Nice 5 min revision for selected topics DM Antithyroid drugs Drugs for peptic ulcer Diuretics BPH

1. Clinical Pharmacology
revision
SEM 3
Nehal M. Ramadan
Lecturer of clinical pharmacology
Faculty of medicine, Mansoura university
Amira Eladl
Lecturer of clinical pharmacology
Faculty of medicine, Mansoura university

2. Pharmacotherapy of
DM
Targets of therapy
● HbA1c less than 7%
● fasting blood glucose 80-130mg/dl
● 2 h post prandial blood glucose less than 180 mg/dl
Type I Type 2

3. insulin
1. Type I DM
2. Type 2 DM
○ Not controlled on OHA
○ pregnancy
○ Complications -> DKA & hyperosmolar
coma
○ Stressful conditions -> infections and
surgery etc.
3. Acute hyperkalemia
Mech. of action of insulin
SE..
1. Most common -> hypoglycemia -> treated by
glucose (oral or i.v.) or glucagon (i.v.).
2. Lipodystrophy
3. Allergic reactions like lipoatrophy

4. Anti-diabetic drugs
● Drugs → increase insulin
secretion from pancreas:
○ Sulphonylureas
○ Glinides
○ GLP-1 analogues
○ DPP-4 inhibitors
● Drugs → increase insulin action
→ (increase glucose uptake by ms
& fat cells + decrease glucose
production by liver):
○ Metformin
○ Thiazolidinedione
● Drugs → decrease insulin
reabsorption:
○ SGLT2 inhibitors

5. Anti-diabetic drugs
● GI upset
● Rarely -> fatal
lactic acidosis.
● Long-term use ->
interfere with vit
B12 absorption.
● CI -> in patients
with renal (SrCr
< 1.6 mg/dl)
and/or hepatic
disease & those
with DKA
● Hypoglycaemia ->
more in elderly &
with longer-acting
sulphonylureas).
● Weight gain.
● CVS:
○ HF-> Weight
gain -> Šfluid
retention
○ Angina and MI
->Rosiglitazone
● Hepatotoxicity ->
Troglitazone ->
monitoring of hepatic
function
● Pioglitazone -> risk of
bladder cancer
GI upset -> flatulence
& diarrhea
Metformin SUs
Glipizide
Glimepiride
Meglitinides
Repaglinide
TZDs
Pioglitazone
Acarbose
Incretin
mimetics
GLP-1
analogies
DDP-4
inhibitors
GLP-1 agonists
● GI upset
● Risk of
pancreatitis
PP-4 inhibitors
● Headache &
nausea,
● Hypersensitivity,
& skin reactions.
Stim. AMPK Stim. ATP
dependent K
channel PPAR-gamma
agonist
Inhib. Alpha glucosidase

6. Anti-diabetic drugs
● Female genital
mycotic infection
● Urinary tract
infection
● Urinary frequency
● Hypotension
SGLT-2
inhibitors
Dapagliflozin

7. Thyroid disorders

8. Replacement ttt:
1. T4 (levothyroxine) -> the form of choice.
2. T3 (liothyronine) -> faster acting
Mech. of action of antithyroid
drugs
Pharmacotherapy of
hyperthyroidism
Medical treatment (Antithyroid drugs)
1. Thiouracil drugs (thioamides)
2. Iodides
3. Drugs inhibiting the peripheral
conversion of T4 to T3
4. Adjuvant drugs
Radioactive iodine ablation
Surgical treatment
Pharmacotherapy of
hypothyroidism
_

9. Ttt of hyperthyroidism
● Faster onset &
shorter t1/2
● Used in pregnancy
● Inhin. Peripheral
conversion of F4 ->
T3
SE->
● Agranulocytosis & bone marrow depression ->
reversible -> Monitoring
● Hepatotoxicity -> more with PTU
● Hypersensitivity reactions -> vasculitis, a SLE-like
syndrome, myopathy, cholestatic jaundice and nephritis
● Acute hypersensitivity ->
swelling of lips, angioedema,
fever, joint pain
● Chronic overdose -> iodism -
> inflamed mucus
membranes, increased
salivation, lacrimation and
rhinorrhoea.
● Metallic taste.
Thioamide
s
Carbimazole
Methimazole
Propylthiouracil
Propylthiouracil Carbimazole
Iodides
Fastest
action
Radioactiv
e iodine I
131
Patients > 35
years
Patients unfit for
surgery
SE ->
● Hypothyroidism
CIs ->
● Young children
● Pregnancy
● Coexisting
ophthalmopathy
● Thyrotoxic
crisis.
Loading doe (4-8 w) ->
maintenance dose (18-24m)
inhib.
peripheral
conversion of
T4 - T3
Propranolol
PTU
Adjuvant
BB -> propranolol
& atenolol
CCB -> diltiazem
Steroids

10. Peptic ulcer

11. Pharmacotherapy of
PU X X
X
Drugs that decrease HCL secretion:
1. PPIs -> omeprazole
2. H2 blockers -> cimetidine, ranitidine
& famotidine
3. Selective M1 blockers
Drugs that neutralize HCL:
Antacids
Antimicrobial drugs for H pylori:
Drugs that increase mucosal defense:
1. Sucralfate
2. Colloid bismuth
3. Misoprostol

12. Anti-PU drugs
● Change in
bowel habits
● Cations
overload
● Decrease
absorption of
other drugs, e.g
tetracycline , iron
, digoxin
● Weaker action
● Shorter
duration of
action
● Anti-androgen
● Inhib. Liver
enzyme
● Frequent CNS
SEs
● Interfere with intrinsic
factor secretion ->
Decrease vit B12
absorption
● Decrease
bioavailability of
some drugs e.g.
ketoconazole, digoxin,
and iron.
● Omeprazole -> liver
enzyme inhibitor
● risk of fractures.
Antacids
Al(OH)3
Mg(OH)2
CaCo3
NaHCO3
H2
blockers
Cimetidine
Ranitidine
Famotidine
PPIs
Omeprazole
1st line
Ttt of H pylori
PPI+
Amoxicillin
clarithromycin
Mucosal
protection
Misoprostol
Use ->
● Prevention of
PU in those on
long term use
NSAIDs
SE->
● Diarrhea &
cramping
● Uterine
contractions
CI ->
● Pregnancy
Neutralize HCL
Irreversible inhib. H+/K+
ATPase
Cimetidine Others

13. Viral hepatitis

14. Pharmacotherapy of
HCV
● A combination of pegylated interferon
alpha (PEG INF α) + ribavirin (RBV)
(24 or 48 w)
● Direct acting antivirals (DAAs)
a. NS3/4A inhibitors -> inhib. NS3/4A
serine protease -> inhib. cleavage of
the polyprotein into structural and
NS mature viral proteins.
b. NS5B inhibitors -> inhib. NS5B
RNA-dependent RNA polymerase ->
inhib. viral replication.
c. NS5A inhibitors -> inhib. NS5A ->
inhib. Assembly of viral particles.

15. Anti-HCV drugs
● Most common ->
chronic fatigue,
muscle/joint pain.
● Blood -> anemia,
neutropenia,
thrombocytopenia,
hyperuricemia.
● Psychosis
sleeplessness &
depression
● Xero Mucosa & dry
skin.
● Allergies.
● GI disturbances
● Blood ->
Hemolytic anemia
& hyperuricemia
● Sleep problems &
depression.
● Teratogenic.
● Allergy →
Bronchospasm
& rash
PEG INF
alpha
Ribavirin NS3/4 A
Inhibitors
NS5B
inhibitors
NS5A
inhibitors
Daclatasvi
r
Guanine ribo-nucleoside
analogue -> inhib. HCV
replication Protease inhibitors
1st
generation
Boceprevir
Telaprevir
2nd
generation
Simeprevir
3rd generation
Nucleoside/nucleotid
e protease inhibitors
(NPIs)
Sofosbuvir
Non-nucleotide
inhibitors (NNPIs)
Dasabuvir

16. Pharmacotherapy of
HBV
● PEG IFNα-2a
● Nucleotide analogue (NA) (Reverse
transcriptase inhibitors)
a. More potent + low rate of resistance
-> entecavir & tenofovir
b. Less potent + high rate of resistance
-> lamivudine, telbivudine,
adefovir
Finite duration (2 y)
Moderate antiviral effect
Risk of side effects
Weekly s.c. injections
Infinite duration
potent antiviral effect
Inhib. Viral replication
Oral
Improved tolerability

17. Diuretics

18. 5 Different classes:
● Carbonic anhydrase inhibitors
(acetazolamide)
● Loop diuretics (furosemide)
● Thiazide diuretics (hydrochlorothiazide)
● K+ sparing diuretics (spironolactone)
● Osmotic diuretics (mannitol)
Pharmacotherapy of
HBV

19. SE

20. BPH

21. Medical crug
classes
Selective α1A blocker
1st line
Rapid onset
Hypotension
2nd line
Slow onset
Sexual SE
Type I & II 5AR inhibitor
Type II 5AR inhibitor
Selective M3 blocker

22. BPH drugs
● Orthostatic hypotension,
dizziness & fatigue
● Nasal congestion
Non-selective alpha 1A blockers
● Retrograde ejaculation ->
selective alpha 1A blockers
● Intraoperative floppy iris
syndrome: miosis & iris
prolapse -> tamsulosin
● Sexual ->
decreased libido,
ejaculatory
dysfunction, erectile
dysfunction,
oligospermia &
gynecomastia.
Alpha-1
blockers
5AR
inhibitors
Phosphodie
sterase-5
inhibitors
● VD -> Headache, flushing &
nasal congestion
● Loss of blue/green
discrimination -> inhibition
of PDE-6 in retina
● Muscle pain -> inhibition of
PDE-11 in skeletal muscles
● Priapism
● Used cautiously in cardiac
patients