WELCOME TO

PHARMACOLOGY

LECTURE

Year 2 Semester 1

Class 2009

Objectives 1. Define specified terms.2. Discuss the actions effects of

analgesic, anti-inflammatories, antiemetics and immunisations.

3. Describe how they bring about their beneficial effects.

4. Identify how group of drugs cause their side effects.

5. Define the site of actions for each drug group.

6. Describe the pharmacotherapeutics of each drug classification.

Analgesics

Any member of the drug group used to relieve pain

Analgesic – drugs used to relieve pain or remedy for pain

Act in various ways on CNS & PNS Include paracetamol, NSAIDs

(ibuprofen), narcotics (morphine), synthetics with narcotic properties (pethidine)

Analgsics

In choosing analgesics, the severity and response to other medications determines the choice of the agent.

The choice of the analgesics is also determined by the type of pain.

Non-opioid analgesics

Synthetic chemicals that do not have opium-like effects

Eg. Paracetamol and aspirin (& other NSAIDs) are suitable for pain in musculoskeletal conditions

NSIADS/Aspirin

Predispose to peptic ulcers, renal failure, allergic reactions, and occasionally hearing loss.

Can increase the risk of hemorrhage by affecting platelet function.

Inhibit cycloxygenases, leading to a decrease in prostaglandin production and this reduces pain and also inflammation.

Paracetamol

Action of paracetamol is uncertain but believed to be acting centrally

Has no anti-inflammatory activity Has few side effects Less irritating to stomach Generally preferred to aspirin Higher doses can cause damages to

liver

Aspirin (ASA) Indicated for HA, MSK pain,

dysmenorrhea & pyrexia Has antiplatelet properties Act rapidly S/E: gastric irritation Interacts with other drugs like warfarin Useful in the management of arterial

thrombosis and prevention of adverse cardiovascular events.

Non steroidal Anti Inflammatory Drugs Nonsteroidal anti-inflammatory

drugs, usually abbreviated to NSAIDs or NAIDs, are drugs with analgesic and antipyretic (fever-reducing) effects and which have, in higher doses, anti-inflammatory effects (reducing inflammation). The term "nonsteroidal" is used to distinguish these drugs from steroids. As analgesics, NSAIDs are unusual in that they are non-narcotic

Non-steroidal anti-inflammatory drugs (NSAIDs)

Useful in treatment of chronic diseases accompanied with pain & inflammation

Some used in short-term treatment of mild-moderate Musculoskeletal pain

Suitable in dysmenorrhea and pain caused by 20 bone tumors

eg. Ibuprofen, indomethacin, diclofenac, etc

NSAIDS Are generally indicated for the symptomatic

relief of the follwing conditions

- Rheumatoid arthritis

- Osteoarthritis

- Acute gout

- Dysmennorrhoea

- metastatic pain

- Headache and migrane

- Post operative pain

- Mild to moderate pain due to inflammation and tissue injury

NSAIDs cont.

Should not be given to those with peptic ulcers

S/E: GI discomfort, nausea, diarrhea, hypersensitivity rxns, HA, dizziness, drowsiness, insomnia, vertigo, hematuria

NSAIDS- Mechanism of Action Have antipyretic activity and can be

used to treat fever. Fever is caused by elevated levels of prostaglandin which alters the firing rate of neurons within the hypothalamus that control thermoregulation.

Antipyretics work by inhibiting the enzyme cyclooxygenase which causes the general inhibition of prostanoid biosynthesis within the hypothalamus.This signals to the hypothalamus to increase the body’s thermal set point.

Pharmacokinetics- NSAIDS Absorbed well in the stomach and

intestinal mucosa Highly protein bound in plasma

(usually albumin) Most NSAIDS are metabolized in the

liver by oxidation and conjugation to inactve metabolites which are partially excreated in the bile

Ibuprofen and Diclofenac have short half lives.

Adverse Effects Are mainly related to gastrointestinal

and renal However, patients on daily Aspirin

therapy (eg for reducing cardiovascular risk) need to be careful if they als use other NSAIDS as they may block the cardioprotective effects of Aspirin

Effects on the GI Causes irritation of the GI tract Causes nausea and vomiting Dyspepsia Gastric ulceration/bleeding Diarrhoea

Effects on Renal Due to the changes in the renal

hemodynamic (blood flow) Ordinarily mediated by prostaglandins

which are affected by NSAIDS. Prostaglandins normally causes

vasodilation of the afferent artrioles of the glomeruli

Common renal reactions associated with altered renal function include

- salt and fluid retention

- Hypertension

During Pregnancy Not recommended particularly during

3rd trimester NSAIDS are not direct teratogens but

they may cause premature closure of the fetal ductus arteriosus and renal adverse drug reactions in the infants

Can also cause premature birth However, paracetamol is regarded as

being safe and well tolerated.

Narcotic Analgesics Drugs

Narcotic agents are potent analgesics which are effective for the relief of severe pain.

Are selective CNS depressants used to relieve pain

Narcotic Analgesics Drugs

The main pharmacological action of analgesics is on the cerebrum and medulla of the CNS.

Another effect is on the smooth muscle and grandular secretions of the respiratory and the gastro intestinal tract.

Analgesics may relieve pain by preventing the release of acetylcholine.

Non Narcotic Analgesics Acetaminophen Is the most commonly used over the

counter non narcotic analgesic. Is an organic compound that inhibits

synthsis of prostaglandins in the central nervous system thus raising the body’s pain threshold and further impacts the temperature regulating centre of the brain thus reducing fever.

Does not have any anti inflammatory properties

Does not belong to NSAIDS Does not irritate the linning of the

stomach and cause peptic ulcers Does not affect blood coagulation,

kidney’s or the fetal ductus arteiosus Is the possible alternative for the

people who are allergic to NSAIDS or who are using anticoagulants.

Can also damage liver. HOW???

changes into metabolites which are eliminated from the body. By taking more than the required doses more

toxic metabolites are produced then can be eliminated

Opioid analgesics

eg. morphine Used to relieve moderate to severe

pain particularly of visceral origin Occurs primarily by stimulation of

receptors which suppresses the peripheral nociceptive pathway and the pain processing cortex.

Repeated administration cause tolerance and dependence

cont.

Side effects – nausea, vomiting, constipation & drowsiness

Larger doses produce respiratory depression & hypotension

Codeine – for relief of mild to moderate pain but too constipating for long-term use

Opioid Analgesics

Morphine exerts a narcotic action manifested by analgesia, drowsiness, changes in mood, and mental clouding. The major medical action of morphine sought in the CNS is analgesia.

Opiates suppress the "cough center" which is also located in the brainstem,

the medulla. Such an action is thought to underlie the use of opiate narcotics as cough suppressants. Codeine appears to be particularly effective in this action and is widely used for this purpose

Narcotic analgesics cause an addictive physical dependence. If the drug is discontinued, withdrawal symptoms are experienced

Anti inflammatory drugs Many steroids, specifically

glucocorticoids, reduce inflammation or swelling by binding to glucocorticoid receptors. These drugs are often referred to as corticosteroids.

Some clinical studies have suggested that a prolonged intake of certain anti-inflammatory (non-steroid) drugs may have a positive effect on Alzheimer.

Anti-inflammatory drugs Eg. Corticosteroids (glucocorticoids) Glucocorticoid activity of drugs bring

about anti-inflammatory effects Effective only in low mineralocorticoid

activity so that effect of water & electrolytes is not also increased

Betamethasone & dexamethasone has very high glucocorticoid activity in conjunction with low mineralocorticoid activity.

contd. Prednisolone most commonly used by

mouth for long-term disease suppression

Cortisone & hydrocortisone (high mineralocorticoid) result in fluid retention

hydrocortisone used in short-term basis by IV for emergency management of some conditions

contd.

Hydrocortisone also be used topically for skin condition because of its moderate anti-inflammatory properties

Glucocorticoids inhibit synthesis of chemical mediators (prostaglandins, leukotrienes, histamine) and thereby reduce swelling, warmth, redness and pain

Corticosteroids How do they work???? E.g dexamethasone - ??? combination enters nucleus where it

controls synthesis of protein, including enzymes that regulate vital cell activities over a wide range of metabolic functions including all aspects of inflammation

enter cells where they combine with steroid receptors in cytoplasm

Cortcosteroids act on the immune system by blocking production of the substances that trigger allergic and inflammatory actions such as prostaglandins.

Also impede the function of white blood cells which destroy foreign bodies and help keep the immune system functioning properly.

The interference with the white blood cells function yields a side effect of increased susceptability to infection.

Corticosteroids

Also used to control inflammation of the joints and organs in diseases such as

1. Rheumatoid Arthritis

2. Lupus (SLE)

Corticosteroids- Side Effect & Adverse Reactions

Potent effect of corticosteroids can result in serious side effects

- A malfunction of the adrenal glands resulting in an overproduction of cortisol

Side effects include - increased appetite and weight gain - deposits of fat in chest, face ,upper back

and stomach - water and salt retention leading to swelling

and edema.

Side effects and Adverse reactions cont….. High blood pressure Diabetes Slowed healing of wounds Osteoporosis Cataracts Acne Muscle weakness Thinning of the skin Increased susceptibility to infection Stomach ulcers Increase sweating Mood swings.

Emesis Emesis is brought about by

activation of the vomiting center (located in medulla oblongata)

Some stimuli activate directly and some indirectly

Receptors involved in vomiting response are serotonin, dopamine, acetylcholine, & histamine.

Direct –acting stimuli include signals from:

1. Cerebral cortex

2. Sensory organs

3. Vestibular apparatus of inner ear

Antiemetics Antiemetics are drugs that are used

to prevent or stop nausea and vomiting for at least 24-hours after you receive treatment or undergo certain surgical procedures.

Antiemetics act by blocking one or more of the receptors (serotonin, dopamine, acetylcholine, & histamine)

Antiemetic medicines typically work by blocking the effects of certain chemicals in the body that activate the brain's vomiting center

The main classes of antiemetics include:

1. Serotonin antagonists2. Dopamine antagonists

(eg.metochlopramide)3. Anticholinergics

-antihistamines (benadryl, meclizine)

contd. S/E: depend on what drug is used

Antiemetic The antiemetic action of

metochlopromide is due to its antagonist activity at D2 receptors in the chemoreceptors trigger zone in the central nervous system. This action prevents nausea and vomiting triggered by most stimuli.

Metochlopramide increases tone and amplitude of gastric contractions and relaxes the pyloric sphincter and duodenal bulb.

These effects make metochlopromide useful in the treatment of gastric stasis (after gastric surgery)

Inhibits the action of dopamine ( prolactin inhibiting hormone), metochloromide has sometimes been used to stimulate lactation

Other drugs used as antiemetics include:

- Promethazine- contains antihistamine and sedative properties

- Prochlorperazine- centrally acting antiemetic that selectively blocks dopamine 2 receptors in the brain

Immunization

Vaccine – preparation containing whole or fractionated microorganisms.

Killed vaccines – contain whole, killed microbes or isolated microbial components eg polysaccharide of Hib

Live (attenuated) vaccine – contain live microbes that have been weakened. E.g BCG

Toxoid – a bacterial toxin that has been changed to a nontoxic form. Admin causes body to manufacture antitoxins (eg. Tetanus & diptheria t.)

Vaccination – broadly used to mean administration of any vaccine or toxoid

Active immunity

develops in response to infection or to administration of vaccine or toxoid

the result is endogenous production of antibodies

takes weeks or months to develop long lasting

Passive immunity

Giving pts preformed antibodies (immune globulins)

Protects immediately Persists only as long as the antibodies

remain in the body

Specific Immune Globulins

Preparation contain a high concentration of antibodies

Directed against a specific antigen (eg. Hep B virus)

Administration provide immediate passive immunity

Made from donated blood and do not transmit infectious diseases