1. Clinical pharmacology Lecture 1
By : Dr. MOHAMMED JABBAR AL MANNA
Clinical Pharm. and Toxicology
Aesthetic medicine

2. Definitions
Pharmacology may be defined as the science of drugs, their preparation, their uses, and their effects.
 Drug is derived from French word ‘drogue' means a dry herb; is a single chemical entity that may be one of the constituents of a medicine.
Medicine: product that contain one or more active constituents together plus additives* intended to be used.
Prescription: the written direction for the preparation and the administration of the drug.

3. The therapeutic effect: is the primary effect intended that is the reason the drug is prescribed such as morphine sulfate is analgesia.
Side effect: secondary effect of the drug that is unintended ; side effects are usually predictable and may be either harmless
e.g, a hemorrhage from an anticoagulant (i.e related to mechanism of action)
Adverse effect : unpredictable action of drug such as allergic reaction or organ toxicities
e.g. Fever associated with vaccination
Seizures caused by withdrawal from benzodiazepines
Suicide, increased tendency associated to the use of Fluoxetine 
(i.e not related to mechanism of action)

4. Side effects (SE) of drugs
Take 5th place among causes of mortality on the Earth after cardiac-vascular diseases, malignant tumors, lungs diseases, traumas
Among stationary patients frequency of SE after introduction of drugs makes 2-40 %

5. Phocomelia
Thalidomide became in Germany around 1960 used as anti-emetic ; 5,000 and 7,000 infants were born with phocomelia.
The statistic was given that "50 % of the mothers with deformed children had taken thalidomide during the first trimester of pregnancy.

6. Cont …..
Drug interaction: also may occur when two drugs that have similar (additive) effects or opposite (canceling) effects on the body are administered together.
For example, there may be major sedation when two drugs that have sedation as side effects are given, for example, narcotics and antihistamines.

7. Cont …..
Drug abuse: is an inappropriate intake of substance either continually or periodically.
e.g laxative or emetogenic as sliming agents
Drug dependence: is a persons reliance on or need to take drug or substance there are two type of dependence:

8. Cont …..
Physiological dependence: is due to biochemical changes in the body tissue these tissue come to require substance for normal function.
Psychological dependence: is emotional reliance on a drug to maintain a since of wellbeing accompanied feeling of need.

9. Source of drugs Plants: such as digitalis, vincristine.
Fungals : penicillins
Human and animals: such as epinphrine, insulin and adrenocoticotrpoic hormone.
Minirals: as iron, iodine and zinc
Synthetic and chemical substance: as sodium bicarbonate

10. Medications are used in 6 principle ways:
1. Curative as primary therapy: e.g. bacterial infection.
2. Suppressive of disease e.g. hypertension.
3. Preventive or prophylaxis e.g. malaria.
4. Diagnosis e.g. use of dexamethasone for diagnosis of Cushing's syndrome.
5. Alleviate symptoms e.g. antacid in dyspepsia.
6. Replacement e.g. replacement of hormones .

11. The dentists should be aware of drug interactions and capable of handle any emergency during any dental procedure.
Moreover , pharmacological therapy may be responsible for an adverse effects that may be faces the dentist in clinical practice as the following examples:
E.g1:Lichen planus – like (lichenoid) reactions

12. 2: Drugs induced dental or mucosal Pigmentation
Minocycline-associated pigmentation
Nicotine stomatitis
Tetracycline induced teeth Staining

13. 4. Bisphosphonate -induced jaw osteonecrosis
3 . Drug-induced gingival hyperplasia
4. Bisphosphonate -induced jaw osteonecrosis

14. 5)Fixed drug eruption
6) Drugs induced Aphthous -Like Ulcers

15. 8) Drugs induced Cheilitis
7) Drugs induced Alveolar Osteitis .
8) Drugs induced Cheilitis
9) Drugs induced Bruxism .

16. 10) Drugs induced Oral Mucositis
11)Drugs induced Black Hairy Tongue

17. 12) Drugs induced Erythema Multiforme
13) Drugs induced Burning Mouth Syndrome

18. 14) Drugs induced Glossitis

19. Routes of drug administration :
Is the method of administering or taking the drugs into the body internally or external; systemic or local.

20. 1)Oral Route
This is the most commonly used route for drug administration.
Advantages:
1) Most Convenient to the patient
2) Acceptability
3) Painless
4) Safe
Disadvantages:
1)• Not suitable for emergencies.
2)• Incapability to absorb some drugs, due to their physical characteristics i.e. polarity of the drug.
3)• Unpalatable and other irritant drugs cannot be administered.
4)• Cannot be used for unconscious and uncooperative patient.
5)• May not be useful in the presence of vomiting and diarrhea.
6)• Drugs, which can be destroyed by digestive juices (i.e. insulin, penicillin G) or in liver (i.e. testosterone, nitroglycerine) cannot be administered orally.
7)• The absorption of certain drugs is negligible e.g. streptomycin.

21. 2)Sublingual Administration
The highly lipid soluble and nonirritating drugs (i.e. nitroglycerine, nifedipine, misoprostol) in the form of tablets or pellet is placed under the tongue, where they rapidly dissolve and are absorbed quickly in the general circulation.
Advantages:
1) Very rapid onset of action* because of abundant blood supply in the sublingual area so the drug reaches systemic circulation quickly.
2) Easy to be used
3) The effect can be terminated or reduced by spitting out the tablet.
4) Avoiding the degradation of certain drugs by gastric acid and first pass metabolism in the liver

22. first pass metabolism in the liver

23. *Onset of action: is the time from the administration of drug till the drug begins its effect.
** Duration of action: is the time from beginning of action to the end of drug action
3) Rectal administration:
(suppositories or solutions)
Advantages :
1) A drug that is irritant to the stomach can be given by suppository {e.g. indomethacin, diclofenac}
2) This route is suitable in case of vomiting, migraine or when the patient cannot swallow.
3) When cooperation is lacking {pediatrics}.
4) In cases of unconsciousness or during fit (seizures) e.g. diazepam or carbamazepine are rectally administered.

24. 4) PARENTERAL ROUTES (par = beyond, enteral = intestinal)
Types of parenteral routes are:
A)Subcutaneous {SC}
The non-irritant substances can be injected by this route.
The site of injection is usually the outer surface of the arm, or front of the thigh.
Drugs which are administered are insulin , adrenaline and hormonal preparations.
Advantages:
1) Reliable
2) Can be given by self administration
Disadvantages:
1) Poor absorption in case of peripheral circulatory failure
2) Repeated injections at one site may cause lipoatrophy, resulting in erratic absorption

26. .Angle for inserting injection

27. 2)Intramuscular{IM}
The soluble substances, mild irritants and suspensions can be injected by this route in the large skeletal muscles (deltoid, triceps, gluteus maximus, and rectus femoris.).
These muscles are less richly supplied with sensory nerves and are more vascular, so irritant solutions can be injected.
Small volumes (up to 2 ml) are injected into the deltoid muscle, and small or large volumes (up to 10 ml) are injected into the gluteal mass.
Advantages:
1) Reliable route
2) Depot preparation { Benzathine penicillin, Depo-Provera ® , Modicate ® } can be used at monthly or longer intervals
3) Suitable for irritant drugs.
4) Absorption is more rapid than subcutaneous injections (soluble preparations are absorbed in min.)

28. TYPES OF SK MUSCLES INVOLVED FOR IM INJECTIONS: 

29. Disadvantages:
1) Painful
2) Adverse effect to depot it cannot be removed
3) It is usually unacceptable for self- administration.
H W: List the factors affecting on the painful effect of IM Injection??

30. 3)Intravenous {IV}
Intravenous route is the most rapidly effective with 100% bioavailability(….?) but it is the most dangerous route of administration.
 This route is usually reserved for emergencies when a rapid action is required and infusion of large amounts of fluids to overcome dehydration or to supply nutrition to patients who cannot take food/fluids orally.

31. Note : Drugs in an oily vehicle or those which precipitate blood constituents or haemolyze erythrocytes should not be given by this route.
Disadvantages:
1) If given too rapid it may cause severe toxicity or adverse effect.
2) Can cause local venous thrombosis especially with prolonged infusion and with bolus doses of irritant formulation.
3) Infection of intravenous catheter.
4) Less safe, more expensive.
5)Inconvenient (painful) for the patient.
6)Chances of local injury at the site of injection.

32. 4) Intradermal (intralesional )
The drug is injected into the skin raising a bleb. This route is employed for vaccination e.g. BCG vaccine , treatment of alopecia areata and keloid , and for testing the sensitivity e.g. penicillin injection { procedure??}.

33. Intradermal injection can be used by dentists for some practical work for example intradermal injection of fillers {hyaluronic acid} for correction of nasolabial fold ,tears trough, and lips and cheek augmentation}.

34. 5)Intra-arterial
Certain cytotoxic compounds are administered by intra-arterial perfusion in localized malignancies.
6) Intrathecal or Intraspinal:
For local and rapid effect of drugs on the meninges or cerebrospinal axis, drugs are injected directly into the spinal subarachnoid space. This is also used to produce spinal anesthesia.
7) Intramedullary
By this method, the drug is introduced into the bone marrow of the sternum or tibia.

35. 8) Intracardiac
In sudden cardiac arrest and other cardiac emergencies, the adrenaline (1ml of 1:10000) is directly injected into the heart by a long needle in the left fourth intercostal space close to the sternum.
9) Intraperitoneal
This route is a common laboratory procedure, but it is seldom employed
clinically in infants for giving fluids like glucose saline, as the peritoneum offers a large surface for absorption.

36. 10) Intra- articular
Certain drugs (i.e. glucocorticoid) can be administered directly into a joint space for the treatment of local condition i.e. rheumatoid arthritis.

37. 11) Intra- heels
A calcaneal spur (or heel spur) is a bony outgrowth from the heel bone which are typically detected by a radiographic examination ("x-ray"). When a foot is exposed to constant stress, calcium deposits build up on the bottom of the heel bone.
Depot glucocorticoid injection can be administered directly into a heels for the treatment of calcaneous spur

38. INHALATION ROUTE
The volatile liquids and gases are given by inhalation route.
Various bronchodilators and mast cell stabilizers are used in the treatment and prophylaxis of bronchial asthma i.e. salbutamol and sodium cromoglycate inhaler.
Advantages:
1) Can be rapidly taken
2) Provide high response with minimizing systemic effect.
3) Self administration
4)aerosol and powder provide high local concentration for action on bronchi .

40. Home Work
Write advantages and disadvantages of each route of drug administration.

41. Sample Question
A client is nauseated, has been vomiting for several hours, and needs to receive an anti -nausea medication. The doctor recognizes that which of the following is accurate?
A. An enteric-coated medication should be given.
B. Medication will not be absorbed as easily because of the nausea.
C. A parental route is the route of choice.
D. A rectal suppository must be administered

42. 1)Solid Dosage Form (Internal Use)
Capsules: a drug formulation encapsulated in a hard gelatin shell .
Drug particles in the capsule are not subjected to high compression that tend to compact the powder & to reduce the effective surface area.

43. Capsules are of two types – hard & soft capsules.
Hard capsules are used for powdered drugs e.g. capsules ampicillin, tetracycline
Soft capsules are used for oils and solution of active drugs e.g. cap. Vitamins A,
A & D, E
garlic pearls, etc.

44. Spansule: is a capsule containing drug granules with special pharmaceutical formulation to be disintegrated and dissolved in different times for prolonged action (ferofolic , Olfen).

45. Tablets:
These are the most extensively used solid dosage form containing granulated or powdered drugs with inert binders as starch or lactose that are compressed into a hard mass which disintegrate in water.
A tablet before being absorbed it should disintegrate into granules and dissolute into primary drug particles. .

46. Enteric-coated tablets:
They are used to protect the drug from disintegration in the stomach (e.g. tab. erythromycin.)or to minimize gastric irritation caused by some drugs (e.g. aspirin).
Coated tablets:
They are used to mask unpleasant tastes or odor, to protect tablets ingredients from decomposition during storage , also to improve the appearance of tablet.
Sustained release tablets (S/R):
This is designed to release their content over an extended period of time e.g. diclofenac tab 100mg last 24hrs .

47. • Implants: • Chewable tablets: • Buccal or sublingual tablets:
– Are chewed in the mouth for systemic action e.g. tab. vitamin C , mebendazole (for pediatric use) etc.
• Buccal or sublingual tablets:
– Are chewed and placed under the tongue. When it dissolved and exert their action e.g. tab. nitroglycerine.
• Implants:
– Are tablets use for sustained action and implanted under the skin e.g.Deoxycortone acetone (for contraception).

48. Suppositories 2)SOLID DOSAGE FORM (EXTERNALLY USED)
are conical or ovoid solid preparations for insertion into the rectum, where they exert local or less often systemic effect. Their base is fat, wax or glycerol gelatin .

49. 3)Liquid Dosage Form (Internal Use)
Syrup : Is a concentrated aqueous solution of sugar , used as a vehicle for water soluble drugs and act both as a solvent & flavoring agent .
Suspension is a heterogeneous mixture containing solid particles that are sufficiently large for sedimentation. Usually they must be larger than one micrometer.
Advantages:
1.Immediately available for absorption.
2. Useful for children or in swallow difficulties (elderly).

50. Injections
Drugs given by injections act more rapidly & reliably, thus more useful for emergency situations. They require some technical skills, aseptic technique & suitable equipments
a. Injection:
Highly purified & sterile dosage form either in ampoules or vials (for multidose) .
There are 2 types of injections preparation:
1-Ampoule:- which contains sterile drug preparation liquid or powder to be made up in solution & used once when opened.
2-Vial:- which is designed to contain one or multiple doses & having a rubber cover to avoid contamination.

51. b. Intravenous Admixture:
(i.v. fluid) large volume injection intended to be administered by i.v. infusion , for fluid replacement ;electrolytes balance restoration; supplementary nutrition; & as vehicle for other drug substance (G/W, Albumin, Dopamine). Glucose water{ GW5%}
Normal saline {NaCl 0.9%}
Glucose saline {mixture } GS
Ringer {electrolytes}
Prefilled syringe: e.g. enoxaparin.
Pen: e.g. mixtard insulin

52. Ointments:-
Ointments are semi-solid greasy preparation for local application to the skin, rectum and mucous membrane also. Ointments are used for its soothing, astringent, antiseptic and other selected actions .
Cream:-
They are semisolid solution for external use. They are 2 kinds:-1. aqueous cream 2. oily cream.
In which the emulsions are oil in water or water in oil respectively; the aqueous creams type is relatively non greasy.

53. Cream
Ointment
1-relatively not greasy
1-greasy
2-semisoilid emulsion(oil + water)
2-semisolid anhydrous
3-more skin penetration
3-less skin penetration
4-used for wet lesions of skin
4-used for dry, chronic skin lesion
Applied to skin only
5-applid to skin, nasal mucosa & rectum

54. Drops
Could be to the eye, ear, nasal or oral drops. Nasal drops are usually aqueous waxy drop because oily drops inhibit movement of cilia in the nasal mucosa & if used for a long time, they may reach the lungs & cause lipoidal pneumonia
Ideal ear drops must be viscous (why?) ,its PH< 6(why?) , and contained steroid(why?)

55. Prescription writing :
There are two types of legal prescription according to Drugs and Cosmetics Act; those that can be obtained by prescription only medication (POM) and those that may be purchased without a prescription and one termed as non-prescription drugs or over-the-counter (OTC) drugs.
Elements of prescription:.
(i) Name and address of the prescriber.
(ii) Patient’s name, age, sex, address and date: The date of prescription should be written near the top of prescription form or at the beginning of the chart order.

56. iii) Superscription: It consists of Latin symbol Rx meaning take thau or you take and it has been believed to be an innovation to Horus and Jupiter, the father of Gods whose help is wished to make the prescription effective.
(iv) Inscription: It is the principal part or body of the prescription which specify the medication, its strength, the dosage and direction for use

57. v) Subscription: This part of prescription consists of directions to the pharmacist for dispensing or preparing the prescription.
*The instructions on how and when to take medications, the duration of therapy must be explained to each patient by the physician and the pharmacist.
(vi) Prescriber’s signature and registration number

58. Names of Drugs
The generic name: is given for the drug to being official name.
The chemical name: according to its chemical structure
The trade or brand name (proprietary name) : is name given by the drug manufacture
Example: Paracetamol (official name).
Acetaminophen (chemical name)
Panadol ® ( trade name)

59. Conversions between metric system and apothecary system:
Conversions between metric system and apothecary system:
1 grain (gr)= 60mg
1ounce(oz)=30ml
1teaspoonful=5ml
1tablespoonful=15ml
1ml=20drop
2.2pounds (1b)=1kg
20%= 20 gram in 100ml(20g/dl).
qid= four times a day
supp= suppository
susp=suspension
tab=tablet
tid= three time a day
 bid= twice a day
Cap=capsule

60. e.g. اسم الطبيب / العنوان / رقم الهاتف / اسم المريض/ العنوان / التاريخ
e.g.
اسم الطبيب /
العنوان /
رقم الهاتف /
اسم المريض/
العنوان /
التاريخ
العمر /
الجنس/ RX
1. Tetracycline 250mg.
dispense 20 cap
label : take one capsule four times daily (qid)
2. panadol 500mg
Dispense 10 tab
Label take two tablet three times daily (tid)
Signature

62. Thanks for your attention!
Good-bye !