Pharmacy Drugs Flashcards
Thrombolytics
Streptokinase
Route of Administration - IVIntravenous
Indications
Life-threatening venous thrombosis, pulmonary embolism, arterial thromboembolism, acute myocardial infarction
Contraindications
Recent haemorrhage, trauma, surgery, aortic dissection, coma, history of cerebrovascular disease
Mechanism of Action
Forms a complex with and activates Plasminogen -> Plasmin
Adverse Drug Reactions
Nausea, vomiting, bleeding/haemorrhage
Drug-Drug Interactions
Often used in conjunction with anti-platelet and anti-coagulant drugs.
Therapeutic Notes
Streptokinase is derived from haemolytic streptococci, and is therefore antigenic. Repeated administration of streptokinase could therefore result in anaphylaxis.
If already used once previously, use t-PAs instead
Meglitidines
Examples
o Repaglinide
o Nateglinide
Indications - Uncontrolled non insulin dependant diabetes
Mechanism of action
o K+/ATP channel antagonists on β-cells, resulting in depolarisation, calcium entry and fusion of insulin containing vesicles with membrane
Adverse Drug Reactions
o Relatively lower risk of hypoglycaemia than Sulphonylureas
o Not associated with weight gain – useful in treating obese patients
Monoamine Oxidase Type B inhibitors
Examples
Selegiline
Route of Administration
Oral
Indications
Used on their own in mild cases of parkinsonism
Used in conjunction with L-DOPA to reduce end-dose ADRs
Mechanism of Action
Selegiline selectively inhibits the MAOB enzyme in the brain that is normally responsible for the breakdown of dopamine. By inhibiting breakdown, the dose of L-DOPA
Adverse Drug Reactions
Nausea
Hypotension
Psychiatric symptoms
Sulphonylureas
Examples
Gliclazide
Indications - Diabetes mellitus, in patients with residual β-cell activity
Contraindications - Breastfeeding women, elderly, renal and hepatic insufficiency
Route of Administration - Oral
Mechanism of Action
o Sulphonylureas antagonise β-cell K+/ATP activity, resulting in depolarisation. Voltage gated Ca2+ channels open, Ca2+ entry causes insulin vesicle fusion with cell membrane
Adverse Drug Reactions
o Hypoglycaemia
o GI disturbance
o Weight gain
Drug-Drug Interactions
o Highly protein bound (90-99%)
Glucocorticoids
Examples o Prednisolone (Oral) o Beclometasone - Inhaled o Hydrocortisone - IV o Dipropionate - nasal o Fluticasone - Inhaled
Indications
o Immunosuppression
o Anti-inflammatory therapy
o Replacement of endogenous corticosteroids
Contraindications - Systemic infection
Mechanism of Action
o Diffuse into cytoplasm and bind receptor. Complex moves to nucleus and binds Hormone Response Element (HRE). Inducers/Inhibits transcription.
Adverse Drug Reactions o Cushingoid effects o Suppression of HPA axis o Osteoporosis o Suppression of growth in children o Mineralocorticoid effects if the glucocorticoid also has those actions
Therapeutic Notes - Long term therapy must be withdrawn slowly, due to HPA suppression
Digoxin
Route of Administration
Oral bioavailability 70-80%
Indications Supraventricular Arrhythmias (Atrial fibrillation), Heart Failure
Contraindications
Heart block, hypokalaemia
Mechanism of Action Inhibits Na/K-ATPase Increased Inotrope – Used in heart failure, no mortality benefit Decreased Sympathetic outflow Increased Parasympathetic outflow Sensitises baroreceptor reflex Combined Effects Decreased Automaticity of SAN and AVN
Adverse Drug Reactions
Narrow therapeutic index
Toxicity enhanced with hypokalaemia
Cardiac toxicity – bradycardia, AVN block, atrial tachycardia
Drug-Drug Interactions
o Pharmacokinetic
Increased Digoxin Levels – Popafenone, Quinidine, Amiodarone, Verapamil, Spironolactone, Cylosporine
Redcued Digoxin Levels – Erythromycin, Tetracycline (gut bacteria metabolise digoxin)
o Pharmacodynamic
β-blockers, Verapamil, Diltiazem
Loop and Thiazide Diuretics (Hypokalaemia)
Therapeutic Notes
o Large volume of distribution, loading dose required for
o Loading dose split into 2 doses to minimise toxicity risk.
o Plasma levels checked 6-8 hours after dose at steady rate
o 20-30% protein bound
o Digoxin clearance is proportional to GFR (Reduce dose in elderly and renal impairment)
Mycophenolate Mofetil
Indications - Transplant immunosuppression (agent of choice)
Mechanism of Action
o Inhibits the enzyme Inosine Monophosphate Dehydrogenase, which is required for Guanosine synthesis
o Impaired B-cell and T-cell proliferation
Adverse Drug Reactions
o Myelosuppression -> Leukopenia, neutropenia
o Increased risk of infection (especially viral)
Therapeutic Notes
o Highly selective. Spares other rapidly dividing cells, due to the presence of guanosine salvage pathways
Faecal Softeners
Examples
Glycerol Suppositories
Route of Administration
Arachis Oil – Enema
Glycerol – Suppository
Indications Constipation Faecal impaction Haemorrhoids Anal fissures
Contraindications
Children less than 3 years old
Mechanism of Action
Lubricate and soften stools
Therapeutic Notes
Safe, but not always effective
Relatively slow to take effect
Thiazolineinediones
Examples
o Rosiglitazone
o Pioglitazone
Indications - Uncontrolled non insulin dependant diabetes
Contraindications
o Compromised HRH function
o Especially heart failure – can cause oedema
Mechanism of Action
o PPAR-γ agonist. Agonistically bind to a nuclear hormone receptor site.
o Reduction in gluconeogenesis and an increased glucose uptake into muscles
Adverse Drug Reactions
o GI disturbance
o Weight gain
Drug-Drug Interactions - Very heavily protein bound (~99%)
K+ channel blockers
Examples
Sotalol
Route of Administration
Orally or intravenously
Indications
Ventricular and supraventricular arrhythmias
Contraindications
AV block
Mechanism of Action
Block K+ channels (Phase 3)
Adverse Drug Reactions
Can cause arrhythmias (Torsades de Pointes)
Drug-Drug Interactions
Amiodarone inhibits CYP3A4, CYP2C9 and P-glycoprotein
Dose reductions of Warfarin, Digoxin, Flecainide needed
M2 Ion Channel Blockers
Examples
o Amantadine
o Rimantadine
Route of Administration - Oral
Indications
o Prophylaxis and treatment of acute Influenza A in groups at risk.
Mechanism of Action
o Inhibits the un-coating of a virus, therefore preventing it from being able to infiltrate into the cell. This occurs by the action of:
o Inhibits H+ influx into the cell, therefore preventing the change in pH which stimulates the viral un-coating.
o Blocks M2 Ion Channel, preventing breakdown of viral coat and release of viral RNA into host cell.
Adverse Drug Reactions
o Amantadine has more marked ADR risk than Rimantadine of ~5-10%, therefore Rimantadine is usually preferred
o Dizziness
o Hypotension
o GI disturbance
o Confusion, insomnia and hallucination can be problematic in the elderly (CNS)
o Is nephrotoxic in high doses
Therapeutic Notes
o Limited to Influenza group A, ineffective against group B
o Rapid emergence of M2 mutations in H5N1 viruses
o Resistance can develop quickly as only a single point mutation is needed in order to change the shape. This causes the binding site to move away from the channel, so that when the drug binds it will no longer block the channel E.g. amantadine in chicken feed leading to resistance
Heparin
Route of Administration Unfractionated – Intravenous
LMW – Subcutaneous
Indications o Prophylaxis Peri-operative (replace Warfarin) Immobilised patients o Treatment DVT, PE, AF, MI, Unstable Angina
Contraindications
Haemophilia, Thrombocytopenia, Peptic Ulcers
Mechanism of Action
Activates Anti-Thrombin III
Unfractionated – Inhibits Thrombin (Factor IIa) and Factor XaLMW – Inhibits Factor Xa
Adverse Drug Reactions
Bleeding/Bruising/Haemorrhage
Heparin Induced Thrombocytopenia
Therapeutic Notes
Immediate onset, so can be used in an emergency / Warfarin cover
Monitor Unfractionated with aPTT, LMWH no need to monitor
Reverse effects with Protamine Sulphate
Lamotrigine
Route of Administration
Oral
Indications
All forms of epilepsy
Contraindications
Hepatic impairment
Not first line use in paediatric patients due to ADRs
Mechanism of Action
Prolongs VGSC inactivation state
Adverse Drug Reactions
Less marked CNS dizziness, ataxia, somnolence (drowsiness)
Nausea
Some mild (10%) and serious (0.5%) skin rashes, which limits child use
Drug-Drug Interactions
Adjunct therapy with other anti-epileptic drugs
Oral Contraceptives reduce Lamotrigine plasma levels
Valproate increases Lamotrigine plasma levels (protein binding)
Therapeutic Notes
Increasingly first line anti-epileptic drug
Appears to be safer in Pregnancy
Calcineurin Inhibitors
Examples
Cyclosporin (Binds Cyclophilin)
Tacrolimus (Binds Tacrolimus-Binding-Protein)
Indications
o Prevention of graft and transplant rejection
o Prevention of graft vs. host disease
o Atopic dermatitis, psoriasis
Route of Administration - Oral, intravenous
Mechanism of Action
o Reduction in IL-2 synthesis and release, via Calcineurin inhibition suppressing both cell-mediated and antibody-specific adaptive immune responses. Active against T helper cells.
o Ciclosporin binds to Cyclophilin and Tacrolimus binds to Tacrolimus-Binding-Protein
o Drug/Protein complexes bind to and inhibit Calcineurin, which normally has a phosphatase activity on the Txn factor for IL-2. Therefore, inhibition of Calcineurin reduces IL-2
Adverse Drug Reactions
o Nephrotoxic (proximal tubule), renal damage almost always occurs
o Hypertension in 50% of people
o GI disturbances
Drug-Drug Interactions
o Metabolism is by CYP450, so is affected by inducers/inhibitors
Therapeutic Notes
Unlike most immunosuppression agents, Cyclosporin does not cause myelosuppression
Rituximab
Indications - RA
Rituximab tends to stick to one side of B cells, where CD20 is. Increasing the effectiveness of natural killer (NK) cells in destroying these B cells
Amantadine
Route of Administration
Oral
Indications
Synergistic effect when used in conjunction with L-DOPA
Mechanism of Action
Stimulates neuronal dopamine release and inhibition of its reuptake
Additional muscarinic blocking actions
Adverse Drug Reactions
Anorexia
Nausea
Hallucinations
Therapeutic Notes
Modest anti-parkinsonian effects, but it is only of short-term benefit, since most of its effectiveness is lost within 6 months
Neuramidase Inhibitors
Examples
o Zanamivir
o Oseltamivir
Route of Administration
o Zanamivir – Inhaled
o Oseltamivir – Oral (80% bioavailability)
Indications
o Treatment of Influenza A or B virus within 48 hours after onset of symptoms when influenza is endemic in the community
Contraindications - Breast feeding
Mechanism of Action
o Inhibits neuraminidase enzyme which cleaves the virus from receptors on the membrane, once the virus has been produced. It causes aggregation of the virus at the cell surface, therefore preventing the virus from spreading throughout the body and therefore to other people also.
o Sialic acid analogues, with very high binding affinities for Neuramidase.
o The receptor is not involved with antigenic shift or drift
Adverse Drug Reactions o Headache o Nose bleed o Respiratory depression (rarely) o Bronchospasm o GI disturbances
Therapeutic Notes
o Zanamivir has low bioavailability therefore is given as a dry powder inhalant. It is not used for prophylaxis.
o Oseltamivir is a pro-drug and by contrast is well absorbed, with 80% bioavailability. This enables it to be given orally for both treatment and prophylaxis.
o Gives rise to:
• 35-38% reduction in severity
• 25-36% reduction in duration when given as soon after infection as possible
Azathioprine
Indications
o Rheumatoid Arthritis, Inflammatory Bowel Disease
o Prevention of graft and transplant rejection
o Autoimmune conditions where corticosteroid therapy o alone inadequate
o Leukaemia
Route of Administration - Oral / IV
Mechanism of Action
o Azathioprine is a pro-drug, which is converted into 6-Mercaptopurine in the liver
o 6-Mercaptopurine is a fraudulent purine nucleotide that impairs DNA synthesis and has a cytotoxic action on dividing cells
Adverse Drug Reactions
o Myelosuppression -> Leukopenia, thrombocytopenia, anaemia
o Increased infection susceptibility
o GI disturbances (nausea, vomiting, diarrhoea)
o Drug-Drug Interactions
o Interacts with Allopurinol (treats gout), necessitates lowering of dose
Therapeutic Notes
6-Mercaptopurine is eliminated by the enzyme TPMT, which is subject to a high rate of genetic polymorphism. High levels of TPMT expression will lead to under-treatment, low levels of TPMT expression gives toxicity.
Cholesterol Absorption Inhibitors
Examples - Ezetimibe
Route of Administration - Oral
Indications
o Hyperlipidaemia resistant to dietary control, in statin intolerant patients
o Given in combination with a statin
Contraindications - Breastfeeding
Mechanism of Action
o Blocks NPC1L1 in the intestinal brush border, inhibiting cholesterol absorption, increasing LDL receptor upregulation leading to further reducitons
o Reduce LDL levels by 15-20%
o Ezetimibe also undergoes enterohepatic circulation, increasing its half-life.
Adverse Drug Reactions
o Gastrointestinal disturbances (Diarrhoea, pain)
o Headache
It is normally given as monotherapy in statin intolerant patients, however it will reduce LDL by a further 20% when given in combination with a statin. This is a better reduction than is gained by doubling statin dose and also reduces the risk of statin ADRs.
Ca2+ Channel blockers
Examples
Verapamil
Diltiazem
Amlodipine
Route of Administration
Oral
Indications
Supraventricular arrhythmias
Prophylaxis and treatment of angina and hypertension
Contraindications
Heart failure, bradycardia
AV Node Block
Mechanism of Action
Blocks Ca2+ channels responsible for depolarisation of pacemaker cells.
Adverse Drug Reactions
Hypotension, bradycardia, heart failure, heart block
Serotonin (5-HT3) Antagonists
Examples
Ondansetron
Route of Administration
Oral, IV or IM
Indications
In high doses in radiation sickness, chemotherapy sickness, post operatively
Mechanism of Action
5-HT is released into the gut, reducing Vagus activity, therefore effective at deactivating the vomiting centre (the Postrema on the floor of the 4th ventricle)
Blocks Serotonin receptors in Chemoreceptor Trigger Zone
Adverse Drug Reactions
Headaches, constipation, flushing
Drug-Drug Interactions
Anti-Emetic effect can be enhanced by a single dose of a corticosteroid
methylxanthines
Examples
o Theophylline
o Aminophylline
Indications
o Status asthmaticus
o COPD
Mechanism of Action
o Antagonise Adenosine receptors
Adverse Drug Reactions
o Psychomotor agitation
o Tachycardia
Therapeutic notes
o ADR profile means methylxanthines are 3rd or 4th line use for Asthma
o Narrow therapeutic window
Benzodiazepines
Examples
Diazepam
Lorazepam
Route of Administration
Oral, intravenous
Indications
Diazepam / Lorazepam – Status Epilepticus
Clonazepam – Absence seizures, short term use
Anxiety
Contraindications
Respiratory depression
Mechanism of Action
Act at a distinct receptor site on GABA Chloride channel
Binding of GABA or Benzodiazepines enhance each others binding, acting as positive allosteric effectors
Increases Chloride current into the neurone, increasing threshold for action potential generation
Adverse Drug Reactions Sedation Tolerance with chronic use Dependence/Withdrawal with chronic use Confusion, impaired co-ordination Aggression Abrupt withdrawal – seizure trigger Respiratory and CNS depression
Drug-Drug Interactions
Highly protein bound (85-100%)
Some adjunct use
Therapeutic Notes
Well absorbed (90-100%), highly plasma bound (85-100%)
Linear Pharmacokinetics, t½s vary between 15-45hours
Side effects limit first line use
Overdose reversed by IV Flumazenil
Use may precipitate seizure/arrhythmia
Loop Diuretics
Examples
o Furosemide – 50% uptake
o Bumetanide – 90% uptake. More effective if there is presence of gut oedema, as the drug crosses the gut wall better. Can change to IV from oral to avoid this.
Route of Administration
o Oral, intravenous or intramuscular. Intravenous route used in emergencies as therapeutic effect is much faster (30 mins compared to 4-6 hours orally).
Indications o Acute pulmonary oedema o Oliguria (acute renal failure) o Resistant heart failure o Hypertension
Contraindications - Severe renal impairment
Mechanism of Action
o Inhibit the Na/K/Cl co-transporter in the luminal membrane
o Blocks reabsorption of Na+ and therefore water. Can block up to 5% of Na reabsorption
Site of Action - TAL of the loop of Henle
Adverse Drug Reactions
o Hypokalaemia, Hyponatraemia, hyperuricaemia, hypotension, hypovolaemia, metabolic alkalosis
o Bumetanide can cause Myalgia (occasionally, not very common)
o Furosemide can cause Ototoxicity
Drug-Drug Interactions
o Cardiac Glycosides – Hypokalaemia caused by loop diuretics potentiates the action of cardiac glycosides, increasing the risk of arrhythmias
o Aminoglycoside Antibiotics – (E.g. Gentamycin) Will interact with loop diuretics and increase risk of ototoxicity and potential hearing loss
o Steroids – Increased risk of hypokalaemia
Thiazide Diuretics
Examples
Bendroflumethiazide
Indapamide
Indications
Hypertension
Oedema secondary to congestive cardiac failure, liver disease or nephrotic syndrome
Contraindications
Hypokalaemia, Hyponatraemia, Hypercalcaemia
Mechanism of Action
Thiazide diuretics inhibit the Na+/Cl- co-transporter in the luminal membrane in the distal tubule of the kidney. This blocks the reabsorption of Na+ and therefore water. Result is lower blood volume and pressure.
Adverse Drug Reactions
Hypokalaemia, hyperuricaemia,
Impaired glucose tolerance
Hyponatraemia, hypermagnesemia, Hypercalcaemia,
Metabolic alkalosis
Cholesterol and triglyceride levels increase
Anti-TNF Agents
Examples
o Infliximab (Monoclonal Antibody)
o Adalimumab
Mechanism of Action
o Blocks the effects of TNF-α
o Decreased inflammation, decreased Angiogenesis, decreased joint destruction
Adverse Drug Reactions o Increased infections o Tiredness, dizziness o Itching o GI disturbances
Emergency Contraceptive
Levonorgestrel
Emergency Contraception
‘Morning after pill’ – Up to 72hrs after sex
Very high oral doses of progesterone (1.5mg) alone, or a Progestogen with an oestrogen to prevent implantation of fertilised egg
o 75% effective
o Indications – Emergency Contraception after unprotected sex
o Contraindications – Oestrogen contraindications, need to ask about cycle and when they had sex to determine if the woman is already pregnant. If this is the case it would be illegal to prescribe (abortion).
Atypical Antipsychotics
Examples Olanzapine Risperidone Quetiapine Clozapine
Route of Administration
Oral
Mechanism of Action Higher affinity for 5-HT2A receptors than Dopamine D2 Receptors Sedation – Within hours Tranquilisation – Within hours Antipsychotic – Several days or weeks
Adverse Drug Reactions
Vary between drugs
Olanzapine – Significant weight gain, suppressed “full” signals
Risperidone – Increased prolactin
Sedation
Extrapyramidal side effects at high doses
Toxicity CNS depression Cardiac toxicity Risk of sudden death with high dose Prolonged QT interval -> Torsades de points Risk of sudden death with large dose
Therapeutic Notes
Atypical antipsychotics have less extrapyramidal side effects, so are therefore more acceptable to patients
First line treatment in schizophrenia
Aspirin
Route of Administration - Oral
Indications
o Prevention and treatment of MI / Ischaemic stroke, Analgesic
o Anti-inflammatory agent
Contraindications - Children under 12 years who are at risk of Reye’s Syndrome, Breastfeeding, Haemophilia, peptic ulcers, known hypersensitivity
Mechanism of Action - COX-1 Enzyme inhibitor, Prevents the formation of Thromboxane A2 from Arachidonic Acid in platelets. Thromboxane A2 stimulates phospholipase C, increasing calcium levels and causing platelet aggregation
Adverse Drug Reactions - Bronchospasm, GI haemorrhage
Drug-Drug Interactions - Displaces Warfarin from plasma proteins (PKs)
Increases Anti-Coagulant effect of Warfarin at a different site (PDs)
Therapeutic Notes
Aspirin at 150mg daily after MI has been shown to decrease mortality
Biguanides
Examples - Metformin
Indications- Type II diabetes – Endogenous insulin presence required
Contraindications
o Compromised HRH function
o In respiratory disease
Mechanism of Action
o Unknown
o Increases insulin receptor sensitivity, enhancing skeletal and adipose glucose uptake
o Inhibits hepatic gluconeogenesis
o Reduces hyperglycemia, but does not induce hypoglycemia
o Tends to be give 2-3 times a day prior to meals to provide acute negative feedback on top of a basal endogenous insulin signal
Adverse Drug Reactions
o GI disturbances – ameliorated by slow dose titration
o Lactic Acidosis
Irritant / Stimulant Laxatives
Examples
Senna
Route of Administration
Oral
Indications
Constipation and bowel evacuation prior to medical/surgical procedures
Contraindications
Intestinal obstruction
Mechanism of Action
Increase gastrointestinal peristalsis and water and electrolyte secretion by the mucosa. Possibly by excitation of sensory enteric nerves.
Adverse Drug Reactions
Colonic atony (thus constipation)
Hypokalaemia (Changing electrolyte balance in the gut)
Therapeutic Notes
Anthraquinone group is the most frequently used.
Senna can be bought O.T.C. (Senokot)
Abuse can be detected via Melanosis Coli (pigmentation of bowel wall)
Aminosalicylates
Antirheumatic Drugs (DMARDs) (DRUGS SLOW DOWN DISEASE PROGRESSION, DON’T JUST TREAT INFLAMMATION)
Examples - Sulfasalazine
Indications
o Rheumatoid arthritis
o Inflammatory bowel conditions
Contraindication
o Renal impairment
o Hypersensitivity
Mechanism of Action
o Sulfasalazine is broken down in the gut to the active component 5-aminosalicylate (5-ASA) and sulfapyridine, which acts as a vehicle to transport the drug to the colon.
o Inhibition of T-cell proliferation and IL-2 production. Reduced Neutrophil chemotaxis and degranulation.
Adverse Drug Reactions
o Mostly due to sulfapyridine (10-45% of patients)
o Myelosuppression
o Hepatitis
o Rash
o GI disturbances (Nausea, vomiting, abdominal pain)
Therapeutic Notes
o Few ADRs/DDIs seen in Pregnancy
o Treating Rheumatoid Arthritis
o Only 30-40% 5-ASA is absorbed
o Molecular mechanism does not involve COX inhibition
o Inhibit T-cell proliferation and IL-2 Production, reduced neutrophil chemotaxis and degranulation
o Treating Inflammatory Bowel Disease
o 5-ASA reaches the colon in large quantities, but acts via an unknown mechanism (again not COX inhibition)
Fibrinolytics
Examples -
Alteplase
Reteplase
Route of Administration - Intravenous
Indications
Myocardial infarction, pulmonary embolism
Contraindications
Recent haemorrhage, trauma, surgery, aortic dissection, coma, history of cerebrovascular disease
Mechanism of Action
t-PAs are tissue-type plasminogen activators, Plasminogen -> Plasmin
Adverse Drug Reactions
Nausea, vomiting, bleeding/haemorrhage
Anti-muscarinics
Examples
o Ipratropium bromide
o Tiotropium bromide
Indications
o Adjuncts to β2 agonists in asthma treatment
o COPD
Route of Administration
o Inhaled
Mechanism of Action
o Bind to and antagonise M3 cholinergic receptors on bronchial smooth muscle. This blocks the constricting effect of Ach and also inhibits mucus secretion.
Adverse Drug Reactions
o Not well absorbed through the lungs, avoiding major systemic ADRs
o Dry mouth
