Pharmacology

Question 1

What is an Analgesic ?

Answer 1

A drug that that relieves PAIN

Question 2

What is an Antipyretic ?

Answer 2

A drug used to prevent or reduce FEVER

Question 3

What is an Anti-inflammatory ?

Answer 3

A drug used to decrease inflammation.

Question 4

Name some Inflammatory mediators ?

Answer 4

Prostaglandins
Leukotrines
Nitric Oxide
Bradykinin
HIstamine
Cytokines

Question 5

What is the physiological inflammatory response to inflammatory mediators ?

Answer 5

Vasodilation and endothelial restriction ( endothelial cells line the lumen)

Question 6

Where are prostaglandins and leukotrienes produced?

Answer 6

Phospholipids glycerol chain. The last 20 carbons are called Arachidonic Acid.
Arachidonic acid produces prostaglandins and leukotrienes.

Question 7

We can categorize prostaglandins into 2 main subtypes, what are the properties of each ?

Answer 7

Type 1:
- Increases inflammation
- Increases pain
- Increases fever
- Increases GIT (gastrointestinal tract) integrity. Helps maintain mucus barrier between stomach and strong HCL.
- Produce Thromboxane (TXA2) which promotes platelet aggregation therefore clotting. – Increases platelet aggregation - this promotes clotting

Type 2:
- Increases inflammation
- Increases pain
- Increases fever
- This type of prostaglandin is in high quantities in synovial fluid. Synovial fluid is found around synovial joints and more synovial fluid will increase inflammation of pain.
- This can lead to rheumatoid arthritis
- Decreases platelet aggregation

Question 8

What does NSAIDs stand for ?

Answer 8

Non Steroidal Anti - Inflammatory Drugs.

Question 9

Which inflammatory inhibitor do NSAIDs affect ?
Which enzymes do NSAIDs inhibit?

Answer 9

1. Prostaglandins
2. COX-1
   COX-2

Question 10

Which prostaglandin enzyme does Aspirin inhibit more?
Why do doctors say take Aspirin on a full stomach?

Answer 10

1. COX-1
2. Aspirin decreases GIT(gastrointestinal tract) integrity. To reduce irritation to the stomach lining you should eat Aspin with a meal.

Question 11

Why is aspirin recommended for people with cardiovascular disease or increase risk of stroke or heart attack ?

Answer 11

Aspirin reduces platelet aggregation, therefore reduces liklehood for blood to clot.

Question 12

Give an example of a NSAID that is a COX-2 specific inhibitor ?

Answer 12

CELECOXIB. Its a good COX-2 inhibit because it doesn’t increase patient likeliness of clotting.

Question 13

What is paracetamol good and bad for?

Answer 13

Good for pain ( Analgesic) and fever (Antipyretic).
Does not help decrease inflammation

Question 14

Give examples of NSAIDs which inhibit both COX-1 and COX-2 enzymes?

Answer 14

Aspirin, Ibuprofen and paracetamol

Question 15

What is the function of Leukotrienes ?

Answer 15

Increases inflammation
Increases mucous (airways)
Increases Bronchoconstriction

Leukotrienes play a big role in asthma

Question 16

Which drugs stop the function of leukotrienes ?

Answer 16

Drug type which is a Leukotriene receptor antagonist.

Question 17

What is another name for corticosteroids ?

Answer 17

Glucocorticoids

Question 18

Give examples of glucocorticoids?

Answer 18

hydrocortisone (cortisol)
cortisone

Question 18

Give examples of glucocorticoids? (steroids)

Answer 18

hydrocortisone (cortisol)
cortisone

Question 19

How do glucocorticoids decrease inflammation ?

Answer 19

They inhibit the formation of arachidonic acid which is what forms prostaglandins and leukotriene.

Question 20

What is Atropine: An antimuscarinic agent

Answer 20

Summary:
Atropine is a muscarinic antagonist used to treat poisoning by muscarinic agents, including organophosphates and other drugs.

Blocks the effects of acetylcholine and other choline esters.

Atropine drug class:
Muscarinic cholinergic receptor antagonist

What is a muscarinic cholinergic receptor?
A muscarinic acetylcholine receptor is a type of acetylcholine receptor which forms G protein-receptor complexes in the cell membranes of certain neurons. They are more sensitive to muscarine than their counterparts, nicotinic receptors, that are more sensitive to nicotine.

What is muscarine ?
is a natural product found in certain mushrooms.

Drug mechanism?
Blocks the effects of acetylcholine at the postganglionic parasympathetic nerve terminals.

Atropine binds to and inhibits muscarinic acetylcholine receptors, competitively blocking the effects of acetylcholine and other choline esters

Indications ( uses) :

In anaesthesia, blocks vagal slowing of the heart and inhibits bronchiole secretion.

To reduce intestinal spasm (e.g. for IBS).

To reduce the tremor in Parkinson’s Disease.

To prevent motion sickness.

To dilate the pupil for opthalmological examination.

Side effects: bradycardia

Contraindications:
Atropine generally is contraindicated in patients with glaucoma, pyloric stenosis, thyrotoxicosis, fever, urinary tract obstruction and ileus.

Question 21

What is
Betamethasone: A glucocorticoid receptor agonist

Answer 21

Betamethasone is a glucocorticoid receptor agonist (binds to receptor). Binding of Betamethasone to the glucocorticoid receptor, forms a complex, which moves to the nucleus, binds DNA causing alteration in gene transcription. This alter gene transcription causes the production of lipocortins, which inhibits phospholipase A2, and therefore reduces the biosynthesis of prostaglandins and leukotrienes.
Prostaglandins are lipid autacoids derived from arachidonic acid. They both sustain homeostatic functions and mediate pathogenic mechanisms, including the inflammatory response.
Leukotrienes - inflammatory molecules
In addition, corticoid steroid reduces the gene expression of interleukin-1, which is an important inflammatory cytokine.
The overall effect of both actions drives the anti-inflammatory, immunosuppressive and anti-mitogenic effects of steroids. In the plasma binds to transcortin, and it becomes active when it is not bound to transcortin.

If prescribed to be taken orally it is best to use in combination with beclomethasone. If prescribed as a glucocorticoid then better with hydrocortisone or prednisolone.

Betamethasone is a steroid medication. Reduces infalmmation

Used to treat skin diseases such as dermatitis and psoriasis.
Also used to treat rheumatic disorders e.g rheumatoid arthritis and systemic lupus erythmatosus.
Also used to treat asthma and angioedema.

Question 22

What is Digoxin: A cardiac glycoside

Answer 22

Digoxin drug class:
Cardiac glycoside
Sodium potassium ATPase inhibitor

Mechanism:
Inhibits Na/K ATPase
Which means there is more intracellular NA+
Which means there is more intracellular Ca+
Which increases the force of myocardial infraction.

Indication (reason for the drug) :
Heart failure
Supraventricular (above the ventricles) fibrillation
Atrial flutter

Contraindications:
- Recent MI (myocardial infraction)
- thyroid disease
- severe respiratory disease
- hypoxia
- ventricular tachycardia
- myocarditis

Side effects:
arrhythmias
anorexia
nausea
vomiting
diarrhea
intoxication

Question 23

What is Naloxone: An opiate antagonist ?

Answer 23

Naloxone is an opiate antagonist that prevents or reverses the effects of opioids such as respiratory depression, sedation and hypotension. As such it is described as a pure narcotic antagonist (and therefore does not induce respiratory depression). Its mechanism of action is not clear but it is thought to be able to antagonise all three opioid receptors (Mu, Kappa, and Gamma), although it has the strongest binding to the Mu receptor. It onset of action is dependent on how it is given but intravenously, the onset of action is within 2 minutes, whilst its effects are slower if given subcutaneously or intramuscularly’

Naloxone can reverse the psychotomimetic and dysphoric effects of agonist-antagonists such as pentazocine.

Question 24

What is Paracetamol: An analgesic and Antipyretic compound?

Answer 24

Another name for paracetamol: Acetaminophen
or Tylenol

Paracetamol drug class:
COX inhibitor

Background: Cyclo-oxygenase is an enzyme that converts arachidonic acid into prostaglandins, which are part of the bodies inflammatory respone, contributing towards pain. COX exists in 2 forms, COX-1 and COX-2. They both possess long channels, COX-2’s channel being slightly wider. COX-1 is involved in tissue homeostasis and is responsible for prostaglandin production in gastric cytoprotection and platelet aggregation. COX is also involved in the formation of thromboxanes - lipids that are involved in clot formation.

Drug mechanism: Paracetemol is a weak inhibitor or prostaglandin synthesis, the exact mechanism is not clear. Paracetemol has no demonstratable anti-inflammatory activity.

Indications (uses) : Mild-moderate pain and reduction of fever.

Side effects: Side effects are rare. Rashes, blood disorders, hypotension.

Contra-indications: Alcohol dependence

Paracetamol is used when NSAIDs cannot be. An example is a patient with peptic ulcer. It has analgesic and antipyretic effects, but lacks ant platelet, anti-inflammatory, and gastric ulcerative effects. The mechanism of action is complex and not well understood. There are three possible mechanisms
1) It indirectly inhibits COX, which is ineffective in the presence of peroxides. This could explain why it does not work well within platelets.
2) It inhibits COX-3. This enzyme is not well understood.
3) Its antipyretic effects are due to effects on the hypothalamus, resulting in peripheral vasodilation and sweating.

Question 25

What is Pyridostigmine: A cholinesterase inhibitor?

Answer 25

A
Pyridostigmine is a quaternary amine. As such it is poorly absorbed in the gut and doesn’t cross the blood-brain barrier. However the mode of action of Pyridostigmine is the reversible inhibition of acetylcholinesterase in the synaptic cleft by competing with acetylcholine for attachment to acetylcholinesterase. This inhibition leads to a reduction in the hydrolysis of acetylcholine, prolonging its effects. Furthermore this reduction in hydrolysis increases efficiency of cholinergic transmission in the neuromuscular junction.

Pyridostigamine has a slightly longer duration of action than neostigmine and is used in the treatment of myasthenia gravis and to reverse the actions of muscle relaxants.

Question 26

What is Rifampicin: A broad spectrum bactericidal?

Answer 26

Rifampicin is a broad spectrum antibiotic (targets both gram-positive and gram-negative organisms), which is easily absorbed and distributed within the body. Its mode of action is via the inhibition of DNA-dependent RNA polymerase, leading to a suppression of RNA synthesis and cell death. Importantly Rifampicin can target bacterial but not mammalian versions of the enzyme. Due to the emergence of resistant bacteria, the use of Rifampicin is restricted to Tuberculosis. Rifampin is metabolized in the liver and eliminated mainly in bile and, to a limited extent, in urine.

Question 27

What is Flunconazole ?

Answer 27

Summary: Fluconazole is a triazole antifungal used to treat various fungal infections including candidiasis.

Candidiasis: fungal infection caused by yeast.

Fluconazole Drug class : triazole antifungal

Indication (reason) :
- Treatment of the following fungal infections:

Fluconazole can be administered in the treatment of the following fungal infections27:

1) Vaginal yeast infections caused by Candida

2) Systemic Candida infections

3) Both esophageal and oropharyngeal candidiasis

4) Cryptococcal meningitis

5) UTI (urinary tract infection) by Candida

6) Peritonitis (inflammation of the peritoneum) caused by Candida

Mechanism of action:

Fluconazole is a very selective inhibitor of fungal cytochrome P450 dependent enzyme lanosterol 14-α-demethylase.

This enzyme normally works to convert lanosterol to ergosterol, which is necessary for fungal cell wall synthesis.

These accumulated sterols negatively affect the structure and function of the fungal cell plasma membrane

Contraindications ( reasons cant have):

• If you’ve had an allergic reaction to fluconazole or any other medicines in the past.
• heart disease, including heart rhythm problems (arrhythmia)

-kidney or liver problems

-a rare, inherited blood disorder called acute porphyria

-had a blood test that showed you have abnormal levels of potassium, calcium or magnesium

Side effects:
headache
diarrhea
nausea or upset stomach
dizziness
stomach pain
vomiting
changes in the way food tastes
severe rash in people with lowered immunity

Question 28

What is Rivastigmine ?

Answer 28

Summary: Rivastigmine is a cholinesterase inhibitor used to treat mild to moderate dementia in Alzheimer’s and Parkinson’s.

Rivastigmine drug class:
cholinesterase inhibitor

Indication (reason):

For the treatment of mild to moderate dementia associated with Parkinson’s disease or of the Alzheimer’s type.

Mechanism of action:

Rivastigmine is a carbamate derivative that is structurally related to physostigmine, but not to donepezil and tacrine.
The precise mechanism of rivastigmine has not been fully determined, but it is suggested that rivastigmine binds reversibly with and inactivates chlolinesterase (eg. acetylcholinesterase, butyrylcholinesterase), preventing the hydrolysis of acetycholine, and thus leading to an increased concentration of acetylcholine at cholinergic synapses.
The anticholinesterase activity of rivastigmine is relatively specific for brain acetylcholinesterase and butyrylcholinesterase compared with those in peripheral tissues.

Contraindications ( reason you cant have):
Cardiac conduction conditions.
Bradyarrhythmia or sick sinus syndrome.
Chronic obstructive pulmonary disease or asthma.
Bleeding ulcer history or risk.
Seizure risk or history.
Patient weight under 50 kg.

Side effects:
Rivastigmine may cause nausea, vomiting, diarrhea, stomach pain, loss of appetite, or weight loss.

Question 29

What is Pyridostigmine ?

Answer 29

Summary:
Pyridostigmine is a cholinesterase inhibitor used for symptomatic treatment of myasthenia gravis and congenital myasthenic syndromes and to reverse neuromuscular blockade by nondepolarizing muscle relaxants.

Pyridostigmine drug class:
Anticholinesterases
Cholinesterase inhibitor

What is an acetylcholinesterase:
acetylcholine is broken down by acetylchlinesterase in 2 steps
- 1) acetylcholine is hydrolysed to free choline and acetylated enzyme.
2) The covalent acetyl-enzyme bond is split with the addition of water.

Pyridostigmine drug mechanism:

Has the same action as acetylcholine, except that the breakdown of the acetyl-enzyme bond is much slower, occupying up the acetylchlinesterase and preventing it from binding to acetylcholine.

Indication (reason): Treatment of Myasthenia gravis.

Contraindications: Asthma, bradycardia, arrythmias, recent MI, epilepsy, hypotension, intestinal or

Side effects: nausea, vomitting,, increased salivation, abdominal cramps.

Question 30

What is myasthenia gravis?

Answer 30

Myasthenia gravis is a rare long-term condition that causes muscle weakness.
It most commonly affects the muscles that control the eyes and eyelids, facial expressions, chewing, swallowing and speaking. But it can affect most parts of the body

Common symptoms:
droopy eyelids
double vision
difficulty making facial expressions
problems chewing and difficulty swallowing
slurred speech
weak arms, legs or neck
shortness of breath and occasionally serious breathing difficulties

The symptoms tend to get worse when you’re tired. Many people find they’re worse towards the end of the day, and better the next morning after getting some sleep.