Documenti di Didattica
Documenti di Professioni
Documenti di Cultura
COLLEGE OF MEDICINE
List of Contents
To i#
Ho% to %&ite ! '!(o&!to&) &e o&t +- H!n,'in" of !ni-!'s /- Ro0ts of !,-inist&!tion $- T2e Res onse of 20-!n s3in to Hist!-ine & A,&en!'ine *- Effe#t of P!&!s)- !t2o-i-eti#s on "'!n,0'!& se#&etions .- D&0"s !#tin" on e)e 6- Effe#ts of D&0"s on t2e A&te&i!' B'oo, P&ess0&e of H0-!n 7- E8!'0!tion of se,!ti8e !n, to9i# effe#ts of A'#o2o's 1- E8!'0!tion of Anti-inf'!--!to&) D&0"s 4- E8!'0!tion of An!'"esi#s +5- Gene&!' !nest2esi! ++- Anti#on80's!nts +/- Antie i'e ti#s +$- Dos!"e fo&+*- P&es#&i tion %&itin"
!"e
$ * . 1 4 +5 +$ +. +6 +7 +1 +4 /5 /+ /.
E9 : No: +
HANDLING OF LABORATORAY ANIMALS
The pharmacological experiments will be mostly done on laboratory animals (mice, rats, ) rabbits*, so the animals should be treated well, as improper handling and treatment of animals may lead to failure to observe the effects, and will give rise to bad results. +o we examine the animals as following:
I-
Gene&!'
1- ,ealth: healthy or sic' animal 2- -ctivity: hyperactive, irritable, aggressive (./+ stimulants e.g. strychnine* 0 hypoactive (e.g. sedatives* 0 normally: mouse is hyperactive, rat is aggressive, and rabbit is 1uite. - 2ait: ataxic or drun'en gait (e.g. alcohol* 0 normal. !- Erection of tail: in rats due to stimulation of spinal cord by narcotics (e.g. morphine* called straub phenomenon. #- $ighting reflex: placing the animal on the lateral side, the animal will retain its normal position. &ecreased by ./+ depressants (e.g. dia3epam* and increased by ./+ stimulants (e.g. strychnine* %- 4ain reflex: reflex to painful stimulation by twisting the patella in rabbit or pinching the tail by forceps in rats ) mice. (&ecreased by narcotics ) non-narcotics*.
II-
Vit!' si"ns Each reading to be ta'en several times by different persons, ignore the odd one and ta'e the mean of remaining readings: $espiratory rate (abdominal breathing 0 nostrils* heart rate (flic'ering*
III-
E9!-in!tion of e)e 1- .on5unctival blood vessels: - congested (dilated blood 6essels* - pale (constricted blood 6essels* 2- 4upil si3e: - dilated (mydriasis* or constricted (miosis* - 7ight reflex: by shading the eye for 8 seconds then switch the light on and this will result in miosis. !- .orneal reflex: attaching cornea by piece of cotton wasp from the lateral side resulting in eye blin'ing.
Ro0tes of !,-inist&!tion #!n (e #'!ssifie, !s fo''o%s; -. Enteral (29T*: oral :. 4arenteral: intramuscular (9"*, intravenous (96*, subcutaneous (+.*, inhalational. 9n the beginning measure the weight of the animals to ensure the precision of dosage of the given drugs by using measuring scale (balance*. +: O&!' &o0te: :y placing mouth gag into the mouth of rabbit, insert rubber tube to about 28 cm. To ma'e sure that the tube is in the esophagus and not in the trachea, dip the end of the tube into a bea'er containing water (bubbling indicates wrong position*. :y using medical syringe, push 2.# ml of normal saline (/.+* into the stomach through the rubber tube. A,8!nt!"es: +imple, convenient, and acceptable. ;ral drugs can be given in different dosage forms. +afe route: since in overdose, it can be managed easily. The drug can be placed at the site of action (e.g., antihelminthics*. Dis!,8!nt!"es: +ome drugs are ,est&o)e, in t2e "0t (e.g., some penicillins, insulin, oxytocin*
#
Tablets ta'en with too small a 1uantity of li1uid and in supine position can lodge in the oesophagus with delayed absorption and may even cause ulceration (e.g., doxycycline*. +ome drugs may cause "!st&i# i&&it!tion. A(so& tion may be affected by foo, or by ot2e& ,&0"s which inhibit gut motility e.g., antimuscarinic and opiods. Fi&st !ss -et!(o'is- (by intestinal wall and by the liver* limits the efficacy of some drugs when ta'en orally. /: Int&!8eno0s <IV= &o0te; +have the hair over the ear of rabbit< rub vigorously the marginal vein with xylol to dilate the vessels, insert butterfly canula beginning from the distal end towards the proximal one. 6erify the position of needle and in5ect heparin (#88 9.= > 8.82 ml* by insulin syringe. &rugs should be given slowly. 4ress cotton onto the wound. A,8!nt!"es; 7arge volumes can be given via this route. =nconscious patient. $apid onset of action. +uitable for continuous infusion (for rapidly destroyed drugs* +uitable for too irritant drugs (anticancer drugs*. /o first pass metabolism. Dis!,8!nt!"es; 96 fluid should be a1ueous, and (isotonic* 9nfection and local venous thrombosis. The in5ected drug can not be recalled simply in case of toxicity. $: Int&!-0s#0'!& <IM= &o0te; .ommon route, and less affected by peripheral circulatory failure. 4reparation is about 2 ml, and isotonicity is not essential except for the comfort of the patient. &rug can be a1ueous or speciali3ed depot preparations. +ites of in5ection: gluteal region in the upper lateral 1uarter. A,8!nt!"es; "ore rapid than subcutaneous route as the absorption is more rapid. =nconscious patient. Dis!,8!nt!"es;
%
/ot acceptable for self administration "ay be painful *: S0(#0t!neo0s <SC= &o0te; 9n5ection (1ml or less*. "echanical pumps (insulin*. The solution to be in5ected should be a1ueous and isotonicity is not essential except for the comfort of the patient. 4oor absorption in case of peripheral circulatory failure. -dvantage: reliable and acceptable for self administration. &isadvantage: s'in reaction. .: Int&! e&itone!' <I:P= &o0te; $elatively large volume of non-irritant drugs. -bsorption is faster in the peritoneal cavity than 9" or +.. Site of in?e#tion 9n mice and rats: in the lower half of abdomen. 9n rabbits: in the lower left 1uadrant of abdomen to avoid in5uring the liver. ,old the animal and insert needle at angle of !# degrees. 6: In2!'!tion!' &o0te: The drug is ta'en through the inspired air (gas, or aerosol*. $apid absorption (wide surface area* with rapid effect almost as rapid as 96 route. 4articularly effective for respiratory disorders because the drug is delivered directly at the site of action and systemic +.E. are minimi3ed. 4ut a piece of cotton soa'ed with ether in a closed glass container, place rat or rabbit inside the 5ar and observe it. ?henever there is a change in behavior, remove the animal. A,8!nt!"es +elf-administration. .lose control of the dose. $apid onset due to wide area of absorption. Dis!,8!nt!"es; /eed special apparatus +hould not be irritant if the patient is conscious.
@
E9 : Nee,s; Mo0t2 "!"> NG t0(e> (e!3e&> s)&in"es <ins0'in> /:.>$> . -'=> ('!,e> 9)'o'> !'#o2o'> #!n0'!> 2e !&in> '!ste&> nee,'es> #otton> ?!&> et2e&> N:S> (!'!n#e:
E9 : No: $
T2e Res onse of 20-!n s3in to Hist!-ine & A,&en!'ine
Ai-; To show the effect of ,istamine and -drenaline on the human s'in. P&in#i 'e; ,istamine affects the human s'in in the term of Triple response of 7ewis .This action can be antagoni3ed by a - -ntihistamines (e.g. diphenhydramine* by bloc'ing histamine receptors in the s'in, so this is called competitive antagonism. b A -drenaline by producing action that reverses the action of histamine, so this is called physiological antagonism. Met2o,; Birst, cleanse the forearm with a swab of cotton wool soa'ed in alcohol and leave it to dry. Then by using a lancet, ma'e four transverse parallel pric's on the s'in of forearm separated from each other by distance of five centimeters. The depth of pric'ing should be superficial i.e. the route of administration is intra-dermal (9.&* namely such as not to draw blood. Then do the following steps: a- 4lace few drops of ,istamine (1:1888* on the first bric'. b- -s a control, place few drops of normal saline on the second bric'. c- ;n the third bric' ,place few drops of 1:1888 solution of antihistamine as competitive antagonist ,then after 1-2 minutes add few drops of histamine (1:1888* on the same site. d- ;n the fourth bric', place few drops of adrenaline as physiological antagonist. e- .ompare the results seen on each site.
N:B:
+- To o(t!in (ette& &es0't> it is &efe&!('e to ,o t2e !(o8e &o#e,0&e on e&sons %it2 f!i& s3in: /- T2is e9 e&i-ent is not to (e ,one on !to i# in,i8i,0!'s: E9 : Nee,s; N:S> !nti-2ist!-ine> !,&en!'ine> 2ist!-ine> D&o s> '!n#et> #otton> !'#o2o':
P!&!s)- !t2eti#
G!n"'ion
Effe#to& o&"!n
P&e"!n"'ioni#
ost"!n"'ioni#
M- &e#:
A#2
Ni#otini# &e#:
A#2 Ai- of e9 e&i-ent;
9s to show the stimulatory effect of 4arasympathomimetics on the secretion of tears in the rat.
Met2o,s;
1- 9n5ect 8.# mg0'g of .arbachol 9.4 into a rat. Examine the eyes for tears by wiping the eyelids with cotton to detect the bloody tears. /ote salivation and nasal secretion. 2- 9n5ect another rat with 2mg0'g of atropine 9.4, wait about 1#-2# minutes, and in5ect the rat with .arbachol (8.# mg0'g* 9.4 and examine for bloody tears, salivation and nasal secretion.
D
Bigure 1: The composition of the human eye I&is; That involves: .ircular muscle ("uscarinic receptors*. $adial muscle (-lpha-receptors*. Miosis; is due to either contraction of circular muscle or relaxation of radial muscle. M),&i!sis; is due to either contraction of radial muscle or relaxation of circular muscle. -lpha-agonist .ontraction of radial muscle of 9ris ("ydriasis*. Bear (+ympathetic discharge*. &eath (7ac' of muscular tone due to lac' of -ch.* Except opiod intoxication ("-agonist E 4in point "iosis* -lpha-:loc'er E $elaxation of radial muscles of 9ris ("iosis* 7ens: -ttached to the ciliary body by ligaments (figure 2*.
18
Bigure 2: +agittal section in the eye showing the lens and ciliary body Ci'i!&) (o,); that involves - .iliary epithelium (:2 receptors*: responsible for secretion of a1ueous humor. - .iliary muscle (" receptors*: responsible for near or far vision.
Ci'i!&) M0s#'e <M0s#!&ini# &e#e to&s= "-agonist .iliary ". .ontraction 7ens contraction near vision -nti-"uscarinic .iliary ". $elaxation 7ens relaxation far vision -s shown in figure . Ci'i!&) E it2e'i0- <B/-Re#e to&s= $esponsible for secretion of a1ueous humor. .ontraction of ciliary muscle presses trabecular meshwor' enhancing the flow of a1ueous humor through canal of +chlemm. .iliary muscle contraction 9ncreases flow &ecreases 9;4. .iliary muscle $elaxation &ecreases flow 9ncreases 9;4 (2laucoma*. Met2o,s; 4lace few drops of the agents in the following table into the eyes of rabbits and chec' for the parameters mentioned in the same table, and the results are as follows: Li"2t A##o--o,!tion Con?0n#ti8!' Co&ne!' Ref'e9 B'oo, sens!tion A"ent 8esse's -drenaline Fve 4ale Fve 4henylphrine "ydriasis Fve 4ale Fve 4ilocarpine "iosis Fve /ear 6ision .ongestion Fve -tropin "ydriasis -ve Bar 6ision 4ale Fve
(.ongested in ,igh &ose*
!&!-ete&
P0 i' Si@e
Gylocaine procaine
Fve Fve
-ve Fve
<A8e= in,i#!tes t2e &esen#e of t2e &ef'e9 <-8e= in,i#!tes t2e !(sen#e of t2e &ef'e9 <B= in,i#!tes t2!t t2e&e is no #2!n"e -drenaline acts on alpha-receptors causing vasoconstriction of the epithelium of con5unctiva, but it does not cause mydriasis as it cannot be absorbed by the iris. This is also true for procaine (local anesthetic* as the cornea does not absorb it, so it cannot cause loss of corneal reflex. E9 : Nee,s; At&o ine> !,&en!'ine> Pi'o#!& ine> X)'o#!ine> &o#!ine> P2en)' 2&ine> ,&o s> 'i"2t so0&#e> 0 i' s#!'e> !n, #otton.
12
P&in#i 'e;
1- Ephedrine is a sympathomimetic agent i.e. it has presser effect through stimulation of H-receptors (centrally*. ?here as, chlorproma3ine has H-bloc'ing action through its effect on the autonomic nervous system .+o it acts as antihypertensive. 2- 4lacebo drug is an inert substance that has no pharmacological action (as lactose*.
M!te&i!'s;
1- &rugs: ephedrine (1#mg*, chlorproma3ine (#8mg*, lactose powder. 2- -pparatus: sphygmomanometer, stethoscope. - Three volunteers to ta'e the drugs.
Met2o,s;
There are two methods to measure the blood pressure< firstly, the single blind techni1ue, where the volunteer does not 'now the nature of the drug that he administered, where as the examiner (the person that measures the blood pressure* 'nows that drug. +econd method is called the double blind techni1ue, that involves neither the volunteer, nor the examiner 'nows the nature of the drug that administered. The second method is more accurate than the first one because it excludes the psychological effect of 'nowing the drug that affects the measurements and the results.
T2e ,o0('e ('in, te#2niC0e #!n (e !#2ie8e, !s fo''o%in"; 1- The students are divided into groups, each group is consist of three volunteers (to ta'e the three drugs*, an examiner (to chec' the blood pressure*, and a registrar (to write down the measurements for each volunteer*. 2- -t the beginning (3ero time*, the examiner should chec' the blood pressure of the three volunteers before administration of the drugs. This is considered as baseline :.4. which should be noted by the registrar of the group. - The three drugs should be referred to as drug -, drug :, and drug . and not by their generic names. !- /ow, each volunteer will administered a certain drug orally. #- The blood pressure of the three volunteers should be chec'ed by the examiner of the group every 18 minuets after ta'ing the drugs and the measurements should be wrote down by the registrar of the group in a form of table. %- "easuring the blood pressure in one group should be done by the same examiner, using the same apparatus and by ta'ing three successive readings each time.
Res0'ts;
:y comparing the measurements and the results obtained, you can discover what is drug -, :, and .. &iscuss that accordingly.
1!
P&in#i 'e;
:oth methanol and ethanol are competing for the same en3yme for their hepatic metabolism that is alcohol dehydrogenase. This fact can be useful in the management of methanol poisoning:
Et2!no' -----------D A#et!',e2),e ----------------D A#et!te E A'#o2o' ,e2),&o"en!se F Met2!no' --------D Fo&-!',e2),e ---------------D Fo&-!te
-s ethanol has higher affinity for alcohol dehydrogenase en3yme than methanol, so it is life saving in the emergency treatment after accidental administration of methanol. "ethanol causes blindness, acidosis, respiratory depression and death.
Met2o,s;
1- measure the weight of two rats and chec' the following parameters: G!it> !in &ef'e9> &es i&!to&) &!te> onset of !nest2esi! !n, ,e!t2 if o##0&s: 2- 9n5ect one rat with methanol in a dose of mg0'g 9.4 and the other rat with ethanol in the same dose. - $ecord the time of administration and rechec' the above parameters every # minutes to see the effects of both alcohols.
1#
| |
|
| |
|
|
NSAIDs
.- Li o9)"en!se in2i(ito&
Met2o,; 1- "easure the weight of two rats to determine the dose of drugs. 2- 9n5ect one rat with acetylsalicylic acid in a dose of 188 mg0'g 9.4. and another rat with normal saline 9.4. - -fter 1# min, in5ect both rats with 8.1 ml of fresh egg white into the dorsal side of foot web of the rat. !- ;bserve for the absence of edema in the foot of the rat that received acetyl salicylic acid, and the presence of edema in the rat that did not receive the drug. E9 : Nee,s; E"" %2ite> !#et)' s!'i#)'i# !#i, <!s e"i#=> N:S> s)&in"es> nee,'es> (!'!n#e:
1%
Ne0&o e ti,e &e'e!se Inf'!--!tion ---- Me,i!to&s &e'e!se <BG> .-HT> PGs= | | | OPIATES | | | | E9#it!tion of t&!ns-ission ne0&ons ------------- No9io0s Sti-0'0s P!in
Met2o,s;
1- .hec' the weight of two rats, then observe and record the following parameters: - Ri"2tenin" &ef'e9 - P!in &ef'e9 - G!it - E&e#tion of t!i' (or what is called st&!0(Hs 2eno-enon, which occurs due to stimulation of the spinal cord by the narcotics*. 2- 9n5ect one rat with morphine (9.4* in a dose of % mg0'g and the other rat with acetyl salicylic acid (9.4* in a dose of 18 mg0'g. - $echec' the above parameters in the two animals after 1# min. and 8 min. of in5ection, and record the difference in observation.
E9 : Nee,s; C'!- in" fo&#e s> N:S> -o& 2ine> !#et)' s!'i#)'i#
!#i,> S)&in"es> nee,'es> (!'!n#e:
E9 : No: +5
1@
Gene&!' Anest2esi!
9tIs the absence of sensation associated with reversible loss of consciousness. &uring induction of anesthesia, distinct stages occur with some agents that include: St!"e +; <st!"e of !-nesi!= initially there is analgesia without amnesia, later on both analgesia and amnesia have occur. St!"e /; <st!"e of e9#ite-ent= there is irregular respiration, violent movement and urinary incontinence. St!"e $; <st!"e of s0&"i#!' !nest2esi!= there is loss of eye reflexes and the respiration is regular. St!"e *; <st!"e of -e,0''!&') ,e &ession= there is no spontaneous breathing, coma and death <t2is st!"e s2o0', not (e &e!#2e,=: The recovery from anesthesia involves the occurrence of the above stages but in reversed order, and the duration of these stages will be slower than induction.
-et2o,s ;
1- 4ut one rat in a glass 5ar with a piece of cotton soa'ed in ether. 2- ?hen the animal loses its righting reflex (fall on the side* and respiration becomes regular ( rd stage of anesthesia*, remove it from the 5ar and watch its recovery. - Ta'e care during observation of stages as the gap between stage ! and death is very narrow.
E9 : No: ++
1C
Effe#ts of Anti#on80's!nts
P&in#i 'e;
+trychnine is a ./+ stimulant that interferes with the central inhibitory processes with a powerful toxic effects.
Ai-;
To show the convulsive rigidity in rats 0 mice when strychnine is in5ected subcutaneously and to evaluate the action of anticonvulsants.
Met2o,s;
1- .hec' the weight of two mice 0 rats. 2- 9n5ect one animal with normal saline 9.4 and mar' it as control, and another animal with 4henobarbital 9.4 in a dose of #8 mg0'g. - 1# minutes later, in5ect both animals with 2.# mg0'g of strychnine +... !- $ecord the observations and time of occurrence in a table form.
E9 : No: +/
1D
Ai-;
To determine the action of dia3epam as antiepileptic in the chemical model of generali3ed convulsive St!t0s E i'e ti#0s in rats.
Met2o,;
1- .hec' the weight of two rats 0 mice. 2- 9n5ect one animal with normal saline 9.4 and mar' it as control, and another animal with dia3epam 9.4 in a dose of 2 mg 0 'g. - 1# minutes later, in5ect both animals with 7idocaine 9.4 in a dose of 1#8 mg 0 'g. !- ;bserve and record the following parameters: !(#,T2&es2o', of sei@0&e: D0&!tion of sei@0&e: T2e #!&,io J &es i&!to&) st!t0s: De!t2 if o##0&:
E9 : No: +$
28
DOSAGE FORM
IINTERNAL PREPARATIONS AEnte&!' <O&!'= !,-inist&!tion +- So'i, fo&-0'!tions T!('ets; Fi'- #o!te,> Ente&i# #o!te,> S0st!ine, &e'e!se> C2e%!('e> Effe&8es#ent: C! s0'es; O&,in!&)> S0st!ine, &e'e!se Po%,e& /LiC0i, fo&-0'!tions AC0eo0s; So'0tion> S)&0 A'#o2o'i#; Tin#t0&e> E'i9i& S0s ension & "e' B- P!&ente&!' !,-inist&!tion +- In?e#tions; A- o0'es> Vi!'s /- In2!'!tions; G!s> Ae&osol IIEXTERNAL PREPARATIONS A- S3in P&e !&!tions; C&e!-> Oint-ent> Lotion> P!int> D0stin" o%,e& B- E)e> E!&> Nose &e !&!tions; D&o s> Oint-ent C- Re#t!' & V!"in!' &e !&!tions; Re#t!' s0 osito&)> 8!"in!' s0 osito&) <Pess!&)=
D- Lo@en"es
So'i, fo&-0'!tions
21
T!('ets
Tablets are solid dosage forms in which the drug is compressed with pharmacologically inert substances called EG949E/T+. Tablets are circular in shape with flat or convex surface, and film coated to improve their appearance and stability and to mas' unpleasant taste.
C! s0'es
.apsule is a solid dosage form in which the drug is provided with gelatin shell. =sed for drugs with unpleasant taste.
Po%,e&
9t is a mixture of two or more powdered drugs intended for internal use, e.g. antacid powder.
LiC0i, fo&-0'!tions
A,8!nt!"es of 'iC0i, o8e& so'i, ,os!"e fo&-;
1. +uitable for patients who cannot swallow solid forms 2. "ore rapidly and efficiently absorbed than solid forms.
So'0tion
;ne or more soluble ingredients dissolved in water, intended for external or internal use.
S)&0
-ctive drug in a concentrated a1ueous solution of sugar.
Tin#t0&e
-lcoholic li1uid containing (in a low concentration* the active ingredient of the crude drug, e.g. tincture of iodine.
E'i9i&
22
.lear, pleasantly flavored li1uid preparation of potent drug. The vehicle contains high proportion of alcohol, sugar, or glycerol.
S0s ension
Bine solid particles of a drug suspended in a1ueous solution.
Ge'
+emi-solid a1ueous preparation prepared with the aid of gelatin.
In2!'!tions;
1. 2as: e.g. volatile anesthesia (nitrous oxide, ether* 2. -erosol: particles dispersed in a gas under pressure to deliver the drug directly into the respiratory tract.
C&e!6iscous emulsion that is either a1ueous (oil-in-water* or oily (water-inoil* and used as a vehicle for water-soluble or lipid-soluble drugs respectively. .reams are used to moisten the s'in and produce a cooling effect as water evaporates.
Oint-ent
They are semi-solid, greasy preparations for application to the s'in or mucous membranes. The base is usually anhydrous and immiscible with s'in secretions. ;intments are insoluble in water and may be used as emollients or to apply suspended or dissolved medicaments to the s'in.
Lotion
-1ueous solution or suspension used to cool and relieve pruritis in acutely inflamed lesions.
P!ints
7i1uid preparation applied with a brush to the s'in or mucous membranes.
D0stin" o%,e&
"ixture of two or more substances in fine powder form, used to reduce friction and absorb moisture.
osito&ies;
V!"in!' s0
osito&) <Pess!&)=
Lo@en"es
.onsist of medicaments incorporated in a flavored base and intended to dissolve slowly in the mouth.
2!
III- S0 e&s#&i tion < R9 =; $ecipe (treat with* IV- Ins#&i tion; &rugs +- D&0" n!-e <"ene&i# L T&!,e=
Trade name may refer to: - A#tion; -ntipyrol syrup (paracetamol*, Enterostop (diphenoxylate*, Tussiram syrup. - Co- !n); -mpidar (ampicillin*, -smasam (thiophylline*
/- Dos!"e fo&-;
Tablet, .apsule, 9n5ection (vial 0 ampoule*, +yrup, ;intment, +uppository.
*- Dose;
(/o. of forms x fre1uency per day* or :id (x2* 0 Tid (x * 0 Jid (x!*
.-
V-
2#
2%