Drugs summary

Valproate (drug clas + MOA + indications + contraindications)

Drug class: anti-epileptic drug

MOA: increase number of vg Ca2+ channels in an inactivatived state, as well as increasing brain concentrations of GABA, an inhibitory neurotransmitter. This suppresses neuronal discharges that generate epileptic seizures

Indications: epilepsy, migraine prophylaxis, treatment and prophylaxis of main in BPD

Contraindications: nausea, weight gain, transient hair loss, bleeding, severe hepatic toxicity, attention issues in children, PREGNANCY

Levetiracetam (drug class + MOA + indications + ADR’s)

Drug class: anti-epileptic drug

MOA: thought to block vg Ca2+ and/ or bind to and inhibit SV2A proteins. This modulates neurotransmitter release to inhibit seizure activity

Indications: focal and generalised seizures in epilepsy

ADR’s: lethargy, fatigue, motor coordination problems, behavioural psychotic symptoms and suicidal ideation

Phenytoin (drug class + MOA + indications + contraindications + ADR’s)

Drug class: anti-epileptic drug

MOA: blocks vg Na+ channels and stabilises excitatory neuronal membranes. This suppresses repititive neuronal discharges which generates seizures

Indications: focal and generalised epileptic seizures, status epilepticus

Contraindications: avoid in patients with Stocks-Adams syndrome

ADR’s: narrow therapeutic range - vertigo, ataxia, (severe) - confusion, cognitive dysfunction, megaloblastic anaemia, hepatitis

Diazepam + midazolam (drug class + MOA + indications + ADR’s + cautions + emergency reversal)

Drug class: benzodiazepine

MOA: act as positive alloseric modulators to increase the effect of GABA on GABA-A receptors. These act as neurotransmitters to suppress electrical activity which generates seizures, as well as causing CNS inhibition to reduce anxiety. Specifically, binds allosterically between alpha and gamma subints to increase the frequency of Cl- channels opening to cause hypoerpolerisation.

Indications: short-term anxiety and insomnia, status epilepticus

M__: pre-anaesthic and dental surgery

ADR’s: drowsiness, decreased alertness, ataxia, agitation in elderly, respiratory depressiona and coma at high doses

Caution: tolerance and dependence

emergency reversal: flumazenil

Levodopa + carbidopa (Drug class + MOA + indications + ADR’s + long term effects)

Drug class:

• L__: dopamine precursor

• C__: dopa-decarboxylase inhibitor

MOA:

• L__: dopamine precursor which is converted to dopamine by dopa-decarboxylase. This replenishses striatal dopamine levels to alleviate PD symptoms

• C__: inhibits dopa-decarboxylase to prevent peripheral breakdown of levodopa to DA. This increass the amount of Levodopa available in the brain

Indications: PD symptoms: particularly bradykinesia and rigidity

ADR’s: nausea and vomiting, cardiovascular disturbance, psychiatric disturbance including vivid dreams, hallucinations, psychotic states, confusion

Long-term effects: decrease in efficiacy after 5 years

Ropinirole (Drug class + MOA + indications + ADR’s)

Drug class: dopamine receptor antagonist

MOA: acts as agonist for D2, D3, and D4 receptors. This improved PD symptoms by stimulating post-synaptic dopamine receptors in the striatum

Indications: PD symptoms

ADR’s: somnolence, hypotension, hallucinations and psychotic behaviour, dyskinesia

Management of acute ischaemic stroke

1. Stabilisation (endotracheal tube and oxygen if needed)

2. If <6hrs: mechanical thrombectomy OR

3. If <9hrs: alteplase (<4.5hrs if no surviving penumbra)

4. Aspirin + clopdogrel (AFTER 24 hrs from administering a thrombolytic agent)

5. Management of underlying pathologies e.g. HTN, AF, high cholesterol

Management of AF

Rate control: CCB’s, beta-blockers, digoxin, amiodarone

Stroke prevention: warfarin, dabigatran

Rhythm control: catheter ablation, pacemaker

Alteplase (drug class + MOA + indications + contraindications + administration)

Drug class: tissue plasinogen activator

MOA: increases cleavage of plasminogen to activate plasmin. This degrades fibrin to allow for thrombolysis

Indications: MI, PE, acute ischaemic stroke

Contraindications: patients with severe hepatic impairment, haemorrhage

Administration: 0.9mg/ kg (maximum 90mg); 10% bolus over 1 min, remaining 90% via IV-transfusion ver 60 minutes

Warfarin (drug class + MOA + indications + contraindications + emergency reversal)

Drug class: anticoagulant

MOA: inhibits hepatic production of vitamin K. This prevents activation of FX, FIX, FVII, FII and protein C and S to reduce fibrin formation

Indications: PE and stroke prevention in MI, AF, prosthetic heart valves

Contraindications: haemorrhage, 2-3rd trimester of pregnancy

Emergency reversal: prothrombin (narrow TI)

Dabigatran (drug class + MOA + indications + contraindications + administration + emergency reversal)

Drug class: direct oral anticoagulant

MOA: directly inhibits thrombin to prevent thrombin formation

Indications: DVT, PE, stroke prophylaxis

Contraindications: renal impairment, haemorrhage, prostethic heart valves

Administration: 150mg PO, BD

Emergency reversal: idarucizumab

Management of TIA

• Antiplatelets: aspirin and clopidogrel

• Atorvastatin

• Management of comorbidities (e.g. HTN)

Fluoxetine + venlafaxine (drug class, MOA, indications, contraindications, ADR’s, caution in discontinuation)

Drug class: selective serotonin reuptake inhibitor (SSRI)

MOA: selectively inhibits the reuptake of serotonin in the presynaptic terminal, thus increasing the serotonin supply to the brain. Also inhibits NA to a certain extent

Indications: depression, OCD, bulimia nervosa, premenstrual dysphoric disorder

Contraindications: manic phase, use of MAOI within 14 days

ADR’s: nausea, vomiting, diarrhoea, constipation, sexual dysfunction

Caution in discontinuation: may case dizziness (f__) and severe effects (v__)

Amitriptyline (drug class + MOA + indications + contraindications + ADR’s)

Drug class: tricyclic antidepressant

MOA: inhibits the reuptake of both 5-HT and NA, increasing the availability of these neurotransmitters in the brain

Indications: depression, neuropathic pain (low dose), migraine prophylaxis

Contraindications: immediate recovery from MI, arrhythmia, manic phase of BPD, within 14 days of MAOI

ADR’s: dry mouth, blurred vision, constipation, urinary retention, tachycardia, postural hypotension; overdose: confusion and mania

Lithium carbonate (drug class + MOA + indications + contraindications + ADR’s + cautions)

Drug class: antimanic agent

MOA: still not understood - thought to block many receptor-mediated effects via depletion of phospatidyl inositol as well as inducing BDNF and blocking NMDA receptors

Indications: acute management and prophylaxis of manic episode in BPD

Contraindications: dehydration, low Na+ diet, thyroid disorders, pregnancy and breastfeeding

ADR’s: mild cognitive deterioration, thyroid disorders

Cautions: narrow TI and long duration of action - may cause cerebellar ataxia and renal failure

Drug tolerance

Reduction in the effect of a drug with repeated administration

Mechanisms of pharmacodynamic drug tolerance

• Decrease in the number of receptors (down-regulation)

• Decrease in receptor affinity for the drug

• Decrease in the efficacy of the receptor binding to the drug

Drug dependence

A condition in which abstinence from a drug results in withdrawal syndrome, which can be alleviated by further drug use

How does drug tolerance and dependence to cannabis develop?

Tolerance: CB1 receptors in the brain are down-regulated when over-exposed to cannabinoids

Dependence: increased dopamine released from nucleus ambiguus in response to cannabis

Main psychoactive element in cannabis

Delta-9-THC

Main causes of drug-induced psychosis

• Amphetamines (e.g. metamphetamine)

• Ketamine & PCP

• Cannabis

Halopiredol (drug class + MOA + indications + ADR’s)

Drug class: typical antipsychotic

MOA: selectively antagonises post-synaptic D2 receptors, reducing dopaminergic neurotransmission in the mesolimbic pathway. This reduces hallucinations and delusions

Indications: schizophrenia, psychosis, mania and hypomania

ADR’s: extrapyramidal/ anti-cholingeric effects like tardive dyskinesia, sedation, constipation, dry mouth, blurred vision, tachycardia, urinary retention

Clozapine (drug class + MOA + indications + ADR’s)

Drug class: atypical antipsychotic

MOA: acts as weak D2-receptor antagonist, but also 5-HT2A and D4 receptor antagonist. This reduces dopamine neurotransmission to reduce hallucinations and delusions

Indications: schizophrenia in patients unresponsive to typical antipsychotics (fewer extrapyramidal side effects and fewer negative symptoms)

ADR’s: sedation, tachycardia, dizziness, seizures

Zopiclone (drug class + MOA + indications + ADR’s)

Drug class: cyclopyrrolone

MOA: acts as a positive allosteric modulator to GABA-A receptors of all different subunit types. This increases the effect of GABA, reducing neurotransmission across the brain for a calming effect

Indications: insomnia (short-term)

ADR’s: taste disturbance

Anti-cholingeric side effects

• Constipation

• Dry mouth

• Blurred vision

• Tachycardia

• urinary retention

Lignocaine (drug class + MOA + indications + contraindications + ADR’s + administration + elimination + emergency reversal)

Drug class: local anaesthetic

MOA: amide LA which acts on peripheral and central small afferent sensory fibres to block nerve transmission by blocking VSSC’s at the Nodes of Ranvier inside the axon. This prevents Na+ influx and AP transmission, causing loss of pain (and other sensation). Administered w NA (vasoconstrictor) to localise effects and NaHCO3 to increase non-ionised (active) form

Indications: surgery when consciousness is required

Contraindications: extensive procedures, hypersensitivity to some LA’s, local inflammation, infection, or ishceamia at injection site)

ADR’s: LA systemic toxicity causing cardiovascular collapse and/or LA-induced hypertension, hypersensitivity

Administration: epidural, intracathetal, nerve block, infiltration, topical

Emergency reversal: lipid emulsion (e.g. intralipid)

Process of adminstering GA

1. (Pre-medications: midazolam)

2. Rapid induction: propofol (IV)

3. Maintenance: sevoflurane +/N2O, and O2

4. Recovery: anaesthetic withdrawal + O2

Propofol (drug class + MOA + indications + ADR’s + adminstration + PK)

Drug class: sedative-hyponotic GA

MOA: acts as a GABA-A allosteric modulator to increase the effect of GABA on GABA-A receptors. This slows down closure of Cl- channels causing hyperpolarisation of the cell. This inhibits pain sensation and induces sedation

Indications: induction and (short) maintenance of anaesthesia, amnesic, anticonvulsant

ADR’s (narrow TI):

• CV and respiratory depression

• Hypotension

• Airway obstruction

• Apnoea

• Pain at site upon injection (adminster lidocaine before)

Administration: IV

PK:

• Fast onset (15-30s)

• Fast recovery (5-15mins)

• Hepatic metabolism and renal excretion

Effect of blood solubilty on volatile anaesthetics

Low solubility in blood = rapid induction (reaches blood saturation quickly)
e.g. sevoflurane

Effect of oil solubility on volatile anaesthetics

High oil solubility (low MAC) = High potency

e.g. sevoflurane

Minimum alveolar concentration (MAC)

The concentration of gas in the lungs that is needed to eliminate reflexive movement to a surgical incision in 50% of patients (measures potency)

Sevoflurane (drug class + MOA + indications + ADR’s + PK)

Drug class: volatile general anaesthetic

MOA: unclear, thought to bind to specific receptors and channel proteins within the cell membrane to inhibit post-synaptic transmission to modulate CNS activity. This induces sedation

Indications: induction and (long) maintenance of anaesthesia

ADR’s: CV and respiratory depression

PK:

• Low blood solubility: fast induction

• Good lipid solubility: potent

Insulin aspart (drug class + indications + ADR’s + administration + structure)

Drug class: rapid-acting human insulin analogue (pro → asp substitute creates steric hinderance to increase clearance)

Indications: T1D (and late stage T2D in some)

ADR’s: hypoglycaemia, weight gain

Administration: SC, before meals in basal-bolus regimen (w insulin glargine)

Structure: aa-substitution of pro → asp which created charge repulsion and steric hinderance, thus quick onset and clearance

Insulin glargine (drug class + indications + ADR’s + administration + structure)

Drug class: long-acting human insulin analogue

Indications: T1D (and late stage T2D in some)

ADR’s: hypoglycaemia, weight gain

Adminstration: SC, in evening in basal-bolus regimen

Structure: 2x arg at end of beta-chain and gly, altering isoelectric point (reduces pKa) to reduce solubility and clearane (thus longer-acting)

Metformin (drug class + MOA + indications + ADR’s + contraindications + administration)

Drug class: biguanides

MOA: inhibits mitochondrial respiration and increases AMP/ATP ratio. This activates hepatic and muscle AMPK, which signals for increased energy requirements. This increases insulin-sensitivity and inhibits hepatic gluconeogenesis, increases insulin-mediated peripheral glucose uptake in skeletal muscle and fat, and increases enterocyte glucose absoption (decreases FPG 1-4mmol/L and HbA1c 5-10)

(Functions of AMPK: SHAPE (decreases SREBP-1 associated with insulin reisstance, decreases hepatic gluconeogenesis, inhibits ACC enzymes in gluconeogenesis, promotes periheral uptake of glucose in skeletal muscle, enterocyte absorption of glucose)

Indications: 1st line for T2D, weight loss in obese

ADR’s: diarrhoea and abdominal discomfort, vitB12 malabsorption, lactic acidosis (rare)

Contraindications: severe renal injury (GFR <30ml/ min/ 1.73m2)
Administration: 250mg PO, 1-2/day, take with food to reduce stomach and bowel ADR’s

Dulaglutide (drug class + MOA + indications + ADR’s + administration)

Drug class: GLP-1 agonist

MOA: binds to and acivates GLP-1 (incretin) receptors on pancreatic beta-cells.This enhances insluin secretion in beta cells, decreases postprandial glucagon secretion in alpha cells, and slows gastric emptying to promote satiety and appetite. Also shown to have coronary benefits by increasing coronary BF and HR

Indications: 1st line for T2D w metformin, prevention of cardiovascular complications in T2D

ADR’s: nausea and vomiting, diarrhoea

Administration: SC

Vildagliptin (drug class + MOA + indications + ADR’s)

Drug class: DPP-4 inhibitor

MOA: Inhibits DPP-4, thus preventing endogenous GLP-1 breakdown. This prolongs the activity of endogenous incretin hormones (GLP1 and GIP), thus promoting insulin secretion in response to glucose and decreasing glucagon secretion and improving postprandial glycaemic control

Indications: monotherapy or add-on therapy in T2D

ADR’s: RTI, nasopharyngitis, headache

Empagliflozin (drug class + MOA + indications + ADR’s)

Drug class: SGLT2 inhibitor

MOA: selectively inhibits SGLT2 receptors (a sodium-glucose cotransporter) in the PCT, thus increasing urinary glucose excretion and reducnig plasma glucose. This also prevents water reabsorption causing short-term diuresis which lowers BP, and reduces activation of the RAAS to promote efferent arteriole vasodilation to reduce intralgomerular P

Indications: T2D as monotherapy or in combination; T2D with increased cardiovascular risk, CKD

ADR’s: hypotension, renal impairment, UTI, ketoacidosis

Frusemide (drug class + MOA + indications + ADR’s+ caution)

Drug class: loop diuretic

MOA: after secretion into PCT by OAT’s, these inhibit NKCC2 co-transporters in the TAL by competing w Cl- for binding. This prevents bulk reabsorption of Na+ and thus water. Also disrupts lumen +ve transepithelial potential difference, preventing paracellular reabsorption of Ca2+ and Mg2+. This also increases water excretion

Indications: chronic HTN in patients w impaired renal function, oedema, hyperkalaemia, hypercalcaemia, drug overdose

ADR’s: hypotension, hypokalaemia and electrolyte depletion, metabolic alkalosis, hyperuricaemia, ototoxicity

Cautions: increase dose in hypoalbuminemia (nephrotic syndrome): lack of albumin prvents frusemide binding, thus more free frusemide and less frusemide transported to tubule

Major causes of diuretic resistance

• Variable GI absorption

• Hypoalbuminemia

• Decreased kidney perfusion and/ or function

• Competition for OAT’s and transport channels

• Heightened Na+ reabsorption

Treatment of diuretic resistance

1. Increase dose/ frequency of diuretic

2. Switch frusemide to bumetanide

3. Add thiazide, MRA, or +ve inotrope

4. Restrict water, Na+, interacting meds

Bendroflumethiazide (drug class + MOA + indications + ADR’s)

Drug class: thiazide diuretic

MOA: After secretion into PCT by OAT’s, competitively binds to and inhibits apical ENCC1 transporters in the DT. This prevents Na+/Cl- and thus water and K+ reabsorption (and increases excretion_

Indications: oedema in early CKD, HTN, hypercalciuria

ADR’s: hypokalaemia, metabolic alkalosis, hypercalcamia, uricaemia, glycaemia, hypovolemia

Spironolactone (drug class + MOA + indications + ADR’s)

Drug class: mineralocorticoid antagonist/ K+ sparing diuretic

MOA: competitively binds to and prevents translocation of MR receptors on the basolateral surface of epithelial cells in the DCT and CD. This prevents aldosterone formation, thus inhibitng Na+/K+ATPase. This prevents Na+ reabsorption while sparing K+ excretion

Indications: oedema in liver and heart failure, reisstant HTN and diuretics, proteinuria, hyperaldosteronism

ADR’s: hyperkalaemia, gynaecomastia, GI disturbances

Amiloride (Drug class + MOA + indications)

Drug class: K+ sparing diuretic

MOA: inhibits ENaC channels under the influence of aldosterone in the DCT. This consequently inhibits Na+/K+ATPase, preventing Na+ reabsorption while maintaining K+

Indications: complementary action to thiazides

Enalapril (drug class + MOA + indications + ADR’s)

Drug class: ACE-I

MOA: hydrolysed into angiotensin-converting enzyme inhibitor, thus inhibiting ACE from converting Ang-I to Ang-II, and associated bradykinin breakdown. This promote bradykinin-induced vasodilation, and prevents Ang-II induced vasoconstriction and aldosteron release (which reduces GFR and promtoes Na+ and water excretion)

Indications: HTN, proteinuria and diabetic nephropathy, HF

ADR’s: hypotension, bradykinin-indcued cough and mucous augmentation, hyperkalaemia, rash, angioedema, foetal abnormalities, dysgeusia

Candesartan (drug class + MOA + indications + ADR’s)

Drug class: ARB

MOA: selectively inhibit Ang-II from binding to AT1R’s, thus inhibiting Ang-II-induced vasoconstriction (which decreases GFR and BP), and promotes Ang-II binding to AT2R’s for vasodilation

Indications: HTN, proteinuria and diabetic nephropathy, HF

ADR’s: hypotension, rash, hyperkalaemia, teratogenic

Sacubitril (drug class + MOA + indications)

Drug class: Angiotensin receptor neprilysin inhibitor (ARNI)

MOA: inhibits Ang-II from binding to neprilysin, thus inhibiting breakdown of natriuretic peptides to increase natriuresis and dieuresis. IN CONJUNCTION W VALSARTAN, this lowers BP

Indications: HTN and CHF in conjunction w valsartan

Carbimazole (MOA + indications + ADR’s + contraindications)

MOA: inhibits thyroid peroxidase, which prevents the iodination of TGB into T3 and T4, thus inhibiting synthesis of thyroid hormones

Indications: hyperthyroidism (Grave’s), thyrototoxicosis

ADR’s: bone marrow suppression, granulocytopenia (bleeding, infection), jaundice and liver toxicity

Contraindications: bone disorders, liver disease, pregnancy

Levothyroxine (MOA + indications + contraindications)

MOA: recombinant analogue of T4, thus increasing T4 uptake in cells and conversion to T3 for nuclear translocation

Indications: hypothyroidism

Contraindications: TSH suppression, acute MI or adrenal insufficiency, diabetes mellitus or insipidus

Ketoconazole + metyrapone (MOA + indications + caution)

• MOA: inhibits synthesis of cortisol, aldosterone, and androgen

  • K__: inhibits CYP11A1 and CYP11B1)

  • M__: inhibits CYP11B1 an CYP11B2

• Indications: cushing’s disease

• Caution: avoid in pregnancy and QTc prolongation, avoid abrupt withdrawal

Prednisone (drug class + MOA + indications + ADR’s + interactions)

Drug class: corticosteroid

MOA: acts as a synthetic corticosteroid to suppress inflammation by reducing expression of pro-inflammatory and increasing expression of anti-inflammatory genes

Indications: anti-inflammatory effects, corticosteroid replacement (e.g. Addison’s)

ADR’s: diabetes, CVD, infectious and autoimmune disease, Cushing’s

Interactions: affect CYP3A4 inhibitors and inductors, K+ excreting drugs (e.g. diuretics, amphotericin B)

Methotrexate (drug class + MOA + indication + ADR’s)

Drug class: folate antagonist

MOA: inhibits dihydrofolate reductase and hence folate synthesis. This prevents T nucleotide synthesis at the S phase

Indications: RA, variety of cancers (breast, bladder, head and nec, leukaemia, osteosarcoma)

ADR’s: hepatotoxicity, stomatitis, myelosuppression, nausea, abdominal pain, faitgue, dizziness, adrenal insufficiency, teratogenic

Opioids e.g. morphine, codeine, tramadol (MOA + indications + ADR’s)

MOA: bind to u, s, and k receptors in the CNS. These are GPCR receptors which inhibit adenylate cyclase, reducing cAMP production. This opens K+ channels causing hyperpolarisation of neuron cell membranes to postsynaptic neurons are unresponsive to AP’s. Calcium entry into the same cells are also restricted, inhibiting neurotransmitter release in presynaptic neurons. This leads to a decrease in transmission of pain impulses

Indications: moderate-severe pain following injury/ surgery, moderate-severe cancer-related or terminal life pain

ADR’s: constipation, hypotension, addiction, respiratory depression, nausea and vomiting, itching, bradycardia, sedation

How does drug tolerance to opioids develop?

Desensitisation of u receptors and long-term adaptive changes in nerve cells

Octreotide (MOA + indications)

MOA: acts as a somatostatin analogue to inhibit secretion of GH and glucagon

Indications: acromegaly

Levonogestrel + ethinyestradiol (drug class + MOA + indications + ADR’s + administration)

Drug class: combined oral contraceptive

MOA: contains estrogen and progesterone which cause -ve feedback on the hypothalamus to suppress follicle recruitment and ovulation. Also thicken cervical mucous and thin endometrium to prevent implantation

Indications: prevention of pregnancy, regular periods (increasing bone mineral density, prevention of atherosclerosis and RA)

ADR’s: breast tenderness, mood changes, nausea, weight gain, acne; DVT and PE RISK

• Risk increases with smoking

Administration: 21 day tablets + 7 days placebo, avoid with rifampicin, avoid with St John’s wort

Desogestrel (drug class + MOA + indications + administration)

Drug class: progesterone-only pill

MOA: contains a higher dose of P which thickens cervical mucous and thins endometrium to prevent implantation

Indications: pregnancy prevention where COC not suitable (e.g. DVT risk, smokers)

PK: daily tablet

Gabapentin (drug class + MOA + indications+ cautions)

Drug class: anticonvulsant/ analgesic

MOA: binds to vg-calcium channels, reducing calcium influx into pre-synaptic terminals, and decreasing the release of excitatory neurotransmitters associated with neuropathic pain and seizure propagation

Indications: uncontrolled epilepsy, neuropathic pain

Cautions: reduce dose in those w low eGFR (renal clearance)

Which 3 drugs (‘tripple whammy’) should never be used together to avoid CKD

• ACE-I

• ARB

• NSAID

• (all decrease GFR)

Why should NSAID doses be reduced in sevre CKD?

Inhibit COX-2-mediated renal vasodilator prostaglandins, preventing vasodilation of renal blood vessels and reducing renal blood flow (which drops GFR)

What should lidocaine be administered with?

• NaHCO3: buffers solution (increases pH) resulting in faster onset, longer duration, and less pain

• Vasoconstrictor (e.g. NA): localises LA to injected side and decreases sytemic toxicity