22. Extra Pharmacology Questions Flashcards
Which of the following drugs is an agonist at muscarinic receptors?
- A. Acetylcholine
- B. Adrenaline
- C. Morphine
- D. Histamine
- E. Angiotensin II
Muscarinic Receptor Agonist
- A. Acetylcholine → Ach acts at nicotinic and muscarinic receptors
- B. Adrenaline → receptor ligands to α1, α2, or β-adrenergic receptors
- C. Morphine (opioid analgesic) → agonists on opioid receptors = mu (μ), kappa (κ), and, delta (δ) opioid, opioid receptor like-1 (ORL1)
- D. Histamine → H receptor agonists
- E. Angiotensin II → AT1 and AT2 receptors
All Muscarinic Receptors = GCPRs → 5 subtypes
Muscarinic Receptors are found in/at
- All organs innervated by parasympathetic postganglionic nerve fibres
- Sweat glands
- Autonomic ganglia
- CNS
Drugs are subject to first pass metabolism when administered by which one of the following routes of administration?
- A. Sublingual
- B. Oral
- C. Intramuscular
- D. Rectal
- E. Intravenous
First Pass Metabolism
- A. Sublingual
- B. Oral
- C. Intramuscular
- D. Rectal
- E. Intravenous
Drugs that are absorbed via the GIT are circulated to the liver first via the hepatic portal vein.
When a drug is swallowed it is absorbed from the stomach/small intestine. It enters the portal circulation and is carried by the portal vein to the liver. The liver is the major organ for drug metabolism and if the drug is extensively metabolised only a small amount of non-metabolised drug may leave the liver, go to the heart and enter the systemic circulation.
Routes of administration which avoid first pass metabolism include:
- Sublingual
- Rectal
- Transdermal
- Subcutaneous
- Intramuscular injections
• Drugs from these sites are absorbed into veins which drain to the heart without entering the portal system and liver
In the treatment of bacterial infections which of the following drugs inhibits bacterial cell wall synthesis
- A. Erythromycin
- B. Penicillin
- C. Doxycycline
- D. Gentamicin
- E. Trimethoprim
Antibiotics - Mechanism of Action
A. Erythromycin = Macrolide → Inhibits protein synthesis by binding to the 50s subunit of bacterial ribosomes.
B. Penicillin = Beta lactam → Interfere with bacterial cell wall peptidoglycan synthesis by binding to penicillin-binding proteins, leading to cell lysis and death
C. Doxycycline = Tetracycline → Inhibits protein synthesis by binding to the bacterial ribosomal 30S subunit which blocks the entry of tRNA molecules into the A site of the ribosome
D. Gentamicin = Aminoglycosides → Inhibits protein synthesis by binding to 30S subunit (different area of subunit to tetracyclines) which then results in misreading of mRNA by the ribosome
E. Trimethoprim = its own classes r→ Reversibly inhibits enzyme dihydrofolate reductase which reduces DNA synthesis.
Which of the following drugs inhibits platelet aggregation?
- A. Candesartan
- B. Atenolol
- C. Aspirin
- D. Tiotropium
- E. Omeprazole
Platelet Aggregation Inhibition
A. Candesartan → -sartan = Angiotensin II Receptor Blocker (ARB)
B. Atenolol → -olol = Beta blocker
C. Aspirin → Antiplatelet drugs reduce thrombus formation by inhibiting platelet aggregation
In platelets the enzyme cyclooxygenase 1 (COX 1) converts arachidonic acid to thromboxane A2. Thromboxane A2 induces platelet aggregation and vasoconstriction. Aspirin irreversibly inhibits COX 1, inhibits the production of thromboxane A2 and reduces platelet aggregation. Platelets do not have a nucleus and cannot regenerate COX 1.
D. Tiotropium (Spiriva)→ Long- acting antimuscarinic antagonists (LAMAs), such as tiotropium, aclidinium, glycopyrronium bromide and umeclidinium have prolonged binding to M3 muscarinic receptors, with faster dissociation from M2 muscarinic receptors, thus prolonging the duration of bronchodilator effect.
E. Omeprazole → Proton Pump Inhibitor (PPI)
Which of the following drugs inhibits the enzyme cyclooxygenase 2 (COX 2)?
- A. Celecoxib
- B. Amlodipine
- C. Amitriptyline
- D. Tramadol
- E. Cyclophosphamide
COX 2 Inhibitor
A. Celecoxib (Celebrex) → Non-traditional NSAID
B. Amlodipine → Dihydropyridine Calcium Channel Blocker - antagonist at L type channels which are an important calcium source for contraction of smooth and cardiac muscle.
C. Amitriptyline → Analgesic Adjuvants: Tricyclic antidepressants such as amitriptyline are used in the treatment of neuropathic pain. They relieve pain independently of their antidepressant effect. Exact MoA is not known but may involve inhibition of noradrenaline and serotonin reuptake, and an increase in GABA activity.
D. Tramadol (Ultram) → Opioid - weak agonist at mu (μ) receptors. Metabolised by the cytochrome P450 enzyme 2D6 to an active metabolite, O- desmethyltramadol, which is a more potent agonist at mu (μ) receptors.
E. Cyclophosphamide → Alkylating agent (Cancer drug) - form covalent bonds across the strands of DNA to produce intrastrand links and interstrand cross links. Inhibits transcription, modifies DNA structure, inhibits DNA synthesis and inhibits cell division.
Which of the following drugs binds to H+/K+ ATPase and inhibits the proton pump
- A. Famotidine
- B. Cephalexin
- C. Ranitidine
- D. Pantoprazole
- E. Verapamil
Proton Pump Inhibitors
A. Famotidine → histamine H₂ receptor antagonist - H2 receptors on parietal cells are stimulated by histamine to release HCl acid
B. Cephalexin → Beta lactam antibiotic - Interfere with bacterial cell wall peptidoglycan synthesis by binding to penicillin-binding proteins, leading to cell lysis and death.
C. Ranitidine (Zantac) → histamine H₂ receptor antagonist
D. Pantoprazole → PPI: bind to H+/K+ ATPase and inhibit the proton pump. Produce a potent and long lasting suppression of basal and stimulated gastric acid secretion. As they act distal to the receptors they can reduce gastric acid secretion irrespective of the stimulus (acetylcholine, histamine or gastrin).
E. Verapamil → Non-dihydropyridine Calcium channel blocker
Which of the following drugs is most likely to produce a cough as a side effect?
- A. Candesartan
- B. Amoxicillin
- C. Amlodipine
- D. Ramipril
- E. Celecoxib
Which of the following drugs is most likely to produce a cough as a side effect?
A. Candesartan → Angiotensin ll Receptor Antagonists - do not increase bradykinin levels (they do not inhibit ACE)
B. Amoxicillin → penicillin antibiotic = beta-lactam
C. Amlodipine → calcium channel blocker (Dihydropyridines)
D. Ramipril → -pril = ACE inhibitor - May produce a persistent, dry, non-productive, often worse at night cough. Up to 20% of patients, more common in females. Thought to be due to a build up of bradykinin.
E. Celecoxib → Non-traditional NSAID (COX 2 inhibitor)
Which of The Following Drug Combinations May Produce the Triple Whammy?
- A. ACE inhibitors, beta blockers, diuretics
- B. Angiotensin II receptor antagonists, NSAIDS, diuretics
- C. Calcium channel blockers, ACE inhibitors, NSAIDS
- D. Diuretics, paracetamol, calcium channel blockers
- E. Diuretics, ACE inhibitors, beta blockers
Triple Whammy
The following combination of medications in susceptible patients may produce renal impairment
- Angiotensin converting enzyme (ACE) inhibitor (-pril) or an angiotensin II receptor antagonist (-sartans)
- NSAID including COX 2 inhibitors (celecoxib, ibuprofen, naproxen)
- Diuretic (hydrochlorothiazide, frusemide)
How?
- An NSAID may inhibit the vasodilator effect of prostaglandins on afferent vessels, reduce renal blood flow and reduce renal function
- An ACE inhibitor (or A II receptor antagonist) may inhibit the vasoconstrictor effect of angiotensin II on efferent vessels, reduce glomerular perfusion pressure and reduce renal function.
- A diuretic may produce dehydration.
Ranitidine
- What type of drug is it?
- What is its mechanism of action?
- What is it used for?
Ranitidine
• What type of drug is it? → H2 receptor antagonist
• What is its mechanism of action?
- They are competitive antagonists of histamine at histamine H2 receptors
- By inhibiting the action of histamine at H2 receptors on the parietal cell they reduce the secretion of gastric acid
• What is it used for?
- gastric and duodenal ulcers
- dyspepsia and reflux oesophagitis (heart burn, GORD)
Ibuprofen
- What type of drug is it?
- What is its mechanism of action?
- What is it used for?
Ibuprofen
• What type of drug is it? → Traditional NSAID - exert the following effects:
- Analgesic
- Anti-inflammatory
- Antipyretic
- Anti-platelet
• What is its mechanism of action?
- Block the production of prostaglandins by inhibiting the enzyme cyclooxygenase
- Prostaglandins such as PGE2 and PGI2 are involved in pain and inflammation
- produce vasodilation
- potentiate the increased permeability of blood vessels caused by substances such as histamine and bradykinin
- sensitise nerve terminals and potentiate the pain producing effects of substances such as bradykinin and 5-hydroxytrypamine (they do not directly produce pain themselves)
• What is it used for? → NSAIDS are used in a wide variety of conditions including:
- Backache, headache, toothache
- Muscular aches and pains
- Osteoarthritis, rheumatoid arthritis
- Dysmenorrhoea, gout, some cancer pain
- Thrombotic events (low dose aspirin)
Salmeterol
- What type of drug is it?
- What is its mechanism of action?
- What is it used for?
Salmeterol
• What type of drug is it? → Long-Acting β2 Receptor Agonists (LABA) = ‘Asthma Relievers’
• What is its mechanism of action?
- Stimulate β2 receptors on bronchiole smooth muscle and produce bronchodilation
- Stimulate β2 receptors on bronchiole smooth muscle → ↑ adenylate cyclase → ↑ cAMP → bronchodilation
- Their longer duration of action is thought to be due to the fact that they are more lipid soluble than the short acting β2 agonists
• What is it used for?
- Maintenance treatment of asthma in patients receiving inhaled or oral corticosteroids (except olodaterol)
- COPD
Pantoprazole
- What type of drug is it?
- What is its mechanism of action?
- What is it used for?
Pantoprazole
• What type of drug is it? → Proton Pump Inhibitor
• What is its mechanism of action?
- They bind to H+/K+ ATPase and inhibit the proton pump
- Produce a potent and long lasting suppression of basal and stimulated gastric acid secretion
- As they act distal to the receptors they can reduce gastric acid secretion irrespective of the stimulus (acetylcholine, histamine or gastrin)
• What is it used for?
- gastric and duodenal ulcers
- dyspepsia and reflux oesophagitis (heart burn, GORD)
Alteplase
- What type of drug is it?
- What is its mechanism of action?
- What is it used for?
Alteplase
• What type of drug is it? → a serine protease tissue plasminogen activator (tPA) in the presence of fibrin = tissue plasminogen activation
• What is its mechanism of action?
- Alteplase binds to fibrin in a thrombus and converts the entrapped plasminogen to plasmin
- This initiates local fibrinolysis (thrombolysis)
- They convert plasminogen to plasmin
- Plasmin breaks down fibrin (fibrinolytic effect) which results in degradation of the thrombus
• What is it used for?
- Used in the acute tx of occlusive coronary artery disease and myocardial infarction (STEMI)
- Stroke & STEMI
- Initiated within 6 to 12 hours of onset of symptoms
- May produce bleeding and haemorrhage, which can be life threatening (e.g. intracranial, gastrointestinal)
Glyceryl Trinitrate
- What type of drug is it?
- What is its mechanism of action?
- What is it used for?
Glyceryl Trinitrate
• What type of drug is it? → Organic nitrate
• What is its mechanism of action?
- Metabolised to nitric oxide (NO), in a reaction possibly involving sulfhydryl (SH) groups
- Increase cyclic guanosine monophosphate levels (cGMP) and activate protein kinase G
- Produce vascular smooth muscle relaxation
- Relaxation of vascular smooth muscle produces vasodilation
- Relax and dilate both arteries and veins
• What is it used for? → Are effective in the treatment of coronary syndromes because they:
- Cause venous dilation which reduces venous return and preload, and reduces cardiac work and oxygen demand
- Cause artery/arteriolar dilation which reduces peripheral resistance and afterload, and reduces cardiac work and oxygen demand
- Dilate coronary vessels and increase coronary blood flow, particularly to ischaemic areas, which increases myocardial oxygen supply
Trimethoprim
- What type of drug is it?
- What is its mechanism of action?
- What is it used for?
Trimethoprim
• What type of drug is it? → Antibiotic
• What is its mechanism of action?
- Trimethoprim reversibly inhibits the enzyme dihydrofolate reductase, and inhibits the formation of tetrahydrofolic acid from dihydrofolic acid
- Human cells synthesise tetrahydrofolic acid using the enzyme dihydrofolate reductase
- Trimethoprim reversibly inhibits the enzyme dihydrofolate reductase, and inhibits the formation of tetrahydrofolic acid from dihydrofolic acid
- Human cells synthesise tetrahydrofolic acid using the enzyme dihydrofolate reductase
- It is also used in combination with sulfamethoxazole (cotrimoxazole)
- block two consecutive steps in the biosynthesis of purines and nucleic acids → ↑ antibacterial spectrum of activity
• What is it used for?
- Used to treat UTIs causedby susceptible organisms e.g. Escherichia coli (E coli)
Tamoxifen
- What type of drug is it?
- What is its mechanism of action?
- What is it used for?
Tamoxifen
• What type of drug is it? → Selective oestrogen receptor modulator (SERM)
• What is its mechanism of action?
- It blocks oestrogenreceptors in the breast, but stimulates oestrogen receptors in the uterus
- By blocking oestrogen receptors in the breast tamoxifen prevents oestrogen from binding to the oestrogen receptors
- This reduces gene transcription and inhibits tumour growth
• What is it used for?
- Cancers arising in hormone-dependent tissues may have hormone receptors on the malignant cells which can stimulate growth.
- many cancers of the breast are oestrogen dependent
Irbesartan
- What type of drug is it?
- What is its mechanism of action?
- What is it used for?
Irbesartan
• What type of drug is it? → Angiotensin ll Receptor Antagonists (ARB) = Antihypertensive
• What is its mechanism of action?
- Act as competitive antagonists of angiotensin ll at angiotensin ll type one (AT1) receptors
- Do not antagonise the effects of angiotensin II produced by the stimulation of angiotensin ll type two (AT2) receptors.
- Do not block the production of angiotensin II.
- Produce a fall in blood pressure by
- inhibiting angiotensin ll induced vasoconstriction leading to vasodilation and a drop in peripheral resistance
- inhibiting the secretion of aldosterone leading to diuresis and sodium loss
- Do not increase bradykinin levels (they do not inhibit ACE)
- Produce similar drops in BP to ACE inhibitors
• What is it used for? → Hypertension
