioid molecules and, therefore, is able to reverse the effect of a morphine overdose
  20. Flumazenil
    • Drug Class: Antidotes (given to reverse an overdose)
    • - a GABA-receptor antagonist that can rapidly reverse the effects of benzodiazepines.
  21. Treating epilepsy; Name the types of seizures and types of drugs (4)
    • Epileptic seizures (2):
    • - partial seizures; those beginning focally in a cortical site, and
    • - generalized seizures; those that involve both hemispheres widely from the outset. 3 types; absence, myoclonic and tonic-clonic seizures
    • Simple vs complex: A simple partial seizure is associated with preservation of consciousness. A complex partial seizure is associated with impairment of consciousness.
  22. Phenytoin*
    • Drug Class: Antiepileptic
    • Indications: For all seizure types except absence seizures (i.e. Abrupt onset of impaired consciousness associated with staring and cessation of ongoing activities typically lasting less than 30 seconds)
    • - Effective for generalized tonic-clonic seizures in 70-80% of cases but effective only for about 30-40% of partial seizures
    • - good for prevention of seizure post neurosurgery
    • Pharmacokinetics: narrow range of plasma concentrations to cause adverse side effects
    • - hence therapeutic drug monitoring (TDM) is essential
    • *interesting note*- Small increases in a daily dose can produce large increases in the plasma concentration, resulting in drug induced toxicity. Although phenytoin = low cost per tablet, the cost of therapy may be much higher when the potential for serious toxicity and adverse effects is weighed.
    • Mechanism/Target: blocks voltage-gated sodium channels by selectively binding to the channel in the inactive state and slowing its rate of recovery.
    • - prolongs effective refractory period and suppresses ventricular pacemaker automaticity, and shortens action potential in the heart
    • Adverse effects: Decreased bone mineral density
    • - suicidal ideations
    • - Can be associated with fetal abnormalities
  23. Carbamazepine
    • Drug Class: Antiepileptic
    • - For all seizure types except absence seizures (i.e. Abrupt onset of impaired consciousness associated with staring and cessation of ongoing activities typically lasting less than 30 seconds)
    • Other uses: Bipolar disorder, Neuropathic pain, and Tinnitus
    • Common Adverse Effects: nausea, dizziness, drowsiness, ataxia and blurred vision; rarely, agranulocytosis
  24. Valproate
    • Drug Class: Antiepileptic
    • - For all seizure types, but especially absence seizures
    • Other uses: Bipolar disorder, migraine
    • MOA: are believed to work by inhibiting repetitive firing, by increasing the number of Na+ channels in the inactivated state;
    • - valproate also increases GABAergic inhibition
    • - Inhibiting T-type calcium channels (absence seizures) in the thalamus, reducing thalamocortical oscillations
    • Common Adverse Effects: relatively few sedative side effects; nausea, weight gain, transient hair loss, bleeding; rarely, severe hepatic toxicity
  25. Lamotrigine
    • Drug Class: Antiepileptic
    • - For all seizure types (esp. absence or partial)
    • - often used in drug-resistant patients
    • Other uses: Bipolar disorder, Neuropathic pain
    • Common Adverse Effects: blurred vision, dizziness, drowsiness
  26. L-Dopa/Carbidopa*
    • Drug Class: Antiparkinsonian
    • - a decarboxylase inhibitor
    • Pharmacokinetics:
    • Mechanism/Target: Targets DOPA decarboxylase which converts L-DOPA into dopamine; a precursor for noradrenaline
    • - inactive and circulates the plasma until it undergos metabolism by a enzyme into an active drug (in the BBB).
    • What is carbidopa?: it inhibits the peripheral plasma breakdown of levodopa by inhibiting its decarboxylation, and thereby increases available levodopa at the BBB
    • - it is a peropheral decarboxylase inhibitor with little or no pharmacological activity when given alone in usual doses,
    • - and it does not pass the blood brain barrier, so allows for efficient delivery of L-DOPA through the BBB
    • Adverse effects: Reduced peripheral dopamine can cause nausea and vomiting, cardiac arrythmias etc
  27. Selegiline
    • Drug Class: Antiparkinsonian
    • Selectively inhibits MAO Type B (which metabolizes dopamine) at low to moderate doses but does not inhibit MAO Type A (which metabolizes norepinephrine and serotonin)
    • - unless given at above recommended doses, where it loses its selectivity.
    • #
    • * Monoamine oxidase (MAO) functions as a “safety valve” to oxidatively deaminate and inactivate any excess neurotransmitter molecules (norepinephrine, dopamine, and serotonin)
  28. Ropinirole
    • Drug Class: Antiparkinsonian
    • = Dopamine-receptor agonist
  29. What are antipsychotic drugs?
    • N.B. antipsychotic drugs are used primarily to treat schizophrenia, but they are also effective in other psychotic states, including manic states with psychotic symptoms such as grandiosity, paranoia, and hallucinations, and delirium.
    • - risk of wide variety of troubling adverse effects.
    • - not curative and do not eliminate the chronic thought disorder, but they often decrease the intensity of hallucinations and delusions and permit the person with schizophrenia to function in a supportive environment.
  30. Haloperidol (hal·o·per·i·dol)*
    • Drug Class: Antipsychotic
    • Indications: management of schizophrenia
    • - control of tics and vocal utterances of Tourette's disorder
    • Pharmacokinetics:
    • Mechanism/Target: blockade/antagonist of dopamine receptor
    • - may also produce parkinsonian symptoms. These drugs should not be used in parkinsonian patients.
    • Adverse effects:
  31. Clozapine
    • Drug Class: Antipsychotic
    • Serotonin receptor–blocking activity: inhibition of serotonin receptors (5-HT),
    • Clozapine has high affinity for D1, D4, 5-HT2, muscarinic, and α-adrenergic receptors, but it is also a weak dopamine D2-receptor antagonist
  32. Quetiapine
    • Drug Class: Antipsychotic
    • Serotonin receptor–blocking activity: Quetiapine blocks D2 receptors more potently than 5HT2A receptors but is relatively weak at blocking either receptor
  33. Risperidone
    • Drug Class: Antipsychotic
    • Serotonin receptor–blocking activity: Risperidone blocks 5-HT2A receptors to a greater extent than it does D2 receptors
  34. Alendronate*
    • Drug Class: Bisphosphonate
    • Indication: Treatment of osteoporosis
    • Mechanism/Target: inhibits bone resorption via actions on osteoclasts or on osteoclast precursors
    • 1) decrease in osteoclastic formation/activation,
    • 2) increase in osteoclastic apoptosis (programmed cell death), and
    • 3) inhibition of the cholesterol biosynthetic pathway important for osteoclast function
    • Adverse effects: Severe bone/joint/muscle pain
  35. Zoledronate
    • Drug Class: Bisphosphonate
    • Indication: Treatment of osteoporosis
    • Mechanism/Target: inhibits bone resorption via actions on osteoclasts or on osteoclast precursors
    • - Decreases the rate of bone resorption, leading to indirect increase in bone mineral density
    • Adverse effects: Severe bone/joint/muscle pain
  36. Levonorgestril/Ethinylestradiol*
    • Drug Class: Contraceptive
    • Drug administration:
    • Pharmacokinetics:
    • Mechanism/Target:
    • Adverse effects:
  37. Paracetamol*
    • Drug Class: Simple analgesic,
    • Drug administration: orally taken
    • Pharmacokinetics:
    • Mechanism/Target: For a mild analgesic, it is preferred in patients with Aspirin intolerance/allergy,
    • - or people with haemophilia or history of peptic ulcers and bronchospasm.
    • - Poor ability to inhibit COX at sights of inflammation (due to peroxidase presence)
    • Adverse effects: Liver damage with overdose
  38. Codeine*
    • Drug Class: Simple analgesic
    • Mechanism: Binds opioid receptors (μ) in CNS; moderate agonist
    • - much less potent analgesic than morphine, but it has a higher oral efficacy.
    • - less addictive/abusive and less euphoria, longer halflife than M
    • cough-suppressant: (antitussive) effect produced by inhibition of the cough reflex is independent of the effects on nociception or respiration
    • *Nausea*: Ethanol is an inducer of CYP2E1; helps phase I metabolism. May cause increased metabolism = nausea
  39. Cilazapril*
    • Drug Class: ACEi → overall increases cardiac output;
    • Indications: help reduce hypertension, and decrease the elevated preload and afterload in congestive heart failure (CHF) through vasodilation.
    • Pharmacokinetics: Cilazapril is efficiently absorbed and rapidly converted to the active form
    • - food has minimal effect, with elimination through urine
    • - Cilazapril metabolised to active drug cilazaprilat by 1st pass
    • * Hepatic impairment affects cilazaprilat formation but not clearance, while Renal impairment reduces clearance resulting in raised plasma concentrations of cilazaprilat.
    • Mechanism/Target: ACEi block the enzyme which cleaves angiotensin I → II which is a potent vasoconstrictor
    • - also decrease the secretion of aldosterone, resulting in decreased sodium and water retention by nephron.
    • Adverse effects: postural hypotension, renal insufficiency, hyperkalemia, and a persistent dry cough.
    • - ACE inhibitors should not be used in pregnant women, and those with a history of angioedema related to previous treatment with an ACE inhibitor
  40. Enalapril
    • Drug Class: ACEi 
    • - overall increases cardiac output; help reduce the elevated preload and afterload in congestive heart failure (CHF) through vaso/venodilation.
    • Major effects: Treatment with enalapril also reduced arrhythmic death, myocardial infarction, and strokes.
    • - Similar data have been obtained with other ACE inhibitors.
  41. Quinapril
    • Drug Class: ACEi
    • - overall increases cardiac output; help reduce the elevated preload and afterload in congestive heart failure (CHF) through vaso/venodilation.
    • Major effects: Treatment with enalapril also reduced arrhythmic death, myocardial infarction, and strokes.
    • - Similar data have been obtained with other ACE inhibitors.
  42. Glyceryl Trinitrate*
    • a.k.a. nitroglycerin
    • Drug Class: Antianginal;
    • Indications: symptomatic relief of Angina & MI
    • - Nitrates decrease coronary vasoconstriction or spasm and increase perfusion of the myocardium by relaxing coronary arteries; helping relieve (all types of) angina
    • Drug administration: administered sublingually
    • Pharmacokinetics: fast acting (2‐5 mins). 100% first pass metabolism therefore given sublingually.
    • Mechanism/Target: relaxes vascular smooth muscle by their intracellular conversion to nitrite ions and then to nitric oxide (NO), causing;
    • – relaxing vascular smooth muscle (vasodilation = ↓ afterload); and venodilation resulting in reduced preload; increasing blood supply and decreasing oxygen demand
    • – inhibiting platelet aggregation (anti‐thrombotic/Antiplatelet),
    • – inhibiting leukocyte‐endothelial interactions (antiinflammatory).
    • - NO in turn activates guanylate cyclase and the cells' cyclic GMP. Elevated cGMP ultimately leads to dephosphorylation of the myosin light chain, resulting in vascular smooth muscle relaxation
    • Adverse effects: Dose related effects. Mainly due to vasodilatation
    • - Headache. High doses of organic nitrates can also cause postural hypotension, facial flushing, and tachycardia.
    • - Avoid abrupt nitrate withdrawal; Can cause rebound angina attacks or MI
    • Tolerance to the actions of nitrates develops rapidly.
  43. Isosorbide
    • Drug Class: Antianginal
    • Orally active nitrate
    • - Nitrates decrease coronary vasoconstriction or spasm and increase perfusion of the myocardium by relaxing coronary arteries; helping relieve (all types of) angina
  44. Perhexiline
    • Drug Class: Antianginal
    • Perhexiline is thought to act by inhibiting mitochondrial carnitine palmitoyltransferase-1.
    • This shifts myocardial metabolism from fatty acid to glucose utilisation which results in increased ATP production for the same O2 consumption and consequently increases myocardial efficiency
  45. Penicillin*
    • Drug Class: Antibacterial
    • - Beta-lactam group of antibiotics
    • Indications: treatment of severe infections caused by susceptible microorganisms (usually gram +ve)
    • Pharmacokinetics: Most of the penicillins are incompletely absorbed after oral administration, and they reach the intestine in sufficient amounts to affect the composition of the intestinal flora.
    • - Absorption of all the penicillinase-resistant penicillins is decreased by food in the stomach, because gastric emptying time is lengthened, and the drugs are destroyed in the acidic environment. Therefore, they must be administered 30 to 60 minutes before meals or 2 to 3 hours postprandial. Other penicillins are less affected by food.
    • Mechanism/Target: penicillins interfere with the last step of bacterial cell wall synthesis (transpeptidation or cross-linkage), resulting in exposure of the osmotically less stable membrane.
    • - cell lysis then occurs
    • Adverse effects: Penicillins are among the safest drugs
    • - Hypersensitivity and anaphylaxis.
    • *cannot be used for tuberculosis – specific antibiotics for mycobacteria
    • * for MRSA use Vancomycin instead
  46. Gentamicin*
    • Drug Class: Antibacterial
    • - Aminoglycosides group of antibiotics
    • Indications: effective in combination for the empirical treatment of infections suspected of being due to aerobic gram-negative bacilli, including Pseudomonas aeruginosa (as well as Staph. aureus)
    • Mechanism/Target: Susceptible gram-negative organisms allow aminoglycosides to diffuse through porin channels in their outer membranes.
    • - The antibiotic then binds to the 30S ribosomal subunit prior to ribosome formation. There, it interferes with ribosomal function.
    • - The aminoglycosides synergize with β-lactam (or vancomycin) antibiotics because of the latter’s action on cell wall synthesis, which enhances diffusion of the aminoglycosides into the bacterium; e.g. in Subacute bacterial endocarditis (SBE)
    • Adverse effects: important to monitor plasma levels as it can be quite toxic
    • - Ototoxicity; i.e. vestibular and cochlear, Nephrotoxicity, Neuromuscular paralysis and Allergic reactions
  47. Erythromycin
    • Drug Class: Antibacterial
    • - Macrolide group of antibiotics
    • - first choice and as an alternative to penicillin in individuals who are allergic to β-lactam antibiotics
    • Major effects: Bacteristatic; macrolides bind irreversibly to a site on the 50S subunit of the bacterial ribosome, thus inhibiting the translocation steps of protein synthesis
    • - Good for mycoplasmas & intracellular bacteria
  48. Ciprofloxacin
    • Drug Class: Antibacterial
    • - Fluoroquinolone group of antibiotics
    • - Good alternative to beta lactams. Especially against Gram-ve bacteria
    • - effective against many systemic infections, with the exception of serious infections caused by MRSA, the enterococci, and pneumococci
    • Major effects: inhibit the replication of bacterial DNA by interfering with the action of DNA gyrase (topoisomerase II) and topoisomerase IV during bacterial growth and reproduction
    • *moxifloxacin (a Fluoroquinolone) for RTI
  49. Ceftriaxone
    • Drug Class: Antibacterial
    • - Cephalosporin group of antibiotics
    • Major effects: The cephalosporins are β-lactam antibiotics that are closely related to the penicillins.
    • - Cephalosporins have the same mode of action as penicillins, and they are affected by the same resistance mechanisms.
    • - However, they tend to be more resistant than the penicillins to certain β-lactamases
    • Ceftriaxone has become an agent of choice in the treatment of meningitis because it can reach therapeutic levels in CSF
  50. Enoxaparin*
    • Drug Class: Anticoagulant/antithrombotic
    • - is a low molecular weight heparin (LMWH)
    • Indications: used for IV or subcut prophylaxis of arterial or venous thrombosis.
    • - acute coronary syndromes
    • Drug administration: can be conveniently injected subcutaneously (NOT IV OR IM)
    • - Heparin is used to anticoagulate patients where an increased risk for thrombosis exists; e.g. extracorporeal circuits during cardiac bypass surgery, haemodialysis, and the initial phase of treatment after thromboses.
    • Pharmacokinetics: half-life is relatively short (50mins), but with wide variation
    • Mechanism/Target: LMWHs complex with;
    • - antithrombin III which increases its activity several hundredfold
    • - inactivate Factor Xa (including that located on platelet surfaces)
    • - but do not bind as avidly to thrombin.
    • Adverse effects: Bleeding
    • - Laboratory monitoring is not required except in renal failure.
    • - LMWH has lower risk for anti-heparin antibodies.
  51. Warfarin*
    • Drug Class: Anticoagulant/antithrombotic
    • Indications: Prophylaxis and treatment of thromboembolic disorders and embolic complications arising from atrial fibrillation or cardiac valve replacement
    • - Adjunct to reduce risk of systemic embolism after MI
    • Pharmacokinetics: Highly fluctuant in blood
    • - excreted by CYP450 liver metabolism so competition with other drugs can tip the INR
    • Mechanism/Target: Vitamin K metabolism blocker = blocks vit. K epoxide reductase
    • - reduced form of Vit. K required to carboxylate neccesary residues on these factors to activate them
    • - Several of the protein coagulation factors (including Factors II, VII, IX, and X) require vitamin K as a cofactor for their synthesis by the liver.
    • - two-fold increase in prothrombin time
    • As the dose of warfarin is increased, a greater fraction of the patients respond until eventually all patients respond.
    • - at higher doses of warfarin, a toxic response occurs, namely a high degree of anticoagulation that results in hemorrhage.
    • Therapeutic uses: prevent the progression or recurrence of acute deep vein thrombosis or pulmonary embolism after initial heparin treatment.
    • - Prophylactically, it is used in patients with acute myocardial infarction, prosthetic heart valves, and chronic atrial fibrillation.
    • Adverse effects: VERY NARROW THERAPEUTIC INDEX; and delay to get to INR between 2-3
    • - Bleeding
    • - should never be used during pregnancy, because it is teratogenic and can cause abortion as well as birth defects
    • - Antidote = vitamin K
  52. Dabigatran
    • Drug Class: Anticoagulant/antithrombotic
    • Major effects: a direct thrombin inhibitor currently approved for prevention of stroke and systemic embolism in patients with atrial fibrillation
    • Dabigatran does not require routine monitoring (INR) and has few drug interactions compared to warfarin. But still bleeding = major adversity
  53. Alteplase
    • Drug Class: antithrombotic (thrombolytic agent)
    • - Acute thromboembolic disease in selected patients may be treated by the administration of agents that activate the conversion of plasminogen to plasmin, a serine protease that hydrolyzes fibrin (which stabilises platelets) and, thus, dissolves clots
    • - Purpose is to acutely destroy (lyse) or prevent thrombus formation that occurs within the coronary artery at the time of the myocardial infarction.
    • Major effects: release plasmin to break down thrombus which has already formed, (iv. admin)
    • - Alteplase acts more locally on the thrombotic fibrin to produce fibrinolysis = "fibrin selective"
    • - has a low affinity for free plasminogen in the plasma, but it rapidly activates plasminogen that is bound to fibrin in a thrombus or a hemostatic plug.
    • Therapeutic uses: Alteplase is approved for the treatment of myocardial infarction, massive pulmonary embolism, and acute ischemic stroke.
    • - Use within 3-4 hours from the onset of ischaemia (75% success)
  54. Metoclopramide*
    • Drug Class: Antiemetics
    • Indications: ameliorate nausea and vomiting that often accompany GI dysmotility syndromes
    • - with chemotherapy, and gastroesophageal reflux
    • Drug administration/ Pharmacokinetics: absorbed rapidly after oral ingestion
    • Mechanism/Target: complex and involve;
    • - 5-HT4 receptor agonism, vagal and central 5-HT3 antagonism,
    • - possible sensitization of muscarinic receptors on smooth muscle,
    • - in addition to DA receptor antagonism
    • - Its effects are confined largely to the upper digestive tract, where it increases lower esophageal sphincter tone and stimulates antral and small intestinal contractions.
    • Adverse effects: extrapyramidal effects
    • - e.g. various movement disorders such as acute dystonic reactions, pseudoparkinsonism, Tardive dyskinesia or akathisia
  55. Ondansetron
    • Drug Class: Antiemetics
    • Major effects: 5-HT3 receptor blocker in the periphery (visceral vagal afferent fibers) and in the brain (chemoreceptor trigger zone)
    • - the 5-HT3 receptor antagonists have become the most widely used drugs for chemotherapy-induced emesis
    • #
    • *The 5-HT3 receptor is a member of the superfamily of ligand-gated ion channels, a superfamily that also includes the neuronal nicotinic acetylcholine receptors (nAChRs), and the inhibitory neurotransmitter receptors for GABA (both GABAA and GABAA-ρ receptors) and glycine
  56. Cyclizine
    • Drug Class: Antiemetics
    • Major effects: Histamine H1-receptor antagonists
    • - very useful in motion sickness but are ineffective against substances that act directly on the chemoreceptor trigger zone
    • - They act on vestibular afferents and within the brainstem
  57. Itraconazole*
    • Drug Class: Antifungal
    • Indications: Treatment of susceptible fungal infections in immunocompromised patients and onchomycosis of the toenail and fingernail in nonimminocompromised patients
    • - drug of choice for patients with indolent, nonmeningeal infections due to B. dermatitidis, H. capsulatum, P. brasiliensis, and C. immitis
    • Drug administration: oral
    • Mechanism/Target: same as the other azole antifungals, it inhibits the fungal-mediated synthesis of ergosterol.
    • Adverse effects: hepatotoxicity
  58. Terbinafine
    • Drug Class: Antifungal
    • Major effects: Topical or oral
    • Topical: effective in tinea corporis, tinea cruris, and tinea pedis.
    • - is less active against Candida species and Malassezia furfur, but the cream also can be used in cutaneous candidiasis and tinea versicolor.
    • Systemic: Drug accumulates in skin, nails, and fat
  59. Clonidine*
    • Drug Class: Antihypertensive (Sympatholytics)
    • Drug administration: oral
    • Pharmacokinetics:
    • Mechanism/Target: α2-Selective adrenergic agonists
    • - activation of α2 receptors in the cardiovascular control centers of the CNS (interestingly because many blood vessels vasoconstrict with α2 agonism)
    • - Clonidine decreases discharges in sympathetic preganglionic fibers in the splanchnic nerve and in postganglionic fibers of cardiac nerves.
    • - Clonidine also stimulates parasympathetic outflow, which may contribute to the slowing of heart rate as a consequence of increased vagal tone and diminished sympathetic drive
    • Adverse effects: dose dependant
    • - dry mouth and sedation
    • - Sexual dysfunction also may occur.
    • - Marked bradycardia is observed in some patients
    • Other therapeutic uses: useful in treating and preparing addicted subjects for withdrawal from narcotics, alcohol, and tobacco. Clonidine may help ameliorate some of the adverse sympathetic nervous activity associated with withdrawal from these agents, as well as decrease craving for the drug.
  60. Alpha-Methyldopa
    • Drug Class: Antihypertensive (Sympatholytics)
    • - preferred drug for treatment of hypertension during pregnancy based on its effectiveness and safety for both mother and fetus
    • Target: is a false substrate for DOPA decarboxylase which converts L-DOPA into dopamine; a precursor for noradrenaline
    • - this abnormal metabolite acts to antagonise α1 and β adrenergic receptors
    • Effect: α-Methyldopa is converted into an abnormal metabolite.
    • - The abnormal metabolite subverts the normal metabolic pathway
  61. Aspirin*
    • Drug Class: Antiplatelet (prevents blood clotting)
    • Aspirin is often used as the preferred antiplatelet agent as its effects last many days, whereas many similar inhibitors effects last a much shorter period of time.
    • - also used as an analgesic and antipyretic
    • Administration: orally, with 4 hour duration
    • - aspirin is a weak acid which are more ionized in high pH conditions → easily absorbed
    • Pharmacokinetics:
    • Mechanism/Target: inhibits cyclo-oxygenase enzyme (COX-1), blocking its activity to produce thromboxane A-2 which causes platelets to clump.
    • Adverse effects:
    • - Gastrointestinal: The most common GI effects of the salicylates are epigastric distress, nausea, and vomiting. Microscopic GI bleeding is almost universal
    • - Blood: inhibition of platelet aggregation and a prolonged bleeding time. For this reason, aspirin should not be taken for at least 1 week prior to surgery.
    • - In pregnancy: salicylates are excreted in breast milk, aspirin should be avoided during pregnancy and while breastfeeding.
    • - hypersensitivity, metabolic processes, respiratory depression and other drug interactions
  62. Clopidogrel
    • Drug Class: Antiplatelet
    • - by a mechanism different from that of aspirin.
    • Major effect: irreversibly inhibit the binding of ADP to its receptors on platelets and,
    • - thereby, inhibit the activation of the GP IIb/IIIa (fibrinogen) receptors required for platelets to bind to fibrinogen and to each other
    • Therapeutic uses: Clopidogrel is approved for prevention of atherosclerotic events following recent myocardial infarction, stroke, and established peripheral arterial disease.
    • - prophylaxis of thrombotic events in acute coronary syndrome (unstable angina or non–Q wave myocardial infarction).
    • - clopidogrel is used to prevent thrombotic events associated with percutaneous coronary intervention with or without coronary stent.
    • - Compared to ticlopidine, clopidogrel is the preferred agent in ischemic heart disease events
  63. Acyclovir*
    • Drug Class: Antiviral
    • Indications: against herpes viruses; HSV and Varicella-Zoster virus
    • Drug administration: Oral or IV
    • Pharmacokinetics: *affinity of acyclovir for HSV thymidine kinase is ~200 times greater than for the mammalian enzyme
    • Mechanism/Target: Guanosine analogue which inhibits DNA/RNA synthesis
    • - it incorporates into new viral DNA/RNA and blocks further replication
    • Adverse effects: Acyclovir generally is well tolerated
  64. Ritonavir*
    • Drug Class: Antiviral
    • Drug administration: Oral
    • Mechanism/Target: HIVprotease inhibitor
    • - drugs prevent proteolytic cleavage of HIV gag and pol precursor polypeptides that include essential structural (p17, p24, p9, and p7) and enzymatic (reverse transcriptase, protease, and integrase) components of the virus.
    • - This prevents the metamorphosis of HIV virus particles into their mature infectious form
    • Adverse effects: dose-dependent nausea, vomiting, diarrhea, anorexia, abdominal pain, and taste perversion
  65. Oseltamivir
    • Drug Class: Antiviral
    • Major effects: potent selective inhibitor of influenza A and B virus neuraminidases
  66. Metoprolol*
    • Drug Class: β-blocker; reduce blood pressure primarily by decreasing cardiac output
    • - also decrease sympathetic outflow from the central nervous system (CNS) and inhibit the release of renin from the kidneys
    • Therapeutic uses: use cautiously in the treatment of patients with acute heart failure or peripheral vascular disease
    • - Not generally used for treating hypertension
    • - used to treat angina, and as an Antiarrhythmic in atrial fibrillation
    • Drug administration: orally
    • Pharmacokinetics: β-blockers may take several weeks to develop their full effects
    • Mechanism/Target: Primarily antagonise Cardiac and Renal β1 adrenoreceptors. Decrease CO & B.P. by;
    • - negative cardiac chronotropic action, (decreases rate of contraction).
    • - negative inotropic (decreases force of contraction).
    • Adverse effects: β-blockers may cause bradycardia and CNS side effects such as fatigue, lethargy, insomnia, and hallucinations (as lipophilic and can cross BBB)
    • - can also cause hypotension.
    • - may decrease libido and cause impotence (severely reduce patient compliance)
    • - more effective for treating hypertension in white than in black patients and in young compared to elderly patients
    • - Serum lipid patterns; The β-blockers may disturb lipid metabolism, decreasing HDLs, cholesterol and increasing plasma triglycerides.
    • - Drug withdrawal
  67. Propranolol
    • Drug Class: β-blocker
    • - blocks both β1 and β2 receptors
    • - lipophilic and can cross BBB
    • Major effects: negatively chrono and inotropic, whilst decreasing renin secretion
    • Asthma: nonselective β-blockers, such as propranolol and nadolol, are contraindicated due to their blockade of β2-mediated bronchodilation.
    • Portal hypertension: used to help limit splanchnic blood flow; at the heart and peripheral resistance?
  68. Atenolol
    • Drug Class: β-blocker
    • Major effect: Selective blocker of β1 receptors
    • - negatively chrono and inotropic, whilst decreasing renin secretion
    • - selective β-blockers may be administered cautiously to hypertensive patients who also have asthma
  69. Carvedilol
    • Drug Class: β-blocker
    • - a nonselective β-blocker (β1 and 2) and alpha-1 blocker indicated in the treatment of mild to severe congestive heart failure (CHF) and high blood pressure.
    • Major effects:
  70. Salbutamol*
    • Drug Class: Bronchodilator
    • Drug administration: Absorbed by inhalation; whereby we limit systemic side effects due to highest concentration in the lung
    • - Short Acting Beta Agonist; SABA → use on an “as required” basis and not used for nocturnal asthma
    • - acute inhalation and helps to prevent exercise induced asthma
    • Pharmacokinetics: treats symptoms - onset 5-15 mins;
    • - bronchodilatory effect lasts 2-5h
    • Mechanism/Target: is a β2 adrenergic receptor agonist
    • - activates cAMP activating PKA → Increase conductance of Ca2+-sensitive K+ channels in airways SM
    • → hyperpolarisation & relaxation therefore inhibits bronchial constriction
    • - results in bronchial smooth muscle dilation
    • Adverse effects: the most common side effects of these agents is tremor (/cramps) but tolerance built up fast
    • - Other side effects include headache, tachycardia, arrhythmia, and flushing.
    • - reduced by starting with low doses → higher doses with tolerance.
    • *Inhalation helps minimise side effects -> localised to bronchial tissue rather than systemically
  71. Ipratropium
    • Drug Class: Bronchodilator
    • Drug administration: Absorbed by inhalation; whereby we limit systemic side effects due to highest concentration in the lung
    • - does not diffuse into blood/BBB = low systemic side effects
    • - short acting
    • Major effect: Muscarinic receptor antagonist
    • - Blockade of muscarinic acetylcholine receptors (which agonises bronchoconstriction) in the bronchioles causes bronchodilation.
    • Systemic side effects: dry mouth, sedation, flushing, tachycardia, ocular acute angle closure
    • - resemble that of atropine; a competitive muscarinic acetylcholine receptor antagonist
  72. Salmeterol
    • Drug Class: Bronchodilator
    • - Long Acting Beta Agonists → Not rapid enough to be used as a reliever
    • - Use in nocturnal asthma and exercise-induced asthma
    • - used in conjunction with preventer corticosteriods; helps minimise dosage and hence reduce ADRs. (e.g. seretide = salbutamol and fluticasone)
    • Mechanism/Target: is a β2 adrenergic receptor agonist
    • Major effect:
    • Drug administration: Absorbed by inhalation
    • – onset of action 10-20 mins, peak effect ~1-2h; bronchodilatory effect lasts 12h
    • – Dosing given in regular, twice daily dosing
  73. Amlodipine*
    • Drug Class: Calcium channel blocker (Dihydropyridines = vasoselective)
    • - have a much greater affinity for vascular calcium channels than for calcium channels in the heart = attractive in treating hypertension
    • - dihydropyridines have the advantage in that they show little interaction with other cardiovascular drugs, such as digoxin or warfarin, which are often used concomitantly with calcium-channel blockers.
    • Drug administration: oral
    • Pharmacokinetics: short half-lives (3–8 hours)
    • Mechanism/Target: L‐Type Calcium channel antagonist = “long lasting” strictly important for cardiac & vascular SM.
    • - Calcium enters muscle cells through special voltage-sensitive calcium channels. This triggers release of calcium from the sarcoplasmic reticulum and mitochondria, which further increases the cytosolic level of calcium.
    • - Calcium-channel antagonists block the inward movement of calcium by binding to L-type calcium channels in the heart and in smooth muscle of the coronary and peripheral arteriolar vasculature. This causes vascular smooth muscle to relax, dilating mainly arterioles. Calcium-channel blockers do not dilate veins.
    • Therapeutic uses: useful in the treatment of hypertensive patients who also have asthma, diabetes, angina, and/or peripheral vascular disease
    • Adverse effects: Dizziness, headache, and a feeling of fatigue caused by a decrease in blood pressure
  74. Diltiazem*
    • Drug Class: Calcium channel blocker (Benzothiazipines = cardioselective)
    • - affects both cardiac and vascular smooth muscle cells, but it has a less pronounced negative inotropic effect on the heart compared to that of verapamil (i.e. more intermediate in its actions)
    • Drug administration: oral administration.
    • Pharmacokinetics:
    • Mechanism/Target: effective against the voltage-sensitive channels, causing a decrease in the slow inward current that triggers cardiac contraction
    • - By decreasing the inward current carried by calcium, verapamil and diltiazem slow conduction and prolong the effective refractory period in tissues dependent on calcium currents, such as the AV node.
    • These drugs are therefore effective in treating arrhythmias that must traverse calcium-dependent cardiac tissues.
    • Therapeutic uses: more effective against atrial than ventricular dysrhythmias.
    • - reentrant supraventricular tachycardia and reducing ventricular rate in atrial flutter and fibrillation.
    • - used to treat hypertension and angina
    • Adverse effects: a favorable sideeffect profile. Do not induce bronchoconstriction or affect lipid profiles
    • - may be contraindicated in patients with preexisting depressed cardiac function.
    • - decrease in blood pressure caused by peripheral vasodilation.
    • #
    • Don’t use verapamil or diltiazem in conjunction with β‐blockers, cause cardiac depression!
    • - caution with other drugs; Diltiazem is involved in a variety of drug interactions both PK & PD
  75. Verapamil
    • Drug Class: Calcium channel blocker (Phenylalkylamines = cardioselective)
    • Major effects: the least selective of any calcium-channel blocker and has significant effects on both cardiac and vascular smooth muscle cells.
    • - used to treat angina, supraventricular tachyarrhythmias, and to prevent migraine and cluster headaches.
    • Therapeutic uses: Angina;
    • - Reduces myocardial oxygen demand
    • - Reverses coronary vasospasm
    • Hypertension: Verapamil produces an antihypertensive effect by a combination of vascular and cardiac effects.
    • #
    • Contraindications:
    • In heart failure
    • With concomitant β‐blocker use; Synergistic effect with CCBs and β‐blocker which will slow heart rate and decrease cardiac contractility...
    • In the presence of bradycardias, conduction defects
  76. Prednisone* in asthma
    • Drug Class: Corticosteroid (a preventer)
    • Drug administration: for asthma it is oral
    • Pharmacokinetics:
    • Target: acts on the glucocorticoid receptor
    • Mechanism: Very upstream effector which modulates cytokine levels; Inhibits transcription factor NF-kB which prevents cytokine expression
    • - Inhibits the function of phospholipase A2, preventing other inflammatory messengers from forming
    • - PLA2 inhibited and downregulated, while cyclooxygenase (COX) is also inhibited
    • - overall it is immunosuppresant via. regulating gene expression
    • Asthma related effects:
    • - Reduce recruitment / number of airways inflammatory cells and consequently reduce damage to airways epithelium
    • - Inhibit function of macrophages hence reduces antigen response.
    • - Reduce vascular permeability which decreases histamine release from basosphils and mast cells.
    • *No effect on bronchodilation and cannot reverse airways remodelling brought about by poorly managed asthma.
    • Adverse effects:
    • - Causes immunosuppression and therefore reduces inflammation of the airways
    • - Has a localised effect on inflammation (if used in inhalers for asthma), but systemic delivery causes general immunosuppression and can lead to Cushing’s syndrome
    • - hypercholesterolemia, cataracts, osteoporosis, and hypertension with prolonged use
    • - metabolic actions: cause fat gain and muscle wastage, carbohydrate and protein metabolism shifts in a non-anabolic way
  77. Prednisone*
    • Drug Class: Corticosteroid
    • Drug administration:
    • Pharmacokinetics:
    • Target: acts on the glucocorticoid receptor
    • Mechanism: Very upstream effector which modulates cytokine levels; Inhibits transcription factor NF-kB which prevents cytokine expression
    • - Inhibits the function of phospholipase A2, preventing other inflammatory messengers from forming
    • - overall it is immunosuppresant via. regulating gene expression
    • Adverse effects:
    • - Causes immunosuppression and therefore reduces inflammation of the airways
    • - Has a localised effect on inflammation (if used in inhalers for asthma), but systemic delivery causes general immunosuppression and can lead to Cushing’s syndrome
  78. Fludrocortisone
    • Drug Class: Corticosteroid (but used for its mineralocorticoid effects)
    • Major effects: Same as aldosterone (with some cortisol overlap?)
  79. Fluticasone
    • Drug Class: Corticosteroid (a preventer)
    • Drug administration: for asthma it is inhaled
    • Adverse effects: With chronic high dose use, enough drug may be absorbed from GI tract and pulmonary epithelium to cause systemic effects
    • It also results in suppression of endogenous glucocorticoids, which leads to production of insufficient adrenal reserve to respond to stress resulting in
    • - HPA axis suppression
    • - Infection and Immunosuppression
    • - Poor Wound healing in trauma
    • - Osteoporosis
    • - Delayed growth in children (no clear results on this with inhaled steroids)
  80. Bendroflumethiazide*
    • Drug Class: Thiazide Diuretic (decrease blood pressure)
    • Drug administration: oral
    • - thiazide diuretics are not effective in patients with inadequate kidney function (may need loop Ds)
    • Pharmacokinetics: Absorption and elimination rates vary considerably
    • Mechanism/Target: inhibit Na+/Cl- co-transport & reabsorbtion in cortical diluting segment of distal tubule (Only reabsorbs ~5% filtered Na+)
    • - lower blood pressure initially by increasing sodium and water excretion
    • - causes a decrease in extracellular volume, resulting in a decrease in cardiac output and renal blood flow
    • - With long-term treatment, plasma volume approaches a normal value, but peripheral resistance decreases.
    • Adverse effects: induce hypokalemia and hyperuricemia in 70 percent of patients
    • - hyperglycemia in 10 percent of patients.
    • - Acute gout attacks may be triggered
  81. Furosemide*
    • Drug Class: Loop Diuretic
    • Drug administration: Tightly bound to plasma proteins, and needs to act on the kidney lumen;
    • - less active with proteinurea and actively placed in lumen through Organic Acid transporters (OATs)
    • Theraputic uses include;
    • - Hypertension: effective even in patients with impaired renal function
    • - Oedema: of Cardiac, renal or hepatic origin
    • Pharmacokinetics: Rapid absorption. Max effect 1-2 hrs Duration: 4-6 hrs
    • Mechanism/Target: Primarily inhibit luminal NKCC2 (Na+ K+ Cl-) cotransporter by competing with Cl- for binding in the Thick Loop of Henle
    • - cause decreased renal vascular resistance and increased renal blood flow
    • #
    • Adverse effects: Hypovolemia!, dizziness, syncope
    • - Na+ loss (hyponatraemia) and K+ loss (hypokalaemia); may predispose to digoxin toxicity
    • - Mg2+ and Ca2+ depletion
    • - Metabolic Acidosis
    • - Hyperuricaemia (uric acid retention) - may precipitate gout
    • Prolonged use:
    • - ototoxicity - hearing loss (loss of endolymph electrolytes)
    • - Can increase renal toxicity of cephalosporin antibiotics (compete for weak organic acid transporters on PT)
  82. Spironolactone
    • Drug Class: Potassium-sparing Diuretic
    • - aldosterone-receptor antagonists
    • - Does NOT require access to lumen
    • Major effects: reduce potassium loss in the urine
    • - has the additional benefit of diminishing the cardiac remodeling that occurs in heart failure.
  83. Omeprazole*
    • Also known as Losec
    • Drug Class: Gastric acid suppressant
    • Drug administration: Oral
    • Pharmacokinetics: Activated by stomach acid; -> converted to sulfenic acid where there is high acid concentrations (e.g. in canaliculi of parietal cells)
    • Mechanism/Target: Sulfenic acid then covalently binds to the proton pump (H+/K+ exchanger ATPase), inactivating it in the parietal cells of the stomach
    • - long acting (24-48 hrs) as need to synthesise new protein
    • - Because they block the final step in acid production, the proton pump inhibitors
    • are effective in acid suppression regardless of other stimulating factors. E.g. if somebody was getting ulcers from constant NSAID use, H2 antags wouldn't do jack
    • Adverse effects: Generally well tolerated
  84. Ranitidine (and others?)
    • Drug Class: Gastric acid suppressant
    • Major effects: H2 antagonist like climetidine
    • Vs. other drugs; e.g. H2 antagonists not as effective and cause rebound hyperacidity
    • - can build up a tolerance to ranitidine/clemitidine
  85. Digoxin*
    • Drug Class: Heart rate control
    • Drug administration: oral
    • Pharmacokinetics:
    • Mechanism/Target: Free cytosolic calcium concentrations at the end of contraction must be lowered for cardiac muscle to relax (repolarisation). The Na+/Ca2+-exchanger plays an important role in this process by extruding Ca2+ from the myocyte in exchange for Na+
    • - Digoxin acts through inhibition of this plasma membrane Na+/K+-ATPase
    • - thereby increasing contraction of the atrial and ventricular myocardium (positive inotropic action)
    • Adverse effects: digoxin causes the resting membrane potential may increase (–70 mV instead of –90 mV), which makes the membrane more excitable, increasing the risk of arrhythmias (toxicity).
    • - digoxin shows only a small difference between a therapeutically effective dose
    • and doses that are toxic or even fatal. Therefore, the drugs have a low therapeutic index
  86. Amiodarone
    • Drug Class: Heart rate control
    • Major effects: exerts a multiplicity of pharmacologic effects, none of which is clearly linked to its arrhythmia-suppressing properties
    • Mechanism: Amiodarone is a Class 4 Anti-arrythmic agent which acts to decrease the heart rate by inhibiting the K+ efflux channel.
    • - This delays repolarisation and thus increases the refractory period decreasing the amount of action potentials that can be conducted per minute.
    • *NB* Amiodarone is a structural analog of thyroid hormone, and some of its anti-arrhythmic actions and its toxicity may be attributable to interaction with nuclear thyroid hormone receptors
  87. Allopurinol*
    • Drug Class: Hypouricaemic
    • Drug administration: oral
    • Pharmacokinetics:
    • Mechanism/Target: inhibits xanthine oxidase and prevents the synthesis of urate from hypoxanthine and xanthine
    • - Allopurinol facilitates the dissolution of tophi and prevents the development or progression of chronic gouty arthritis by lowering the uric acid concentration in plasma below the limit of its solubility
    • Adverse effects: in acute gout incidence of acute attacks of gouty arthritis may increase during the early months of allopurinol therapy as a consequence of mobilization of tissue stores of uric acid.
    • - Co-administration of colchicine helps suppress such acute attacks (inhibiting leukocyte entry into the affected joint).
    • * After reduction of excess tissue stores of uric acid, the incidence of acute attacks decreases and colchicine can be discontinued.
  88. Probenecid
    • Drug Class: Hypouricaemic
    • Major effects: mainly acts in inhibition of the transport of organic acids across epithelial barriers
    • - Probenecid inhibits the reabsorption of uric acid by organic anion transporters, principally URAT-1.
    • - Probenecid increases urinary urate levels. Liberal fluid intake therefore should be maintained throughout therapy to minimize the risk of renal stones.
    • - Probenecid should not be used in gouty patients with nephrolithiasis or with overproduction of uric acid
    • Probenecid was developed for the purpose of delaying the excretion of penicillin for treatment of gonorrhea or neurosyphilis infections or to cases in which penicillin resistance may be an issue
  89. Azathioprine*
    • Drug Class: Immunosuppressant
    • Drug administration: oral
    • Mechanism/Target: a purine analogue which inhibits DNA synthesis
    • - Cell proliferation thereby is inhibited, impairing a variety of lymphocyte functions. It prevents T/B-cell proliferation
    • - indicated as an adjunct for prevention of organ transplant rejection and in severe rheumatoid arthritis
    • Adverse effects: may cause bone marrow suppression, pancreatitis, hepatitis and GI upset
  90. Methotrexate
    • Drug Class: Immunosuppressant (antifolate drug)
    • Major effects: methotrexate is an inhibitor of dihydrofolate reductase (DHFR), hence directly inhibits the folate-dependent enzymes of de novo purine and thymidylate synthesis
    • Therapeutic uses: low-dose MTX is effective as a single agent against certain inflammatory diseases, such as severe psoriasis and rheumatoid arthritis as well as Crohn disease
    • - psoriasis = immune-mediated skin disease
    • - a critical drug in the management of acute lymphoblastic leukemia (ALL) in children
  91. Cyclophosphamide
    • Drug Class: Immunosuppressant (alkylating agent)
    • - cytotoxic; capacity of alkylating agents to interfere with DNA integrity and function and to induce cell death in rapidly proliferating tissues provides the basis for their therapeutic and toxic properties.
    • Therapeutic effects: The clinical spectrum of cyclophosphamide is very broad.
    • - lymphomas and cancers
    • - immunosuppressive properties → auto-immune disorders, including rheumatoid arthritis, and the nephrotic syndrome.
    • *Caution with non-neoplastic conditions, not only because of its acute toxic effects but also because of its potential for inducing sterility, teratogenic effects, and leukemia.
  92. Infliximab
    • Drug Class: Immunosuppressant
    • - Anti-TNF-α; in the form of an anti-cytokine antibody. chimeric immunoglobulin (25% mouse, 75% human)
    • Major effects: inhibits binding of TNF-α with its receptors.
    • - Infliximab is approved for use in combination with methotrexate in patients with RA who have had inadequate response to methotrexate monotherapy.
    • This agent is not indicated for use alone, because monotherapy allows the body to develop anti-infliximab antibodies, with a reduction in efficacy.
    • Additional indications include plaque psoriasis, psoriatic arthritis, ulcerative colitis, ankylosing spondylitis, and Crohn disease, for both fistulizing and nonfistulizing disease.
  93. Atorvastatin*
    • Drug Class: Lipid lowering
    • - potent LDL cholesterol–lowering statin drugs, useful in all types of hyperlipidemias
    • Drug administration: Oral dosing
    • Pharmacokinetics: Poor bioavailability 14%, Highly protein bound (98%)
    • Mechanism/Target: HMG CoA reductase inhibitor or statin; i.e. it inhibits the first committed enzymatic step of de novo cholesterol synthesis
    • - hence they deplete the intracellular supply of cholesterol -> resulting in upreg. of surface LDL receptors
    • - plasma levels of LDL are decreased from endocytosis into cells
    • Adverse effects: Myopathy & Rhabdomyolysis rare but significant; i.e. breakdown of muscle fibres resulting in the release of myoglobin into plasma and eventually kidney
    • - patients who are homozygous for familial hypercholesterolemia lack LDL receptors and, therefore, benefit much less from treatment with these drugs
    • - Avoid in Pregnancy! Affects developmental genes. Also should not be used in children or teenagers. It may also increase warfarin levels
    • #
    • NB: in spite of the protection afforded by cholesterol lowering, about one fourth of the patients treated with these drugs still present with coronary events. Thus, additional strategies, such as diet, exercise, and additional agents, may be warranted.
  94. Bezafibrate
    • Drug Class: Lipid lowering
    • - Effective at reducing VLDL & TG (10% ↓LDL). Increases HDL levels
    • Major effect: Fibrates bind to and activate peroxisome proliferator activated receptor alpha (PPARα), nuclear receptor
    • - expressed in hepatocytes, skeletal muscle, macrophages, and the heart.
    • - lower LDL levels modestly by a PPARα- shift in hepatocyte metabolism toward FA-oxidation.
  95. Morphine*
    • Drug Class: Major analgesic
    • Drug administration: IV
    • Pharmacokinetics: significant first-pass metabolism of morphine occurs in the liver, intramuscular, subcutaneous, and IV injections produce the most reliable responses
    • Target: acts on the μ and κ opioid receptor
    • Mechanism: Opioids cause hyperpolarization of nerve cells, inhibition of nerve firing, and presynaptic inhibition of transmitter release.
    • - Morphine acts at κ receptors in laminae I and II of the dorsal horn of the spinal cord, and it decreases the release of substance P, which modulates pain perception in the spinal cord.
    • - also inhibits the release of many excitatory transmitters from nerve terminals carrying nociceptive (painful) stimuli.
    • Adverse effects: Severe respiratory depression can occur and result in death from acute opioid poisoning.
    • - stoppage of respiratory exchange in patients with emphysema or cor pulmonale. [If used in such individuals, respiration must be carefully monitored.]
    • - Other effects include vomiting, dysphoria, and histamine-enhanced hypotensive effects.
  96. Methadone
    • Drug Class: Major analgesic
    • - orally effective opioid
    • Major effects: The actions of methadone are mediated by μ receptors.
    • - In addition, methadone is an antagonist of the N-methyl-D-aspartate (NMDA) receptor, which is useful in the treatment of neurogenic pain.
  97. Fentanyl
    • Drug Class: Major analgesic
    • - 100-fold the analgesic potency of morphine and is used in anesthesia
    • - rapid onset and short duration of action (15–30 minutes)
  98. Diclofenac*
    • Drug Class: NSAID
    • Administration: can be as a skin cream
    • Mechanism: NSAIDs inhibit the activity of both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), and thereby, the synthesis of prostaglandins and thromboxanes.
    • - It is thought that inhibiting COX-2 leads to the anti-inflammatory, analgesic and antipyretic effects
    • - and that those NSAIDs also inhibiting COX-1, particularly aspirin, may cause gastrointestinal bleeding, ulcers and GIT toxicity (other drugs in conjunction can protect from this e.g. prostaglandin analogues).
    • For this reason, the advantages of COX-2 selective inhibitors may be indicated.
    • Pregnancy: not recommended due to associations with early closure of fetal ductus arteriosus, fetal renal toxicity, premature birth
    • - Acetaminophen more safe during pregnancy
    • Therapeutic uses: long-term symptomatic treatment of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, pain, primary dysmenorrhea, and acute migraine.
  99. Naproxen
    • Drug Class: NSAID
    • Major effects: anti-inflammatory, analgesic, and antipyretic activity
    • - symptomatic treatment of rheumatoid arthritis and osteoarthritis
  100. Ibuprofen
    • Drug Class: NSAID
    • Major effects: anti-inflammatory, analgesic, and antipyretic activity
    • - symptomatic treatment of rheumatoid arthritis and osteoarthritis
    • - NSAIDS can cause stomach ulcers, and this has a trade name of Nurofen
  101. Paracetamol*
    • Drug Class: Simple analgesic,
    • Drug administration: orally taken
    • Pharmacokinetics:
    • Mechanism/Target: For a mild analgesic, it is preferred in patients with Aspirin intolerance/allergy,
    • - or people with haemophilia or history of peptic ulcers and bronchospasm.
    • - Poor ability to inhibit COX at sights of inflammation (due to peroxidase presence)
    • Adverse effects:
  102. Codeine*
    • Drug Class: Simple analgesic
    • Mechanism: Binds opioid receptors (μ) in CNS; moderate agonist
    • - much less potent analgesic than morphine, but it has a higher oral efficacy.
    • - less addictive/abusive and less euphoria, longer halflife than M
    • cough-suppressant: (antitussive) effect produced by inhibition of the cough reflex is independent of the effects on nociception or respiration
    • *Nausea*: Ethanol is an inducer of CYP2E1; helps phase I metabolism. May cause increased metabolism = nausea

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